Vf§P 3 I \- iS/ NATIONAL LIBRARY OF MEDICINE NATIONAL LIBRARY OF MEDICINE NATIONAL LI dNiDiadw do Aavaan ivnoiivn snidiqsw do Aavaan ivnoiivn 3nidio3w j NATIONAL LIBRARY OF MEDICINE NATIONAL LIBRARY OF MEDICINE NATIONAL LI 3NI3ia3W JO 3NI3IQ3W d NATIONAL LIBRARY OF MEDICINE NATIONAL LIBRARY OF MEDICINE NATIONAL L 3NI3ia3W JO AMVUBD IVNOIIVN =1 iEbDiTSD WIN a0860IZS£ 868X W68ZW 089 0/V\ NLM051709276 OF MEDICINE NATIONAL LIBRARY OF MEDICINE NATIONAL LIBRARY OF MEDICINE Uf RETURN TO NATIONAL LIBRARY OF MEDICINE BEFORE LAST DATE SHOWN i OF MEDICIN 3an tmi TVNOUVf Y OF MEDICIN ?aan ivNOiivr 1 OF MEDICIN 7 1983 / 'aan ivnoiivn snidiosw do Aavaan ivnoiivn 3nidio3w do Aavaan ivnoiivn f>1 V a QbQ ,-> K^J d\^*' ^ tf'Ul ff * - «^£ *, is the cause of what was formerly, and is still, known as " malarial disease." The following are the principal reasons for this belief :— 1. The occurrence of the plasmodium in the blood is always, sooner or later, associated with the clinical phenomena of malarial infection. 2. Malarial fever throughout, or at one time or another during its course, is practically invariably associated with the presence of this parasite in the blood. 3. The phases of malarial fevers bear a definite relation to the phases of the life cycle of the parasite. 4. Those absolutely characteristic features of malarial disease—melansemia and malarial pigmenta- tion of viscera—are fully accounted for by the melanin- forming property of the plasmodium. 5. Intravenous injection of blood from a case of malarial infection—that is, of blood containing the plasmodium—is generally, after an incubation period of eight to twelve days, followed by an attack of malarial fever and by the appearance of the plas- modium in the blood of the person injected. 6. The administration of quinine, which brings about the cessation of the clinical symptoms of acute malarial infection, rapidly causes most phases of the plasmodium to disappear from the blood. Hitherto all attempts to cultivate the parasite, whether in the ordinary culture media or inside the bodies of the lower animals, have failed. Until this has been successfully effected, and until experimental infection of man from a pure culture has been fol- lowed by typical malarial disease, absolute proof of * The malaria parasite is not a plasmodium in the zoological meaning, of the word. To this extent the introduction of the name plasmodium malnrirc is to be regretted. However, of the many names given to the organism this is the one most usually employed; and as it is now in such general use, I have thought it advisable to adopt it, notwithstanding its inaccuracy in a scien- tific sense. The Parasite. 3 the causal relationship of the parasite to the disease may be said to be wanting; short of this, however, proof is complete, and, as already remarked, the plasmodium may with confidence be accepted as the cause of malaria. Necessity for a practical knoirledge of the plas- modium.—For the full understanding, therefore, of the aetiology and pathology of malaria, apart from the very practical consideration of diagnosis, it is of the first importance that the student should be thoroughly familiar with what is known of the life- history of the plasmodium, and with the various appearances it assumes in the blood. To enable him to acquire this knowledge it is absolutely necessary that he should acquaint himself with, and practise himself in, the art of demonstrating the parasite. MORPHOLOGY AND HISTOLOGY OF PLASMODIUM MALARLE. Its zoological affinities.—Zoologically, the plas- modium is placed by most recent authorities among the sporozoa. It is closely allied to the coccidia.* Like these, for the greater part of its known life, it is an intra-cellular parasite, its special habitat so far as man is concerned being the red blood corpuscles. Many of the other vertebrata are affected by similar, though specifically distinct, parasites; that of man, so far as known, is special to himself. Of the human plasniodia there are several varie- ties, possibly species. The distinctive characteristics of each of these will be detailed farther on. The following brief description is confined to what may be regarded as the generic features common to all. * Recent observations, particularly those of R. Pfeiffer and of Simond {Ann. de Vlnst. Pasteur, July 27, 1897), by showing that many coccidia possess a double life cycle—one adapted for the multiplication of the parasite in the original host, and one adapted for its transmission to fresh hosts—have thoroughly established the close relationship, previously merely conjectured, of the plasmodium to this order of sporozoa. B 2 4 Malaria. Its three phases.—The plasmodium, like all true parasites, must be adapted not only for a life inside its host but also, in order that its continuance as a species may be assured, for a passage from one host to another. Consequently it exhibits two distinct phases —an intra-corporeal or human phase, and an extra- corporeal phase. Clinical observation makes it certain that there is yet another phase—the latent phase. Intra-corporeal or human cycle. Each variety or species of the intra-corporeal plas- modium has its special and more or less definite life- span of twenty-four hours, of forty-eight hours, or of seventy two hours. On examining malarial blood towards the end of one of these cycles, an hour or two before the occur- rence of one of the paroxysms of the characteristic periodic fever it induces, the parasite may be recog- nised as a pale, somewhat ill-defined disc of proto- plasm, occupying a larger or smaller area within a proportion of the red blood corpuscles (Fig. 1, a). JJy repeating his examinations and making them at short serial intervals, the observer is enabled Morphology of Parasite. 5 to ascertain that certain changes systematically occur in this disc of pigmented protoplasm. He will find that after a time the scattered pigment particles collect into little groups, sometimes into radiating lines. These pigment groups subsequently concentrate into one or two larger and more or less central blocks, around which the pale protoplasm of the plasmodium arranges itself in minute segments which finally acquire a globular form and appear as well- defined spherules—spores (Fig. 1, b, c, d). The including blood corpuscle then breaks down and the spores, none of which contain pigment, fall apart and, along with the clump or clumps of melanin, become free in the liquor sanguinis (Fig. 1, e). The phagocytes now quickly absorb the melanin and many of the spores. A proportion of the latter, however, escape the phagocytes and attach themselves to other blood corpuscles which, in some unknown way, they contrive to enter (Fig. 1, f). In the interior of these newly infected corpuscles the young parasites exhibit active amoeboid movement, shooting out and retract- ing long pseudopodia, and growing at the expense of the haemoglobin (Fig. 1, g). This substance they assimilate, converting it into the pale protoplasmic material constituting the mass of the parasite, and into the melanin particles (Fig. 1, h, i). As the parasite becomes larger its amoeboid movements gradually slow down until all motion finally ceases ; just before sporulation (Fig. 1, j)} beyond slight translation movement of the pigment particles, the plasmodium is passive. By staining with methylene blue, the plasmodial spore (Fig. 2, b, c, d) is found to consist of a minute, deeply tinted nucleolus surrounded by an unstained (in its early stage not very apparent) vesicular nucleus, and this again by a somewhat lightly tinted covering of protoplasm. After the spore has entered a blood corpuscle (Fig. 2, e), stain- in" shows that the vesicular nucleus has become larger and more distinct, that the protoplasm has 6 Malaria. increased in bulk, and that the deeply stained nucle- olus, which is sometimes double, has come to lie eccentrically in the nucleus. On account of the rela- tively large size of the unstained nucleus, the eccen- tric position of the deeply stained nucleolus, and the narrow rim of stained protoplasm, the younger ' Fig. 2.—Evolution of the benign tertian parasite ; stained with methylene blue. (Compiled from Mannaoerg.) parasites when stained look like so many minute blue signet-rings stuck on to the blood corpuscles. As the parasite grows and approaches maturity the nucleolus disperses and the vesicular nucleus becomes less distinct (Fig. 2, /, g, h, i) ; finally, just before sporulation, both nucleus and nucleolus have ceased to be distinguishable (Fig. 2, j, a). Apparently at this stage these elements, in some undetermined way, become fragmented or diffused throughout the protoplasm. Later the nuclear elements reappear as numerous, minute, scattered nucleoli ; and it is around these that the protoplasm of the now seg- mented parasite arranges itself to form "the spores (Fig- 2> /j>> c)- Tne vesicular nucleus does not usually appear in the spoivs until after they become free in the liquor sanguinis (Fig. 2, d). The melanin particles, so characteristic of the malaria germ, occur either in dust-like specks, in Latent Phase of Parasite. 7 coarse grains, in short rods, or aggregated into dense clumps. Until the concentration of pigment which precedes sporulation takes place the particles are scattered, being located principally in what, were we to regard the plasmodium as an amoeba, might be described as the ectosarc. Such is a brief account of the structure and life cycle of one phase of the plasmodium. From it we may understand how the parasite maintains itself and multiplies inside the human body. It does not explain, however, two important features in the life of the plasmodium, which analogy and observation clearly indicate—namely, latency and the life of the parasite outside the human body. Latent phase.—It is a well-established fact that, concurrently with the subsidence of acute clinical symptoms, the plasmodium may disappear from the general circulation and pass into a latent condition. This it does either spontaneously or as a result of the administration of quinine. As to the organ or tissue it selects, or as to its appearance and structure during this state of latency, or as to the exact conditions which cause it once more to resume active, propagating, circulating life, nothing whatever is known. This much, however, we do know—namely, that physiological strain or vital depression in the host tend to bring about conditions which break up, and that quinine and vital vigour tend to bring about conditions which favour, latency. Extra-corporeal cycle.—As it is unreasonable to suppose that an organism which propagates so actively, in the human body has no opportunity, either by passing from one host to another or in other ways, of continuing its species, we are forced to conclude that some provision must exist in the economy of the para- site that enables it to leave and enter successive hosts. And as malaria is well known to exist in many places where man is rarely found, it follows that provision must also be made in the economy of the plasmo- dium for a life, either free or parasitic, which is not 8 Malaria. dependent on man. The problems suggested by these considerations are : First, how does the malaria para- site leave the human body to get a chance of following an extra-corporeal life ; second, what is this life; and, third, how does the parasite enter the human body 1 I have advanced a theory in explanation of these points, and, together with Surgeon-Major Ronald Ross, X iooo dm. pf |V[uir Fig. 3.—Malaria parasite : flagellated body. I.M.S., have brought forward a considerable body of fact and argument in its support. I shall describe this theory, which may or may not be correct, because it seems to articulate logically many well-ascertained facts in the life-history of this important parasite, and because it gives a certain completeness to our conception of the subject. Before doing so it will be necessary to point out certain additional features or phases of the plasmodium, not yet alluded to. The flagellated body.—When fresh malarial blood is examined some time after it has been mounted it is no unusual thing to see what is known as the Parasite: The Flagellated Body. g " flagellated body " (Fig. 3).* Varieties of this body are found in all forms of plasmodial infection, in the case of the corresponding parasites of the lower warm- blooded animals as well as in the forms special to man. It is a strange-looking, octopus-like creature, with long, actively-moving arms. Though composed of the same materials—namely, colourless protoplasm and dark melanin granules—it differs from the ordinary xiooo dm. ft4[y|uir. Fig. 4.—Malaria parasite : flagellated body with free-swimming flagellum. parasite inasmuch as it is not intra-corpuscular. The long, whip like arms, numbering from one to six, or even more, are usually designated flagella. They are exceedingly delicate and pliant filaments; often difficult to see, not only on account of their delicacy but also on account of the rapidity of their move- ments. Sometimes bulbous at the free extremity, sometimes presenting one or more swellings in their continuity, the flagella are three or four times as long * The expressions "flagellated body" and "flagellum," applied to this phase of the malaria parasite are somewhat misleading. The flagella of the malaria parasite are in no sense analogous to the flagella of the flagellata. io Malaria. as a blood corpuscle is broad. At first they are attached to the periphery of the pigmented central, more or less spherical, body, which is about half the diameter of a red blood corpuscle. The movements of the flagella are so vigorous that, without seriously injuring them, they double up and distort temporarily those corpuscles with which they chance to come in contact. Occasionally it may be observed that one Fig. 5.— Malaria parasite : the crescent body ; stained, (x 1000.) or more of the flagella break away from the central sphere and swim free in the blood (Fig. 4), remaining active for a considerable time—several hours perhaps —before they finally vanish. Careful observation shows that the flagellated bodies are developed from two forms of the intra- corpuscular parasite—namely, in certain types of malarial infection from what is known as the " cres- cent body "; in other types from certain lar^e intra- corpuscular plasmodia. It is of importance to bear in mind that they are never seen in newly-drawn blood and that they come into view only after the slide has Parasite: The Crescent Body. ii been mounted for some time—ten to thirty minutes or even longer, according to circumstances. The crescent body.—The shape, size, and struc- ture of the crescent body can best be comprehended from the illustration (Fig. 5). The principal features to be noted are its very definite mathe- matical shape ; the probable existence of a delicate limiting membrane; the presence of melanin particles usually about the centre of the parasite, though sometimes nearer one end ; and a peculiar bow-like and ex- ceedingly delicate line that, springing from the horns of the crescent, bridges its con- cavity. Manifestly this bow represents the outline of the remains of the blood cor- puscle in which the parasite had developed. In many in- stances, especially in stained specimens, the continuation of the red blood corpuscle can be distinctly traced around the convexity of the crescent. This circumstance—together with the fact that the material in- cluded by the bow and also occasionally seen as a delicate, sometimes slightly jagged, rim around the convexity of the crescent, gives the staining re- actions of haemoglobin—proves that this form of the malaria parasite, like the ordinary plasmodium, is also intra-corpuscular. Slight differences, par- ticularly as regards the sharpness or obtuseness of the horns, occur; but, on the whole, the crescents are very uniform in appearance. Very rarely twin or double crescents—that is, two crescents in one corpuscle— are encountered (Fig. 6). Although the origin of the crescent body has not been conclusively explained, it seems to me that Mannaberg's suggestion that it is the result of the conjugation of two ordinary i. — Malaria parasite twin crescents. 12 Malaria. plasmodia—a syzygium, in fact—in a doubly infected blood corpuscle, is likely to prove the true one. Formation of the flagellated body.—Although there may be doubt about its mode of origin, it can be said with confidence that the destiny of the crescent has been determined. This destiny is the formation of the flagellated Jfc. body belonging to the special a f j§ type of plasmodial infection in \Jm which the crescent occurs (Fig. 7, b). If a number of crescent ® bodies are kept for a time under observation on the micro- scope slide, a certain proportion of them will be seen slowly -,p^ to undergo change of shape, c \^J gradually becoming converted first into oval bodies and then j^. into spheres (Fig. 7, b, c), whilst d y§M the remains of the enclosing blood corpuscle fall to pieces -_ or melt away. At first the c (jfip) pigment particles, both in the crescent, in the oval body, and in the sphere, are motionless and central—more rarely ec- centric. By and by these parti- cles tend to arrange themselves as a ring, lying in contact with the inner surface of what may be a very fine, invisible mem- brane, and occupying the cen- tral third of the sphere, and forming, as it were, a small central sphere within the larger sphere. After a time the pigment particles begin—at first slowly intermittently, afterwards more energetically about. As the movement of the pig- ment increases in rapidity and energy, the entire sphere seems to partake in the agitation—to quiver Fig. 7.—Malaria parasite : evolution of the flagellated body from the crescent Plasmodium. and —to dance Parasite: The Flagellated Body. 13 to change form, and to be jerked about as by some unseen force. The pigment particles may now become diffused through the general mass of the sphere (Fig. 7, d), or they may not. Whether this does or does not happen, the agitation of the sphere now becoming intense, one or more flagella are sud- denly shot out from its periphery, and begin at once Fir.-, s.—Evolution of the flagellated body in the tertian (a, b, c) and ° quartan {d, e, f) parasites. (Compiled from Thayer and Hewetson.) to indulge in characteristic waving, lashing move- ments (Fig. 7,/).* The flagella, if they do not succeed in breaking away as already described, may continue to move for an hour, or even longer—that is, if the flagellated body is not engulfed by a phagocyte, an occurrence very frequently witnessed. Finally, they slow down, cease to move, curl up perhaps, and then gradually * Careful focussing, especially of stained crescent-derived spheres, may sometimes show that for a short time before their eruption the flagella exist preformed inside the limiting membrane of the sphere (Fig. 7, e). Doubtless the agitated movements of the sphere are produced by the efforts made by the flagella to break through this membrane. 14 Malaria. fade from view. Should the flagella succeed in break- ing away, the remains of the flagellated body, consist- ing of pigment particles included in a small amount of residual protoplasm, tend to assume a somewhat spherical, passive form, the hitherto violent changes of shape, and the movement of the pigment ceasing almost abruptly. In another variety of plasmodial infection certain bodies (Fig. 8, a, d), which look like ordinary full- grown intra-corpuscular parasites prior to the form- ation of spores, may sometimes be seen to slip out from their enclosing corpuscles (Fig. 8, b, e). If these escaped plasmodia are watched, in some instances the pigment they contain is seen to indulge in violent dancing movements, the body of the parasite being at the same time violently agitated and jerked about. Finally, flagella may be suddenly projected from the periphery of these plasmodia (Fig. 7, c,f), very much in the same way as the flagella are projected from the periphery of the crescent-derived sphere. Manifestly, these large spherical plasmodia and the flagellated bodies arising from them correspond to the crescent- derived sphere and crescent-derived flagellated body. Ross has recently shown that, provided the blood containing the crescent body is prevented from coining in contact with the air as when the finger is pricked through vaseline, the evolution of the parasite does not proceed. He has further shown that if the drop- let of blood is exposed to the air for a minute or two before being mounted on a slide, exflagellation is markedly encouraged. Similarly, Marshall has shown that by mixing the blood with a trace of water ex- flagellation is also favoured. I find that by com- bining these methods, namely, exposure to the air with slight aqueous admixture, as by breathing on the slip before applying the cover-glass, it is gener- ally easy to procure quickly specimens of the flagel- lated body from crescent-containing blood. Probably, although I have not experimented with this object in suitable cases, flagellation will be favoured in Mosquito and Parasite. 15 the non-crescent forming plasmodia by the same means. Function and nature of the flagellated body.— From the fact that the flagellated body does not come into existence until the blood has left the vessels—in other words, is outside the human body— I have ventured to suggest that the function of the flagellum must also lie outside the human body; and because the flagella are formed from plasmodia of large size and apparently mature, and for other reasons, I have also suggested that the flagella are flagellated spores, the extra-corporeal homologues of the intra- corporeal spores ; in fact, that the flagellated body constitutes the first phase of the extra-corporeal life of the plasmodium. The mosquito considered as the e.itra-corporeal host of the plasmodium.—Further, as the plasmodium whilst in the circulation is always enclosed in a blood corpuscle and is therefore incapable of leaving the body by its own efforts, and as it is never, so far as known, extruded in the excreta, I have suggested that it is removed from the circulation by some blood- eating animal, most probably by some suctorial insect common in the haunts of malaria. This insect, as Laveran has also suggested, I believe to be the mos- quito * ; an insect whose habits seem well adapted for such a purpose, and whose distribution in nature would seem to satisfy the demands entailed by the well-ascertained habits of malaria. In ordinary liquid slides of crescent-containing malarial blood, only a very small percentage of crescents proceed to flagellation ; by far the larger proportion never change form, or proceed merely to the oval or, at the most, to the spherical stage. In support of the theory I advocate Surgeon-Major Ross, I. M.S., proved that it is otherwise with the crescents ingested by mosquitoes fed on malarial blood. * For a fuller statement of the facts and arguments bearing on this theory the reader is referred to the writer's Goulstonism Lectures, Brit. Med. Journal, March 14th, 21st, and 28th, 1896. 16 Malaria. In such circumstances he finds—and I can confirm from inspection of his preparations the accuracy of his statements—that the crescents in the majority of instances become transformed into spheres (Fig. 9) and then into flagellated bodies, the Jjk flagella subsequently breaking away O and becoming free in the stomach of W the insect. This constancy of ex- W flagellation in the mosquito's stomach cannot be accidental. I consider that Sthe flagella—which, as already stated, are to be regarded as flagellated spores —are endowed with their peculiar shape and properties, in other words, with loco- motive powers, in order that they may be able to pass from the blood in the mosquito's stomach to the tissues of the insect. I conjecture that the flagellum enters some cell of the mosquito and therein, like any gregarine or cocci- dium, becomes parasitic, growing and sporulating afterwards ; just as the non- flagellated plasmodium enters, grows, and sporulates in the human blood corpuscle. The plasmodium, I hold, is an intra-cellular parasite both out- side as well as inside the human body, and that when outside the human body it is parasitic in the mosquito. In further support of this hypo- crescent body in ■ i . -r> > j_ j. i i_- the mosquito. thesis Ross s most recent observations, to be alluded to presently, may be quoted. Certain it is that the phenomena of exflagel- lation are no mere freak of nature, and certain it is that they have direct reference to the welfare of the organism exhibiting them. The details I have ven- tured to fill in may not be correct in every particular, but the principle must be conceded. I have further conjectured that the continuation and multiplication of the plasmodium outside the 'ig. 9. — Earlier stages of the evolution of the Mosquito and Parasite. 17 human body is secured by the passage of the mos- quito-bred plasmodial spore into the larvae of the same insect. The mosquito generally dies in the water beside the eggs she has deposited. When the eggs are hatched the young larvae commonly devour the body of their parent and, consequently, her parasites. Moreover, being very voracious, the larvae eat any organic matter they come across. We can easily understand from this in what way parasites from the mosquito may get access to the mosquito's offspring. On the infected larvae becoming mature insects the Fig. 10.—Pigmented cells from stomach wall of mosquito. plasmodia they have swallowed continue, I conjecture, to develop. These insects, in their turn, infect their larvte, and so on. Continuation and multiplication of the plasmodium outside the human body is in this way secured. Man, I conjecture, may become infected by drinking water contaminated by the mosquito; or, and much more frequently, by inhaling the dust of the mud of dried-up mosquito-haunted pools ; or in some similar way. It seems to me that this hypothesis explains many facts in the aetiology of malarial infection. If true, it would account for the long-recognised relationship of malaria to swamps ; for the influence of drainage and of deep flooding in rendering malarial lands salu- brious ; and for many other points in the ;ctiology of paludism. I do not maintain that this mosquito hypothesis has as yet been thoroughly proved, but I do maintain that it is so probable, and of a character so important, from both a scientific and practical point of view, that every effort should be made to establish or confute it. c i8 Malaria. Another and plausible interpretation of the function of the flagellum has (Lancet, November 13th, 1897), been advanced by MacCallum of the Johns Hopkins Hospital; an interpretation, moreover, entirely compatible with the mosquito hypothesis. MacCallum has found that an endocorpuscular pig- mented parasite (halteridium of Labbe) occurring in an American crow, and analagous to the plasmo- dium of man, when it has attained its adult size is, in certain instances, extruded from the including cor- puscle. After escape it assumes a spherical form, in some instances having a granular and opaque appear- ance, in other instances being hyaline and trans- parent. After a time the hyaline halteridia project flagella which, breaking away from the parent sphere, accumulate around and vigorously seek to enter the granular, non-flagellated, free halteridia. Ultimately one of the flagella succeeds in effecting an entrance, causing considerable agitation among the pigment particles. The halteridium, being thus impregnated, as it were, slowly changes form, becoming elongated into a pigmented, spindle-shaped body or vermicule, which presently begins to move about through the blood traversing red and white blood corpuscles indifferently and continuing active for a considerable time. MacCallum further states that in blood from a woman, in whom the crescent form of the malaria parasite was unusually abundant, he twice witnessed a somewhat similar phenomenon. He saw a flagel- lum enter a crescent-derived sphere, agitate the pigment and spin round the central portion of the parasite. The sphere, however, underwent no further change of shape, nor anything like develop- ment into a vermicule. It is conceivable, however, that under more natural conditions some such trans- formation might occur; indeed, if MacCallum's observations are correct, analogy would indicate that some such transformation does occur. Ross has (Brit. Med. Journ., December 18th, 1897) observed certain pigmented cells (Fig. 10) in Theory of Degenerated Parasites. 19 the wall of the stomach of a peculiar species of mosquito which he had fed on crescent-containing blood. From their appearance, and from the circum- stances in which they occurred, these cells were evidently, or in all probability, associated in some way with the malaria parasite; indeed, it seems highly probable that they contained the parasite, for their pigment was, so far as the microscope entitled him to infer, in every respect similar to the malarial pigment. Assuming that these cells were, or that they contained, the malaria parasite, it is somewhat difficult to understand from what source their pigment was derived if, as conjectured, the flagellum, which is always non-pigmented, were the direct infecting agency. But in the light of MacCallum's discovery it can be readily understood how, if certain of the crescent^derived spheres were impregnated by free flagella in the stomach of the mosquito and subsequently became travelling pigmented vermicides like those of halteridium, they could carry with them into the cells of the stomach wall of the insect their melanin granules. Bignami conjectures that the plasmodium is con- veyed to man by the bite of the mosquito, its proboscis carrying malaria germs acquired from the water or soil of a malaria-infested locality. Experiment has not encouraged this idea. Crescents, spheres, and flagellated bodies regarded as degenerated parasites.—Though strongly opposed to the view, I consider it right to mention that many high authorities—Marchiafava, Bignami, Blanchard among them—regard the malaria crescent, sphere, and flagellated bodies as being degenerated, dead, or moribund plasmodia. In support of this opinion they adduce the fact that the red blood corpuscles, when heated, sometimes project waving filaments something like flagella. They also state that the nucleus of the parasite has not been shown to take any part in the formation of the flagella, and that similar phenomena accompany the death of other c 2 20 Malar/a. protozoa. Grassi and Feletti maintain that the crescent is a distinct and independent species of parasite, quite different and in no wise, except by accidental concurrence, connected with the ordinary intra-cor- puscular plasmodium. Recent advances in our know- ledge seem to me to render such views untenable. Preparation of blood for detecting the Plasmodium.—For a thorough appreciation of the principles on which blood examinations for the demonstration and study of the plasmodium should be conducted, it is necessary to bear in mind that fhe parasite is intra-corpuscular. To see it with the microscope, therefore, it is necessary, particularly for the beginner, so to dispose the corpuscles in the preparations that a proportion of them shall lie flat f^uir Fig. 11.—Microphotogram showing the necessary disposition of blood corpuscles in slides for examination for the Plasmodium. To the right of the white blood corpuscle in the centre of the held a red blood corpuscle thieefourths tilled with a tertian (benign) parasite is visible. (From, microphotogram by Dr. Cosens.) Preparation of Slide. 21 on the slide, in a single layer, and presenting their surfaces and not their edges to the observer (Fig. 11). It is mainly from ignoring this fundamental principle that so many fail to find the plasmodium. To secure this disposition of corpuscles the follow- ing procedure, the smallest detail of which must be scrupulously carried out, is recommended. Thoroughly cleanse with alcohol three or four thin cover-glasses and as many slips, and cover them immediately with some convenient vessel so as to pro- tect them from the minutest particle of floating dust. After lightly ligaturing one of the patient's finger- tips, cleanse it with alcohol and dry it. Prick the congested finger pad with a clean needle, and wipe away the first drop of blood that exudes. Then gently, with finger and thumb, squeeze the finger pad and express a second minute droplet of blood ; this should be very small—no larger than a pin's-head. Touch the droplet lightly with the centre of a cover-glass, taking care that the latter does not come into contact with the skin, and immediately lay it on the slide. No pressure should be used to cause the blood to spread out. If glasses and finger are quite clean, the blood will at once run out in a very fine film. Several preparations should be made, the requisite blood being obtained by renewed gentle compression of the finger-tip. After waiting a few minutes to allow the blood to spread out completely between the glasses, it is well to ring the preparations with vaseline; this will effectu- ally stop all movement, all evaporation of the blood, and, consequently, over-compression and crenation of the corpuscles, and will thereby greatly facilitate examination. In preparing slides care should be taken to sterilise the needle employed, otherwise grave accidents might occur. It is of course unnecessary to sterilise the slides used. On holding a successful preparation up to the light, one or more areas, each made up of three zones, 22 Malaria. the different zones shading into each other, can be made out by the naked eye. Each such area includes a peripheral zone of a reddish tinge, a middle zone having a somewhat iridescent look, and a central zone absolutely devoid of colour. Successful preparations may be recognised by the presence of these zones. Preparations not exhibiting this appearance should be rejected; it is waste of time to examine them. On examining successful preparations with the microscope, it will be found that the central zone or area contains few or no blood corpuscles. This zone may be designated the "empty zone." Proceeding outwards from this we come on an area occupied by scattered, isolated, compressed, and much-expanded corpuscles; this zone I shall designate the " zone of scattered corpuscles." Farther out the corpuscles become more numerous and less expressed (Fig. 11) and, gradually, as we trace the slide still farther outwards, the corpuscles are found approximated to each other until, finally, the peripheries of the corpuscles are mostly in touch ; this zone I shall call the " single- layer zone." Farther out the corpuscles, though still lying flat, are found to overlap each other or are piled one on the top of the other; this zone I shall call the " zone of heaped up corpuscles." Beyond this zone the corpuscles are arranged in rouleaux, "the zone of rouleaux." At the extreme margin of the preparation the corpuscles tend to break up and run together so as to form a narrow border of free haemoglobin, the individual corpuscles, perhaps, being indistinguishable ; this I shall call the " zone of free haemoglobin." Each of these zones should be studied, for each carries special information about the plasmodium. microscopical examination.—The beginner will save time if he gets someone who is familiar with the necessary technique and with the appearance of the parasite in the blood to give him one or two lessons. Accuracy and quickness can be acquired only by practice. It is a good plan to practise pre- paring films from one's own blood. Microscopical Examination. 23 The examination is best conducted with TV of an inch oil immersion lens, a rather low eyepiece, a sub stage condenser, and not too dazzling an illumination. It is not always possible to choose, but, if prac- ticable, a case of quartan infection should be selected for examination in the first instance. Failing a quartan, a well-defined benign tertian infection might be chosen. Failing either of these, a long-standing case of recurring malaria with marked cachexia will afford the next best opportunity. It is best to examine the patient's blood just before or at the time of rigor. In quartans and benign tertians, at the time named, there should be little difficulty in discovering large plasmodia ; in their case attention is called to the relatively large parasites by the abund- ance of coarse pigment which they contain. In the blood of malarial cachectics with recurring febrile attacks it is generally an easy matter to find crescents and crescent-derived spheres, as this form of the parasite is of considerable size, carries abundance of pigment, and possesses a very definite and striking shape. When the beginner has learnt to recognise one form of the parasite, he will begin to appreciate what sort of body he has got to look for, and thereafter should be able to educate himself, and to pick out the smaller and all the other forms. In proceeding to make his first examination of a liquid blood slide, the beginner, in the first in- stance, should confine his attention to the " single- layer zone." Field after field of this he must pass in review, carefully scrutinising the interior of every blood corpuscle, every leucocyte, and every pigmented body even though it be not included in a corpuscle. He must not expect to find parasites in every cor- puscle or even in every field; and he certainly must not expect, as the beginner usually does, to find in every slide the beautifully regular sporu- lating form or " rosette body," or the weird-looking flagellated body made familiar to us by so many 24 Malaria. illustrations. Such bodies, though really present somewhere and in some form at one time or another in every case, are among the least commonly encoun- tered of the many phases of the plasmodium ; they are met with only under very definite and not very constantly encountered conditions, and are not very often seen at an ordinary clinical examination. In most cases the plasmodium is discovered in the first field or two examined; but in not a few instances dozens of fields may have to be scrutinised before a single parasite is encountered. Therefore no examina- tion can be said to be complete, in a negative sense, until at least half an hour has been spent over several suitably prepared slides. The forms of intra-corpuscular plasmodia most frequently met with have the appearance either of small specks of pale protoplasm, or of larger masses of pale protoplasm containing grains of black pigment. Close watching discovers that the former are endowed with active amoeboid movement, and that they continually change shape and position in the affected corpuscles. As these movements are an important test of the parasitic nature of the body sought, they should be carefully looked for. These protoplasmic specks look like little washed-out smudges of dirty white paint, half hidden by the haemoglobin ; they are sometimes hard to see. Their parasitic nature can readily be determined by their movements ; their soft, ill-defined margins ; and by the fact that they tend now and again, on first removal from the body, and per- manently later, to assume the appearance of tiny white rings which show up very distinctly in the haemoglobin of the corpuscle. These features readily distinguish them from the sharply defined, clear, motionless vacuole (Fig. 12). The other common forms —the larger or smaller intra-corpuscular pigmented parasites—occupy anywhere from a sixth to nearly the entire area of the affected corpuscles. They are recognised by their pale protoplasm ; the black melanin particles sprinkled about or, if towards the Examination of Blood. 25 period of rigor, concentrated in their interior ; and by their more or less active amoeboid movements. In quartans and tertians, but especially in the former, sporulating rosette forms are seen occasionally. Examination of blood for flagellated bodies.— When the student has become familiar with these appearances, and has thoroughly seized the fact that the sporulating forms are to be found only, or usually, at and just before or soon after the rigor stage of fever, he should endeavour to follow up the extra- corporeal, or the initial steps of what, under natural conditions, I hold to be the mosquito stage of the parasite. So far as ordinary preparations permit, this phase is best studied in the zone of "heaped-up corpuscles" and in the "zone of rouleaux"; because in these zones the parasite, not being subjected to pressure, has more freedom to undergo its evolutionary change into the flagellated body. In ordinary quartans and tertians the flagellated body is but seldom encountered. The best time to find them in such cases is during the hot stage of the fever. In cases of crescent infection flagellated bodies are much more frequently encountered as, in this form of malaria, they are more numerous and appear at any time of the clinical cycle, and perhaps for weeks after fever has disappeared. In most cases of crescent infection the gradual evolution of the flagellated body from crescent through oval and sphere can, with patience, be easily followed. Diagnostic value of the "zone of free hmmoglobin." —The zone of free haemoglobin is of value as enabling the practical observer to pronounce very rapidly on the presence or absence of pigmented parasites in the blood. The relatively large quantity of blood in each field of this zone, and therefore the proportionally large number of parasites in any given field lends itself to this, as does the fact that tile black pigment shows up very distinctly m the homo- geneous lake-coloured sheet of free haemoglobin. _ Phagocytosis and pigmented leucocytes.—Striking 26 Malaria. examples of phagocytosis are often witnessed in the zones of neaped up corpuscles and of rouleaux. It will be found that so soon as a malarial parasite, whether spontaneously or as a result of pressure, escapes from the blood corpuscle in which it had developed, it becomes exceedingly liable to attack by the phagocytes. More especially is this the case with the flagellated organism ; this body seems to have a powerful attraction for the phagocyte, which is often seen to travel long distances to attack it. Pigmented leucocytes—that is to say, leucocytes containing grains or blocks of melanin—are very often encountered in all of the zones ; they can best be seen in the single-layer zone during, or shortly after, fever. The leucocytes may sometimes be observed to swallow the pigmented centre of the broken-up sporulating bodies. Often they derive their pigment from the remains of some sphere or flagellated body which they have engulfed sub- sequently to the preparation of the slide. In peripheral blood the phagocytes are rarely, if ever, seen to attack the plasmodium so long as the parasite is inside a blood corpuscle. Both the mono- and the poly-nucleated leucocytes may contain malarial pigment. Great care, however, must be exercised in drawing conclusions from the discovery of finding black material in these bodies in imperfectly cleaned slides; fragments of dirt, which the leucocytes rapidly take up, are apt to mislead. According to Metschnikoff, the lymphocyte has no phagocytic action in malaria. This observation I believe to be correct. Several writers, however, have described and figured what they regard as malarial pigment in the lymphocyte. This, I am convinced, is founded on an error in interpretation and has arisen from ignorance of the fact that in all bloods, healthy and malarial alike, from 20 to 50 per cent, of the small mono-nucleated lymphocytes con- tain, lying in the narrow zone of cytoplasm, one or two minute round dots of intensely black material Diagnosis of Vacuoles. 27 optically indistinguishable from malarial melanin. I am not aware that this appearance has been described hitherto, but multiplied observation has convinced me of the accuracy of my statement. The discovery, therefore, of a speck of intensely black pigment in the lymphocytes must not be regarded as evidence of malarial infection. Diagnosis of vacuoles.—The beginner may have a difficulty in determining whether certain appear- ances in the corpuscles are vacuoles, or whether they Fi". 12.—Vacuolated and crenated blood corpuscles. (After Laveran and Blanehard.) a b c l)lood corpuscles with central vacuoles, c is crenated; d, e, /, A, blood corpuscles with central vacuole, in the middle of. which there is some teg- mental haemoglobin. Sometimes exceedingly minute egg-shape Jjorm ( Tertian j ascents. Classification of Parasites. 37 Formerly, classification being based entirely on clinical phenomena, malarial diseases were divided into quotidian, tertian and quartan intermittents or agues, and remittents; but. since it has been found that what was designated remittent fever is produced both by quartan, tertian, and quotidian parasites—- the fact of intermittency or remittency being more or less a matter of accident—it has been considered advisable to expunge the term remittent fever as indicative of a distinct species of plasmodium disease. Any one of the five kinds of parasites enumerated may cause what was known as remittent fever. The intermittency or remittency of any given fever depends, in great measure, on the simultaneousness or the reverse of the maturation of the crowd of parasites giving rise to it. If all the parasites present are of nearly the same age, they mature approximately simultaneously and we have an intermittent ; if they are of different ages, they mature at different times scattered over the twenty-four hours and we have what was known as a remittent. Further, two generations of tertian parasites maturing on successive days will produce a quotidian fever, tertiana duplex; two generations of quartan parasites maturing on successive days will produce fever fits on two suc- cessive days followed by one day of freedom, quartana duplex; three generations of quartan parasites will produce what clinically appears to be a quotidian fever, but in reality is a quartana triplex. The classification adopted must not be accepted as final; at best it is merely provisional. In actual practice it may be hard, often impossible, to bring the cases met with into exact line with such an arrangement. Moreover, it is necessary to bear in mind that this classification is based principally on observations made in a very limited district, prin- cipally in Italy, and principally on Roman fevers. It may not apply, therefore, to the entire malarial world. That it lies on a substratum of fact there can be no doubt; nor can there be much 38 Malaria. doubt that it has in many particulars a general application to malarial disease as found all over the world. Still, judging from clinical facts, there seems ground for believing that there are other species or varieties of the plasmodium besides those described by the Italians, and that the list here given will have to be enlarged or recast in the future. Men with extensive experience of malarial disease in their own persons tell us that they can discriminate by their sensations and symptoms between the fevers of dif- ferent localities. Analogy would incline us to believe that clinical differences of this sort depend on dif- ferences in the causal parasites. How very different, for example, are the haemoglobinuric fevers of Africa and the bilious remittents of India. Is it not prob- able that they depend on specifically distinct parasites or, at least, on more or less definite varieties 1 CLINICAL PHENOMENA OF MALARIAL FEVER. Before proceeding with a description of the various plasmodia and their associated fevers, there are certain generalities which, to save repetition, had better be mentioned here. Intermittent fever or ague.—Every typical malarial fever is made up of a series of pyrexia! attacks which recur at definite intervals of twenty- four, forty-eight, or seventy-two hours. Each attack consists of a stage of rigor, a stage of heat, and a stage of sweating; these are followed by a period, " the in- terval," of apyrexia, actual or relative. The duration and intensity of the constituent stages vary consider- ably. On the whole, they observe a certain proportion to each other; the more pronounced the rigor, the higher the fever, and the more profuse the sweating. Such attacks, with well-marked intervals of apyrexia, are designated intermittent fevers or agues. The ex- pression "ague" is by many applied only to inter- mittents having a pronounced rigor stage. Premonitory stage.—Before rigor sets in, and sometimes for several days before the actual disease Ague. 39 declares itself, there may or there may not be a premonitory stage marked by lassitude, a desire to stretch the limbs and to yawn, aching of the bones, headache, anorexia, perhaps vomiting, perhaps a feeling as of cold water trickling down the back. If the thermometer be used at this stage, it will be found that body temperature begins to rise some two or three hours before the other and more striking symptoms which ensue set in. Cold stage.—When rigor sets in the feeling of cold spreads all over the body, becoming so intense that the teeth chatter and the patient shivers and shakes from head to foot. He now seeks to cover himself with all the wraps he can lay hands on. Vomiting may become distressing. The features are pinched, the skin blue and cold-looking, the fingers shrivelled. The feeling of cold is entirely subjective; if the temperature be taken, it is found to be already several degrees above normal, and to be rapidly mounting. In young children it is not at all unusual to have a convulsive seizure at this stage; a fact that has to be borne in mind, as it is very apt to lead to ideas of epilepsy. Hot stage.—After a time the shivering gradually abates, giving place to, or alternating with, waves of warmth and, before long, to persistent feelings of intense heat and febrile distress. The wraps, which before were so eagerly hugged, are now tossed off; the face becomes flushed ; the pulse is rapid, full, and bounding; headache may be intense ; vomiting frequent; respiration hurried; the skin dry and burning ; the thermometer mounting to 104°, 105°, 106°, or even higher. Sweating stage.—After one or more hours of acute distress, the patient breaks out into a profuse perspiration, the sweat literally running off him and saturating his clothes and bedding. With the ap- pearance of diaphoresis the fever rapidly declines; headache, vomiting, thirst, and febrile distress giving place to a feeling of relief and tranauillity. By 4° Malaria. the time the sweating has ceased the patient may feel quite well; a little languid, perhaps, but able to go about his usual occupation. The bodily tem- perature is now often sub-normal, and may remain so until the approach of the next fit one, two, or three days later. Duration of the fit.—The duration of an ague fit and of its constituent stages is very variable. On an average it may be put at six to ten hours; the cold stage occupying about an hour, the hot stage from three to four hours, the sweating stage from two to four hours. The urine in ague.—During the cold stage the urine is often limpid and abundant, and is passed frequently; but during the hot and sweating stages it is scanty, loaded, sometimes albuminous. The amount of urea is increased^ particularly during the cold stage, and so are the chlorides. The phosphates, on the contrary, diminished during the rigor and hot stages, are increased during defervescence. The aug- mentation in the excretion of urea commences several hours before the subjective symptoms of the attack begin, attains its maximum towards the end of rigor, and decreases during the hot and sweating stages although still continuing above the normal standard. The excretion of carbonic acid follows a correspond- ing course. Dr. Sydney Ringer was the first to point out the interesting fact that, although the return of fever may be prevented by the administration of quinine, yet, for a time, a periodic increase in the excretion of urea occurs on the days on which the fever fit was due. The urine is often deeply coloured, giving with nitric acid the play of colour charac- teristic of bile pigment, or the brown colour described by Giibler as " haemapheic." Glycosuria does occur, but is by no means common. The spleen during the fit.—The spleen becomes enlarged to a greater or less extent during rigor. The swelling disappears at first in the interval, but tends to become more or less of a chronic feature ■ if Atypical Agues. 41 the attacks recur frequently, more especially if they are associated with pronounced cachexia. Period of the day at icliich ague commences.— Two-thirds of agues come off between midnight and midday. This is an important fact to remember in diagnosis ; especially when we have to face the possi- bility of recurrent pyrexial attacks being dependent on such conditions as liver abscess, tuberculosis, and septic states—conditions, be it remarked, in which febrile recurrence takes place almost invariably during the afternoon or evening. Atypical agues.—Such is a brief sketch of the leading features of a classical ague fit. Cases, how- ever, are frequently met with in which all of these symptoms are very much toned down; in which, perhaps, a periodically recurring feeling of coldness followed by languor, or a slight headache, or a slight rise of temperature, are the only symptoms indicating the presence of the malaria parasite in the blood. In some fevers, and these by no means the least danger- ous, the subjective symptoms may at first be of so mild a character that the patient is able to go about his duties with a body temperature of 103° or 104° ; he may have no severe rigor, no headache, no severe gastric symptoms, no acute febrile distress of a disabling character. Some of the African fevers— so liable to assume suddenly a pernicious character —are of this nature. On the other hand, notwith- standing a comparatively slight rise of temperature, headache, languor, vomiting, may be extremely dis- tressing. There is an infinite variety in this respect. Evidently the toxin of the plasmodium is far from being a simple body ; probably, like turberculin, it contains several ingredients arranged in different proportions in the several varieties of the parasite. Doubtless, also, the degree of infection, various com- binations of the varieties of plasmodia, and individual idiosyncrasy play a part in determining the intensity and character of the reaction of the body to the toxins created by the plasmodium. 42 Malaria. Terms employed.—Acute malarial attacks which recur daily are called quotidian ague ; if they recur every second day they are called tertian ague; if every third day, they are called quartan ague. As a rule, the attacks tend to occur about the same time every day. In some cases the time of recurrence becomes earlier each day ; such fevers are said to anticipate. Or they may occur at a later hour, in which case they are said to postpone. When the attacks are prolonged, so that one attack has not concluded before the next commences, the fever fits are then said to be subintrant. When the fit is pro- longed and periodicity is marked by only a slight fall of temperature, a slight sweating, a slight feel- ing of chilliness, the fever is said to remit—to be a remittent. Sometimes there is no remission; such a fever is called continued. It occasionally happens that two distinct pyrexial attacks come off on the same day; such a fever is said to be double. All sorts of blendings of quotidians, tertians, and quartans occur; in such the infection is said to be a mixed infection. Relation of the phenomena of the fever fit to the stages of the parasite.—All these differences and peculiarities in the clinical phenomena of a malarial attack, as indicated by the foregoing terms, complicated and hard to interpret in many cases though they be, are, it is believed, directly cor- related to the phases of the intra-corporeal life of the plasmodium; this organism is, in fact, the key to their interpretation. As already mentioned, as the time of rigor approaches the pigment of the parasite, hitherto scattered throughout the substance of the little animal, becomes concentrated, and the sporulating body develops. Shortly before and during rigor, and as a direct cause of rigor, these sporulating bodies are breaking up and, presumably, liberating their toxins. At the end of rigor, during the hot, and during the sweating stages, the young parasites of the new fener- ation, the small intra-corpuscular bodies, and the Parasite of Quartan Fever. 43 leucocytes carrying the pigment liberated at the break- ing up of the sporulating bodies are in evidence, and the toxins liberated at the same time are being eliminated. During the interval the intra-corpus- cular parasites grow, become pigmented, and prepare for maturation. From the fact that parasites are present in the blood during apyrexia, and often in great abundance, it is evident that it is not the mere presence of the parasite in the blood corpuscles that causes the fever ; most likely the pyrogenic agency is some toxin which is liberated when the sporulating parasite breaks up and becomes free in the liquor sanguinis. Consequently, we find that in remittent and continued types of malarial fevers sporulating plasmodia may be met with at all stages of the fever; and, conversely, that when plasmodia are met with at all stages of development the associated fever is prob- ably remittent or more or less continued in type. The foregoing are generalities which apply to all the types of malarial fever. BENIGN QUARTAN INFECTION. The parasite.—The parasite of quartan fever (Plate I., Fig. 1) has a cycle of seventy-two hours. At its earliest stages of epi-corpuscular and of early un- pigmented intra-corpuscular life it takes the form of a small, roundish, clear speck (Plate I., Fig. 1, a), show- ing up somewhat distinctly against the haemoglobin of the invaded corpuscle. At this stage, as contrasted with the other varieties of plasmodia, it is further distin- guished by the feebleness of its amoeboid movement. Later, as soon as it becomes pigmented (Plate I., Fig. 1, b, c, d, e.f), all amoeboid movement ceases. Re- latively to the other plasmodia, the pigment carried by the quartan is large in amount and coarse in grain, sometimes forming short rods. The sporulating body (Plate I., Fig. 1, g, h)t is made up of eight to ten elements arranged daisy fashion and, usually, very symmetrically around the now centrally placed and massive block of very black pigment. About the 44 Malaria. centre in each of the spherical or pear-shaped spores, which are slightly rough in outline, a shining nucleolus can usually be readily made out. The quartan para- site, never forming crescents, derives its rarely seen flagellated form from what looks like an ordinary large intra-corpuscular pigmented parasite (Plate I., Fig. 1, i) that has escaped from the red corpuscle in which it has developed. This phase, rarely seen, occurs almost exclusively during the pyrexial stage of the cycle. Further, the quartan parasite does not, as does that next to be described—the tertian parasite, cause marked hypertrophy of the blood corpuscle in which it lies. When mature it completely fills the normal- sized corpuscle, scarcely a rim of haemoglobin being visible (Plate I., Fig. 1, e) ; so that it sometimes looks at this stage as if it were a free and independent body floating about in the liquor sanguinis. All quartan parasites do not proceed to spore formation or flagellation; some are said to degenerate into peculiar clear, dropsical-looking spheres filled with dancing particles (Plate I., Fig. 1, i), which form a striking feature in certain malarial bloods. A considerable proportion of these free, dropsical-looking bodies are probably parasites which, after being placed on the microscope slide, and after escaping from corpuscles, have failed to project flagella. This failure to exflagel- late is probably not normal, but an effect of mechanical disturbance from pressure of the cover-glass, or of other circumstance inherent in the artificial conditions under which we necessarily observe these bodies. In more normal conditions, as in the mosquito, ex- flagellation may be more frequently effected. The "daisy"—as it is sometimes called—or sporu- lating form of the quartan parasite is more frequently seen in the peripheral blood than is the corresponding phase of the other malarial parasites. For this reason, and because of the easy visibility of the parasite at all its stages, owing to its size and to the large amount of pigment it carries, and because the entire intra-corporear cycle is completed in the peripheral Distribution of Quartan Fever. 45 blood, the quartan is the best form of plasmodium for the beginner to study. Geographical distribution.—The fever which the quartan parasite gives rise to—single, double, or Nov. 26 27 28 29 30 Dec. 1 2 A.M.lP.M. A.M. P.M. A.M. P.M. A.M. P.M. A.M. P.M. A.M. P.M. A.M. P.M. IME 4 8 12i4 8 12 4 8 12 4 8 12 4 8 12 4 8 12 4 8 12 4 8 12 4 8 12J4 8 12 4 8 12 4 8 12 4 8 12 4 8 12 0 |\ ]\ 1 ' \ r— \ &1 \ 97° 96° 1 \ ✓ \\ 4 Fig. 16.—Chart of quartan ague. treble quartan ague—is, relatively, much more common in temperate latitudes than in the tropics. Formerly it was common enough in England, and is still far from rare in the malarious districts of north and mid- Europe, and, doubtless, elsewhere in similar climatic and telluric conditions. But, as we proceed south, it becomes, relatively to the other forms of malaria, rarer, until in the tropics in some places it almost disappears. Thus in a paper read at the Calcutta Medical Congress of 1894, Dr. Crombie mentions that in his large experience he rarely sees quartan ague. 46 Malaria. As his experience applies particularly to Calcutta and its environs, it may not hold for the whole of India; in fact, Ross (Ind. Med. Gaz., Feb. 1896) and others state that the quartan parasite is common enough in Madras and elsewhere in India. The general statement, however, that quartan ague is more a disease of the temperate zones than of the tropics, probably expresses the truth. The associated fever.—The ague fit in quar- tan is generally smart while it lasts, and well de- fined as regards its constituent stages (Fig. 16). It does not tend so markedly, as is the case with the other malarial infections, to the rapid develop- ment of cachexia. BENIGN TERTIAN INFECTION (SPRING TERTIAN OF THE ITALIANS). The parasite.—The early stage of the benign tertian parasite (Plate I., Fig. 2) resembles that of the quartan inasmuch as it consists of a small pale speck on, or in, the invaded red blood corpuscle (Plate I., Fig. 2, a); it differs in exhibiting very much greater amoeboid activity, changing its form incessantly, be- sides pushing out and retracting pseudopodia (Plate I., Fig. 2, b). This amoeboid activity persists during growth and the acquisition of pigment, though in a progressively diminishing degree; it gives rise to great and rapidly changing irregularities in the con- tour of the parasite (Plate I., Fig. 2, c, d, e). It is almost entirely suspended by the time pigment con- centration is effected. In the tertian parasite the pigment particles are, on the whole, finer than in the quartan parasite; and, moreover, are . in a state of much more active and incessant movement, constantly changing their position in the peripheral layer—the ectosarc of the amoeba-like parasite__in which they, for the most part, lie (Plate I., Fig. 2,f). Another, and markedly characteristic, accompani- ment of tertian parasite infection is the considerable hypertrophy and marked decolorisation of many of Parasite of Benign Tertian. 47 the corpuscles containing the organism (Plate I., Fig. 2, d, e,fg). Sometimes the affected corpuscles seem nearly twice the diameter of the healthy ones ; and nearly always, if the plasmodium is of any magni- tude, the rim of haemoglobin surrounding the parasite June 13 14 15 16 17 18 X < A.M. P.M. A.M. P.M. A.M. P.M. A.M. P.M. A.M. P.M. A.M. "[ 4 812 4 812 4 812 4 812 4 812 4 812 4 812 4 812 4 812 4 812 4812 2 105° 104° 103° 102° 101° 100° 99° Normal Icmperat of body 98 97° > t • ocq 0 L -R-l \ A 1 V Fig. 17.—Chart of benign tertian ague. has a "washed-out" look, sometimes being almost colourless. In the tertian parasite when segmentation is com- pleted the resulting body, instead of the very sym- metrical, daisy-like figure of the quartan sporulating body, resembles rather a cluster of grapes in some more or less central part of which one or two masses of black pigment have accumulated among the berries (Plate T., Fig. 2, h; also, Figs. 1 and 2, b). The little spores forming the cluster—fifteen to twenty in number 48 Malaria. —are smaller, smoother, and more spherical than those of the quartan parasite, seldom, in the unstained con- dition, exhibiting their nucleoli. I believe that in natural, uncompressed conditions the tertian rosette tends to pass from the disc form, impressed on it originally by the shape of the corpuscle, to something more approaching a globular form. In benign tertian the flagellated body is formed in the same way as in the quartan parasite—that is, from an escaped intra-corpuscular pigmented body (Plate I., Fig. 2,j). It is seen particularly, just as in the case of the quartan infection, and not infre- quently about the time of rigor. Geographical distribution. — The benign tertian parasite, probably the commonest form of plasmodium, occurs in temperate and tropical latitudes alike. It is often found as a double infection and is, perhaps, the most frequent cause of quotidian as well as of tertian agues. The associated lever.—The fever it gives rise to, except in the matter of the spacing, which is one of forty-eight hours, resembles that caused by the quartan parasite (Fig. 17). MALIGNANT INFECTIONS (^ESTIVO-AUTUMNAL OF THE ITALIANS). The three parasites (Plate I., Fig. 3, and Plate II., Fig. 1) described by the Italian pathologists in connection with malignant malarial infection, although often associated together as well as with the benign parasites, are each of them occasionally found in what might be termed a pure culture. From a study of such cases the morphological and distinguishing char- acters of the different species, and their special patho- logical effects, have been more or less satisfactorily made out. Although much remains to be done, enough is already known to enable us, in a measure, to differentiate the parasites from each other as well as from the benign plasmodia, and to justify their being placed in a group by themselves. Fig. 1 Wi m-,--:s ctfr /•■' a ^" h h %« r > Fig. 2. • ••£ '*.•" V- itf'-"1^ ^Wf • •*. ;•<**': v^ - fe /> #/ r.} -.. -o gg/ ^%■■ *** j ' . ■*■ A. "X \»y ,■ "■■. - J. •-•' • ■4J* -■ ift'-'i*-- / ,'••(' ;- ' 'A Fig. 3. PLATE II. Fig. 1.—Paiasitcs of the pigmented malignant quotidian (Marehiafava and liliinami). Fig. 2.—Brain capillaries containing malaria parasites. a, transverse section ; the blood corpuscles at periphery invaded by un- pigment eel parasites; b, vessel tilled with sporulating unpigmented parasites; c. blood corpuscles in capillary, and others free in the brain substance, each containing small pigmented parasites (Mannaherg). Fig. 3.—Pernicious malaria (spleen). Fig. 4.—Pernicious malaria (liver). (Kelsch and Kiener.) Characters of Malignant Parasites. 49 Characters possessed in common by the malignant parasites.—One notable feature in regard to them is that they are very much smaller than the benign parasites. The earlier unpigmented phase, owing partly to minuteness, partly to its forming but a thin and very transparent amoeba in the haemoglobin, is hard to see. When first mounted on the slide the amoe- boid movements are very active (Plate I., Fig. 3, d). In a short time this subsides somewhat, and then the little parasites tend to assume a more passive condition and to arrange themselves as tiny, though very definite and easily recognised, rather bright, colourless rings (Plate I., Fig. 3, a, b, c, e). Sometimes these rings may revert to the amoeboid condition, and this per- haps for several times in succession ; ultimately the ring form becomes permanent. Multiple infection of individual corpuscles (Plate I., Fig. 3, g) is often encountered, and this much more frequently than in the benign infections; doubtless this is owing to the prodigious number of parasites which, in these in- fections, are sometimes present in the circulation. As development advances the plasmodium-infected cor- puscles seem to be filtered out by the capillaries and small arteries (Plate II., Fig. 2, A, b, c) of the deeper viscera and of the bone marrow ; so that even in severe infections the pigmented stage is by no means propor- tionately represented by, or even frequently encount- ered in, finger blood, the sporulating stage (Plate I., Fig. 3, i,j) still less so. To find numerous examples of the more advanced stages of these parasites it is neces- sary to aspirate splenic blood, or to search in fatal cases in the deeper viscera, or in the bone marrow im- mediately after death. Owing to the absence of the more advanced forms from the peripheral circulation, the duration of the life span of these parasites is difficult to fix ; probably it varies between twenty- four and forty-eight hours, being not very constant even in the same types. " Brassy bodies."—The malignant parasite fre- quently leads to a peculiar shrivelling of the invaded E 5° Malaria. corpuscle, resulting in the formation of a crenated, or folded, very dark corpuscle. This dark, irregularly- shaped corpuscle the Italians, from its colour, have designated " brassy body "(Plate I., Fig. 3, e). In the interior of these dark, shrivelled corpuscles the para- site can generally be made out as a minute, pale ring. The crescent body characteristic.—Most distinctive feature of all, the malignant parasites alone form crescent bodies. Time when crescents appear ; not a, fever form.— It is to be remarked that these crescent bodies are not to be seen at the very commencement of an in- fection. A week usually elapses between the first appearance in the peripheral blood of the small, intra- corpuscular plasmodia and the first appearance of the crescent bodies. Once the latter begin to appear they generally tend to increase in number during a few days. They may persist, though, after a time, in decreasing numbers, in the circulation for one, two, or three weeks after the small, fever-causing, intra- corpuscular plasmodia and their associated fever have disappeared, whether spontaneously or in consequence of the administration of quinine. Although when given early in an infection quinine may prevent the appearance of crescents, yet, once formed, this drug has apparently no influence on these bodies nor on their capacity for ex flagellation. The crescent body does not cause fever; it is usually associated, how- ever, with marked cachexia. Characters of the fever.—It is found that the fevers these parasites give rise to are apt to be very irregular in their course. The rigor stage is relatively less marked, the pyrexial stage is more prolonged, and is often characterised by a tendency to adynamic conditions, vomiting, intestinal catarrh, pains in the limbs, anorexia, severe headache, depres- sion. After apparent recovery from the fever, there is a great proneness to relapse at more or less definite intervals of from eight to fourteen days. Such fevers are accompanied by rapid destruction of corpuscles, Malignant Quotidian Infection. 51 and are usually followed by marked cachexia. At any time in their course pernicious symptoms of the gravest character may declare themselves. MALIGNANT QUOTIDIAN INFECTIONS. The parasite.—The parasite of these infec- tions is of two kinds, very generally in association —the pigmented (Plate II., Fig. 1) and the un- pigmented. In both the cycle is approximately one SUMMER QUOTIDIAN E M E M E M E M E M E M E M E M E [ M -L|__j_ ! ... -i. . ... :l ' -U. I ^ TT : I J '.. ... T. .. „ : t:. .".: ::". ll l :_ 40 ~:~:i :: " fr. _' 1 39 :: ::_ :: :: 1.1 . 1 H - ■ 4- ff . 4- I 38 :: :i.::_._" ll \ ": :::::;v.~ r . 1 1 - -- - \ j..Vi^j \ 1 •„ + V J V / 1 \ ^7 .1. />' \ r V l I ■ /■ '-N 1 \ I I 7 —/■ IT I r^ - \ ih- .. L-/.+ . 1 _i -W-- . ±j/- I "T"|-----1 i ■ . _ . ::::__: :.x_ Trl -^J- . j ' i _..:::____± :.""±.±___::±t 11 11 I iti- •1 1 1 In .II II I I ' I • I Fig. 18.—Chart of malignant quotidian infection. of twenty-four hours ; in both the young parasites exhibit very active movements, and tend to assume the ring form. Before sporulation, they grow so as to occupy from one-fifth to one-third only of the corpuscle. Both form little heaps of from six to eight very minute spores. In the unpigmented parasite pigment is never seen unless in the crescent phase ; in this phase, how- ever, pigment is never absent. In the pigmented parasite there is a considerable amount of fine pigment which, at the sporulating stage rarely seen in peripheral blood, collects in the usual way into one or two more or less central lumps. E 2 52 Malaria. Character of the fevers.—The fever these parasites give rise to is such as just described, a typhoid-like depression being generally a prominent feature in well-marked cases (Fig. 17). MALIGNANT TERTIAN INFECTION. The parasite.—The parasite (Plate I., Fig. 3) of this infection is, in many respects, like that of ordinary benign tertian, only smaller, attaining when mature from a half to two-thirds the size of the cor- puscle it occupies. The infested blood-corpuscle may be altered in colour in the direction of being either darker or lighter; sometimes it shrinks, or it may become a " brassy body." The segments of the rarely encountered mature parasite number usually ten or twelve, and are arranged along with the associated clump or clumps of pigment in an irregular heap. The crescent is also, of course, a distinguishing feature of the infection. The associated fever.—The symptoms this parasite gives rise to are, in many respects, very different from those caused by the benign tertian parasite. In the first place, though rigor is not so marked, the hot stage lasts longer—often exceeding twenty-four hours ; in fact, the tendency for the successive paroxysms to overlap, to become sub- intrant, is very marked. Moreover, where the inter- missions are distinct, Marchiafava and Bignami have pointed out that the crisis is unlike that of ordinary tertian. There is what is called a double crisis ; that is to say, when the fever has attained its apparent fastigium there is a drop of one or more degrees of temperature—the "false crisis," to be followed by a fresh rise, which is then followed by the true crisis. This peculiar phenomenon the writers referred to attribute to the presence of two swarms of parasites, one of which matures somewhat later than the other (Fig. 18). The tendency to the development of pernicious symptoms, to the production of cachexia, and to Malignant Tertian Infection. 53 relapse is similar to what occurs in the case of the malignant quotidian infections. Geographical distribution.—All these malig- nant parasites are confined to the warmer regions of the earth, and to the more intensely malarial districts in these. In the sub-tropical zones they 7th.day MALIGNANT SUMMER-AUTUMN TERTIAN Fig. 19.—Chart of malignant summer-autumn tertian. occur as first infections only in late summer or early autumn ; hence the name " aestivo-autumnal." microscopical examinations in malignant fevers.—It is important to bear in mind that in malignant infections the pigmented fever-causing forms of the parasite are not very frequently met with in peripheral blood. When found, and when it is ob- served that the pigment has become concentrated, it is a sure indication that a paroxysm is impending. On the occurrence of rigor, and at least during the earlier stages of the paroxysm, many small unpigmented 54 Malaria. plasmodia, sometimes exhibiting active amoeboid move- ment, sometimes appearing as rings, will be found in finger blood ; but towards the end of fever these unpigmented plasmodia often diminish in number, and all evidence of parasitic infection may even dis- appear from the blood till the approach or incidence of the next paroxysm. Crescents and pigmented leucocytes may be numerous in the intervals of absence of the intra-corpuscular parasites. The seg- menting forms of the malignant parasite are best found by aspirating the spleen with a hypodermic needle—hardly a justifiable procedure unless in very exceptional circumstances ; only very occasionally are they encountered in peripheral blood. CLINICAL FORMS OF BENIGN AND PERNICIOUS MALARIAL FEVERS. General statements.—The foregoing account, so far as it goes, and so far as it relates to the clinical manifestations produced by uncomplicated and typical infections, is true enough. It must be borne in mind, however, that as there may be an infinite variety as regards the dosage of the parasite, and as regards individual susceptibility, and as there may be a concurrence of several species of plasmodia (mixed infection being far from uncommon), or of several generations of the same species of plasmodium matur- ing at different times, so there may be corresponding infinite variety in the clinical manifestations. Certain general statements maybe made about them, however. In more temperate climates, and in the winter and spring seasons of warmer latitudes, malarial fevers are usually distinct intermittents; and fresh infections occurring in these places and seasons, so far as the subject has been studied, are found to be produced by the benign tertian and quartan parasites, and are, therefore, of little danger. Relapses, how- ever, of previous malignant crescent-forming parasite infections, originally contracted during the hot Benign Fevers. 55 weather, may occur during the cold season ; in fact, they are far from uncommon. First attacks, though produced by one of the benign parasites, may assume the characters of a remittent; generally, in temperate latitudes, they are frank intermittents. First attacks of malignant malaria, although they may in a few instances be intermittent, are in the majority of cases re- mittent in type ; and so are attacks the result of extensive reinforcement by fresh parasites (through fresh exposure) of the old stock which the old fever subject may carry about him in a latent condition. The first attack experienced by a newcomer to a highly malarious district with a hot climate is, therefore, generally remittent and severe. It is neither necessary nor desirable to attempt to describe in detail the infinite variety malarial attacks assume. It would be impossible in a limited space to do so; and, if done, the result would amount only to an uninteresting and unprofitable ringing of the changes on rigor, pyrexia, diaphoresis, bilious vomiting, bilious diarrhoea, constipation, catarrhal gastritis, headache, bone-ache, prostration, and so forth. The picture would be further confused by the fact that the natural pro- cession of events is generally, nowadays, broken in on by the action of quinine, the use of which is almost universal with Europeans in the tropics; so that it is difficult to say how any given malarial fever would develop, or how it would terminate, if left alone. Sometimes, in the case of natives of tropical countries, who may not always command a few grains of quinine, such fevers pass into a typhoid state, with dry brown tongue, sordes in the mouth, muttering delirium, and may terminate in collapse and death. In others, un- treated remittents and intermittents gradually subside spontaneously in the course of a week or fortnight; or the remittent may merge into an intermittent, which, in the course of weeks or months, subsides for a time, to recur every now and again at longer or shorter intervals. The Italians describe a form of malarial 56 Malaria. fever the natural evolution of which seems to be in intervals of several days' or weeks' duration—" long interval fevers," they call them. In these the fever seems to subside spontaneously. Kelsch and Kiener allowed certain cases of remittent to run their course unchecked by quinine; they found that in ten or twelve days the fever gradually expended itself. Under favourable hygienic conditions the plasmodium and the associated fever frequently disappear together spontaneously. REMITTENT TYPES. Bilious remittent.—One type of fever, known as bilious remittent, has long been recognised on account of the bilious vomiting, gastric distress, some times bilious diarrhoea, sometimes constipation, which accompany the recurring exacerbations. It is further distinguished by the pronounced icteric or, rather, reddish yellow or saffron tint of skin and sclerae; a tint derived, probably, not from absorption of bile as in obstructive jaundice but from modified haemo- globin (luemapheine) free in the blood or deposited in the derma. These bilious remittents are very com- mon in the more highly malarious districts of Africa, America, the West Indies, India and, in fact, in all tropical countries. They are not specially nor directly dangerous in themselves, but they result usually in profound anaemia, and are often but the prelude to chronic malarial saturation, bad health and invaliding. Typhoid remittent. — A modification of the bilious remittent — what Kelsch and Kiener call " typhoid remittent"—is very much more grave as affecting life than the simple bilious remittent. In the typhoid remittent, typhoid symptoms—such as low delirium, prostration, dry tongue, swelling of spleen and liver, subsultus tendinum, marked melanaemia— are superadded to the usual symptoms. Though recovery is the rule, a considerable proportion of such attacks prove fatal. Adynamic remittent.—The same writers class Pernicious Fevers. 57 by themselves a set of cases they call "adynamic remittent" ; cases which are characterised by fatuous- ness, restlessness, nervous depression, intense muscular and cardiac debility, profound and rapid blood de- terioration, icterus, leucocytosis, melanaemia, liability to syncope, occasionally haemoglobinuria, liability to haemorrhages, and a marked tendency to local gangrene. PERNICIOUS ATTACKS. Many writers have drawn attention to what are called pernicious attacks or pernicious symptoms— the French neatly designate them " acces pernicieux " —a series of phenomena, the possibility of the appear- ance of which, not only in the course of remittents but in the course of what is seemingly only an ordinary paroxysm of intermittent fever, should never be lost sight of by the practitioner in tropical climates. These "acces pernicieux" may supervene in apparently mild cases, and carry off the patient with horrifying suddenness—as suddenly as an at- tack of malignant cholera. The wary practitioner is always on the look-out for them, and is always prepared with measures to meet them promptly when they threaten. Pernicious attacks are roughly classified into cerebral and algide. The cerebral are divisible into hyperpyrexial, comatose, convulsive, paralytic, and so forth ; the algide into syncopal, choleriform, dysenteric, haemoglobinuric, etc. Cerebral Forms. Hyperpyrexial.—There can be little doubt that many of the cases of sudden death from hyperpyrexia and coma, usually credited to what has been called "ardent fever" or to "heat apoplexy," are really malarial. If careful inquiry be made into the ante- cedents of many of these cases a history of mild intermittent will often be elicited ; or it will be found that the patient had been living in some highly malarious locality. 58 Malaria. In the course of what seemed to be an ordinary malarial attack, temperature, instead of stopping at 104° or 105° Fahr. may continue to rise, and passing 107°, rapidly mount to 110° or even to 112°. The patient, after a brief stage of wild maniacal, or, perhaps, muttering delirium, becomes rapidly un- conscious, then comatose, and dies within a few hours, or perhaps within an hour, of the onset of the pernicious symptoms. Comatose.—Or the patient, without hyper- pyrexia, the thermometer perhaps not rising above 104°, may lapse into coma. The coma may pass away with crisis of sweating; on the other hand, an asthenic condition may set in, and death from collapse supervene. Other cerebral forms.—In addition to these hyperpyretic and comatose conditions, other forms of cerebral attack are met with in the course of malarial fevers, such as sudden delirium ending in coma and, perhaps, death; convulsive seizures of an epileptic or of a tetanic character, with or without delirium or coma, which seizures, if not fatal, may eventuate in ■permanent psychical disturbances ; various forms of apoplectic-like conditions, and paralysis which may be complicated with aphasia. Embolism of cerebral capillaries.—These cerebral attacks are now explained, and, it appears to me, correctly explained, by the suj^position, founded on actual post-mortem observation, that they depend on embolism by the malaria parasite of the capillaries of the various nerve centres (Plate II., Fig. 2) involved ; in hyperpyrexia, the thermic centres; in aphasia, Broca's convolution; and so on. By micro- scopical examination of properly prepared sections of the brain in fatal cases, such a plugging of the vessels can generally be readily observed. The earlier students of malarial melanaemia had remarked the presence of pigment in the cerebral capillaries in many cases of this description, and attributed the associated symptoms to thrombosis by the pigment. Frerichs Ama urosis. 59 having failed to find pigment in certain fatal malarial cases attended with cerebral symptoms, whilst he found it in abundance in others in which there had been no special cerebral manifestations, rejected this hypothesis. At that time the malaria parasite had not been discovered, and Frerichs was not aware, of course, that there is a variety of the malaria parasite which does not form pigment; nor were the facts of localisation of the cerebral functions so well under- stood then as they are at the present day. Malarial amaurosis.—In rare instances the patient may come out of the comatose condition of a pernicious malarial attack quite blind. The amaurosis is usually very transient, lasting for an hour or two only. On the other hand, it may be persistent; in which case, according to Poncet, optic neuritis, peripapillary oedema, extravasation of leucocytes, plugging of retinal and choroidal vessels by parasites or pigmented leucocytes and consequent multiple haemorrhages, may be found in the fundus. If the haemorrhages are minute they are discoverable by the microscope only. These fundus changes differ from those in quinine amaurosis. In the latter the amaurosis is more persistent; the disc is white and the vessels are shrunken; there are no inflammatory symptoms, and central vision is the first to recover. Algide forms. The algide forms of pernicious attack, as indicated by the name, are characterised by collapse and extreme coldness of the surface of the body, and a tendency to fatal syncope. These symptoms usually coexist with elevated axillary and rectal temperature. Gastric form.—This condition may be associated with, and in a measure dependent on, acute catarrhal dyspeptic trouble. It is accompanied by severe epi- gastric distress, tender retracted abdomen and incessant vomiting. Choleraic form.—Malarial attacks are some- times accompanied by choleraic symptoms. The stools 60 Malaria. suddenly become loose, profuse and numerous ; though not so profuse or colourless as the rice-water discharge which pours from the patient in true cholera, Generally they retain a certain amount of biliary colouring and may be mucoid or even bloody. As in cholera, the serous drain may lead to cramps in the limbs, loss of voice, pinched features, washer- woman's fingers, almost complete suppression of urine and, perhaps, to fatal collapse. Such attacks are very deceptive, and may be mistaken for true cholera. The high axillary temperature if present, a history perhaps of recent ague fits, the subsequent rapid disappearance of the choleraic symptoms on the appearance of the hot and sweating stages, the colour of the stools and other collateral circumstances usually suffice for diagnosis; particularly if they are supplemented by a microscopical examina- tion of the blood. Although not usual, recurrence of the choleraic symptoms may take place at the next fever period. A dangerous type of malarial fever, which prevails in the Punjab, is often ushered in by such symptoms; without the microscope, its true nature may be hard to recognise. Dysenteric form.—Another form of pernicious attack is characterised by the sudden appearance of dysenteric symptoms, perhaps by haemorrhage from the bowel or elsewhere. The possibility of a suddenly developed dysentery being of malarial origin must therefore be kept in view; particularly if, in what appears to be ordinary dysentery, axillary temperature is found to be unusually high. In every case of dysentery of this description an examination of the blood should be made before the usual treatment for that disease is instituted—a treatment which, in the adynamic state the patient is probably in, might very well prove fatal. Syncopal form.—In the preceding types of algide pernicious malarial attack the dangerous symptoms show themselves in the rigor stage of the fever. There is yet another form in which the danger appears IDemoglobinuric Fever. 61 to depend on an exaggeration of the symptom usually hailed as bringing relief, and, for the time, freedom from danger. Thus the sweating of the stage of defervescence may be excessive and cause collapse which, if the patient rise up suddenly or make an undue effort, may lead to fatal syncope. Weak and cachectic patients, therefore, should be warned of this possibility, and not be permitted to rise suddenly or to exert themselves in any way during the defer- vescence of an ague. The pathology of these various forms of algidity is probably of a very mixed character. In the gastric, choleraic, dysenteric types probably there is an accu- mulation of plasmodia in the vessels of the intestinal mucosa; such accumulations of parasites have been described. In those attacks in which profuse sweating is the dangerous element, the diaphoresis may be re- garded, at all events in part, as symptomatic of ex- cessive blood destruction—of what is, in reality, equivalent to a sudden and extensive haemorrhage ; or it may be that it is only an excessive reaction to the malarial toxin. The dangerous syncope attend- ing all types of algidity is secondary, and merely an expression of collapse. Haemoglobimiric fever. There is one form of what is believed to be malarial infection, which, though fatally common in certain countries, and though possessing very alarming and distinctive symptoms, has only comparatively recently been differentiated and studied. I refer to bilious haemoglobinuric fever, sometimes erroneously called " haematuric fever," sometimes " blackwater fever." This most dangerous disease prevails especially in the more malarial districts of tropical Africa. It was first described by French naval surgeons stationed at Nossibe, a French settlement off the north-west coast of Madagascar. Subsequently it was found to have a more extensive distribution, and to be common, 62 Malaria. as mentioned, in many parts of tropical Africa. It is also found in the hotter regions of America, in the West India islands, in parts of the Eastern penin- sula and archipelago, in the South of China, in Assam, and in some districts of India. Until quite recently, strange to say, no Indian writer had mentioned haemoglobinuria as a feature in the pyretology of Hindustan or of the East. The disease occurs, but is rare, in South Europe; cases are sometimes met with in Greece and Italy. It was epidemic among the labourers employed in making the canal through the Isthmus of Corinth. Possibly it has been over- looked in many places. There may be another explanation for the singular silence, on the subject of haemoglobinuric fever, of the classical writers on Indian diseases; they may have confounded it with bilious remittent. It is difficult to believe, however, that the large number of acute observers who have studied Indian diseases so care- fully, and for so many years, could have system- atically overlooked this striking disease. Possibly, therefore, it is only of recent introduction into India. Such an idea is countenanced by the fact that certain medical men practising in Africa, good observers, declare that this form of malaria is of comparatively re- cent introduction there; and, moreover, that it is yearly becoming more common in that continent. There is another remarkable fact about haemoglobinuric fever, which would lead us to believe that it is dependent on a form of the malarial parasite peculiar to itself; and that is, that in its recurrences malarial haemo- globinuric fever often retains its peculiar characteristics for months after the patient has left the endemic area in which the germ was originally acquired.* Those who have suffered from it in Africa are liable not only to malarial attacks of the ordinary kind but to a recurrence of haemoglobinuric symptoms for some * Yersin and Breaudat assert that they found a special bacillus in the urine in several cases of "haematuric fever. Archives de Medicine Navale, July, 1895. and June, 1896. H.EMOGLOBINURIC FEVER. 63 little time after their return to Europe; they may even die of it. I know of four such fatal cases which occurred recently in Great Britain, three in England and one in Scotland. The European resident in tropical Africa regards three, or four, or more attacks of malarial fever as a regular feature in his annus medicus. Some of these attacks are of little gravity; others may be severe and inconvenient. On the whole, these attacks are not very much dreaded. When haemoglobinuric symptoms declare themselves, however, such fevers are invariably regarded, and very properly so, with the utmost apprehension; for not only are they dangerous in themselves—at least one in every three or four proving fatal—but, even if .recovered from, they leave the patient intensely anaemic, with damaged kidneys perhaps, and strongly predisposed to a recur- rence of similar attacks in one of which he will probably succumb. Haemoglobinuric fever is not common during the first year of residence in Africa, though, in rare in- stances, it does occur even as early as the second or third month. It is usually after a year or two of malarial saturation, and after many attacks of an ordinary character, that it shows itself. From statistics prepared from certain returns regarding the white employees of the Congo Free State, and from the evidence collated by other writers, it would seem that the third year of residence is the one most liable to this disease. Longer residence with immunity seems to imply in the European special re- sisting powers as against the diseases of Africa, and special suitability for the African climate. Native Africans, though subject enough to intermittents, enjoy a relative immunity from ha-moglobinuric attacks. This is not absolute, however; Easmon, Eyles, and Quartev-Papafio have recorded cases of the disease in natives. Many of the Chinese labourers on the Congo railway died of haemo- globinuric fever. 64 Malaria. Symptoms.—A European, who has been subject to occasional attacks of malarial fever which hitherto had been more or less successfully controlled by quinine, has a recurrence of what at first appears 'to be the familiar symp- toms. A slight, or a more considerable rigor is followed by intermit- ting, or remitting, or irregular fever, with or without marked bilious symptoms. Earlier or later in the attack he becomes conscious of ach- ing, perhaps severe pain, in the loins and in the region of the liver. In consequence of a some- what urgent desire he passes water, when he is astonished to see that his urine has become very dark in colour, perhaps malaga-coloured, or pos- sibly almost black. The fever continues, though not necessarily very high. Very likely he suffers from epigastric pain and distress, bilious vomiting to an unusual extent, and, it may be, bilious diarrhoea; or he may be constipated. The pain in the loins and the liver-ache continue, and the urine be- comes darker and darker. By-and-by the sufferer breaks into a profuse sweat and the fever gradually subsides. (Fig. 20.) The urine, which hitherto had been some- what scanty, now flows more freely; and, after passing May2 1 22 23 24 25 26 M.E. M.E. M.E. M.E. M.E M.E. u. s i-107 Hi1 H. H. H. 106 105 '04* Nr? 7. lOp.m A 10.30J m. 102' 101° rigor i: .30'p.n Iflff S.30a.i \ / 2.301 i.m. 0 p.m. W 4.( p.m. 10.31 a.m. NOR g. 20.—Temperature chart of an attack of haemoglobinuric fever occurring in England ; infection acquired on the Congo. Recovery. H, indicates lismoglobinuria. HAEMOGLOBINURIC FEVER. 65 through various paling shades, from dark brown to sherry red, becomes once more natural in appearance. Coincidently with the appearance of the dark colour in the urine, or even be- fore this has been re- marked, the skin and sclerae rapidly acquire a deep saffron-yellow tint. This icteric condition per- sists, and even deepens during the progress of the fever, continuing for several days to be a striking feature in the symptoms. When the fever subsides, the pa- tient is conscious of a feeling of intense weak- ness from which he re- covers but slowly. Fever may recur next day, or for several days; or it may cease; or it may be remittent, or almost continued in type. The haemoglobinuria may re- cur with each rise of temperature; or there may be only one or two outbursts. In the more severe forms of haemoglobinuric fever there is usually a very great amount of bilious vomiting, of in- tense epigastric distress, and of severe liver- and loin-ache. The urine may continue copious and very dark in colour; or, con- tinuing haemoglobinous, it may gradually get more and more scanty, acquiring a gummy consistence, a nov.i: 12 14-15 16-17 DC I M.E. M.E. M. E. M. E. U. 2 0 1 2 10 0 0 1 0 1 S H? H. H. 7.35 p.m.* 7.50p.miA :. S.8p.m.L>i 6.5 p.m.* 4."p.m.» 105c 104c 103' 10? 101° 100c 99° NOR 10.0 a.m. |\ 4.50 xm 1 Jl.Op.m. 12.0 lie AriEror ml 9.1) 1 Vm ' f 7.0a.m. Ml 9.0Ja.ini J I ys.30a.rn. Il.Op.m. ... 11. "8.0 a.m. Fig. 21.—Temperature chart of re- currence of haemoglobinuric fever in same patient (Fig. 20) shortly after his return to Congoland. Death. h, indicates baeinoglobinuria. F 66 Malaria. few drops only being passed at a time. Finally it may be completely suppressed. In severe cases death is the rule. It appears to be brought about in one of three or four ways. The fever may assume the typho-adynamic type ; or suddenly developed pernicious cerebral, hyperpyrexial (Fig. 21), or algide symptoms may supervene. In other cases the symptoms may be like those consequent on sudden and profuse haemorrhage—jactitation, sweating, sigh- ing, syncope. Or it may be that suppression of urine, persisting for several days, terminates, as cases of sup- pression usually do, in sudden syncope, or convulsions and coma. Or nephritis may ensue and the patient die from uraemic trouble three or four weeks after all signs of haemoglobinuria and fever have disappeared. Such is a brief and imperfect sketch of the symptoms of this, the most important of the African forms of malarial poisoning. It is a disease which, as this continent becomes more opened up and more frequented by Europeans, is bound to occupy a greater amount of attention from medical writers than it has hitherto done. The urine.—If the characteristic dark brown urine of a haemoglobinuric case be stood for some time in a urine glass, it separates into two well-marked layers : an upper of a clear though very dark port-wine tint, and a lower—perhaps amounting to one-half or one- third of the entire bulk—of a somewhat brownish- grey colour, and consisting of a sediment in which an enormous number of hyaline and haemoglobin tube casts are to be found, together with a large quantity of brownish granular material. Epithelium is also met with; but blood corpuscles may be entirely absent, or very few in number. With the haemo- globin there is also an escape of the serum of the blood, for the urine turns almost solid on boiling; and for some days after it has regained a normal appear- ance the urine will still contain albumen, though in gradually diminishing amount. The kidneys.—If the kidneys of a fatal case are HAEMOGLOBINURIC FEVER. 67 examined at an early stage of the disease, they are seen to be enlarged and congested, the tubules blocked with haemoglobin infarcts, the cells laden with yellow pigment grains, and the capillaries with black malarial pigment. If the case survive for three or four weeks and then die of uraemia, the appearances are those of large white kidney. The parasite.—The parasitology of haemoglobinuric fever has hardly been worked at. Plasmodia have been found in the blood and organs ; but their specific characters have not been accurately determined, further than that they are small, and rarely sporulate in the peripheral blood, belonging, doubtless, to some form of the crescent-forming malignant type. Con- sidering the peculiar clinical manifestations it gives rise to, and the facts of geographical distribution, it seems likely that the parasite of malarial haemoglo- binuric fever is specifically different from the malaria parasites usually met with in Europe and, perhaps, in India. A practical experience of these suddenly developed pernicious fevers of the tropics teaches that we should never make light of any malarial attack ; particularly if it be of a mild irregular character and imperfectly controlled by quinine, and if small parasites, or the crescent form, be present. It further teaches that the subjects of such fevers should be particularly careful to guard against chills, fatigue, insufficient and unwhole- some food, and all causes of physiological depression. The subjects of African haemoglobinuric fever must exercise special caution in these respects, not re- laxing their care, for some months even, after their return to a cold climate. If possible, they ought not to return to Africa. F 2 68 Malaria. TABULAR STATEMENT OF THE CHARACTER. Modified from Duration of Movement. Pigmentation-. Development. 1. Benign quartan parasite 72 hours Slight movement in the imma-ture forms Coarse grains; little or no movement 2. Benign tertian parasite 48 hours or less (in anticipa-ting types) Active amoeboid movement in the immature and also in the middle - aged forms Fine granules in immature forms, often in the larger actively swarming 3. Malignant pig-mented quoti-dian parasite 24 hours The unpigmented immature form very actively amoeboid ; less active when pigment accu-mulates Very fine; later co-alesces in one or two lumps ; does not swarm 4. Malignant unpig-mented quoti-dian parasite 24hoursorless Very active amoeboid move-ment None 5. Malignant tertian parasite 48 hours Active ;the move-ment remains present in the pigmented bo-dies Moderately fine; often shows oscil-latory move-ment Characteristics of Various Parasites. 69 ISTICS OF THE VARIOUS PARASITES. Mannaherg. Num- Cres- Alterations in Form of Spore ber the Infested Maximum Size. Formation. of CENTIC Bodies. Blood Cor- Spores. puscles. The size of Daisy form ; the 6-12 None The red blood the red single spores corpuscles are blood cor- roughish, with little disco- puscles distinct nucle- loured, and do olus. not alter their size. Size of the red Sunflower or grape- 15-20 None The red blood blood cor- like ; single spores (often corpuscles are x puscles,some- small, round ; nu- less) often hypertro- tiines even cleolus rarely phied, and lose larger seen colour quickly and completely. i-i the size of Irregularly formed 6-8 Present The led blood a red blood heap (even corpuscles corpuscle more) shrink often, and are then either darker - stained (copper colour) or may be com-pletely deco-lourised. £-J the size of Star-shaped, or in 6-8 Present The red blood a red blood irregular heaps corpuscles corpuscle shrink fre-quently, and are darkly stained. J-§ the size of Irregular heaps 10-12, Present The red blood a red blood rarely corpuscles corpuscle 15-16 shri nk fre- quently ; they are darkly stained, or may be perfectly co- lourless. 7° CHAPTER III. MORBID ANATOMY AND PATHOLOGY. The blood in malaria.—As the plasmodium is a blood parasite we naturally expect that the primary effect of its presence will be exercised on, and mani- fested in, the blood; and as the parasite lives in and at the expense of the corpuscles, destroying a certain proportion of them—in fact all those attacked—we look, in the first instance, for a corresponding diminution in the number of these corpuscles—an oligocythaemia. Oligocythaimia.—Accordingly, when in malarial disease we come to measure accurately the corpuscular richness of the blood, we do find a decided oligocy- thaemia ; and, not only this, but we find a degree of oligocythaemia greatly in excess of anything we might expect, or which can be accounted for by, or is in correspondence with, the proportion of corpuscles attacked and directly consumed by the plasmodium, judging by what we see in finger blood—peripheral blood. If, for example, every hundredth corpuscle contains a parasite, we might look for something like a quotidian, tertian, or quartan 1 per cent, reduction in the total number of blood corpuscles; if every twentieth corpuscle contains a parasite—a very high and unusual proportion—we might look for a similarly timed 5 per cent, reduction. Now this is an amount of haemolysis which should be easily compensated by the latent physiological haemogenetic margin, and which one would not expect to show itself as a definite anaemia, or to show itself only after the recurring drain had been kept up for some considerable time. But what are the clinical facts 1 Effect of Parasite on Blood. 71 One or two paroxysms only, of some malarial fevers, may be immediately followed by an anaemia so pro- nounced as to be discernible to the eye in the intense pallor of the skin and visible mucous surfaces. On counting the corpuscles in such a case we note a regular drop in their number of from 5 to 10 per cent. per paroxysm. Often after a single paroxysm of some pernicious fever as many as half a million, or even one million, corpuscles per c.mm. drop out of the normal five millions; and this reduction may go on, as paroxysm follows paroxysm, until the corpuscular richness has fallen to one million, or even less. Diminished haemoglobin value of corpuscles.—Not only is there in many, in fact in most, cases of malarial disease a pronounced oligocythaemia, but there is, in addition, a marked diminution in the haemoglobin value of the surviving corpuscles; it may fall 10, 20, or even as much as 50 per cent. Diminished amount of blood.—And not only is there this marked diminution in the proportion of the corpuscles to the bulk of the blood and marked diminution in their haemoglobin value, but there is, furthermore, in all malarial conditions of any con- siderable standing, a marked diminution in the volume of blood. Thus it comes that at the post- mortem examination of such a case we do not always meet with that congestion of the organs which is so usual a feature in most specific fevers. On the contrary, although in quite recent cases visceral congestion may be marked enough, if a malarial fever has been of any considerable duration, the venous system, with the exception of that apper- taining to the spleen, liver and portal system gener- ally, may be markedly empty. And thus it is that often, when we would make a preparation of blood from the living malarial patient, we may find that not only is the blood pale, lake-coloured, thin, and watery, but that it does not flow freely from the pricked finger. Destruction and reparation of blood in first attacks 72 Malaria. and in relapses.—There appears to be no very defi- nite or manifest law governing the degree, progress, and quality of the anaemia of malarial disease. On the whole, and as rough general rules, it may be laid down that in any given case the anaemia is in pro- portion to the severity of the febrile attacks ; that although the loss of corpuscles following first attacks is usually very marked, this loss is rapidly made good; whereas, that although in relapses the loss of corpuscles is less pronounced, the tendency to reparation is also less. Morbid anatomy : Macroscopic.—If the body of a patient who has died in the course of an acute attack of malarial disease be dissected, certain appearances are generally found. In the first place, and invariably, the spleen is enlarged — often very much enlarged; its surface is dark—black some- times, what is called pigmented. On section, the gland tissue is also found to be dark. Generally the parenchyma of the organ is so much softened as to be almost diffluent, so that the tarry pulp can sometimes be washed away by quite a gentle stream of water. The liver, too, is softened, congested, enlarged, and pigmented. The vessels of the pia mater and brain cortex are full, and the grey matter may present a peculiar leaden hue. The marrow of the spongy bones, such as the sternum and the bodies of the vertebrae, is also dark and congested ; and a similar state of pigmentation and perhaps congestion may be dis- covered in the lungs, alimentary canal, and kidneys. Microscopic : Malarial pigmentation.—The pig- mentation referred to is pathognomonic of malaria. On submitting malarial blood from any part of the body to microscopical examination, it will be found to contain grains of black pigment. Particularly is this the case with blood from the organs just men- tioned. If microscopical sections of these organs (Plate II., Figs. 2, 3, 4) be examined there will be found, more or less thickly distributed in the blood, and within the endothelium of the arterioles and Nature of Pigment. 73 capillaries, minute grains, or actual blocks, of the same intensely black substance. For the most part these pigment grains are enclosed in leucocyte-like bodies which are either clinging to the walls or lying loose in the lumen of the vessels. Here and there the pigmented bodies may be so aggregated together that they form veritable thrombi, and actually occlude the vessels. It is possible that many of these bodies are not pigmented leucocytes, but are really dead and breaking-down parasites ; for, if the body from which preparations were made be quite fresh—that is, if the preparations were made within two or three hours of death, it may be possible to see that the capillaries of some of the organs are full not only of pigment but also of plasmodia, a very large proportion of the blood corpuscles containing para- sites. Particularly is this the case with the spleen and bone marrow; often, too, with the brain, liver, epiploon, and intestinal mucosa. The spleen and bone marrow are further distinguished from the other organs mentioned by the position in which the pig- ment occurs in them. In all organs the pigment is found in the blood vessels, but only in these two organs is it found in the cells of the parenchyma as well, and outside and away from the blood vessels. This extra- vascular pigment is either free, or it lies in the large cells characteristic of these organs, or in the small cells of the parenchyma. Nature and source of malarial pigment.—What is this black pigment which is so generally diffused throughout the circulation, and which is so specially abundant in the spleen and bone marrow ? In colour, in structure, and in chemical reaction it corresponds exactly with the pigment already described as form- ing so prominent a feature in the malaria parasite itself. Like this, it is insoluble even in strong acids; it is altered by potash, and is entirely and rapidly dissolved by ammonium sulphide. It may occur as minute dust-like grains, or as coarser particles, or as agglomerations of these into irregular, mamillated 74 Malaria. lumps. So far as the circulation is concerned, such a pigment is found in no other disease whatever. As an extra-vascular pathological product it is found only in certain melanotic tumours ; but only in the cells of the tumour, never in the blood vessels. Pigments of several kinds are found in old blood clots; but such are manifestly different from the pigment of malaria, and yield very different chemical reactions. Intra-vascular black pigment, therefore, is absolutely pathognomonic of malaria.* Because of its physical characters, and of the circumstances in which it occurs, it may with confidence be regarded as the specific product of the malaria parasite itself. Source of the pigment in the pigmented leucocyte. —If further evidence be required of the identity of the intra-parasitic pigment and that found in the tissues, it is supplied by a study of the fate of the pigment grains and clumps set free in the blood on the breaking up of the sporulating plasmodium. If malarial blood, drawn during the rigor and early stages of acute attacks, be examined, leucocytes carrying grains or even blocks of black pigment will be encountered frequently. If the observer be for- tunate and persevering, he will sometimes actually see whence this pigment is derived ; he may even detect the leucocytes in the act of taking it up. He may see the pigment set free in the liquor san- guinis by the falling to pieces of a sporulating plasmo- dium ; and he may then see a phagocyte creep across the field of the microscope and slowly engulf the little block. This undoubtedly is one source of the pigment in the leucocytes. Other, though possibly less import- ant, sources, are the effete crescent bodies, and, very especially in the large cells of the spleen, necrosed parasite-containing red blood corpuscles. Phagocytosis in the spleen.—The evidence of phago- cytosis in the spleen in malaria is very remarkable. * The pigment dot occurring in a large proportion of the lymphocytes, even in normal blood (see p. 26), must not be con- founded with malarial pigment. Distribution of the Pigment. 75 Not only are large and small masses of pigment included in the macrophages, in the smaller cells, and in the endothelium, but entire blood corpuscles— sometimes as many as eight or nine, mostly containing parasites—besides free parasites, free pigment, and fragmented haemoglobin are frequently to be seen in one and the same phagocyte. Sometimes even one pigment laden phagocyte may be seen included in another phagocyte, and these perhaps in a third. Blood of the splenic vein and liver.—There is one remarkable fact about the distribution of the pigment which requires mention. Of all the vessels of the body, the splenic vein is that in which malarial pig- < ment is most abundant; and, whereas in other vessels it is found included in ordinary leucocytes, in this vessel the pigment is found included, not only in the leucocytes, but also in certain large white cells identical with those occurring in the spleen, and, doubtless, of splenic origin also. Similar cells may be found in the capillaries of the liver, rarely, how- ever, in the blood beyond this organ; that is to say, they are filtered out by the liver from the blood carried to it by the splenic vein. An additional reason for the abundance of pigment in the splenic vein is, that not only is the spleen the physiological destination of many of the pigment-laden leucocytes and effete parasite-infested corpuscles, but it is like- wise a favourite nursery for the plasmodium. In fact, the parasite is present in this organ in greater profusion than elsewhere. So it happens that the splenic vein, coming direct from a rich breeding- and dumping-ground for the plasmodium, contains a large number of pigment-laden leucocytes. The plasmodium favoured by slow capillary cir- cidation.—One reason for the marked predilection shown by the parasite for the spleen is probably the circumstance that the circulation in this organ is relatively slow, the vascular network, as compared with the arterial supply, being unusually rich and capacious, so that the blood tends to stagnate. It is 76 Malaria. this condition of relative stagnation which seems to be favourable to certain types of plasmodia, and to determine their accumulation and relative abundance in special organs. Apparently it is for this reason that the plasmodium tends to abound in the liver, in the pia mater, the cerebral cortex, the bone marrow, the alveoli of the lungs, and in the villi of the intes- tine—all of them parts in which capillary capacity is relatively in excess of arterial supply. And, just as the parasite prefers a slow current, the pigment- laden leucocytes also seem to linger and to settle down in these quiet backwaters of the circulation, and there to deposit their burden. Thus there is a double reason for the excess of pigmentation in the highly-vascular organs. Extra-vascular pigment.—In the early stages of malarial disease, except in the case of the spleen and bone marrow, the pigment is entirely confined to the lumen of the vessels and to their endothelium. But if we examine tissues from a case which has died at a late period of the disease, the pigment may then be found, not only in the endothelium, but also in the walls of the vessels, and even in the perivascular lymph spaces, whence, it may be inferred, it is subsequently carried to the lymphatic glands, there to be finally dealt with and' broken up. As en- couraging this view about the ultimate fate of the malaria pigment, Kelsch has pointed out the signifi- cant fact that the lymphatic glands in the hilum of the liver are always markedly pigmented in old- standing malarials; a fact evidently referable to the disposal of the large quantities of pigment which, as we have seen, the liver filters out, more especially from the splenic portion of the portal circulation. These facts explain malarial pigmentation and oligocythaimia.—The facts just mentioned explain not only the origin and nature of malarial pigmentation, but also, in part at least, the oligocythaemia of the malarial state, which, as pointed out, is only partially accounted for by the destruction of corpuscles by the The Yellow Pigment. 77 plasmodium in the general circulation as represented by finger blood. They show that what is seen in finger blood does not represent anything like the aggregate mortality going on among the corpuscles from direct destruction by the plasmodium. The principal part of the malarial drama is played out in the spleen, liver, bone marrow, brain, etc., and not in the general circulation. What is seen in finger blood is but an overflow, as it were, of the greater drama going forward in the viscera. The yellow pigment. — Although the black pigment is so prominent a feature in malaria, it is not the only pigment of a pathological nature originating in the action of the plasmodium on the blood cells. The black pigment is a pathognomonic and interesting feature ; but, apart from this, it does not seem to be of any really very great pathological importance. It does not seem to act as a poison, or irritant, or as a cause of degeneration of tissue, any more than a few grains of lampblack would, if so much. It is otherwise, however, with the pigment which Kelsch and Kiener have so carefully described, and which they call the "pigment ochre." If the tissues of a patient who has recently died from a pernicious malarial attack are examined with a high power, there will be found (Plate II., Figs. 3, 4), in addition to the black pigment already de- scribed as lying in the vessels, another pigment—a yellow pigment—incorporated as little granules, or even as larger grains, in the protoplasm of the cells constituting the parenchyma of most of the organs and tissues of the body. The yellow pigment not peculiar to malaria.—This pigment is not peculiar to malaria. It is found in other diseases and conditions, particularly in those associated with extensive and rapid liberation of haemoglobin from the blood corpuscles. Thus it is found in paroxysmal haemoglobinuria, in pernicious anaemia, in extensive burns, in poisoning by pyro- gallic acid, potassium chlorate, arseniate of hydrogen, 78 Malaria. and many other toxic agents. It has peculiar chemi- cal properties, being equally insoluble in acids, in alkalies, and in alcohol. At first, when freshly deposited, it gives no evidence under the usual micro-chemical tests of containing iron; but after it has been in the tissues for some time it appears to be altered in character in this respect, and it then gives a ferrous reaction with ammonium sulphide, and with the double cyanide of iron and potassium. Polycholia andhannoglobinoimia.—Under ordinary conditions of physiological waste the products of the effete blood corpuscles are converted into bile pigment, and so got rid of. Up to a certain degree of pathological haemoglobinaemia the liver can deal in a similar way with free haemoglobin; and so it comes about that, when this substance is free in the blood in unusual abundance, the secretion and flow of bile become correspondingly increased. If this flow of bile be excessive, it gives rise to what are called " bilious symptoms "•—bilious vomiting, bilious diar- rhoea; symptoms which are so common in malarial dis- ease, particularly in that variety known as "bilious remittent." Thus polycholia is a constant and often urgent feature in most malarial fevers, and is good evidence that in malarial infections there is a sur- charge of the blood with free haemoglobin. It is not improbable, although this point is disputed, that the yellowness of the skin and sclerae observed in these fevers is due to tinting by free haemoglobin, to a haemoglobinaemia in fact, and not, as is popularly believed, to biliousness or cholaemia from bile ab- sorption. The yellow pigment is deposited in excessive hauno- globinaimia.—As in those other conditions, referred to as being attended by rapid haemolysis, in severe malarial fevers in which there is great' and sudden liberation of haemoglobin which the liver cannot at once deal with, pending its transformation into bile pigment the liberated haemoglobin is taken up by the protoplasm of the cells of different parts of the Hmmogl obi nmmi a . 79 body and precipitated in them in a slightly altered form; it is stored up in fact, waiting to be worked off as bile pigment by the, for the time being, over- taxed liver. The yellow pigment, the "pigment ochre" of Kelsch and Kiener, is, in all probability, this precipitated haemoglobin. Great excess of hannoglobinaimia results in hemo- globinuria.—Should the liberation of haemoglobin go beyond this, be too great and too suddenly effected for the excretory powers of the liver and the storage capacity of the tissues, then the haemo- globin, little altered in character, seeks a more speedy way of escape by the kidneys, and haemo- globinuria is produced. This is what is found in ordinary paroxysmal haemoglobinuria, and in toxic haemoglobinuria; and in this way we may account for the peculiar features of that most dangerous type of malarial poisoning, " bilious haemoglobinuric fever." Hcemoglobincemia : how produced.—How, it may be asked, does the malaria parasite give rise to haemoglobinaemia, this liberation of haemoglobin from the blood corpuscles] The enormous quantities of haemoglobin free in the blood, deposited in the tissues, escaping in the urine, or elaborated as bile pigment, surely cannot be derived solely from the remains of the corpuscles invaded by the parasite ; for these invaded corpuscles are almost entirely eaten up, and the haemoglobin they once contained has been nearly entirely assimilated by the parasite and transformed into its proper tissue and into melanin. It has already been pointed out that haemo- globinometric observations show that in the sur- viving and non-infected corpuscles there is a pro- nounced deficiency of haemoglobin. May it not be that part at least of the free haemoglobin is derived from these corpuscles 1 May it not be that at a particular stage in all malarial fevers, at the stage of rigor (which, as has been explained, corresponds in time to the breaking down of the sporulated 8o Malaria. plasmodium), there is a sudden liberation of some haemoglobin - dissolving substance which hitherto had subserved the parasite during its growth as a sort of digestive agent, aiding it in the assimilation of the contents of the blood corpuscle 1 May it not be that on the breaking down of the sporulat- ing plasmodium this substance is set free in the circulation, and that, being there, retaining its diges- tive properties, it continues to act as a haemoglobin solvent, and so dissolves out a proportion of the haemoglobin from the otherwise healthy corpuscles ? Size and shape of the blood corpuscles.—On the whole, in malarial conditions the corpuscles are larger than normal; particularly those attacked by the parasite, especially the tertian parasite. Occasionally we come across genuine megalocytes; and, not in- frequently, certain very minute, darkly - coloured spherical corpuscles, which may be nucleated and of embryonic type. There may also be marked irregu- larity of outline in many of the corpuscles, and an indisposition to form rouleaux. Poikilocytosis in haimoglobinuric fever.—The most striking display of blood destruction by the malarial poison is to be seen in cases of haemoglobinuric fever. I once had an opportunity of examining the blood in such a case. There did not seem to be a sound cor- puscle in the patient's body ; nearly all were mis- shapen, tailed, buckled, shrivelled, or otherwise de- formed ; microcytes, megalocytes, and pallid ghost-like corpuscles were present in abundance in every field. In this case the haemoglobin was pouring from the kidneys; the albuminous urine was the colour of porter, and deposited a copious dark brown sediment of slightly altered haemoglobin. The leucocytes in malaria.—Although the leuco- cytes, especially the large mononuclear and polynu- clear, play a very important part in the malaria drama, hitherto their numbers and varieties in this in- fection have not been sufficiently studied. In mild attacks their numbers, as observed in peripheral Behaviour of Leucocytes. 8i blood, decrease somewhat, both relatively to the red corpuscles and absolutely. Possibly this decrease may be accounted for by the tendency the pigment- laden leucocytes exhibit to carry their burden to the spleen and other internal organs, so that the decrease is only an apparent one. Dr. J. S. Billings, who has given attention to the leucocytes in a limited number of cases of malaria, reports that the diminution in their numbers is striking. In benign tertians and quartans their maximum is attained, he says, two or three hours after the onset of chill. From this time there is a progressive diminution until the minimum is reached at the end of the paroxysm and when temperature has become subnormal. After this the number rises somewhat, and during the interval occupies a position midway between the maximum and minimum. The large mononuclear elements are, as a rule, greatly increased, both absolutely and rela- tively. With regard to the leucocytes in that type of fever which is caused by the crescent-forming small parasites, it is impossible, he says, to arrive at so definite a conclusion as in the benign tertian cases. In the former type of case there appears to be a slight diminution in the number of leucocytes towards the end of the attacks, a diminution which is made good during the interval. Curiously enough, in certain severe pernicious attacks there is a decided increase of the leucocytes in the peripheral blood— sometimes an enormous increase, a positive leuco- cytosis, the normal 8,000 per c.mm. rising to 10,000 or even to 30,000, the proportion to red corpuscles rising from 1 to 300 to 1 to 70. The hrematoblasts in malaria.—As regards the haematoblasts, Hayem has shown that the number of these bodies somewhat declines during an acute malarial attack, to rise very considerably above the normal standard during the succeeding days of apyrexia. This apyrexial multiplication he calls the " crise hemato-blastique," and he conjectures that its occurrence is associated with the regeneration of the G 82 Malaria. red corpuscles, so much reduced in number and deteriorated in quality during the attacks. The cause of fever and periodicity in malaria.—The fever caused by the malaria para- site, and associated with the changes in the blood and tissues just described, is characterised by clinical features which, when typically manifested, clearly differentiate it from all other fevers. These features are, more especially, diurnal periodicity and inter- mission. Questions which suggest themselves in this connection are : What is the immediate cause of the fever in malaria1? and, What is the reason for the remarkable intermissions, and peculiar, almost mathe- matical, periodicity which these fevers exhibit 1 Febrogenetic agent.—In all malarial attacks this periodicity tends to become, and in most attacks actually is, quotidian, tertian, or quartan in type. If we study the parasites associated with these various types we find that they too, as has been fully described already, have a corresponding periodicity, the life of the individual parasite being completed in twenty-four hours, in forty-eight hours, or in seventy- two hours. Moreover, we have seen that the com- mencement of the fever in each case corresponds with the breaking up of the sporulating form of the parasite concerned. This last is an important point; for, doubtless, when this breaking up takes place, besides the pigment set free, other residual matters — not so striking optically, it is true, as the pigment, but none the less real—are liberated ; a haemoglobin solvent, for example, as I have suggested. Whether it be this haemoglobin solvent, or whether it be some other substance which is the pyrogenetic agent, certain it is that some toxin, hitherto enclosed in the body of the parasite, or in the infected corpuscle, escapes into the blood at the moment of sporulation; a pyrogenetic substance allied to the toxins of many of the pathogenic bacteria and to that of some animal parasites such as hydatids, bothriocephalus, and dracunculus. If, in addition to what is afforded by Theory op Periodicity. 83 the blood changes already described, proof be re- quired of the existence of such a toxic substance, it is supplied by the fact that during the febrile stage of malarial attacks the toxicity of the urine is markedly increased. The fact that this toxin is liberated periodically accounts for the periodicity of the fever, as its successful elimination does for the intermission. Theory of periodicity.—This is fairly evident and comprehensible. The parasites mature practically simultaneously. But how are we to account for the periodicity of the parasite itself? It is true that it has a life of twenty-four hours, or of a multiple of twenty-four hours; but why should the individual parasites of the countless swarm conspire to mature at or about the same time? That they do so—not perhaps exactly at the same moment, but within a very short time of each other—is a fact, and it is one which can. be easily demonstrated. If we wish to see the sporulating forms of the plasmodium in a pure intermittent, it is practically useless to look for them in the blood during the later stages of fever, or during the interval, or during any time but just before, during, or soon after rigor. And if we wish to see the early and unpigmented forms, we must look for them during the later stage of rigor or the earlier part of the stage of pyrexia. And so with the other stages of the parasite; each has its appropriate relationship to the fever cycle. How is this simultaneity in the development of the individuals constituting the swarm of parasites to be accounted for? Life-span of the parasite subject to variation.— It has already been hinted that the parasites do not all attain maturity at exactly the same moment; some ripen and break up a little earlier, some a little later. That the cycle for the individual parasite is not ex- actly and necessarily one of twenty-four hours, or of a multiple of twenty-four hours, is also certain; for it is a well-ascertained fact that fevers may g 2 84 Malaria. " anticipate " or " postpone "—that is to say, come on a little earlier or a little later in the day. Of course this means that the parasites " anticipate " or " post- pone." Why in such cases should the parasites all anticipate together, or all postpone together; why should they all conspire to live either a little shorter, or a little longer ; why should the swarm keep to- gether, as it were 1 And, if the duration of the life of the individual parasite be thus subject to a certain degree of variation, why should not some of them mature a little earlier and others a little later; and so gradually, in the course of a few days, some of the different individuals constituting the swarm come to be maturing at every hour of the twenty-four, and thus every intermittent become a continued fever ? In the answer to these questions lies the explanation of malarial periodicity. Influence of physiological rhythm on malarial periodicity.—My belief and explanation of this matter is, that malarial periodicity does not altogether de- pend on the more or less definite life-span of the parasite, but that it depends, in part, on the well- known quotidian periodicity in the rhythm of the physiological processes of the human body. Rhythmical immunity.—In all animals, including man, there exists a certain innate physiological pro- tective influence, qua the malarial as well as other parasites. As regards malaria, in most animals this protecting power is absolute—always sufficient, for no vertebrate animal, except man, so far as we know, is subject to malaria. But in the cas-e of man this immunity is not quite absolute in every individual and at all times; although, as experience shows, in some men it is complete, and in many, with time, an increasing degree of protective power is gradually acquired. Thus in highly malarious countries the newcomer's first attack of fever is generally of the remittent or continued type; that is to say, the swarm of parasites is able to mature during a large part of the twenty-four hours, the protective power Spontaneous Recovery. 85 being inoperative, or insufficient, for a considerable period, or for the entire circle of the day. But in the progress of a remittent malarial fever, even when untreated, the remissions tend to become intermissions —that is to say, the space of time during which the protective power of the body is insufficient tends to become contracted, although not altogether bridged over. As the physiological rhythm of the body is diurnal, the spacing of the fever to which this recur- ring susceptibility exposes the body is also diurnal. Should a proportion of the parasites in virtue of the variability which, as we have seen, they possess, mature earlier or later than this period of unprotection, they are destroyed by the still present or developing protective power, and the fever does not become con- tinued. So it comes about that it is only the progeny of those parasites arriving at maturity during the rhythmically daily recurring insufficiently protected period which survive. In this way I seek to explain the phenomenon of malarial periodicity. Spontaneous recovery.—-That there is a protective power in the human body against the plasmodium is certain, otherwise spontaneous recovery from malarial infection could not take place. Such spontaneous recovery is no unusual occurrence. A patient is attacked with typical malarial fever. He is admitted to a well-appointed hospital. Plasmodia are found in his blood. He is kept without quinine. For one or two periods the fever comes off at the usual hour, and the parasites go through their typical course. But one day the parasites are seen to be fewer, and the next attack of fever is milder; thereafter fever does not recur again, and the plasmodia gradually and spontaneously disappear from the blood. The only things that could be credited with the cure in such a case are the rest, the warmth, the good food, and the other favourable hygienic conditions of hospital life. The tonic influence of these things favours the rehabilitation of the self-defending physio- logical element of the body, and raises its amount, 86 Malaria. quality and duration to such a standard of sufficiency that it is enabled to keep the multiplication of the Plasmodium in check during the entire twenty-four hours. This defensive element may be, in part at least, no other than the phagocyte, which we have already seen to be an active agent in attacking and destroying the plasmodial spores on the breaking up of the mature parasites. It is possible, therefore, that the intermittency observed in malarial fevers in great measure arises from two causes, the more or less fixed life span of the plasmodium, and the recurring diurnal deficiency or debility of, a protective, plasmodium-destroying agency inherent in the human body. It might be urged that though such an explanation may be ap- plicable to quotidian periodicity, it could not apply to tertian or quartan periodicity. This cannot be admitted. If there be a regular quotidian occurrence of susceptibility to the malaria germ, this suscepti- bility must be existent on the second and third day as well as on the first; therefore a tertian parasite, on maturing, will encounter it on the second day, and a quartan on the third, just as certainly as if they were daily maturing quotidian plasmodia. Practical lessons from the hypothesis advanced.— This hypothesis may be u wrong one. But al- though it may be wrong, it is not without its use if it impresses the importance of placing malarial patients under tonic influences as an aid to specific treatment; and, on the other hand, of protecting the subject of malarial recurrences from debilitating influences. For just as tonic influences may suffice to cure a fever, so, in many malarials, depressing in- fluences, as a wetting, a surfeit, over-fatigue, anxiety, grief, in fact physiological strains of any description, are sufficient to provoke relapse of fever—presumably by debilitating or, for the time, abolishing the pro- tecting physiological element which holds in check the latent but not quite extinct plasmodium. v 87 CHAPTER IV. MALARIAL CACHEXIA. Definition.—Malarial cachexia is the term applied to a group of conditions, more or less chronic, the re- sult of an antecedent attack of severe malarial fever, or of a succession of such attacks, or of prolonged exposure to malarial influences. Symptoms.—The leading symptoms are those of a special kind of anaemia, characterised objectively by a peculiar earthy sallowness of skin, somewhat yellow sclerotics, enlargement of the spleen and—in the early stages at all events—of the liver. Usually the subject of this cachexia is liable to frequent at- tacks of an irregular type of fever, particularly after exposure or fatigue, or, in fact, after any unusual physiological strain. Malarial cachexia without fever.—It should be mentioned, however, that fever is not a necessary antecedent or accompaniment of malarial cachexia. In highly malarious countries it is not unusual to see typical examples of this condition in which fever had never been a feature, or, at all events, had been of so mild a character as not to have seriously attracted attention. Enlarged spleen.—In such countries a large pro- portion of the population have enormously enlarged spleens. The traveller cannot fail to be struck by the number of people he sees with big bellies and spindle shanks; by their languid and depressed air ; their sallow, dry, rough, unhealthy-looking skins. In many malarial cachectics the skin pigmentation is remarkably dark ; patches of almost black pigmenta- tion are also sometimes discoverable on the tongue 88 Malaria. and palate.* It is said that in some intensely malarial places children are occasionally born with enlarged spleens, as if the malarial poison had already affected them in utero. I cannot personally vouch for this, but I have often seen very young children with bellies enormously protuberant from distended spleen. Ac- cording to Scheube, de Freytag and Van der Elst observed in 1873 and 1878 in Atchin that all the children born were affected at the time of birth with malarial cachexia, and that most of them died in a few months. Bein and Kohlstock found malaria parasites in the blood of the four months old child of a malarial mother, born some time after the arrival of the latter in a non-malarial district. Delayed development. — In some instances of malarial cachexia of early development the general growth of the body is stunted and puberty retarded. I have seen a malarial cachectic who, although twenty- five or twenty-six years of age, had the stature and sexual development of a child of eleven or twelve. Abortion and sterility are common effects of malarial cachexia, which, in this and in other and more direct ways, becomes a potent agent in repressing population. Acquired tolerance of the malarial toxin.—In many of these instances, although the state of cachexia has attained an excessive degree, ague, or, in fact, fever of any kind, has never been a prominent symptom. It would seem that the body can become accustomed to the fever-producing toxin of the malarial parasite, much in the same way that it may become accustomed to opium and many other organic poisons, both animal and vegetable. I have watched for three weeks the rhythmical development of a tertian parasite in a sailor who, although pre- viously the subject of frequent attacks of ague, was quite free from fever during the period I had him under close observation. Just as in (hose habituated * Observations in India tend to show that this condition, melanoglossia, is racial and not pathological (Indian Medical Gazette, 1897). Skin Affections. 89 to the use of opium, a full dose of the drug, which in the unhabituated would produce profound or even fatal narcosis, acts merely as a gentle stimulant; so in those constantly exposed to malaria from infancy the poison sometimes fails to act as a febrogene. And, to continue the comparison, just as the habitual use of opium produces a species of chronic poisoning or cachexia without narcosis, so the habitual presence of the malaria toxin may produce its peculiar cachexia without giving rise to fever. As a rule, however, particularly in the case of Europeans forced to reside in highly malarious countries, attacks of fever are of frequent occurrence in malarial cachectics. Malarial neuroses and skin affections.—Super- added to the febrile attacks, and to the associated anaemia, we may meet in cachectics with a variety of functional troubles. One characteristic of most of these functional troubles is the periodicity they generally observe. Thus we may have quotidian or tertian neuralgias, gastralgias, vomiting, diarrhoea, headaches, attacks of palpitation, of sneezing, and so forth. Besides these, skin eruptions—such as herpes, erythema nodosum, patches of lichen planus, eczema, urticaria, etc.—exhibiting a quotidian or tertian liability to exacerbations and an amenability to quinine, have often been noted in malarial conditions. Herpetic eruptions are very common in malarial attacks. According to Powell (Brit. Jour, of Der- matology, September, 1897), in Assam the appearance of a patch of herpes somewhere about the body is regarded as an infallible sign that the attack of fever is over for the time being. Hemorrhages.—In high degrees of cachexia haemor- rhages of various kinds are apt to occur—epistaxis, haemoptysis, haematemesis, melaena, retinal haemor- rhages, purpura, occasionally haematuria or haemo- globinuria. In such patients trifling operations— tooth extraction, for example—may prove a dangerous matter. I have seen in malarial cachectics, from the latter cause, haemorrhage which was .very difficult to 9° Malaria. control; care must therefore be exercised in advising and in performing even the slightest operations in this class of patient. Intestinal and pulmonary affections.—In addition to the troubles mentioned, we find that the sub- jects of malarial cachexia are apt to be dyspeptic; to suffer from irregularities in the action of the bowels; to suffer from morning diarrhoea, at first of dark bilious, and later, perhaps, of pale, copious and frothy stools. They are also very liable to a low and highly fatal form of pneumonia. Cachexia associated with functional and with organic lesion.—There may be said to be two degrees or kinds of malarial cachexia. In one there is merely anaemia with congestion of the portal system ; this may be quickly recovered from on the patient being removed from endemic malarial influences and sub- jected to specific and proper treatment. In the other there is, in addition to anaemia, organic disease of the abdominal viscera—of the liver, spleen, and kidneys—the outcome of long-standing congestion of these organs. These tissue-changes not only keep up the anaemia, in spite of removal from malarial influ- ences, but, in the long run, inevitably progress to a fatal issue. Pathology and pathological anatomy.— The pathology of malarial cachexia is virtually that of acute malarial disease. There is blood destruction by the direct action of the malaria parasite and of its toxins, which eventuates in oligocythaemia and in the deposit of melanin and altered haemoglobin (the yellow pigment) in the tissues; the activity of the process leading to congestion ending in organic changes in liver, spleen, and kidney. Splenic enlargement.—The spleen may become so enlarged under repeated attacks of the con- gestion attending a succession of fever fits, or in consequence of a less active and perhaps feverless haemolysis, that it may come to weigh many pounds, and so to increase in bulk as to occupy nearly the Spleen Affections. 9i entire abdomen. The capsule of the gland, particu- larly on its convex surface, is thickened, and, per- haps, the seat of fibrous patches, or even of adhesions to neighbouring organs. Many of the trabeculae form- ing the framework of the gland become greatly hyper- trophied. On section, the tissues of such a spleen are found to be moderately firm, and usually of a reddish brown colour ; but when death happens soon after or during a febrile attack, the section of the gland shows a dark surface from deposit of black pigment, the pulp at the same time being softened. Perhaps from over-distension some of the vessels in the interior of the gland give way, and then there is a breaking down of the spleen pulp in patches, the remains of splenic tissue floating about in the extravasated blood. Microscopic inspection of these hypertrophied spleens, especially during fever, shows the black and ochre pigments in the usual situations. Splenic tumour in a district is indicative of en- demic malaria.—There are one or two practical points in connection rath the malarial spleen which deserve mention. The prevalence, or relative absence of these enlarged spleens, or "ague cakes" as they are sometimes called, in the native population is an excellent rough indication of the salubrity, as regards malaria, of any particular district. Wherever they are common the district is malarious and therefore unhealthy, perhaps to Europeans deadly, and should be looked upon as extremely unfavourable for camping or residential purposes. Liability to rupture of splenic tumours.—Another practical point is that these enlarged spleens are easily ruptured by a blow on the belly. In hot and malarious countries many a coolie goes about doing his work although he has a spleen in his abdomen nearly twice the size of his head, which might be easily ruptured. This is a fact to be re- membered in administering even mild corporal punish- ment to natives of malarious countries. Europeans have more than once been tried for manslaughter 92 Malaria. in consequence of neglecting it. Owing to this liability to rupture, the subjects of splenic enlarge- ment must not be allowed to play at violent games, as football or even cricket, or at any game in which the diseased organ is exposed to a blow. Apart from direct violence, an enlarged spleen may rupture spon- taneously owing to sudden accession in size in the course of a fever fit. Splenic ruptures are, of course, generally fatal. It sometimes happens that the presence of adhe- sions limits and restrains the haemorrhage; localised haemorrhages of this description may, in time, lead to splenic abscess. Hepatic enlargement.—Like the spleen, the liver in malarial cachectics becomes enlarged during ac- cessions of fever. Under the influence of a succession of acute attacks, hepatic congestion may gradually acquire a more or less permanent character. After death from such fevers the capsule of the liver is found to be tense; on section, the highly vascular tissue of the organ is seen to be reddish brown or almost black, according to the degree and kind of pigmentation. If this state of congestion be long maintained, it tends to bring about various kinds and degrees of chronic hepatitis with hypertrophy of the interlobular connective tissues, and in time leads to hypertrophic, or to different forms of atrophic, cirrhosis. Thus irremediable organic disease of the liver, portal obstruction, and ascites may ensue. Siderosis.—It is in livers of this description that a form of what is called siderosis is produced—a con- dition resulting from chemical changes undergone by the yellow pigment with which the various cells of the orgau are charged. It has already been stated that, when first deposited, this pigment gives no ferrous reaction with ammonium sulphide, or with the double cyanide of iron and potassium ; and that, as the deposit becomes older, slow chemical changes ensue, resulting in the elaboration of a form of iron which will then yield the characteristic black colour with the former, Liver Affections. 93 and blue colour with the latter reagent. Treated with ammonium sulphide sections of liver, and also of spleen, kidney, and other ochre-pigment-charged tissues from chronic malarials, may turn almost black to the naked eye or, at all events, exhibit abundance of blackened pigment on being placed under the microscope. In such sections it is seen that the ochre pigment is no longer in minute grains, as when first deposited, but in blocks and globules as large as, or even larger than, blood corpuscles. This pigment is, of course, something quite apart from the parasite- derived melanin deposited in the same organs. Practical considerations.—Certain clinical facts about malarial hepatic congestion and malarial hepa- titis are of importance. (1) Such conditions do not tend to terminate in suppuration; (2) they are almost invariably associated with splenic enlargement. These are important facts to recollect when it becomes a question of the diagnosis of malarial hepatitis from abscess of the liver. Another important fact to re- member is that recent malarial enlargement of the liver is usually curable, depending as a rule on simple congestion ; whereas old-standing malarial hepatic en- largement is usually incurable, depending, as it usu- ally does, on hypertrophy of the connective tissue and a cirrhotic condition of the organ. Malaria a cause of nephritis.—Changes similar to those found in the liver in the course of, and in consequence of, malarial disease occur in the kidney ; in time they result in confirmed Bright's disease. Hence, probably, the frequency of Bright's disease in some highly malarious climates. In the British Guiana Medical Annual, Dr. Daniels mentions that in 926 post-mortem examinations in the hospital at Georgetown, Demerara, a highly malarial district, he found evidence of disease of the kidneys in no fewer than 228. Cardiac degeneration.—As a consequence of de- fective nutrition from prolonged anaemia and recur- ring fever the muscular tissue of the heart of chronic 94 Malaria. malarials may degenerate, the ventricles dilate, and, in time, the lower extremities become oedematous. Other sequelai. — Dysenteric conditions, forms of diarrhoea, low forms of pneumonia readily set up by chill and prone to terminate in abscess of the lung or to become associated with empyema, extensive sloughing phagedena, and other forms of gangrene such as noma, or pernicious fever, may supervene at any time and rapidly carry off the subject of advanced malarial cachexia. 95 CHAPTER V. .ETIOLOGY OF MALARIA. Geographical range. — The geographical range of malaria is very great; it extends in the Northern hemisphere from the Arctic Circle to the Equator, and in the Southern probably as widely. Malaria is not uniformly distributed throughout this vast area. It occurs in limited endemic foci which tend, speaking generally, to be more numerous and larger as the Equator is approached. Influence of latitude and season.—In colder lati- tudes the association of malaria with swamps is marked; in warmer latitudes this association is much less ex- clusive and apparent. In colder latitudes the type of disease is milder; in warmer latitudes it is apt to be more severe. In certain warm countries, however, as the Argentine and many of the islands of the South Pacific, malaria is entirely absent, or mild and rare. In colder latitudes it is active only during the summer or early autumn; in warmer latitudes it is perennial, certain seasons—usually, though not invariably, the warmer—being more malarial than others. "Influence of local conditions.—The strip of flat, waterlogged country lying along the foot of mountain ranges, the deltas of large rivers, the beds of dried-up streams, areas of country which have fallen out of cultivation, recently deforested lands, are, in many instances, notoriously malarial. Well-drained up- lands and carefully cultivated districts, as a rule, are healthy. There are instances, nevertheless, of elevated, arid, and sandy plains which are intensely 96 Malaria. malarial. Towns are much less malarial than villages or the open country. Ship malaria.—Although several instances are on record of outbreaks of what was reputed to be malaria on shipboard on the open sea, many epidemio- logists refuse to accept the diagnosis as to the nature of these outbreaks, and maintain that malaria is never contracted away from the land.* Endemic and epidemic fluctuations.— From time to time malaria extends beyond its endemic foci, spreading in epidemic form over large tracts of what is usually healthy country. There are a few well- authenticated instances of countries (Mauritius, Ee- unionf) which, although previously exempt, sub- sequently became endemically malarial; and there are many instances of countries previously malarial which afterwards, especially under the influence of cultiva- tion and drainage, became salubrious. Atmospheric temperature.—One of the most im- portant conditions necessary for the generation or, it may be, for the infective activity of the malaria germ, is a sustained average temperature of at least 60° Fahr. Altitude.—A good deal has been written about the influence of altitude ; but altitude per se has, apparently, no influence whatever. It is the decrease in temperature, usually implied by an increase in altitude, that is the real determining circumstance in bringing about a diminution in the prevalence of malaria in uplands. In the tropics an elevation of * If it be the case that the malaria germ can be conveyed in water, it is conceivable that a ship's company may become infected by this means, and without direct exposure to telluric influences. I know of at least one instance of well-authenticated (micro- scopically) malaria occurring at sea which appeared to have been contracted in this way. If the malaria germ can be conveyed in water, my belief is that the "same water quickly ceases to be infective ; that is, that the germ does not live in water for more than a day or two. Hence, though a ship is supplied with water which might be dangerous to-day, if kept for a week the i-ame water may be wholesome enough. t Davidson, "Geographical Pathology." /Etiology. 97 six or seven thousand feet may not secure immunity from malaria unless there be, at the same time, a corresponding and sufficient lowering of temperature. In Italy there are many malarious spots high up among the hills ; the same is the case in India and elsewhere in those elevated valleys which are also narrow, imperfectly ventilated, and imperfectly drained. Moisture.— Another important condition for the production of malaria is the presence of moisture. In the Sahara there is no malaria unless in the oases ; in many of these it is rife—in Biskra, for example. Decomposing vegetable matter.—It is customary to add yet another condition as being necessary for the existence of malaria—namely, the presence in the soil of a notable amount of decomposing organic matter — particularly vegetable matter. But that this is not an indispensable condition is proved by the fact that there are many almost barren spots in which malaria abounds. Other conditions necessary.—The concurrence of these conditions, high temperature and moisture, even though associated with abundant vegetation, is not sufficient to generate or support malaria; for there are many places in the world—the Argentine and the islands of the South Pacific, for example—in which high temperature, moisture, and decaying vegetable matter are present, but in which malaria is almost unknown. Manifestly there are other and more com- plicated conditions which are equally indispensable, and which must concur with heat and moisture in order to secure the presence of malaria. What these con- ditions are it is impossible to say. My belief is that they are in some way concerned with insect life, particularly with the mosquito, an insect which, as explained, there are strong reasons for regarding as the alternative host of the malaria germ, and neces- sary for its diffusion, as well as for its multiplication, outside the human body. Influence of subsoil moisture.—-The state of the H 98 Malaria. subsoil as regards moisture appears to have con- siderable influence on its malaria-producing pro- perties. Short of general overflow, the higher the subsoil water the greater the chance of a given locality proving malarious. Hence the marked liability to epidemics of malaria on the subsidence of extensive floods; and hence the danger attending the raising of the level of the subsoil water by irri- gation works, canals, embankments, and other en- gineering works. These are facts which are manifestly compatible with, and which may receive their explanation from, the mosquito hypothesis of the extra-corporeal life of the plasmodium. Disturbance of soil may give rise to malarial explosions.—It has often been observed that in malarious countries, so long as the soil remains undisturbed agues and the severer forms of fever are comparatively rare ; but so soon as building, road- making, and other operations implying soil disturb- ance commence, then severe malarial fevers appear. After a time, and when these operations in the progress of events have concluded, and the broken surface of the soil has, so to speak, skinned over again, the place becomes once more comparatively healthy. The medical history of Hong Kong may be cited in illustration of this fact. At the com- mencement of the occupation of this island by the British, for a short time it was healthy enough. Then, on its cession being completed, and when barracks and houses were being built and roads laid out, it became excessively unhealthy, the soldiers dying by the hundred of pernicious fevers. In time the sickness and mortality gradually decreased ; and now, so far as malaria is concerned, the city of Victoria is healthy. But, even at the present day, wherever in the outskirts in the course of the con- struction of houses, roads, forts, and similar works, soil is turned up, fever—often of a most pernicious tyPe—is nearly sure to break out among those /Etiology. 99 engaged in the works. I. cite the case of Hong Kong ; but there are dozens of other instances which might be quoted, and which are quite as apposite and convincing as to the danger of disturbing the soil in malarious localities, particularly during the warm season. Influence of rainfall.—As regards the relation of the prevalence of malaria to rainfall there have been too many generalisations based on the limited experience of one or two districts. Thus, it is often said that the most malarious time of the year is at the end of the rains, when the soil is beginning to dry up. A wider view of the subject shows that, though applying to some places, this statement does not apply by any means to all. There are localities where the fever curve is highest before the setting in of the rains. In some places, particularly in those that are low-lying, flat, and swampy, fevers of first invasion disappear almost entirely when the country becomes flooded. This apparent want of a universal and definite relationship of fever curve to rainfall indicates that the conditions determining the preva- lence of malaria are highly complex, and that they are not by any means merely a matter of heat, moisture, and vegetation. Influence of winds and atmospheric diffusion.— Another subject on which there has also been a large amount of loose generalisation is the relation of malaria to wind. It is said that the wind can carry the malaria germ great distances, roll it along the ground like thistledown, and even force it to ascend high mountains. It is very doubtful, however, if malaria can be transported, in this way, very far from its source. It is certain that some thousand or fifteen hundred yards of water between a ship and a malarious coast suffice to secure immunity to the crew. The circumstances of the notorious Walcheren expedition prove this. A similar distance on land from a malaria source is probably quite as effective. The diffusion of malaria by winds is probably extremely H 2 IOO Malaria. restricted. Inside a city may be quite healthy, whilst outside the walls the country may be pestilential. One village may be sickly, whilst a neighbouring village may be healthy. Surely, if winds transport the malaria germ for any distance from its source, there would not be so great a difference in the relative salubrity of urban and suburban localities, nor of neighbouring houses and villages. Neither does the malaria germ ascend to any great height above the ground. Acting on the empirical observation of this fact, the peasants in many unhealthy spots in Italy and Greece secure a remarkable degree of immunity by passing the night, during the fever season, on plat- forms raised on poles a few metres above the ground. It seems safe, therefore, to conclude that the horizontal and vertical diffusion of the malaria germ are very restricted. As Ross puts it, a square yard of malarious soil a yard away is just as dangerous as a square mile of swamp a mile away. A puddle of water under a bedroom window is more dangerous than acres of rice fields some distance off, whether to windward or to leeward. The diffusion of the malaria germ is in no wise different in this respect from the diffusion of other infective disease germs —small-pox, typhus, scarlet fever ; a very short dis- tance from the infective focus secures immunity. It is as if the malaria germ, like the germs of those other diseases, perished after very brief exposure; or that it requires a high degree of concentration to be pathogenic. Lancisi misled us on this point. Meteorological conditions in relation to relapses. —In estimating the healthiness and unhealthiness of a spot care must be taken to distinguish between fevers of first invasion, the result of recent infection and due to the existing immediate surroundings of the patient, and relapses, from non-specific causes, of a long antecedent infection. Fevers of the latter description are often met with in non-malarial Britain, particularly in the winter time. A malarial subject /Etiology. ioi while in the mild climate of the tropics may keep in fair health; but when he is plunged into the stormy winter of the North, is exposed to cold, and has long watches and fatiguing work, very probably latent malaria will become active and ague follow. This is a common experience with malarials from the tropics. It is almost the rule with people coming from the West Coast of Africa. Stanley says that so long as he and his companions were ascending the Congo, the wind being with them and therefore not much felt, they did not have fever; but that on descending the stream, a strong breeze blowing in their faces and chilling them, they constantly had attacks. The physiological depression and disturbances caused by the cold wind paralysed the self-protecting power of the body, and permitted the hitherto latent plas- modia to get the upper hand. And so it is found, in the highly malarious districts of tropical Africa, that houses perched on elevated and windy situations are not so healthy as those on lower and, therefore, less exposed and more sheltered ground. This latter fact must not be interpreted as showing that wind causes or carries malaria. The wind merely acts as a cause of physiological strain, of chills; it acts just in the same way as fatigue, hunger, a wetting, disease, fear, or depressing emotions might do. Malaria can be con- tracted only in close proximity to the extra-corporeal nidus of the malaria. Time of day in relation to infection.—For some obscure reason, possibly, as is generally supposed, connected with alterations in atmospheric move- ment, with expansions or contractions of the air, exhalations or precipitations brought about by rapid changes in the relative temperatures of the soil and atmosphere incident to this particular time in the twenty-four hours, the periods just before sunrise and just after sunset and the night have the repu- tation of being the most dangerous as regards liability to contract the infection. To those actually engaged in the work, the risk from earth disturbance 102 Malaria. seems at times to extend throughout the twenty-four hours. Bignami, who believes that the mosquito is an active agent in conveying malaria to man, explains the greater danger of night exposure in malarious localities by the supposition that the germ is directly introduced by the bite of this insect, which, as is well known, is mainly nocturnal in its habits. Although I do not agree with this view of the modus operandi of the mosquito, nevertheless, I think that, in view of Brace's notable work on the tsetse fly as a medium in diffusing the trypanosoma of "fly disease," and of the role of the tick in diffusing the Texas cattle fever, this idea of Bignami's should not be lost sight of. The general belief, however, is that the malaria germ enters by the mouth—is inhaled; but as to whether it subsequently gets access to the circulation through the air passages, or whether it is swallowed with the saliva, there are as yet no data to guide us to a trust- worthy conclusion. Neither can it be said that the possibility of infection by drinking water has been either proved or disproved. ACCLIMATISATION. Personal acclimatisation.—Is there such a thing as acclimatisation as regards malaria ? The answer to this is, " Yes and No." It would seem that those who have resided many years in a malarious district are less liable to severe remittents but more liable to mild agues. As already mentioned, the first attack of malarial fever is generally remittent and severe in character ; subsequent attacks are generally frankly intermittent. Old febricitants are more liable to pernicious attacks of an adynamic type than the recently infected; notably to haemoglobinuric fever. Trifling causes, such as do not provoke fever in the fresh arrival, are often sufficient to bring on an ague fit in the old resident. The new arrival in the tropics does not think much of exposing himself to the sun, the rain, and the wind; but the old resident is very ACCLIMA TISA TION. 103 chary about going out without his sun-hat and white umbrella. The latter wears flannel, and changes his clothes after exercise ; he is careful not to cool off' too rapidly by sitting in a draught; he will not sit down in wet clothes. The newcomer may look on these precautions against chill as signs of effeminacy. They are not so, however ; experience has taught the old resident that neglect of them means an attack of fever and a week off work. The newcomer takes a cold bath ; the old resident takes a warm one. The newcomer sits up late, eats and drinks and smokes as in Europe; the old resident goes to bed betimes, and eats and drinks and smokes in moderation. By- and-by, sharp lessons teach the newcomer to respect the sun and the rain and the wind, to clothe with a view to avoiding chill, to live temperately. This is an education all pass through in malarial countries. Acclimatisation, to a great extent, means experience —education; not simply an unconscious adaptation of the physiology of the individual but an intelligent adaptation of his habits. Racial differences of susceptibility.—Nevertheless, there can be no doubt that, for some occult reason, certain races and certain individuals are less sus- ceptible to malarial influences than others. It is a well-established fact that the negro in Africa, although he does get fever, yet he does not get it so frequently nor so severely as the European; even although the latter, from his hygienic ways of living, is of the two much the less exposed to infection. The Chinese, the Malays, and some other dark- skinned races also appear to enjoy a comparative im- munity ; an immunity considerably less pronounced, however, than that enjoyed by the African and West Indian negro. The inhabitants of the malarious districts of Italy, Corsica, Greece, Turkey, and many other South European countries have inherited no marked immunity from malaria in virtue of the thousands of years during which their ancestors lived in malarious districts. But they have inherited 104 Malaria. experience, and many of them know how to keep clear of the infection they cannot overcome; this probably is, in great measure, the extent of their acclimatisation and apparent acquired immunity. Sex, age, occupation.—Sex, per se, seems to have no particular influence as regards liability to, or severity of, malarial attacks. Neither has occupa- tion ; although, of course, those engaged in tilling and working the soil are more exposed to malaria, and therefore more subject to its manifestations, than the townsman or the sailor. Malarial attacks are more severe, more common, and much more dangerous in young children than in adults. i°5 CHAPTER VI DIAGNOSIS AND TREATMENT. The three diagnostic signs of malaria : their respective values. The diagnosis of malarial disease, usually not a difficult matter, is sometimes very hard indeed. Formerly periodicity and the effect of quinine were the tests principally relied on. They are very fallible, however. Nowadays, in all doubtful and serious cases, it behoves the practitioner to have recourse to the only infallible test of malaria—the microscopic ex- amination of the blood. When such an examination yields a positive result, when the plasmodium in any of its forms, or its product—malarial melanin—either free in the serum or enclosed in leucocytes, is found in the blood, the diagnosis of malaria is securely established. Negative results from a single micro- scopical examination are not so trustworthy as posi- tive ; but if the practitioner has experience, and if he has the opportunity to make his examinations at suitable times and in a case untreated by quinine, they too are conclusive. The quinine test is generally conclusive in intermittents and in the various larval forms of malaria, but the more severe types of remittents are often singularly resistant to the drug. Time may not be available in which to test such cases with quinine. They may be cases of a threatening nature in which a speedy diagnosis is of the first importance. In such cases the microscope is the only trustworthy diagnostic agent. Periodicity in diagnosis.—Periodicity is, of course, at times a trustworthy enough clinical test for io6 Malaria. malarial disease. Tertian and quartan periodicity occur only in malarial disease; when either is thoroughly established, its presence is almost conclu- sive as to the case being malarial. But it is otherwise as regards the significance of quotidian periodicity. Quotidian periodicity we find in greater or less degree in nearly all fevers, particularly in fevers associated with suppuration. In hectic conditions, quite un- connected with malaria, one often sees a quotidian afternoon rigor, followed by hot, dry skin, and a tem- perature rising even to 103° Fahr. or 104° Fahr., the febrile movement concluding with a profuse dia- phoresis and complete morning apyrexia. Periodicity of fever in liver abscess; diagnosis from malaria.—Particularly is this the case in sup- puration connected with the liver; and this is just a condition which is very liable to occur and to cause confusion in tropical practice. Simula- tion of malarial fever by hepatic abscess is very common ; it is a pitfall into which the inexperienced tropical practitioner often tumbles. In consequence, we find that most liver abscess cases are drenched with quinine, at one time or another, on the sup- position that the associated fever is malarial. There are three or four points, however, even apart from an examination of the blood, which, if duly considered, should keep us clear of this blunder. In hepatic abscess the liver is enlarged, but the spleen is not necessarily so; splenic enlargement, though an occa- sional, is not a usual feature in liver abscess. In malarial fever, if the liver be enlarged the spleen is still more so and can nearly always be felt extending well beyond the costal margin. In hepatic abscess the fever occurs usually, though not in- variably, in the late afternoon or evening, and the patient may perspire profusely at any time of the day or night—very generally whenever he chances to fall asleep. In malarial fever the paroxysm may, and generally does, occur earlier in the day, and there is no marked tendency to sweat unless Diagnosis. 107 at the defervescence of the fever. In hepatic abscess, if carefully inquired for, there is nearly always a history of dysentery obtainable. If fever be distinctly tertian or quartan in type, it is not hepatic. In all doubtful cases the blood must be examined once or oftener, the rigor stage or early hot stage being selected for the examination, and the examination being made before administration of quinine. Occa- sionally cases are met with in which there is a history of malarial infection and, in addition to this, a his- tory of dysentery, and the liver and spleen are both enlarged. In such cases diagnosis may be impossible without the microscope and the aspirator. Diagnosis of haemoglobinuric from yellow fever.—The diagnosis of haemoglobinuric fever from yellow fever sometimes comes up as a practical point. Apart from microscopical examination of the blood, the following considerations will aid to a correct con- clusion. From the outset haemoglobinuric fever is asthenic in type ; yellow fever, on the contrary, has sthenic features to commence with —violent headache, congested conjunctiva, flushed face, etc. In haemoglo- binuric fever the liver and spleen are enlarged, often painful, the vomiting is bilious, rarely bloody ; the yellowness of the skin concurs in point of time with the haemoglobinuria, and is an early symptom. In yellow fever there is early and increasing albuminuria, sometimes haematuria; but there is no true haemoglo- binuria, no enlargement and tenderness of the liver and spleen of a marked character. In yellow fever there is epigastric tenderness and burning; often vomiting of clear acid mucus, but not of large quantities of bile as in malarial affections. Black vomit and yellowness of skin are late and not necessary features in yellow fever. Then yellow fever is endemic only in certain limited areas, tends to occur as an epidemic, and attacks newcomers much more frequently than old residents. Haemoglobinuric fever has a more extensive distribution, is sporadic, and is more especially a disease of older residents. io8 Malaria. Diagnosis of bilious remittent from yellow fever.—In bilious remittent the icteric tinting of the skin is an early feature ; albuminuria is rare, and not a marked feature; temperature is maintained high for many days, not subsiding in three or four days as in yellow fever; the vomiting is profuse and bilious; the pulse does not become slow as in the later stages of yellow fever; the eyes are not congested and shining to the same degree ; and, of course, the plasmodium is to be found in the blood. Cerebro- spinal meningitis may simulate malarial fever; but the occurrence of rigidity of the muscles of the neck should put the physician on his guard, and lead him in such a case to search the blood and inquire for other diagnostic symptoms. Diagnosis from other types of paroxysmal fevers.—Urethral fever is often mistaken for ague ; so is the fever attending the passage of gall-stones; so is the fever associated with pyelitis and surgical kidney; so is lymphangitis, particularly that form of lymphangitis associated with elephantiasis and other filarial diseases ; so is Mediterranean fever; so are the fevers associated with tuberculous disease, with ulcerative endocarditis, with some types of pernicious anaemia, with splenic leucocythaemia, especially with visceral syphilis, with rapidly-growing sarcoma, with forms of hysteria, and with many obscure and ill- defined conditions. The use of the microscope must not be neglected in such cases if there be the slightest doubt as to their exact nature. Typhoid fever.—Without the microscope it is sometimes impossible to diagnose typhoid types of malarial fever from genuine enteric. In both there may be diarrhoea; in both there may be splenic enlargement; in both there may be typhoid tongue, delirium, and the entire range of typhoid symptoms. As a matter of fact, until recent years all typhoid in India was regarded and treated as malarial fever— malarial remittent—and, doubtless, often with dis- astrous results. In circumstances where Widal's Diagnosis. 109 serum test can be used it is invaluable in such cases. Typho-malarial fever.—One important fact in connection with the diagnosis of typhoid in malaria must ever be kept in mind. In individuals who have previously been subjected to malarial influences and who, perhaps, have suffered at one time from well- marked malarial fever, the oncoming of typhoid is often preceded by three or four paroxysms exactly like those of ordinary ague. This may occur even when the patient has been for several years in a non- malarial country, as England. In such cases quinine is usually given early in the attack; its failure to check the disease should lead to careful prognosis and the avoidance of too active purgation. Similarly, well-marked malarial-like fluctuations of temperature and the appearance of the plasmodium in the blood in the course of a continued fever do not exclude typhoid. These cases are typho-malarial, and have to be treated as such—as typhoid with a malarial complication. Necessity for microscopical examination of blood in pernicious attacks.—Without the microscope it is sometimes impossible to diagnose, in time to direct treatment, pernicious comatose malarial attacks from heat-stroke or, if algide in character, from ordinary apoplexy ; malarial dysentery, which must be treated with quinine, from ordinary dysentery, which must be treated with ipecac, or with the sul- phates ; algide malarial attacks, from cholera; certain types of malarial fever occurring, as it is very apt to do, in the puerperal state, from puerperal fever; malarial pneumonia, from crupous pneumonia ; malaria aphasia, from the aphasia of organic brain disease; and so on. It is manifest that the revelations of the micro- scope have enhanced our powers of diagnosis in malarial affections enormously, and, therefore, our powers of treatment. Every doubtful case must be tested by it. In many forms of malarial disease, if life is to be saved, action must be prompt, decisive, no Malaria. energetic, and based on accurate diagnosis. The diagnosis of ordinary agues may be postponed for a day or two without much danger, and be diagnosed correctly enough without the microscope ; but every now and again a pernicious attack is sprung upon the practitioner, the nature of which he must be able to recognise at once, and recognise with confidence. When the plasmodium is seen in the blood, it is surely known that there is a malarial element in the case and that quinine is indicated. Confidence in directing treatment is a great matter. It cannot, therefore, be too strongly urged on the tropical prac- titioner to avail himself of every opportunity to gain experience in the use of the microscope in blood examinations, and that he should take care to have a suitable instrument in working order and available at a moment's notice. The practical difficulties in carrying out this recommendation are insignificant in comparison with the importance of the results. With practice, five minutes usually suffice to effect a positive microscopical diagnosis of malaria. TREATMENT. Quinine.—Many drugs have been employed in the treatment of malarial disease, and many drugs have some influence on it; all sink into insignificance in comparison with quinine. In serious cases, to use any drug to the exclusion of quinine is culpable trifling. Therefore, so soon as a diagnosis of malaria has been arrived at, unless there be some very mani- fest contra-indication, the first duty of the practitioner is to set about giving quinine. There are many ways of exhibiting the drug; however given, care must be taken that it is given in such a way that there can be no mistake about its being absorbed. If the patient for any reason, such as inability to swallow or persistent vomiting, cannot take quinine by the mouth, and the existing condition be grave, it should be injected by the rectum ; but if the circumstances of the case are such that a rapid action of the drug Trea tment. II1 is imperative, it must be injected at once subcu- taneously, or into a vein. When and in what dose to give quinine in ordinary cases— During a paroxysm of ordinary intermittent fever, it is better, before giving quinine, to wait until the rigor and hot stages are over, and the patient is beginning to perspire. A fever fit, once begun, cannot be cut short by quinine, and to give quinine during the early stages aggravates the headache and general distress; but so soon as the skin is moist and the temperature begins to fall, the sooner the drug is commenced the better. Ten grains, prefer- ably in solution, should be administered at the commencement of sweating, and thereafter five grains every six or eight hours for the next two or three days. This is almost a certain cure. The quinine may not always prevent the next succeeding fit, but it nearly always diminishes its severity. In 99 cases out of 100 the second following attack does not develop. When giving quinine, it is well to administer an aperient and to keep the patient in bed; in ordinary cases neither aperient nor rest in bed is absolutely necessary. In cachectics, however, and in all obsti- nate cases, both are invaluable adjuvants. On the complete subsidence of fever, iron, or iron and arsenic, should be exhibited ; and, with a view to prevent relapses, one or two full doses of quinine—five to fifteen grains—should be taken at intervals of from five to seven days for six weeks or thereabouts. My practice in the treatment of ordinary malarial fevers is to give quinine for two or three days in the doses mentioned, and then to prescribe arsenic and iron in pill or solution. At the same time, with a view to prevent recurrence of fever, I direct the patient, particularly if I have found the crescent form of the parasite in the blood—for such cases are prone to relapse—to leave off the tonic one day a week (to give precision to my directions I generally mention Sunday) and on that day to take a mild IT2 Malaria. saline, sulphate of soda or Carlsbad salts, in the morning, and three five-grain doses of quinine during the day. The iron and arsenic may be taken for a fortnight at a time, and, after an interval of a week, for another fortnight. The weekly aperient and three doses of quinine had better be kept up for six weeks or two months. Dose of quinine: toxic effects.—There is great difference of opinion and practice about the dose of quinine. Some give thirty grains at a dose, some give three. The former, in my opinion, is too large a quantity for ordinary cases, the latter too small. It must never be lost sight of that occasionally quinine in large doses produces alarming effects; not singing of the ears and visual disturbances merely, but actual deafness and even amblyopia, both of which may prove very persistent and occasionally permanent. It may also produce profound cardiac depression, and even death from syncope. Urticaria is another, and not very uncommon, effect of even small doses of quinine; some cannot take it on this account, and prefer to endure the disease rather than suffer the intolerable irritation induced by the remedy. I believe that nothing is gained by excessive doses ; in ordinary circumstances, thirty grains spread over two or three days is usually amply sufficient to check an intermittent. For children under one year half a grain for a dose suffices; for older children the dose must be increased proportionately to age and strength. If a supposed ague resists the doses of quinine mentioned, it is advisable to revise the diagnosis. Quinine in pregnancy.—Care should be exercised in giving quinine to pregnant females, for undoubtedly it sometimes causes miscarriage. The fact of preg- nancy, however, must not debar the use of the drug altogether; only, in such circumstances, it should be given in the minimum dose likely to be effectual, say three grains repeated every eight hours for two days. A pregnant woman will run more risk Trea tment. "3 of miscarriage and to her health from repeated ague fits than she will from a reasonable dose of quinine. Quinine in the puerperal state.—It is a wise precaution in malarious countries to give a few five-grain doses of quinine during labour or soon after. The puerperal state seems to have the effect, as any other shock or physiological strain might, of waking up the slumbering plasmodium. A dose or two of quinine in these circumstances does no harm, and may, by choking off a threatening fever, avert suffering and anxiety, not to mention danger. Form in which to administer quinine.— Quinine is best given in solution, and probably the hydro- chlorate, as containing a larger proportion of the alkaloid than the sulphate, is the best salt. Some, under the impression that hydrobromic acid prevents the ringing of the ears attending the free use of the drug, prefer it to dilute sulphuric acid as a solvent for the ordinary sulphate. When the tongue is fairly clean and digestion not altogether in abeyance, the quinine may be given in freshly prepared pill or in tabloid form; but in serious cases, particularly where the tongue is foul and digestion enfeebled, pills and tabloids are not to be trusted to ; in these circumstances they are apt to pass through the bowels and to appear in the bedpan unaltered. In grave cases this occurrence must not be risked. Milk as a menstruum for quinine.—If the taste of the drug be very much objected to, a good plan is to give it in powder in a tablespoonful of milk 7- after the patient has previously lubricated the mouth with a morsel of bread and butter. In this way the bitter taste is not perceived. This is by far the best way of getting children to take quinine. Hypodermic injection of quinine.—In any type of fever if vomiting is persistent, if the brain is affected, or if the patient is insensible and can- not or will not swallow, and, also, if the rectum is irritable, recourse must be had to the hypodermic I ii4 Malaria. injection of quinine. In all cases in which life is in imminent danger, and in which the earliest possible action of the drug is of importance, it must be given hypodermically. This method of giving the drug is sometimes a painful one, and may be attended with some risk of abscess; in the cir- cumstances, such possibilities count for little. The most suitable salt for hypodermic injection is the hydrochlorate or, better, the acid hydrochlorate, which is soluble in less than its own weight of water. The hydrobromate is equally soluble. If neither of these salts can be procured, the sulphate may be used, solution being effected by adding half its weight of tartaric acid. Ten to fifteen grains dissolved in sterilised water would be a full hypodermic dose; in grave cases this dose should be given three times in the twenty-four hours. The needle should be driven well home, either deep into the subcutaneous con- nective tissue or, better, into the muscles of the gluteal or scapular region, the skin being previously carefully cleansed. The solution must be freshly prepared and boiled, and the syringe and needle thoroughly sterilised. In the malignant fevers of Rome as much as a drachm of quinine, divided into three or four doses, is sometimes administered in this way in the course of twenty-four hours. Benson (Trans. First Indian Med. Cong.), speak- ing from an experience of 1,390 cases, says that the hypodermic injection of quinine is by far the most effectual, as well as economical, way of treating malarial fevers. He used the sulphate dissolved in water with the aid of hydrochloric acid, the strength of the solution being fifteen grains to the drachm; of this he injected twenty minims between the scapulae, or into the outer surface of the arm. In 614 consecutive cases so treated not a single untoward accident occurred, one injection usually sufficing. Dr. George Watt mentions a case of eight years' standing, which had been treated unsuccessfully by quinine in the usual way, and which was promptly cured by Trea tment. "5 hypodermic injections. Benson also succeeded.in the same way in obstinate cases. Hypodermic injection of quinine; precautions against tetanus.—It may be well to mention, not with the idea of deterring the practitioner from using the drug in this way, but to impress upon him the necessity for care in keeping instruments and solutions aseptic, that tetanus has sometimes followed the hypodermic injection of quinine. In these unfortunate cases it was not the quinine that caused the tetanus; it was the tetanus bacillus, and this tetanus bacillus was intro- duced either on a dirty needle, or in a fouled solution. Tetanus is an exceedingly common disease in some tropical countries. In Western Africa, for example, a large proportion of wounds, no matter how trifling as wounds they may be, if they are fouled by earth or dirt result in tetanus. The French in Senegambia have found this to their cost. A gentleman who had travelled much in Congoland told me that certain tribes poison their arrows by simply dipping the tips in a particular kind of mud. A wound from these arrows is nearly sure to cause tetanus. In many tropical countries, so general and so ex- tensive is the distribution of the tetanus bacillus that trismus neonatorum is a principal cause of the excessive infant mortality. Every precaution must therefore be taken to ensure that the little instru- ment, which is so potent in saving life, may not by carelessness be turned into an instrument of death. Intravenous injection of quinine.—In cases of pernicious comatose remittent, in which it is of im- portance to obtain a rapid and concentrated action of the drug, Bacelli recommends the intravenous injection of the following solution : Hydrochlorate of quinine 1 gramme, sodium chloride 75 centigrammes, distilled water 10 grammes. This solution he has employed in those desperate cases with much success, injecting directly into a vein five to seven grammes at a time; he states that whereas with hypodermic injection the mortality in such cases mounted to I 2 n6 Malaria. 17 per cent., with intravenous injection it was reduced to 6 per cent. Warburg's tincture.—A very effective medium for giving quinine, and one of high repute in many places, is Warburg's tincture. This contains, besides quinine a number of drugs, many of them doubtless inert, although some of them certainly possess valuable therapeutic properties. Experience has shown that the combination is really a good one, and that Warburg's tincture sometimes succeeds where quinine alone fails or acts too slowly. It generally proves a powerful sudorific. The dose is half an ounce, and is repeated after two or three hours. The action appears to be somewhat similar to that of the anti- pyretics now in vogue—antipyrin, phenacetin, etc.— drugs which, when given in combination with quinine in the routine treatment of malarial fevers, sometimes contribute very markedly to the relief of headache and febrile distress. Mode of action of quinine.—In what way quinine acts has not yet been satisfactorily explained. Some, reasoning from the toxic influence this drug exerts on all kinds of free amoeba, say that it acts in malaria in the same way—that is, as a direct poison to the plasmodium. Others maintain that it acts by stimulating the phagocytes, stimulating the natural enemies of the parasite. Some experimentalists allege, on the other hand, that it paralyses the white corpuscles. That quinine does not kill all blood protozoa is certain, for it has no effect on the plas- modium-like organisms found in the -blood of birds and reptiles, or on the trypanosoma of surra. Certain it is that in man, with the exception of the crescent body, it quickly causes the plasmodium to disappear from the general circulation. It is said by some to be most effective against the free spores of the malarial parasite and the very young intra-corpuscular forms, but inoperative against the more mature plasmodia ; hence they advocate giving it early in the plasmodial cycle. Others, on the contrary, maintain that it is Trea tment. 117 operative only on the large intra-corpuscular stage of the plasmodium, and therefore advocate its use at a late stage of the cycle. It does not appear to have any effect on the crescent bodies, or to interfere with their evolution into flagellated organisms. As stated, I have seen in the blood crescents and flagellated bodies three weeks after the cure of a malarial fever by full doses of the drug continued for a fortnight. Strange to say, quinine, especially in small doses, seems sometimes to wake up latent malaria and to bring about an ague fit. The same may be said of a course of mineral waters, of hydropathic treatment, and of sea-bathing. Treatment of bilious remittent.—In bilious remittent and other severe forms of malarial fever one must not, as in a simple intermittent, wait for the remission before giving quinine. To wait for remission or sweating used to be the practice; it was said that to give quinine at any other time was wrong, and that something terrible would happen if the superstition were ignored. In all grave fevers, a full dose, ten or fifteen grains, should be at once administered. It is desirable to have the bowels freely opened ; quinine is said to act better then. It is a mistake, however, to delay the administration of the specific pending the action of the aperient. If an aperient be indicated, it should be given along with the quinine. Five or ten grains of calomel is the best. Thereafter the quinine, in five grain doses, should be repeated every three or six hours until fever has subsided. If there be much bilious vomiting, an emetic of ipecac, or of hot water will clear the stomach and perhaps, after a time, enable it to retain the quinine. The drug is sometimes more readily retained if given in chloroform water. Mustard poultices to the epigastrium, small hypo- dermic injections of morphia, ice pills, sips of very hot water, effervescing mixtures, champagne, one- or two-drop doses of tincture of iodine, are each of them, on occasions, aids in stopping vomiting. n8 Malaria. If these measures fail, and if the vomiting is so frequent and so severe that the dose is immediately rejected, and if there is no diarrhoea, it is advis- able to clear out the rectum with an injection of warm water and, when the action of this has con- cluded, to throw up an enema of thirty grains of quinine in three ounces of water with a few drops of acid to aid solution; at the same time, five or ten grains of calomel may be given by the mouth. So soon as the stomach has quieted down, quinine may be given again by the mouth. Treatment of hyperpyrexia.—Hyperpyrexia must be promptly met by prolonged immersion in the cold bath, rectal injections of iced water, ice bags to the head, etc. At the same time quinine must be in- jected hypodermically, or into a vein, in full doses, and repeated every three hours until thirty or forty grains have been given. Prompt action in these cases is of the first importance, and may save life. If tempera- ture be kept down for three or four hours the quinine gets time to act on the plasmodia crowding the intracranial vessels ; but if temperature be allowed to mount and to remain high the patient is destroyed before the specific has a chance. The cold bath, there- fore, is absolutely necessary. In such circumstances, antipyrin and similar antipyretics are worse than useless. Good rules are to prepare to give the cold bath if the axillary temperature reach 106°, and to remove from the bath when rectal temperature has fallen to 102° Fahr. Treatment of algide and dysenteric at- tacks. — Algide and dysenteric attacks demand quinine combined with a little opium. If dysenteric symptoms persist, ipecac, or the aperient sulphates in full doses and opium must also be given. Treatment of hsemoglobiuuric fever.—Of all forms of malaria haemoglobinuric fever is the most resistant to quinine. Some practitioners of experience recommend the exhibition of the drug in heroic doses, giving it every two hours in divided doses to the 'Pre a tment. 119 extent of 120 grains a day ; this they keep up till convalescence is established. On the other hand, haemoglobinuria may come on while the patient is cinchonised; indeed, some writers of experience— the Plehns and many others—declare that quinine conduces to haemoglobinuria. After trying it in these cases, and carefully comparing the results of treatment both with and without quinine, these authorities abandoned its use. So long as the haemo- globinuria continued they treated the case symp- tomatically, resuming the specific should the case merge into and conclude as a simple intermittent. There can be no doubt that in large doses quinine exercises a certain amount of destructive action on the blood corpuscles, rendering their haemoglobin unstable. When, therefore, its toxic influence is superadded to that of the malarial poison, it may be that it supplies the little that is required to determine an extensive liberation of haemoglobin, which, had the quinine been withheld, might not have taken place. Bastianelli (Annali di Medicina, Anno ii., Fasc. 11) lays down" the following sensible rules with regard to the employment of quinine in haemo- 75 The pains are worst usually on getting out of bed in the morning, and on moving the affected part after it has been at rest for some time. They are relieved somewhat by rest and warmth. Passive movements are, as I have said, not painful, but any resistance to the movement of the limb may cause acute suffering. When a muscle is affected the pain is accompanied by a sense of powerlessness. Other complications and sequelce.—Convalescence may be very much delayed by the persistence of these pains; also by anorexia, by general debility, sleeplessness, evanescent feverish attacks, boils, urti- carial, lichenoid, and papular eruptions, and by troublesome pruritus. Among sequelae and complica- tions may be mentioned enlargement of the lymphatic glands—particularly the superficial cervical—orchitis, possibly endocarditis and pericarditis, hyperpyrexia, and haemorrhages from the mouth, nose, bowel, and uterus. Miscarriage is rare. The urine sometimes contains a trace of albumin, but true nephritis does not occur. Such, briefly, is a description of the dengue observed by myself in Amoy in 1872. It would appear, however, judging from the published descrip- tions, that there is considerable variety in the symptoms of this disease in different places and in different epidemics. Some authors mention swelling of one or more joints as a common and prominent symptom; others refer to metastasis of the pains enlargement of the submaxillary glands, orchitis, and so forth, as being frequently present. These, in my experience, were excessively rare. However this may be, the essential symptoms in well-marked cases are the same practically everywhere, and in all epi- demics. Nearly all writers accentuate as the leading and characteristic symptoms the suddenness of the rise of the temperature, the initial stage of skin con- gestion, the pains, and the terminal eruption. Relapses are not uncommon in dengue, and second and even third attacks during the same epidemic 176 Dengue. have been recorded. As a rule, however, suscepti- bility to the disease is exhausted by one attack. The incubation period seems to be somewhat variable. It is certainly not a long one. I have seen a case in which it could not have exceeded twenty-four hours. Some observers place it at five and even seven days ; this, I feel sure, is an over- estimate. One to three days seems to be near the truth. Diagnosis.—Dengue must not be confounded with rotheln, scarlatina, measles, syphilitic roseola, influenza, rheumatic and malarial fevers. A know- ledge of the distinctive features of these diseases, and the fact that dengue is attended with a rash and with articular pains, and that it occurs in great and rapidly - spreading epidemics, should prevent any serious error in diagnosis. mortality.—In uncomplicated dengue the mor- tality may be said to be almost nil. In the case of very young children, convulsions and delirium may occur and cause some anxiety ; and in the aged and infirm, and in those suffering from chronic exhausting disease, an attack of dengue may prove a serious complication. Charles describes a pernicious form which, though rare, was very much dreaded in Cal- cutta. In these cases the lungs became cedematous, and the patient, growing drowsy and cyanotic, rapidly passed into a comatose condition, with a tendency to hyperpyrexia, and died. Some writers state that the gravity of any given case is in direct proportion to the abundance of the eruption ; others deny this. In Euro- peans an attack of dengue very often leads to a condition of debility necessitating temporary change of climate, or even return to Europe. In both Europeans and natives the attendant lowering of the resistive powers predisposes to other and more dangerous diseases, such as malaria, yellow fever, dysentery, phthisis, and so forth; consequently dengue, otherwise a benign disease, may become a source of public danger. It is probable that it is in this indirect Treatment. i77 way that the general mortality rises during a visita- tion of this disease, as has been observed in several epidemics. Treatment—Were it possible to secure perfect isolation for the individual during an epidemic of dengue, doubtless he would escape the disease. Even comparative isolation is attended with diminished liability. In Amoy, in the epidemic of 1872, those foreigners who lived in a more or less isolated sub- urban situation were very much less affected than were those who lived in the native town, or than those whose occupations threw them much into contact with the natives. But though this and similar facts point to the theoretical possibility of avoiding dengue during an epidemic, in the ordinary conditions of life in the tropics prophylactic measures, such as they would suggest, are impracticable. Like the allied fevers, dengue runs a definite course; therefore it is useless to attempt to cut it short. The patient should go to bed so soon as he feels ill, and he should keep his room till the terminal eruption has quite disappeared and he feels well again. Ten days is not too long to allow in severe attacks. As in influenza, light liquid diet, rest, and the avoidance of chill conduce powerfully to a speedy and sound convalescence. At the outset of the fever some saline diaphoretic mixture, with aconite, may be prescribed with advantage. If the pains be severe and the fever high, antipyrin, or phenacetin, or bella- donna will give great relief. Cold applications to the head are comforting. If the temperature rises to 105° or over, cold sponging or the cold bath ought to be had recourse to. If the pains con- tinue very distressing, a hypodermic injection of morphia will afford welcome relief and do no harm. Purgatives and emetics should be avoided unless pronounced constipation, or a history of surfeit, urgently demands their exhibition. The pain caused by the muscular movements entailed by the efficient action of purgatives more than counterbalances any M 178 Dengue. advantage the latter might otherwise bring. Wine in the early stage is not advisable. Freshly made lemonade or iced water will be found the most accept- able drink during the fever. For the pains experienced during convalescence, rubbing with opium or belladonna liniment, gentle massage, electricity, salicylates, small doses of iodide of potassium and quinine have been advocated. Debility and anorexia indicate tonics such as quinine, strychnine, mineral acids, vegetable bitters, and change of air. 179 CHAPTER X. MALTA OK MEDITERRANEAN FEVER {Febris undidans, Hughes). Definition—Malta fever—a disease probably of pythogemc origin, of low mortality, and of limited geographical range—is characterised in its more typical form by, or, rather, is made up of, a series of febrile attacks; each individual attack, after lasting one or more weeks, gradually subsiding into a period of absolute or relative apyrexia of several days' or several weeks' duration. Each spell of relative apyrexia is followed by a period of fever, which is again succeeded by relative apyrexia. So the disease continues more or less indefinitely for weeks or months. Common and characteristic complications are rheu- matic-like swelling of joints, profuse diaphoresis, anaemia, liability to orchitis and neuralgic affections. The duration of the illness is uncertain; it may be anything from three or four weeks to as many months, often longer and even up to eighteen months. Geographical distribution.—Malta or Medi- terranean fever is somewhat unfortunately named, for it is by no means certain that the disease so designated is confined to Malta, or to the Mediter- ranean even. It is very common there, particularly in Malta; but this is all that can be said with con- fidence about its geographical range. It is highly probable, however, that the same, or a similar, fever occurs in many parts of the tropical world, having been confounded hitherto with malarial fever.* * On the strength of some experiments, analogous to those of Widal's typhoid culture agglutination and sediment test, Wright has lately asserted that Malta fever occurs in India. On clinical grounds this has been denied by others. M 2 r8o Malta Fever. This disease is specially interesting to English military surgeons, as it is extremely prevalent at times in the garrisons of Gibraltar and Malta; although only occasionally proving fatal, it is a fruitful source of inefficiency and invaliding there. History.—Formerly it was confounded with typhoid and malarial fever; by some it is still regarded as but a phase of one or other of these. The labours of clinical observers, from Marston (1861) to Maclean (1885), and more especially the recent bacteriological researches of Bruce, Hughes, and Gipps, have established it as a special disease; in the future it must be regarded as such. It requires to be renamed, however, and until this is done there will continue to be confusion on the subject. Symptoms.—Malta fever begins generally with lassitude and malaise, such as we associate with the incubation of many specific fevers, particularly with typhoid. There is headache, boneache, anorexia, and so forth. At first the patient may go about his work as usual; gradually the daily task becomes too much for him, and he has to take to bed. Headache may now become intense, and, in addition, the patient will suffer from thirst and constipation. At the commencement the symptoms, with the exception that there is very rarely diarrhoea, resemble those of typhoid. There are no rose spots, however, then or at any subsequent period. There is evidence in the coated tongue, the congested pharynx, the anorexia, and the epigastric tenderness, of gastric catarrh; and the occasional cough and the harsh, unsatisfactory breathing at the bases of the lungs indicate some degree of pulmonary congestion. There may also be delirium at night. The fever is usually of a remittent type, the thermometer rising towards evening and falling during the night, the patient becoming bathed in a profuse perspiration towards morning. The spleen and the liver, but especially the former, are somewhat enlarged and, perhaps, tender. Lumbar pain may be urgent. Symptoms. 181 After a week or two of this type of fever, specially distinguished by pains and perspirations, the tongue begins to clean, and the appetite may revive ; but, not- withstanding these signs of amendment, the patient still remains listless, and liable to headache and constipation. He continues feverish, and at times perspires profusely. Gradually however, although anaemic and excessively weak, subjective symptoms become less urgent; he sleeps well now, he has no de- lirium at night, and he can take his food, and this even although the body temperature may still range too high. About this time the peculiar fleeting rheumatic- like affections of the joints, so characteristic of the disease, show themselves in a large proportion of cases. One day a knee is hot, swollen, and tender; next day this joint may be well, but another joint is affected; and so this metastatic rheumatic-like con- dition may go on until nearly all the joints of the body have been involved one after the other. The patient may suffer also from neuralgia in different nerves— intercostal, sciatic, and so on. Orchitis is an occasional complication. In some cases these complications are severe and characteristic ; in others they may be mild, or absent altogether. In this respect the same infinite variety shows itself, as regards complications, as in other specific fevers. Perhaps the most characteristic feature of Malta fever is the peculiar behaviour of the temperature. In a mild case there may be a gradual ladder-like rise through a week or ten days to 103° or 104°, and then, through another week or so, a gradual ladder-like fall to normal, the fever, which is of a continued or slightly remitting type, leaving for good without complication of any sort in about three weeks. Such mild cases are the exception. Usually, after a few days of apyrexia, absolute or relative, the fever wakes up again and runs a similar course, the relapse being in its turn followed by an interval of apyrexia, which is again followed by another relapse ; and so on during several months. l82 Malta Fever. Generally remittent or nearly continued in type, occasionally, in some instances, the fever exhibits dis- tinct daily intermissions, the temperature chart suggesting some septic invasion or an ordinary inter- mittent malarial fever. But there is no evidence of suppuration to be found anywhere; neither, if we examine the blood, is the plasmodium malariae to be discovered ; nor is the quotidian rise of temperature accompanied by any ague-like rigor, or at most, only by a feeling of chilliness; nor is the disease amenable in any way to quinine. Sequelae, mortality, and types.—As a rule, the most serious consequences of Malta fever are the debility it entails, the profound anaemia, the rheumatic- like pains, and the neuralgiae. There is little risk to life ; the mortality does not exceed 2 per cent. When death occurs, it is usually from suddenly developed hyperpyrexia; occasionally it is brought about by exhaustion, or by some pulmonary complication such as pneumonia. In a few instances the fever is of a fulminating type, rapidly ending in death from hyperpyrexia. Hughes, who has made an elaborate study of this disease, designates such cases " malig- nant." Those cases with well-marked waves of fever he calls " undulating" ; those with ague-like diurnal fluctuations of temperature, "intermittent." The combination of types is infinite, an " undulating " case sometimes assuming " intermittent" characters, or vice versd; malignant hyperpyrexial symptoms may supervene in either type and at any period in their progress. Diagnosis.—The diagnosis of Malta fever from typhoid is, of course, a highly important practical matter. It is exceedingly difficult in the early stages. Principal reliance has to be placed on the absence of rose spots, the absence of diarrhoea, the presence of joint complications, the sweats, and, if available, the culture precipitation test. Wright has shown that the germ of Malta fever reacts to the serum test in the same way as the bacillus typhosus. After the /Etiology. 183 fever has gone on for several weeks diagnosis is, of course, easy ; in the early stages, on clinical grounds alone it may be almost impossible. It may be that it is only on the post-mortem table that we have the assurance, from the absence of ulceration in the ileum, that we have had to deal with a case of Malta fever. Tuberculosis, abscess, empyema, and all other causes of continued high temperature, have to be carefully excluded in attempting a diagnosis. Pathological anatomy and pathology.— This disease has almost no pathological anatomy. The spleen is the only viscus of which it can be said that it is distinctly diseased. In Malta fever this organ is distinctly enlarged, soft, and diffluent; on microscopical examination, the lymphoid cells are found to be increased in number. .Etiology.— The micrococcus melitensis.—Most important fact of all in connection with the spleen is the presence in it of a peculiar bacterium—the micro- coccus melitensis, as it has been called. For this X discovery, made in 1887, we are indebted to Surgeon- Major David Bruce of the Army Medical Staff. Unfortunately, the bacterium does not occur in th« general circulation, and therefore Bruce's discovery is of little direct use in diagnosis ; but pathologically it is of great importance, as it enables us to say posi- tively that this so-called Malta fever is a distinct disease, altogether different from either typhoid or malaria. The organism is present in the pulp of the spleen, from which it can be separated by cultiva- tion. Bruce found it in this way in ten fatal cases. His results have been confirmed by Hughes and Gipps, the former of whom found the same bacterium in fifteen cases, the latter in two. Injections of pure cultures gave rise to a similar disease in monkeys, from whose blood the micrococcus was recovered, cultivated afresh, and, on injection into other monkeys, again gave rise to the disease. The micrococcus melitensis is somewhat oval in shape, and measures -33 micromillimetre in [84 Malta Fever. diameter. It occurs generally singly, often in pairs, sometimes in fours, but never in longer chains. It is readily stained by a watery solution of gentian violet, and is best cultivated in a 1| per cent, very feebly alkaline, peptonised agar-agar beef jelly, in which, soon after inoculation, it appears as minute, clear, pearly spots. After thirty-six hours the cultures become a transparent amber; later they are opaque. No liquefaction occurs. Influence of age and residence.—The most sus- ceptible age as regards Malta fever is between the sixth and the thirtieth year. Very young children and old people are less frequently attacked. Length of residence does not influence susceptibility. Influence of season.—In Malta and other places where the disease is endemic this fever occasionally assumes an epidemic character. The period of its greatest prevalence is the season of lowest rainfall, embracing June, July, and August; differing in this latter respect from typhoid, which, in that island, is more prevalent during the three succeeding months—• September, October, and November. Local causes.—Great difference of opinion ob- tains both as regards the causes giving rise to this fever, and also as to those influencing its pre- valence. The water supply is blamed by some; others attribute the disease to faecal saturation of the soil, and so on. The disease tends to occur in par- ticular houses, barracks, and rooms, manifestly origi- nating in limited foci of infection. The weight of evidence points to a faecal origin of the virus; and, also, to its diffusion by air currents, and not by food or water. There is no certainty on these points, nor will there be until the habits and haunts of micrococcus melitensis outside the human body are definitely ascertained. Influence of social conditions.—All classes are liable to this disease ; the officer and his family as well as the soldier in barracks. Not infectious.—So far as known, Malta fever is Trea tment. '85 not transmitted directly from one person to another ; that is to say, it is not directly communicable from the sick to the healthy. Incubation period.—The period of incubation is diftidult to fix. Cases have occurred as early as six days after arrival in Malta ; on the other hand, the disease has shown itself as late as fourteen and seven- teen days after the subject of it has quitted Malta, and perhaps after arrival in England. Immunity. — Bruce considers that one attack confers immunity from subsequent attacks; other authorities hold a different opinion, believing that one attack, so far from conferring immunity, actually predisposes to subsequent attacks. Treatment—Malta and those Mediterranean ports in which this fever is endemic should be avoided by pleasure- and health-seekers during the summer months. Those who are obliged to live there all the year round would do well at this season to leave the towns and reside in the country. As a matter of precaution, in the endemic area the drinking water, food, and drains, ought at all seasons to have especial care bestowed on them. When the diagnosis is sure, it is well to give a purge—none better than calomel and jalap—and to instruct the attendants to keep the patient's tem- perature systematically below 103° by cold sponging with vinegar and water or, if necessary, by cold bath or ice variously applied. In view of the prolonged nature of the fever, this measure is one of importance ; at the same time, such treatment need not be applied too energetically, or so as to depress; a fall of 2° or 3° is all that is desirable. Quinine and, on account of the joint affection, the salicylates are very generally prescribed. Both are useless, if not injurious. Antipyrin and other anti- pyretics are also often given to bring down tempera- ture ; but the wisdom of employing depressing drugs in so chronic and asthenic a disease as Malta fever is, to say the least, questionable. Any threat of 186 Malta Fever. hyperpyrexia is best met as directed, namely, by early employment of sponging, the wet pack, or, if necessary, by the cold bath. Sleeplessness may demand hyp- notics ; headache, if severe, moderate doses of anti- pyrin; inflamed joints or testes, the usual local applications ; constipation, enemata or aperients. In fact, the treatment of Malta fever resolves itself into a treatment of symptoms. The diet at first should consist of milk; later, of broths and eggs and, if necessary, stimulants. Solid food must not be given until all fever has disappeared, and the tongue has remained clear for at least ten days. Lemonade or lime juice should be given after a time; not merely as a pleasant, thirst-relieving beverage, but with a view to averting scurvy—not at all an improbable complication if the diet is too restricted over a long period. The return to solid food must be made with the greatest circumspection; impru- dence in this respect may bring on relapse. Flannel clothing should be worn and frequently changed if there is much sweating. Change of climate is not so necessary as in malarial affections, seeing, on the one hand, that the disease may persist in England; and, on the other, that it may gradually wear out in Malta. It is not desirable to move a patient when fever runs high, or when debility is very great, or when the cool and healthy season in the Mediterranean is at hand. It must be considered that at this time winter is approaching in England, with climatic conditions very unsuitable for a patient who has become anaemic and debilitated from a long course of fever; at this season he would do much better in Malta or Gibraltar. When, how- ever, the case occurs early in the summer, or runs over the winter, then, in order to avoid the heat of the Mediterranean, change to England, if at all feasible and if it can be comfortably effected, should be advised. i87 CHAPTER XL JAPANESE RIVER FEVER--NASHA FEVER—KALA-AZAR— TROPICAL TYPHOID--TYPHO-MALARIAL FEVER. THE RIVER FEVER OF JAPAN (SHIMA MUSHl). Definition.—An acute endemic disease running a definite course. It is characterised by the presence on the skin of an initial eschar, followed by an ulcer, inflammation of the lymphatics, fever, an exanthe- matous eruption, bronchitis, and conjunctivitis. It is attended by a considerable mortality. History.—This disease was first described by Palm in 1878, and subsequently, and more fully, by Baelz and Kawakami. Geographical and seasonal distribution. —So far as known, shima mushi is confined to the banks of two rivers on the west side of the island of Nippon—the Shinanogawa and one of its tributaries, and the Omonogawa. Every spring these rivers in- undate large tracts of country. Later in the year hemp is raised on strips of the inundated district. The crop is reaped in July and August, and it is solely among those engaged in harvesting and handling this hemp that the disease occurs. It is not commu- nicable by the sick to the healthy. It is transportable in the hemp to a very limited extent; but it is only in limited spots here and there in the endemic districts that it can originate. , Symptoms.—After an incubation period of from four to seven days the disease usually begins with malaise, frontal and temporal headache, anorexia, chills alternating with flushes of heat, and prostration. Presently the patient becomes conscious of pain and [88 Japanese River Fever. tenderness in the lymphatic glands either of the groin, or of the armpit, or of the neck. On inspecting the skin of the corresponding lymphatic area there is discovered—usually about the genitals or armpits—a small (2 to 4 mm.), round, dark, tough, firmly adherent eschar, surrounded by a painless, livid red areola of superficial congestion. Occasionally two or three such eschars are discovered. Although a line of tenderness may be traced from the sore to the swollen, hard, and sensitive glands, no well-defined cord of lymphangitis can be made out. The superficial lymphatic glands of the rest of the body, espe- cially those on the opposite side corresponding to the glands primarily affected, are also, but more slightly, enlarged. Fever of a more or less continued type now sets in, the thermometer mounting in the course of five or six days to 40° or 41° Cent. The conjunctivae become injected, and the eyes somewhat prominent; at the same time a considerable bronchitis gives rise to harassing cough. The pulse is full and strong, ranging rather low—80 to 100—for the degree of fever present. The spleen is moderately but dis- tinctly enlarged, and there is marked constipation. About the sixth or seventh day an exanthem of large dark red papules appears on the face, tending to become confluent on the cheeks. The eruption then extends to the forearms, legs, and trunk, but is less pronounced on the upper arms, thighs, neck, and palate. Simultaneously with the papules a minute lichenous eruption breaks out on the forearms and trunk. These eruptions last usually from four to seven days ; if but slightly marked, they may fade in twenty-four hours. The patients during the height of the fever are flushed, and at night, it may be, delirious. They complain incessantly, probably on account of a general hyperaesthesia of skin and muscles. Deafness is also a feature. As the disease advances the symptoms become Symptoms. 189 more urgent; the conjunctivitis is intensified, the cough becomes incessant, the tongue dries, the lips crack and bleed, and there may be from time to time profuse perspiration. By the end of the second week —sooner or later according to the severity of the case—the fever begins to remit, the tongue to clean, and, after a few days more, temperature falls to normal, and the patient speedily convalesces. Diarrhoea or diuresis may occur during the decline of the fever. The circular, sharp-edged, deep ulcer left after the separation of the primary eschar—an event which usually takes place during the second week— now begins to heal, and the enlargement of the glands gradually to subside. Such is the course of a moderately severe case. In some instances, however, the constitutional dis- turbance is very slight, although the primary eschar may be well marked and perhaps extensive. On the other hand, the fever may be much more violent, and complications such as parotitis, melaena, coma, mania, cardiac failure, or oedema of the lungs may end in death. Similarly the duration of the disease varies, according to severity, from one to four weeks, three weeks being about the average. Pregnant women contracting shima mushi mostly abort and die. The mortality is approximately about 15 per cent. Pathological anatomy. — Beyond evidences of bronchial catarrh, hypostatic pneumonia, enlarged spleen, perisplenitis, patchy reddening of the intestine near the ileo-caecal valve, injection of the peritoneum, and slight enlargement of the mesenteric and super- ficial lymphatic glands, no noteworthy lesions have been described. /Etiology.—The Japanese attribute this disease to the bite of an acarus (locally called aka mushi— red insect) resembling the leptus autumnalis of Europe. Baelz rejects this idea, but offers no other explanation as to the way in which the virus is 190 Nasha Fever. introduced. Men, women, and children are equally susceptible. One attack does not confer immunity, although it appears to render subsequent attacks less severe. Hitherto the virus of the disease, which doubtless enters in the first instance at the site of the primary eschar, has not been discovered. Treatment.—On the supposition that the disease is introduced by an insect, or through a wound of some sort, care should be exercised by those engaged in hemp culture in the endemic district to protect and keep clean the skin, especially that about the genitals and armpits. There is no specific remedy for the disease ; treatment must therefore be conducted on general principles. NASHA FEVER (NASA, NAKRA). Drs. Fernandez and Mitra describe (Trans. First Ind. Med. Cong., 1895) under the name of nasha fever, a disease which they say is peculiar to India, and especially prevalent in Bengal. Preceding the fever a peculiar congestion of the mucous membrane of the septum nasi shows itself. Sometimes this congestion is confined to one nostril, sometimes both sides are affected. The pain is insignificant, but the surface of the septum is raised and presents a red and swollen appearance, a circumscribed swelling about the size of a pea (Mitra) being readily recognised. The usual symptoms of fever are present, marked constipation and malaise being very prominent. Frequently head- ache and pain in the back of the neck, shoulders, and small of the back are urgent. The face appears flushed ; there is a feeling of heat and fulness about the head and, according to Fernandez, the pupils are contracted. These symptoms continue from three to five days, when the swelling of the nasal mucosa decreases and the fever subsides spontaneously. The swelling never suppurates. In very rare cases sudden subsidence of the swelling is followed by grave symp- toms—high fever, delirium, coma, and death. One attack predisposes to another, the attacks Black Fever. 191 appearing at more or less definite intervals of a month, a fortnight, or a week. Both sexes are liable, but females suffer less frequently than males. Chil- dren are never attacked ; after fifty the disease does not occur. Nasha fever is most prevalent between April and August, being seldom seen during the winter months. In the discussion which followed the reading of Drs. Fernandez and Mitra's papers at the Indian Medical Congress, Drs. Roy and Bose refused to recognise nasha fever as a special disease, believing that the congestion of the nasal mucosa was a common occurrence in many febrile diseases in India. Treatment.—In milder cases a saline purgative suffices. Pricking the swelling in the nostril by a needle, or puncture with a lancet, quickly relieves the congestion and fever. Injections of cold water, or of some mild astringent, into the nostrils two or three times a day are said to be useful. KALA-AZAR. Kala-azar (black fever) is the name applied to an ill-defined and very deadly disease prevalent of late years in Assam, in the low-lying malarious district between the Brahmaputra and the foot of the Garo hills in the Gaolpara district. Commencing some- where about 1887, according to Rogers (Brit. Med. Jour., June 5th, 1897), in Bengal, in the Rungpore district, it crossed the Brahmaputra into Assam, where it has gradually extended its area, depopu- lating whole villages in its gradual but steady advance, and seriously augmenting the mortality and interfering with the material progress of the country. According to Giles, who was commissioned by the local government to investigate the subject, kala-azar is a slow wasting disease, characterised by great and progressive debility ; occasional, though rarely severe, intercurrent attacks of fever; enlargement of the spleen ; darkening of the complexion ; and, at the end, various dropsical affections. Extreme anaemia is a 192 Black Fever. constant symptom. Unless during the transient fevers, the body temperature is persistently and markedly sub-normal. The intercurrent fever and the enlargement of the spleen he does not regard as essential features, but rather as accidental malarial complications, and such as are to be expected in the course of any debilitating sickness in a country so notoriously malarious. The darkening of the skin— from which, presumably, the disease takes its name— he attributes to the leaden tint of anaemia enhanced by accumulations of dirt on the unwashed and natur- ally dark skin of the native. Giles found the ova of the ankylostomum duodenale in the faeces of prac- tically all the cases he investigated. Influenced by this circumstance, and by the anaemia which was so marked a symptom in all, he regarded kala-azar as being merely a severe form of ankylostomiasis. Rogers, on the other hand, after correctly pointing out that the ankylostomum is exceedingly prevalent in many districts of India in which kala-azar is unknown, opposes Giles's views, and maintains that it is but a form of malaria indistinguishable in its early stage from ordinary malaria. He found the malaria para- site a constant feature in the blood of his patients, and always encountered, post-mortem, marked malarial pigmentation of the liver, spleen and kidneys. Rogers further asserts that kala-azar is invariably introduced into hitherto unaffected villages by someone who had contracted the fever in an infected village; the first two or three cases, he says, occur in the same house in which the patient has come to live. He further states that the plasmodium of the kala-azar type of malaria, being of a nature much more virulent than that of the ordinary fevers of Assam, causes a marked cachexia in about as many months as the ordinary fever parasite does in as many years. He also con- siders that the germ, by intensification, has acquired infective properties, and is capable of passing directly from the sick to the sound through the air or through the soil. It is difficult to understand, however, how so Tropical Typhoid. l93 important a biological revolution could be effected in the habits of the plasmodium. Other writers agree with Giles in denying the malarial nature of kala-azar. Gibbons, for example (Lid. Med. Gaz., January, 1890), describes the post- mortem examination of a case, and states explicitly that there was no pigmentation of the spleen. It is evident that much clinical, aetiological, and pathological work has yet to be devoted to the study of kala-azar before its true nature can be definitely affirmed. Certain it is that it has no relationship to beriberi, as at one time was asserted. TYPHOID FEVER IN THE TROPICS. The existence of typhoid fever in the tropics was for long not only ignored but actually denied, even by physicians and pathologists of repute. Formerly, the idea of malaria so dominated all views of tropical fevers that nearly every case of pyrexia, other than those of the most ephemeral description, or those associated with the exanthemata or with manifest inflammation, was relegated to this cause. When ulceration of the ileum was encountered in the post- mortem room, the intestinal lesion was regarded not as the specific lesion of the fever but merely as a complication. More correct views prevail at the present day, and typhoid now ranks not only as a common disease in the tropics but, to the European there, as one of the most commonly fatal. Little is known about typhoid as a disease of natives, beyond the fact that it does attack them; as a disease of Europeans it is only too familiar to the army sur- geon in India and to the civil practitioner in most, if not in all, parts of the tropical world. Typhoid fever is, one might almost say, alarmingly prevalent among young soldiers and civilians in the East. It is very common among them during the first two or three years after their arrival. Fortunately, the liability decreases with length of residence. Appar- ently a sort of acclimatisation, or rather habituation, N 194 Tropical Typhoid. to the poison is established with time, just as tends to be the case with other organic poisons. It is not unlikely that the relative exemption of the native races is owing to a similar immunising effect produced by living in constant contact with typhoid and similar toxic agents. On visiting native cities—Chinese cities, for example—one is filled with amazement at the state of filth in which the people live, and not only live but thrive. The streets are narrow and never cleansed; the common sewer lies beneath the flagstones paving the streets, and through the interstices between the stones can be seen the black, stinking slush in the sewer. The sewerage is not confined in a well-laid cemented drain, but it soaks through the loosely laid, uncemented stones, and thoroughly saturates the ground on which the tumble-down, overcrowded houses are built. Night soil is allowed to remain in wooden buckets inside the houses awaiting collec- tion by the soil merchant who sells it to the market gardener and the farmer. Urine is accumulated in earthenware jars, and is similarly disposed of. The houses are rarely swept and cleaned, hardly ever repaired. In every corner are filth and rubbish. And yet, in such circumstances—circumstances in which the sanitarian would prophesy ityphus and typhoid, the population seems to thrive. Doubt- less, where the European would almost surely contract typhoid and other filth diseases, the natives have ob- tained an immunity by habituation. In Japan the privies are inside the house, under the same roof as the dwelling-rooms, and the whole house is generally pervaded by a peculiar, mawkish, privy odour. The natives do not appear to suffer much from this; but I used to see many cases of typhoid in " globe-trotters " who, after visiting Japan, had come to Hong Kong with unequivocal symptoms of this disease. In China, in Japan, and in India little or no care is taken to prevent contamination of the wells with sewage matter, and unless foreigners are very careful about boiling their drinking water and avoiding bazaar-made drinks, Tropical Typhoid. 195 they are almost sure, sooner or later, to be victimised. Typhoid is common also in Cochin China, in the Malay country, in Mauritius, in Africa ; the French have had large experience of it in Algeria and their WTest African possessions; the English have had similar experience in South Africa. It is also found in the West Indies—in fact, everywhere where it has been properly looked for. It would appear that not only is typhoid a common disease in the tropics, but that it is also a very virulent one, with a death-rate twice as heavy as the death- rate of typhoid in England. According to my experi- ence in China, not only is the tropical form grave from the outset but it is extremely liable to relapse. In England the death-rate is put down at about one in five or six attacked; but in India the elaborate and carefully prepared statistics show a death rate rather over one in three. What with its frequency and its high rate of mortality, typhoid in India kills more European soldiers than cholera. Besides exhibiting increased virulence, experience has shown that as against typhoid those sanitary safeguards which are found to be practically sufficient in England are by no means so effective in India. It would also appear that soldiers on the march contract the disease in passing through uninhabited country, in spite of the fact that the camp may be pitched in spots which, presumably, have never been occupied by man before; and although the men may have drunk only of water from springs and streams that were beyond suspicion of faecal contam- ination. Similar testimony comes from Australia, where typhoid has occurred in the back country in lonely spots, hundreds of miles from fixed human habitations. From these data the inference is suggested that Eberth's bacillus—assuming-it to be the germ of typhoid—under certain conditions of soil and tempera- ture may be possessed of the power to exist as a pure yet virulent saprophyte, for which an occasional pass- age through the human body is by no means necessary. N 2 196 Typho-Malarial Fever. 0 It is not requisite to enter further into the sub- ject of typhoid fever, for although, as I stated, this important disease is abundantly common in the tropics, it is not properly classifiable as a tropical disease; moreover, it is fully dealt with in every text- book on general medicine. It is alluded to here more by way of warning the practitioner in the tropics against overlooking it, and against assuming that every case of fever he may encounter is malarial. TYPHO MALARIAL FEVER. Some years ago a good deal was written and said, particularly by American physicians, about what is called "typho-malarial fever." An idea got abroad —and still exists, apparently—that there is a specific disease which, though resembling both, is neither typhoid, nor malarial, nor any of the other recognised forms of continued fever. There can be little doubt that in warm climates, besides the known fevers, there are several, if not many, undifferentiated specific fevers. But the particular clinical group indicated by the term " typho-malarial" is not one of these; for typho-malarial fever is but an ordinary typhoid occurring in an individual who has been exposed to malarial influences; in other words, who has become infected by the plasmodium malariae. It has already been pointed out that the malaria germ may remain dormant for months or even years in the bod}r, and then, on the occurrence of severe physiological strain—such as a chill, shock, excessive fatigue, and so forth, wake up again, as it were, and once more multiply and flourish in the blood and gi\ e rise to the phenomena of malarial fever. It is a re- cognised clinical fact, one familiar to our predecessors and much insisted on by them, that any disease pro- cess occurring in a person who has once had malarial fever is prone to take on an intermittent or periodic character; as if the previous malarial infection had left a sort of impress of periodicity on the consti- tution. Doubtless this is owing to the fact that Typho-Malarial Fever. 197 in individuals with Laveran's parasite dormant in their tissues, the physiological strain implied by the presence of active disease paralyses for the time being the self-protective power, and the plasmodium is once more permitted to multiply and work its mischief in the blood. There are few more depressing influences than typhoid. Little wonder, then, that typhoid in a malarial is often accompanied by clinical evidences of a resuscitation of the plasmodium. And so it comes to pass that an attack of typhoid in malarial countries, or in persons returned from malarial countries, is prone to assume some of the characters of intermittent or remittent fever. Not infrequently, instead of the slowly increasing- headache, malaise, creeping cold, anorexia, and day by day ladder like rise of temperature, the first sign of typhoid in such circumstances is a violent rigor, imme- diately followed by rapid rise of temperature which, in an hour or two, mounts to 104° or 105°, to be suc- ceeded in a few hours by profuse sweating and a partial remission of fever exactly resembling an attack of ague. For the next two or three days these attacks are re- peated, the remission becoming less complete each time. Quinine may be given but, although the rigors and marked oscillations of temperature are checked, the practitioner is surprised and disappointed to find that the temperature keeps permanently high, and that the typhoid state is gradually developed. Or it may be that a typhoid fever begins in the usual in- sidious way, runs its usual course for a week or two, and then, in the middle of what is regarded as an ordinary typhoid, rigors and temperature oscillations and other malarial manifestations show themselves. If quinine is given, these oscillations cease and the typhoid resumes its usual course. Or it may be that it is not until the end of the fever and during con- valescence that these malarial symptoms are developed. I am not aware of any observations on the blood in typhoid commencing with malarial manifestations, but in an issue of the Boston Medical and Surgical 198 Typho-Malarial Fever. Journal (Vol. cxxxii., No. 6, Feb. 7, 1895) Dr. F. A. Rogers records a case of typhoid in which chill occurred on the twelfth day, followed by quotidian fluctua- tions of temperature and profuse sweating. In this case the plasmodium was found in the blood in abundance. On the administration of quinine the malarial signs subsided, the plasmodium disappeared from the blood, and the typhoid fever ran its course to convalescence in the usual way. The diagnosis between typhoid and some forms of malarial remittent is often exceedingly difficult, in certain cases almost impossible, without the assistance of the microscope. The principal points to be kept in view are, first, the mode of incidence of the disease. In typhoid there is a gradual rise of temperature, a daily gain of a degree or so during several days, the maximum not being attained for five or six days; as against the sharp rigor and sudden rise of tem- perature through five or six degrees in the first twenty- four hours in malarial fever. Secondly, the character of the gastric symptoms differ. Thus there is bilious vomiting and perhaps bilious diarrhoea, tenderness of the liver, epigastrium and spleen, and an icteric tint of skin and sclerae in malarial remittent; in contrast to the abdominal distension, perhaps, the iliac tender- ness and gurgling, and the peasoup stools of typhoid. Such signs as epistaxis, deafness, and cheek flushing in typhoid have a certain weight, but skin eruptions in the tropics are of little aid in the diagnosis of such cases. Prickly heat, or its remains, is present in nearly everyone, sick and healthy, malarial or typhoid patient alike; so that rose spots are to be found in nearly all fevers in hot weather. None of these signs can be considered as absolutely diagnostic ; all or any of them may be present in typhoid, and all or any of them may be present in malarial remittent. The only really diagnostic marks are tertian peri- odicity, amenability to quinine, and, above all, that supplied by the plasmodium malariae and the Widal serum test. In all doubtful cases the plasmodium Trea tment. 199 should be sought for; if it is found, the case has certainly a malarial element, and quinine is indicated. If it is not found, and if quinine has not been administered and several negative examinations of the blood have been made, and if the observer has confidence in his skill as a microscopist, the chances are the case is one of pure typhoid. Nevertheless, if the plasmodium is found typhoid is not necessarily excluded, for the case may be one of typhoid in a malarial, that is typho-malarial fever. Prognosis and management.—Remittents under suitable treatment we expect to see recover; typhoids too often go the other way. A word of caution may be given about these tropical fevers of doubtful character. The caution has reference to prognosis and treatment. In forming diagnosis too much weight must not be attached to the presence or absence of diarrhoea ; constipation is much more common in tropical typhoid than in the disease in Europe. Diagnosis, therefore, must not be too much influenced by absence of diarrhoea, and the practitioner must not be led by the presence of constipation into giving active purgatives. Purgatives are often of the greatest service in malarial remittent; but if, in consequence of a mistake in diagnosis, it is assumed that a case of typhoid is remittent, and large doses of calomel and other cathartics are administered, the result may be disastrous. If doubt exists about diagnosis, and quinine is given, it will not do a typhoid much harm. It is a good rule, therefore, when in doubt to give quinine, but to avoid purga- tives. 200 CHAPTER XII. HEAT-STROKE. The term " heat-stroke" conveys the suggestion that heat is the leading aetiological factor in the various morbid conditions which custom has grouped under this and similar names. Until irrefutable evidence has clearly demonstrated the true cause of any given disease, it is a very grave error to base the name of such disease on some crude hypothetical aetiological conception. Such a nomen- clature is sure to lead to confusion, to mistakes in practice, and to retard progress. There is no better illustration of the truth of this remark than that supplied by the group of diseases under consideration. The expression " heat-stroke" covers several distinct, one might say of two of them almost opposite, clinical conditions. One of these is heat- exhaustion, virtually a syncope, which may occur anywhere and in ;;ny climate, high atmospheric temperature, whether natural or artificial, being its essential aetiological factor. The other, of which hyperpyrexia is the most striking clinical feature, is a well-defined and possibly specific fever, having a peculiar endemicity and assuming at times in the endemic area almost epidemic characters. Like yellow fever, dengue, tropical elephantiasis and other tropical diseases, this second form of heat-stroke occurs only in conditions of high atmospheric temperature; but, as with these diseases, it by no means follows that though occurring in high temperature, it is caused by high temperature." To obviate confusion, and following the excellent example of Dr. L. Sambon (Brit, Med. Journ., March 19, 1898), I shall describe this disease under its ancient name Siriasis. He a t-exha us tion. 201 Besides these two well-defined morbid states associated with high atmospheric temperatures, there is another, but ill-defined, group of heat-stroke cases which, to all appearance, result exclusively from ex- posure to the direct rays of the sun. These cases might be classified under the term Sun-traumatism. Although not all of them strictly classiflable as fevers, in deference to custom and for convenience I shall describe these three phases of so-called "heat- stroke " in this place and as a group. HEAT-EXHAUSTION. Definition.— Sudden faintness, or fainting, brought about by exposure to high atmospheric temperature. Etiology—The healthy human body when untrammelled by unsuitable clothing, when not exhausted by fatigue or excesses, when not clogged by surfeit of food, by alcoholic drinks or by drugs, can support with impunity very high atmospheric temperatures. In many parts of the world men live and work out of doors in temperatures of 100° or even of 120°. Many industries are carried on at temperatures far above this ; glass blowing, sugar- boiling, for example. The stokers of steamers, es- pecially in the tropics, discharge for hours their arduous duties in a temperature often over 150° F. When, however, the physiological activities have become impaired by disease, especially by heart disease, kidney, liver or brain disease, by malaria, by alcoholic or other excesses, by fatigue, by living in overcrowded rooms ; or when the body is oppressed by unsuitable clothing; or in the presence of a combina- tion of some of these, then high atmospheric temperatures are badly supported, the innervation of the heart may fail and syncope may ensue. Chevers, than whom few have had better oppor- tunities of forming a sound opinion, speaking of this subject, says : " Numerous as the constitutional causes of heat-stroke are, all Indian experience 202 HE A T-EXHA US TION. combines to show that drunkenness is the chief." The tropical practitioner will do well to bear this remark in mind ; it applies not only to heat-ex- haustion, but also to all forms of disease grouped under the term "heat-stroke." Heat-exhaustion, then, is one form of what, when the subject of it happens at the time to be exposed to the sun, is called "sun-stroke," or when the patient happens to be at the time under cover is called " heat- stroke." In nine cases out of ten this sun-stroke, or heat-stroke, simply means syncope; syncope caused by solar or atmospheric heat, or a combination of these, acting on a body whose resistance has been impaired by disease, or by trying unphysiological conditions. This form of heat-stroke, consequently, has no special geographical distribution and no special morbid anatomy or pathology. For obvious reasons it is most apt to occur in warm weather, and in tropical climates; and on this account its recognition, prevention, and treatment, have special claims on the student of tropical medicine. Symptoms—When attacked with heat-ex- haustion the patient feels giddy, and perhaps staggers and falls/ He is pale, his pulse is small, soft, and perhaps fluttering ; his breathing shallow, perhaps sighing, never stertorous; his pupils are di- lated ; his skin is cold ; his temperature is sub-normal; and he may be partially, more rarely wholly, un- conscious. Usually, after a short time he gradually recovers; verj?- likely with a splitting headache and feelings of intense prostration. In a small proportion of cases the faint is not recovered from, and death ensues. Treatment.—In syncopal heat-stroke the patient should be laid at once on his back in a cool, airy, and shaded place. His clothes should be loosened, a little water dashed on his face and chest, and ammonia held to his nostrils. If necessary, a stimulant may be given by the mouth, or injected into the rectum or hypodermically. It is a mistake to douche these Sun- tra uma tism. 203 cases too freely. The object is rather to stimulate than to depress. SUN-TRAUMATISM. There is a large, ill-defined, and difficult-to-define class of heat-stroke cases which belong neither to the category of heat-exhaustion, not to the very definite and probably specific disease described under the name siriasis.- The morbid phenomena in this class of sun-induced disease are attributable, appa- rently, to a peculiar physical action of the direct rays of the sun on the tissues. To this category belong, it seems to me, those sudden deaths occurring without warning during, and manifestly in conse- quence of, exposure to the sun. Such may have been the sudden deaths described by Parkes, Maclean, Fayrer, and others, in which soldiers in the excitement and stress of battle, and Avhile oppressed with thick clothing and heavy accoutre- ments and exposed to a blazing sun, suddenly fell forward on their faces and, after a few convulsive gasps, died. In these instantaneously fatal cases the paralysis of the heart or respiration seems to be more of the nature of shock as from a blow or other sudden and violent impression on the encephalon. Doubtless, indeed it is a well-known fact, the strain undergone in these and similar circumstances may cause an apoplexy or rupture of some descrip- tion in tissues prepared for such a cataclysm by morbid degenerations of long standing. Besides these there is another type of case in which, after prolonged exposure to the sun, a febrile condition is established. This is sometimes of great severity, and may be characterised by intense head- ache, a rapid full pulse, a pungent dry skin, intoler- ance of light, sound and movement, and occasionally by vomiting. This condition suggests meningeal congestion, possibly inflammation. The acute phase may be quickly recovered from, or it may prove very persistent and last for days or weeks.. It may 2 o 4 Sun- tra uma tism. leave no injurious effects, or it may be followed by a variety of morbid nervous phenomena which may be transient, or which may be of a more permanent character. Among the distressing sequelae authors have mentioned tremor, loss of memory, amaurosis, deafness, various paretic conditions, epilepsy, insanity, persistent headache, recurring headache, dyspeptic conditions, sensitiveness to heat and especially to exposure to the sun. How far these sequelae are entirely attributable to sun exposure, or how far they depend on independent diseases, as syphilis, for example, the local cerebral manifestation of which many have been provoked, though not actually caused, by the sun-traumatism, it is not always easy to say. The morbid anatomy, as well as the clinical symptoms, indicate meningitis as a feature in these instances of reputed sun-traumatism. Authors refer to thickenings and opacities of the meninges, and even to thickening and roughening of the calvarium. Many speculations have been advanced as to the pathogenesis. Manifestly it is not altogether, if at all, a question of caloric, for such effects do not result from exposure to the heat of a furnace, however intense. There appears to be some special element in the solar spectrum capable of injuriously affecting the tissues, particularly if they have not become gradually habituated to sun exposure. That some such element does exist is proved by the phenomena of sun erythema, of that form of skin pigmentation known as sun-burning, and, possibly, of leucodermia. The sensation of distress brought on by exposure to a hot sun, which is quite a ditlerent sensation from that produced by the heat of a fire, points in the same direction. In this connection we are forcibly reminded of the phenomena of the Rontgen rays and of their effects on the tissues. Treatment.—Patients suffering from sun-trau- matism must be kept as quiet as possible in a cool, airy, and darkened room. For a time the head should be kept shaved and cold applied to the scalp. The S/RIASIS. 205 bowels must be free, food light and unstimulating, and alcohol in every form strictly forbidden. Restlessness and insomnia are best treated by the bromides. For a considerable time the patient will be conscious of loss of memory and feebleness of intellectual power and of the faculty of concentration. He may be irritable, liable to headache, and extremely sensitive to heat— more particularly the heat and glare of the sun. So soon as he is able to be moved he must be sent to a cold climate, and there remain until all trace of his illness has completely disappeared. Indeed, it is questionable if the subject of pronounced sun-trauma should ever again risk the dangers of a tropical climate ; certain it is that he should not return to the tropics so long as the slightest evidence of cerebral trouble remains. For persistent headache and other signs of chronic meningitis, courses of the iodides and bromides, repeated blistering of the neck and scalp, together with careful dieting and general hygiene, should be tried. In not a few instances, in spite of the most careful treatment, medicinal and climatic, serious permanent disease of the encephalon remains, giving rise to various and often incurable troubles, and, very commonly, to distressing intellectual enfeeblement. SIRIASIS. Definition.—An acute disease developing in the presence of high atmospheric temperature, and char- acterised by hyperpyrexia, coma and extreme pul- monary congestion. Aouicnclature.—This is, perhaps, the most important of the several diseases covered by those loosely used terms, sun-stroke, heat-stroke, coup de soleil, insolation, heat-apoplexy, heat-asphyxia, thermic fever, and so forth. As stated, I have followed Dr. Sambon in adopting the name Siriasis, because this term, whilst it is distinctive, embodies no aetiological theory ; it has the further merit of being the most ancient of the many names applied to the disease. The geographical distribution of siriasis, 2o6 Siriasis. like that of yellow fever, appears to be remarkably restricted. It is true that this type, or what passes for this type of disease, has been reported as occurring in many countries. On careful examination, however, it will be found that a large proportion of the reputed cases are really examples of other diseases, more especi- ally of cerebro-spinal fever, apoplexy, tubercular men- ingitis, delirium tremens, pernicious malaria, or some other phase of acute disease, but not of true siriasis. According to Sambon, hyperpyrexial heat-stroke is rigidly confined to certain low-lying, sea-coast districts, and to the valleys of certain rivers. It is never found in high lands, nor above a relatively low altitude—■ 600 feet. It is unknown in Europe. The endemic areas are :—in America, the east coast littoral of the United States, more especially in the great towns; the Mississippi valley ; the coast of the Gulf of Mexico; the valleys of the Amazon, and of the La Plata; and the South Atlantic coast. In Africa, the valley of the Nile ; the coasts of the Red Sea; and a low-lying part of Algeria, near Biskra. In Asia, Syria; the valleys of the Indus and Ganges; Lower Burma; Tonquin; and south-east China. In Australia, the Murray River district; the Queensland coast; and, possibly, the plains of Sydney. No doubt, it occurs elsewhere in corresponding meteorological and telluric conditions; but, undoubtedly, many large areas in the tropical world, and especially so the interior of con- tinents, are exempt from siriasis. It is not met with on the high seas, although it is well known on ships in the narrow land-locked Red Sea and Persian Gulf. Etiology.—Newcomers to the endemic areas and Europeans are more liable than natives or long residents. Apparently, long residence confers a rela- tive immunity, although not an absolute exemption. All ages and both sexes are susceptible; but, in consequence of their habits and more frequent expo- sure to the predisposing and immediate causes, men are more liable to siriasis than are women. /Etiology. 207 Predisposing influences, similar to those in heat syncope and sun-traumatism, powerfully influence the liability to siriasis. Amongst these are all physio- logical depressants; notably intemperance, fatigue, overcrowding, unsuitable clothing, malaria, acute disease, and also chronic organic diseases of the important viscera. Siriasis has generally been attributed to a direct action of atmospheric or solar heat on the body. Many theories of the modus operandi of this assumed cause have been advanced. Among these may be mentioned superheating of the blood by the high temperature of the surrounding atmosphere ; paralysis of the thermic centres causing (a) over-production of heat, or if) retention of body heat; pressure on the brain by expansion from heat of the cerebro-spinal fluid ; vaso-motor paresis ; paresis of the heart ganglia; excess of carbonic acid in the blood; coagulation of myosin; suppression of sweat ; deficient serosity of the blood from excessive sweating, and so forth. It is well known that neither high atmospheric temperature per se, nor high bodily temperature, unless the latter be associated with some special toxin, gives rise to symptoms at all like those of siriasis. Considering these two facts, and at the same time the peculiar and capricious distribution of the disease, the circumstance that its prevalence curve does not always correspond with the atmospheric temperature curve; that the degree of prevalence varies in the endemic area from year to year; that it is not most prevalent in the hottest years, seasons, or places: that it becomes epidemic at times ; that it runs a definite course; that it may relapse; that in many instances it has definite premonitory symptoms ; that it has peculiar lesions; and that it tends to terminate by crisis, in other words, that it behaves like pneumonia or any other specific fever, Sambon has boldly asserted that siriasis is a germ disease, like yellow fever or dengue, and, like these, is caused by some organism which demands for its 208 Siriasis. development a high atmospheric temperature and cer- tain, as yet unknown, local conditions. Time will show how far this hypothesis is correct. In my opinion it has more in its favour than any of the many theories that have been based on a thermic aetiology. Symptoms.—Though sometimes coming on sud- denly during exposure to the sun, siriasis is very often preceded by a distinct prodromal stage. It is very often developed independently of any direct exposure to the sun ; not infrequently the attack comes on during the night. Among prodromata which may show themselves with greater or less distinctness for an hour or two, or even for a day or two, before the full development of the attack, may be mentioned great disinclination for exertion, pains in the limbs, drowsi- ness, vertigo, headache, mental confusion, sighing, anorexia, thirst, intolerance of light—sometimes accompanied by chromatic aberrations of vision, suffused eyes, nausea and perhaps vomiting, prae- cordial anxiety, sometimes a sense of impending calamity, a hysterical tendency to weep, a very hot dry skin, and a quickened pulse. Longmore called attention to excessive irritability of the bladder as a common prodromal symptom. This is a valuable and easily recognised danger signal when present, and one the significance of which has been confirmed and empha- sised by subsequent writers ; it is possible, however, that its frequency has been exaggerated. Though generally present in greater or less degree, and for a longer or shorter time, in many instances these prodromal symptoms are not remarked, the first indication of anything wrong being perhaps a short stage of restlessness, or possibly of wild delirium. This brief preliminary stage rapidly cul- minates in coma, complete unconsciousness, and high fever quickly passing into hyperpyrexia. Wood thus describes the symptoms of the developed attack :—" All the cases of sunstroke which have cbme under my observation have been in Symptoms. 209 hospital, and represent, therefore, only the severe, fully- formed disease. The symptoms have been very con- stant. Total insensibility was always present, with, in rare instances, delirium of the talkative form, and still more rarely the capability of being roused bv shaking or shouting. The breathing was always affected, sometimes rapid, sometimes deep and laboured, often stertorous, and not rarely accom- panied by the rattle of mucus in the trachea. The face was often deeply suffused, sometimes with the whole face deeply cyanosed. The conjunctiva Avas often injected, the pupils various—sometimes dilated, sometimes nearly normal, sometimes contracted. The skin was always intensely hot, and generally, but not always, dry ; when not dry it was bathed in a pro- fuse perspiration. The intense burning heat of the skin, both as felt by the hand and measured by the thermometer, was one of the most marked features of the cases. The degree of heat reached during life was, in my cases, mostly 108°-109°. The pulse was always exceedingly rapid, and early in the disease often wanting in force and volume ; later it became irregular, intermittent, and thready. The motor nervous system was profoundly affected. Subsultus tendinum was a very common symptom ; o-reat rest- lessness was also very often present, and sometimes partial spasms or even violent general convulsions. The latter were at times epileptiform, occurring spon- taneously, or they were tetanoid, and excited °by the slightest irritation. Sometimes the spinal cord ajjpeared to be paralysed, the patient absolutely not moving." The pupils, unless immediately before death, when, along with the other sphincters they relax, are con- tracted. The reflexes are partially or wholly in abeyance. There may also be, especially in the graver cases, free watery purging, the dejecta, as well as the skin of the patient, emitting a peculiar and distinctive mousey odour. The scanty urine may contain blood corpuscles, albumen, and casts. 0 2IO SlRIAS/S. Different writers mention a variety of what may be described as minor symptoms. These vary in different cases, and are by no means always present or characteristic; but in siriasis the essential symp- toms, high fever and profound nervous disturbance, generally associated with insensibility, are invariably present. Unless active measures to lower temperature are taken early in the progress of the case, and unless these measures are vigorously carried out, in the great majority of instances death occurs within a few hours, or even minutes, of the onset of insensibility. The immediate cause of death is generally the failure of respiration. Rarely do cases linger for a day or two. Partial recovery is sometimes followed by relapse. In. favourable cases the disease usually terminates by crisis, and convalescence is rapid. Mortality.—As might be supposed, some types of heat-stroke are much more dangerous than others; siriasis infinitely more so than ordinary heat ex- haustion. Treatment, if early instituted and judi- ciously carried out, has undoubtedly a powerful influence in reducing mortality. Taking one type of heat-stroke with another, the case mortality among English troops in India is about one in four; in the year 1892, of 223 European soldiers admitted to hospital for heat-stroke, 61 died. Morbid anatomy.—A notable feature is the early appearance of rigor mortis. The blood is re- markably fluid, or but feebly clotted. The venous system is gorged, the dark fluid blood pouring from the phenomenally engorged lungs and other viscera on section. Both blood and muscles are said to yield an acid reaction more or less pronounced. The red blood corpuscles are crenated, and do not form rouleaux. If the post-mortem examination is made shortly after death and before decomposition changes have set in, the heart, particularly the left ven- tricle, is found to be remarkably rigid; this rigidity is sometimes described as being of woodeny hardness. Diagnosis. 211 If the examination be made at a later period, the muscle of the heart will be found soft and flabby. There may be some venous congestion of the meninges of the brain, but the brain itself shows no important vas- cular changes. The intestinal mucosa, as well as that of the stomach, is swollen and exhibits patches of congestion. Pathology.—As may be gathered from the remarks on aetiology, the pathology of siriasis, so far, is in a very unsettled state, and will continue to be so until the essential cause of the disease has been finally determined. Diagnosis. — The presence of high fever is sufficient to differentiate siriasis from sudden insensibility caused by uraemia, by diabetic coma, by alcoholic and opium poisoning, and by all similar toxic conditions. Cerebral haemorrhage, particularly pontine, may, after some hours, be followed by high temperature; but here the febrile condition follows the insensibility, whereas in heat-stroke the febrile condition precedes the insensibility. The diagnosis from a cerebral malarial attack may be very difficult; chief reliance has to be placed on the history, if obtainable, on the condition of the spleen, and, especially, on the result of microscopic examination of the blood. Malarial fevers and the early stages of the eruptive fevers in children are very apt to be regarded as heat-stroke, particularly if there has been recent exposure to a hot sun. Cerebro-spinal fever, so often mistaken for siriasis, may be recog- nised by the occipital retraction, the irregular pupils, the frequent occurrence of strabismus, the compara- tively low and fluctuating temperature, the associated herpes, the initial rigor, and its long duration. Treatment.—In all fulminating fevers, including siriasis, occurring in warm climates, if malaria be sus- pected, particularly if the plasmodium be discovered in the blood, quinine should be injected hypodermically at once—seven grains or so of the hydrochlorate; this dose should be repeated three or four times at intervals o 2 21 2 Hea T-STROKE. of four hours. In every case of siriasis, whether it has been deemed advisable to administer quinine or not, attention must at once be given to reduce temperature by such rapidly-acting measures as the cold bath, or ice applied in various ways to the head and body. Antipyrin, antifebrin, and all other anti- pyretic drugs are of very little service, even if, in consequence of their depressing action on the heart, they be not actually dangerous; in all serious cases of siriasis, these drugs must be carefully avoided. Chandler (New York Med. Rec, June 5, 1897), speaking from an experience of 197 cases in which the mortality amounted only to twelve, gives some excellent directions for the management of hyperpyrexial cases. He directs that the patient be placed undressed on a stretcher, the head end of which is raised slightly so as to facilitate the escape of involuntary evacuations and to provide for drain- age. A thermometer is kept in the rectum. The body is covered with a sheet upon which are laid numerous small pieces of ice, larger pieces being closely packed about the head. Iced water is then allowed to drip for thirty or forty minutes on the patient from drippers hung at an elevation of from five to ten feet. A fine stream of iced water poured on the forehead from an elevation will act as a stimulant and rouser; this is a very powerful measure, and must not be kept up for longer than one or two minutes. A hypodermic injection of forty minims of tincture of digitalis is given as soon as possible, its administration being preceded in the case of plethoric patients showing much arterial tension (but not other- wise) by a small bleeding. The application of cold should be at once discontinued in hyperpyrexial cases so soon as the thermometer in the rectum has sunk to 104°; and in cases of simple thermic fever, in which the temperature has not exceeded 106°, when it has fallen to 102°. If these powerful antipyretic measures are carried beyond this point the fall of temperature may continue below the Prevention. 213 normal, even to as low as 91°, and dangerous collapse ensue. On discontinuing the iced sheet, the patient should be wrapped in a blanket, and hot bottles applied to limbs and trunk. Very likely perspiration, a very favourable sign, will then set in. Stimulants may now be necessary. Strychnine, owing to the marked tendency to convulsions present in heat-stroke, must on no account be used as a cardiac stimulant. Convulsions are best controlled by cautious chloroform inhalations. As death in heat-stroke generally results from failure of respira- tion, Chandler strongly recommends artificial re- spiration when the breathing threatens to become suspended ; he claims to have obtained some mar- vellous results from this expedient. It should be kept up for half an hour or longer. During convalesence, great care must be exercised to shield the patient from all influences calculated to provoke relapse. PREVENTION OF HEAT-STROKE. In heat-stroke climates great attention should be paid to the general health ; if this be not satis- factory, exposure to the sun and to high tem- peratures must, so far as possible, be avoided. Alcoholic drinks, gluttony, excess of animal food, too much tobacco smoking, in fact, dissipation of all sorts, are especially to be deprecated. Individuals suffering from malarial or other fevers, or from chronic liver or kidney disease, run great risk if they are careless about exposing themselves to the sun. Violent exercise, excessive fatigue, want of sleep, constipation, are also to be avoided. Clothing ought to be light and loose fitting, the under-garment being of thin woollen material. In going out in the sun the head must be protected by a wide-brimmed pith hat, protecting the temples and neck as well as the top of the head. This hat should be so constructed as to admit of free ventilation around the head. A pad of cotton sewn into the back of the 214 Heat-stroke. coat in such a way as to protect the spine is a wise measure, and one adopted by experienced sports- men in India. The phenomena connected with the Rontgen rays suggest the possibility that there may be solar rays, other than the ordinary heat rays, which, although they may be able to pass through organic materials, can nevertheless be arrested by metals. If this be true for the sun as well as for the electric spark, a useful addition to the sun hat would be a thin plate of some light metal placed between the layers of pith constituting the basis of the ordinary solar topee. A sheet of tinfoil or other light metal would not perceptibly add to the weight of the head-gear. A white umbrella, lined with green, ought never to be despised. Tinted (smoke colour) goggles are probably a protection, as they cer- tainly are a great comfort in mitigating solar glare. Rooms should be kept dark during the day, and cooled by means of punkahs, thermantidotes, tatties, Venetians, and other contrivances. In barracks and ships there must be no overcrowding. In very hot weather European soldiers should, if possible, sleep under punkahs. Military drills should be re- duced to a minimum, and take place in the cool of the morning only, and after the soldier has had a cup of tea or coffee and some light food. Marches should be short, interrupted by frequent halts, and be got through if possible in the early morning. While marching the men ought to be in open order, relieved of all unnecessary weights, and be well supplied with water. Camps should be pitched in spots as cool and airy as may be available and, when practicable, on turf and under large spreading trees free from undergrowth. Double canvas, and grass or boughs laid on the wall of the tent, will do much to mitigate the temperature within. 215 CHAPTER XIII. UNCLASSED FEVERS OF THE TROPICS. There can be little doubt that in the tropics there are a number of fevers specifically distinct from any of the foregoing, and also from the better-known fevers of temperate climates. Such fevers are con- stantly met with and are a perpetual puzzle to the conscientious diagnostician. Up to the present little, if anything, of a truly scientific character has been done towards describing, separating, and classifying them. Some attempts have been made to arrange these imperfectly differentiated fevers on a clinical basis ; but, until their causes have been dis- covered and, above all, until they have been studied in reference to any possible connection they may have with the plasmodium malariae, anything like a sound classification and description has to be post- poned. So far as known, they are not associated with distinctive exanthems or even with distinctive visceral lesions; a circumstance which has contributed, doubtless, to retard our knowledge in a very im- portant department of tropical medicine. Another circumstance which has retarded progress in this matter is the unscientific classification of fevers adopted by our military medical authorities, and to which military medical officers have been obliged, or have elected, in great measure to conform. It would seem that every case of fever of short duration, as well as those cases which show an intermittent character, have to appear in the Army Returns as " ague." This misleading, slovenly, not to say dangerous, practice, must have had a powerful in- fluence in retarding the study of the pyretology of 2l6 Unclassed Fevers. the tropics, at all events by our principal medical pioneers there—the army surgeons. Recently, Crombie (Trans. First Ind. Med. Cong.) has attempted a classification of these fevers on a clinical basis, which, so far as it goes, is of distinct value. His remarks apply solely to the fevers of India ; but I can recognise in his descriptions clinical forms which I frequently met with formerly in China. It is fair to infer from this latter circumstance that, if these fevers are found in India and China, they probably occur in other warm countries. Crombie divides them into simple continued fever, low fever, and non-malarial remit- tent. To these I would add yet another which, from experience in China, I regard as a distinct clinical entity, and which from its peculiar feature I would call double continued fever. Simple < oiifiiioic <| fever—Simple continued fever generally, if not invariably, commences with a rigor, the temperature rapidly or more slowly mount- ing to 104°, 105°, or even 106°. There is headache, malaise, a white furred tongue, anorexia, thirst, and perhaps vomiting. The fever lasts usually from three to eight days; occasionally it is prolonged for two, three, or four weeks. Crombie remarks that these cases are particularly common in towns, and are known locally as Bombay fever, Calcutta fever, and so forth. It might be suggested that such fevers are mild or aborted typhoid ; but in the complete absence of the characteristics of enteric, the insigni- ficant mortality, and the absence of complications, so grave a diagnosis does not seem to be justified. It is customary to attribute them to heat, chills, change of season, acclimatisation, irregularities in diet, exposure to the sun, and the like. As to how far these aetiological speculations are correct, it is hard to say. Eow fever—Like the preceding, this type of fever is not an unusual one among Europeans in the tropics. Its characteristics are indefinite duration- weeks or months—a persistent though slight rise of Non-Ma la rial Re mi ttent. temperature—rarely above 101-5°, but never below 99', anorexia, debility, loss of flesh, and a tendency to bilious diarrhoea. It is unrelieved by quinine or arsenic ; but it almost invariably responds to a change of air, especially to a trip to sea. Non-malarial remittent—Crombie remarks that it is a pity we have no better name for this fever, which is of very frequent occurrence in India, and is one of the most fatal of the fevers there. Remittent is a misnomer, for the symptoms are even less remit- ting than those of typhoid. The temperature runs high, touching 104° or 105° for a long part of its course. It begins not unlike simple continued fever. By some it is considered a variety of typhoid, not- withstanding the absence of many of the symptoms of that disease. Hepatic enlargement and congestion are early and constant conditions ; but the spleen, as a rule, is not distinctly enlarged. " Bilious diarrhoea, in no respect resembling the diarrhoea of typhoid, is also a very frequent symptom. Quinine—often given in large and repeated doses in these cases—is not only not useful but so obviously adds to the distress of the patient, without in any way producing an improvement in the progress of the symptoms, that it is very soon abandoned. Mean- while, the temperature continuing persistently high, marked head symptoms, especially delirium of a muttering and irritable kind, come on, and the patient may even, and often does, pass into a con- dition of coma from which he can hardly be roused. This condition of persistent high temperature without marked remission, a distinctly enlarged and congested liver, bilious diarrhoea, congestion of the back of both lungs, and a low, muttering delirium, is generally reached by the eighteenth to the twenty-fourth day. If coma supervenes, the patient frequently dies about this period. In more favourable cases, where the symptoms are less severe, they may continue for a week or two longer. In such the average duration of the case is six weeks " (Crombie). 2l8 Unclassed Fevers. Crombie, although he has seen this fever in Europeans, regards it as being essentially a disease of natives. It is un- common after thirty, but is frequent enough in childhood. Double con- tinued fever.—In South China I en- countered, both in Amoy and in Hong Kong, a peculiar type of fever, ap- parently of little gravity as affecting life, but sufficiently distressing while it lasted. It was characterised by an initial pyrexial stage of from ten days' to a fortnight's duration, followed by a stage of from three to seven days' rela- tive or absolute apyrexia which, in its turn, was suc- ceeded by another spell of about ten days' duration of smart fever, and then by convalescence (Fig. 23). Both in the primary and in the terminal fever the evening temperature may rise to 104° or 104-5°. It might be said that such cases Double Continued Fever. 219 were relapses of simple continued fever ; but as I have, on at least two occasions, seen the same succession of events occurring almost simultaneously in two patients living in the same house—once in husband and wife, and once in brother and sister—it seems probable that this is a special form of disease, and that the double fever is a constant and characteristic feature. In the case of the brother and sister the march of their fevers was strictly simultaneous, the primary fever, the apyretic interval, and the terminal fever oc- curring in both patients on the same days. Beyond a certain amount of headache and febrile distress there are no special symptoms, so far as I have been able to observe, nor any special complications. Diagnosis.—The diagnosis of these imperfectly differentiated fevers is always a difficult matter, speci- ally so during their early stages. On the one hand, among other possibilities that of typhoid, and on the other that of malaria, have to be considered. The persistent absence from the blood of the plasmodium and of pigmented leucocytes, if vouched for by an experienced observer, and the negative results attend- ing subsequent administration of quinine, together with the absence of marked periodicity in the symptoms, of pronounced anaemia and of marked enlargement of the spleen, should be decisive against malaria. But, in the present state of our knowledge, it is very hard indeed to exclude typhoid until the case is well advanced. It may be that further experience of the Widal blood test will establish its title to be regarded as an absolutely pathognomonic sign of the presence of Eberth's bacillus. In this event the practitioner will have in his possession an invaluable aid in the diagnosis of tropical fevers. As things are at present, in cases in which there is the slightest doubt it is an excellent rule to regard all doubtful fevers as being possibly typhoid. Treatment___It is well at the commencement of doubtful tropical fevers to be as guarded in treatment as in diagnosis, and to eschew active purgatives, to 220 Unclassed Fevers. enjoin rest in bed, to place the patient on a bland, unstimulating fluid diet, and to confine medication to some innocent fever mixture. There is no specific treatment for any of these unclassed fevers. Each case has to be dealt with on its own merits and on general principles. Headache may be relieved by cold applications to the forehead, by an ice cap, or, especially if temperature rises high, by sponging and, if not otherwise contra-indicated, by occasional doses of antipyrin or some similar drug. If quinine, on the supposition that the case is malarial, has been freely tried, and without benefit, it must not be persisted with. As already stated, "low fever" should be treated by change of air, and more especially, where feasible, by a trip to sea. 221 SECTION II.-GENERAL DISEASES OF UNDETERMINED NATURE. CHAPTER XIV. BERIBERI (KAKKE, BARBIERS). Definition.—Beriberi is a specific form of multiple peripheral neuritis occurring endemically, or as an epidemic, in most tropical and sub-tropical climates, and also, under certain artificial conditions, in more temperate latitudes. The mortality is considerable, sometimes very high, death being usually dependent on heart paresis. Historical.—The special nature of beriberi was recognised by the Dutch in the early years of their intercourse with the East. Later, it was studied by British physicians in India, particularly by Malcom- sen, Carter, Waring, and Morehead. It was not until the widespread epidemic in Brazil, to be alluded to presently, that beriberi began to receive attention from the present generation of medical men ; and it was not until Mr. Anderson, of St. Thomas's Hospital and then of Tokio, Japan, Dr. Simmons of Yokohama, and Professors Scheube and Baelz, also of Tokio, took the matter up that it was studied by modern methods, accurately denned, and its pathology correctly appre- hended. Scheube and Baelz were the first distinctly to show that beriberi is of the nature of a specific peripheral neuritis similar to that of diphtheria or alcohol, a view which was subsequently confirmed and adopted by Pekelharing and Winkler and by many other observers. 222 Beriberi. Ideographical distribution.—The area of the endemic distribution of beriberi is co-extensive probably with the tropical and sub-tropical belts; doubtless it exists in many places where its presence is not generally suspected. It is the scourge of many of the mines and plantations of the Malay and Eastern Archipelagoes. It is apt to break out among the coolie gangs engaged on extensive engineering works in the tropics, such as the Panama Canal or the Congo railway. It haunts the Dutch army in Sumatra, and used to be common enough, until better hygienic methods prevailed, in the British armies in India. It is at home in many parts of Japan, particularly in her large, low-lying, damp, over- crowded cities. It is prone to break out in jails, in schools, in ships. Sometimes, as an epidemic wave, it passes over a tropical country, as was the case in Brazil in the early 'sixties, where it still lingers. Sometimes sporadic cases crop up here and there; although generally, when it does appear in a place, it attacks large numbers, picking out par- ticular houses and districts. Lately we had an account of a small epidemic among a group of Western Australian natives, and also, among Chinese on the eastern seaboard of Australia, a continent where beriberi was formerly supposed not to exist. Similarly, it appeared lately, apparently for the first time, in Fiji. A little while ago I saw a case of beriberi from Lake Nyassa, another from the Upper Congo, another from Hayti. We hear of it also from Havana, from New Caledonia, from the Sandwich Islands—all of them places not before known to be liable to this disease. So that the area is, as I have said, probably a very extensive one. Indeed, within the last few years it would seem that it includes the temperate as well as the tropical zones. Recently beriberi showed itself in a lunatic asylum in Ireland—Richmond Asylum, Dublin—and something like it has been seen in lunatic asylums in the United States, and also among the fishermen on the North American coast. Symptoms. 223 Symptoms.—Medical visitors to the native hospitals in many parts of the tropical world are likely to have their attention arrested by the large proportion of cases of partial paraplegia, of cases of oedema of the legs, and of cases of general dropsy. These, for the most part, are cases of beriberi. Paraplegic cases. —On examining one of the paraplegic cases referred to (Fig. 24), it will be found that, besides paraplegia of greater or lesser de- gree, there is a certain amount of anaesthesia or of numbness of the skin; particularly of the skin over the front of the tibiae, the dorsa of the feet, the sides of the thighs, perhaps also of the finger tips, and of one or two areas on the arms and trunk. The visitor may be struck with the thinness of the pa- tients' calves, the flabby state of the gas- trocnemii; and by the fact that if, whilst making the examination, he should handle these and the neighbouring muscles somewhat roughly, par- ticularly if he should squeeze them against the underlying bones, the patient will call out in pain and try to drag the limb away. The thigh muscles, likewise, may be found to be similarly tender, and so Fig. 24. -Beriberi [Bentley). 224 Beriberi. may the thenar, the hypothenar, and the arm muscles ; like the calf muscles, these too may be wasted and flabby. Very probably there is a loss of fat as well, the panniculus adiposus being everywhere very meagre. If tested electrically, the muscles exhibit to perfection the reaction of degeneration. If the knee reflex be tested in the usual way, after the first week there will be no response whatever; nor can any clonus be elicited. As a rule, all the deep reflexes are lost ; but the superficial reflexes, unless in extreme con- ditions of paresis and muscular atrophy, are usually present and more or less active. If the patient is set to button his jacket or to pick up a pin, possibly he has a difficulty about it, or perhaps he cannot; he may bungle and fumble like an advanced ataxic. There is more than ataxia, however; for the hand grasp is so enfeebled that he may have a difficulty, on this account as well, in holding his rice bowl and feeding himself. There is no tremor of the hands; and very rarely is there any paresis of the ocular muscles, or of the muscles of the face, of mastication, of the tongue, or of the pharynx. The sphincters and bladder operate satisfactorily, and the functions of the alimentary canal are carried on fairly well, although there is often some dyspeptic distension and oppression after food. On the patient being got out of bed and started to walk, if he is able to progress at all his gait will be markedly ataxic ; but he is not ataxic merely, for, just as with the hands, it will be seen that, in addition to want of co-ordinating power, there is great muscular weakness. If he is laid on the bed and asked to raise his legs, he is perhaps hardly able to get them off the mat, to cross them, or to place one foot on the top of the other. Very probably he is the subject of marked ankle-drop, so that he drags his toes when he attempts in walking to advance the foot; he has therefore to raise the foot very high, letting it fall on the ground with a flop when he brings it down again. His ataxia and his muscular weakness, as well as the partial anaesthesia from Symptoms. 225 which he suffers, make him adopt all sorts of devices to assist him in progression (Fig. 25). Manifestly these patients are suffering from some Fig. 25.—Beriberi (Bentley). form of peripheral neuritis. But their general health is good for the most part; their tongues are clean, their bowels are fairly regular, and there is nothing amiss with the urine. Digestion, assimilation, and excretion go on fairly satisfactorily. P 226 Beriberi. The heart and circulation.—When the heart is examined, if the case be at all recent or moderately severe, attention is at once arrested. On inspection it may be remarked that the impulse is diffuse or is obscured by pericardial effusion ; that there is epi- gastric pulsation ; that the carotids throb too violently ; that there is that peculiar wobbling, pulsating move- ment in the jugulars that denotes tricuspid insuffi- ciency. On percussion the precordial area is generally found to be enlarged, perhaps very greatly enlarged, particularly to the right; and on auscultation loud bruits, usually systolic in rhythm, may be heard. Marked reduplication of the sounds, particularly of the second sound, are to be noted. The auscultator will also be struck by the peculiar spacing of the intervals between the sounds. It may be hardly pos- sible to tell by the ear alone which is the first pause, and which is the second. They seem alike in point of duration; so that the sounds of the heart are, like the beats of a well-hung pendulum clock, evenly spaced, and not, as they are in health, separated by a long and a short interval, like the beats of an ill-hung clock. It will also be observed that the heart is very irritable, becoming easily quickened by exertion. All these signs vary in degree from time to time in the same case, and differ in degree in different cases. It will be judged, therefore, that, in addition to peripheral neuritis, there is serious disease in the circulatory system, particularly in its innervation ; that there is a dilatation of the right side of the heart; and that there is a state of relaxed arterial tension. Dropsical cases—In the next bed, perhaps, to the patient whose picture I have tried to draw, may be seen another man apparently suffering from quite a different affection (Fig. 26). He is propped up in bed. Instead of being thin and wasted, as the last patient, his face is puffy and heavy ; his lips possibly are slightly cyanosed ; and his arms, hands, trunk, legs, and feet are distended with oedema. It may be thought from the appearance of the oedema that it is a case of Dropsical Cases. 227 acute nephritis, and an examination with this idea may be made of the scanty, dark-coloured urine. But this is found to be of high specific gravity, and to con- tain no albumin, or only a mere trace ; so that the case cannot be one of acute Bright's disease. Careful observation will discover that the oedema is some- what firmer than that of nephritis, and, in not a few instances, that it does not involve the scrotum. Oc- casionally cases are met with in which the oedema is peculiarly localised and fugitive. Attention is now- directed to the heart, and here a bruit is discovered, besides other evidences of dilatation of the organ and of arterial relaxation, just as in the first case. The lungs are now examined, and there, too, one may or may not discover signs of single or double hydro- thorax, although, probably, not to a very great extent. The lungs are themselves healthy. On getting him out of bed it is found that the patient can hardly walk, partly from breath- lessness, partly on account of mechanical interference by the dropsy with the movements of the legs, partly, perhaps, from some degree of paresis. He has ankle-drop possibly; 228 Beriberi. and, if firm pressure be brought to bear on the calf muscles through the oedema, signs of hyperaesthesia of the muscles may or may not be elicited. Knee-jerk is probably absent, and there is numbness of the shins and finger-tips. The tongue is clean, the appetite fair, and there is no fever. But there may be complaint of praecordial distress and even pain ; this is aggravated by a full meal, so that the patient is obliged to eat sparingly. The amount of urine is generally very much reduced—to a few ounces even. In this patient, therefore, there are the same signs of peripheral neuritis and of dilatation of the heart as in the other case. In addition, there is a somewhat firm oedema, which is not altogether cardiac; but, as its character and the circumstances in which it is found suggest, is probably connected partly with lesion of the nerves regulating urinary excretion, and partly with the play of transudation and absorption in the nutrition of the connective tissue. Mixed paraplegic and dropsical cases.— In the next bed to this patient there lies, perhaps, another case which looks like a mixture of the two preceding. There is (edema to some extent, particu- larly of the shins and feet, about the flanks and, very generally, over the sternum and root of the neck. There is numbness of the shins, there is some ataxia, there is muscular weakness and hyperaesthesia—par- ticularly of leg and thigh muscles, there is absence of knee-jerks, there is cardiac bruit, and there are signs of dilatation of the heart and relaxed arterial tension. Just as in the other cases, the general health of the patient is unaffected, the tongue is clean, the urine though scanty is otherwise normal, and there is no fever. Great variety in degree and combination of symptoms.—All through the wards of the hospital dozens of similar cases may be encountered. Some are so trifling that they are up and moving about with more or less freedom ; others are so severely smitten that they lie like logs in their beds, unable Erroneous Diagnoses. 229 to move a limb or perhaps even a finger. Some are atrophied to skeletons; others are swollen out with dropsy ; and some show just sufficient dropsy to conceal the atrophy the muscles have undergone. In some it will be noticed that the laryngeal muscles are affected, the patient being unable to speak above a whisper or to produce an explosive cough. In one or two the abdominal and the perineal muscles may be so profoundly paralysed that, when cough is attempted, at most a husky expiration is produced, whilst the belly is bulged forwards and the perineum shot down- wards by the "sudden contraction of the muscles of expiration. Erroneous diagnoses.—The novice in tropical medicine will be greatly puzzled for a time over these cases. I have seen them diagnosed as many kinds of diseases, and, until I had a little experience, have so diagnosed them myself. I have seen them called cardiac disease, locomotor ataxia, muscular rheumatism, progressive muscular atrophy, ascending spinal paralysis, and have over and over again seen them relegated to that refuge for ignorance—malaria, and called "malarial rheumatism," or "malarial paralysis," or, more pedantically, " malarial para- plegia," or " malarial neuritis."* If the visitor has the curiosity to examine the blood of these patients, possibly in a proportion of them he will find filaria nocturna, or some of the other bloodworms; very likely he will then think that the cases are forms of filariasis, and he may construct theories to explain how the filaria pro- duces the symptoms. Or, if he examines the faeces, * Dr. Strachan has described (Practitioner, 1S97, p. 477) a form of multiple peripheral neuritis which he calls " malarial." The disease is endemic, and very common in Jamaica. It differs from beriberi inasmuch as it is not attended with oedema, is frequently complicated with implication of the cranial nerves, and is rarely fatal. We have no accounts of any similar disease from other tropical countries. Probably, therefore, Dr. Strachan's neuritis is not malarial, but depends on some cause peculiar, so far as known, to Jamaica. The subject requires further study. 23° Beriberi. very probably in over 50 per cent, of the cases, or in some countries in nearly all the cases, he will find the ova of ankylostomum duodenale and, probably, those of trichocephalus dispar also, On this evidence he may conclude that these are cases of ankylosto- miasis. He had better, however, not commit himself to such a diagnosis until he has ascertained how it fares with the rest of the population as regards these parasites, for he will find that the filaria, the ankylos- tomum, and the trichocephalus are quite as prevalent outside as inside the hospital, and in the healthy as well as in the sick. Past history of patients.—On inquiry he will learn that most of, the cases come from two or three centres where similar disease is endemic—from some particular plantation, mine, or village. He will also remark that the same places supply both atrophic- paralytic cases, and dropsical-paralytic cases ; and he will also learn that many of the atrophic cases com- menced with dropsical symptoms. From this he will make the important deduction that he is dealing, not with two diseases, but with two phases of the same disease; that sometimes this disease assumes atrophic features, sometimes dropsical, features, and that some- times it is of a mixed character. Many of the patients will give a history of fever at the outset of their troubles ; in some there is a history of diarrhoea; in some the paralytic or dropsical symptoms developed very slowly; in others, again, they came on rapidly. In some there is a history of a similar attack the previous year, or a yearly attack for three or four years in succession. Some will tell that they have been ill for several months, others that they have been ill for a week or two only. Its uncertain course.—He will learn that this disease, which is beriberi, commences slowly or suddenly; that it may be preceded by a period of intermitting languor, aching legs, slowly advancing oedema of legs or face ; or that the patient may wake up some morning and find that during the night he Course of Disease. 231 has become dropsical or paretic. Thus the disease may develop slowly or rapidly. Equally uncertain is its progress and danger; within a day or a week, or at any time during its course, it may assume fulminating, malignant characters. It may completely subside in a few days, or it may drag on for months. It may get well apparently and then relapse. It may, and generally does, clear up completely; or it may leave a dilated heart, or atrophied limb muscles with corre- sponding deformity. The variety in the severity, progress, and duration of beriberi is infinite; but in all cases the essential symptoms are the same—greater or less redema, especially over the shins; muscular feebleness and hyperaesthesia, especially of the legs; numbness, especially over the front of the shins; liability to palpitation from cardiac dilatation, and to sudden death from the same cause. Progress of the cases.— As the visitor watches the progress of the cases he will be astonished that those whom he thought examples of locomotor ataxia, or of progressive muscular atrophy, or of ascending spinal paralysis, gradually improve, begin to walk about, and finally quit the hospital quite well. He will be astonished to see, after perhaps a diffuse diuresis, the bloated carcass, that could hardly turn itself in bed, rapidly shrivel to nothing but skin and bone, and assume all the appearances of the atrophic cases ; and, later, perhaps after many months, become rehabilitated, and, in due course, also walk out of the hospital quite well. He will notice that the cardiac bruits come and go; that the degree of dilatation of the heart is subject to fluctuations; that what seemed organic disease completely disappears. Cardiac attacks.—But he will also be astonished, as he goes his rounds, to see so often empty beds where the day before lay men whom he considered by no means seriously ill—certainly not dying. Some day he will come on a patient whom the pre- vious day he thought to be by no means seriously ill, actually in extremis. The poor fellow is propped up 232 Beriberi. in bed, he is struggling for breath, his face is purple, his eyes are starting out of his head, his whole atti- tude is expressive of the utmost distress ; he has a horrible, tearing, boring, crushing pain under his sternum and in the epigastrium ; the vessels of his neck are throbbing violently, his pulse is quick, small, intermittent, and his extremities are cold. In a short time the patient is dead. Some of the fatal cases, he will note, die quite suddenly as if from syncope; but most die in the distressing way described, evidently from paresis and over-distension of the right heart, com- plicated and aggravated by oedema of the lungs, or by diaphragmatic paralysis, by hydrothorax, or by hydro- pericardium. Nomenclature and classification in beriberi.—For purposes of description, the paralytic-atrophic cases are designated " dry beriberi " or beriberia atrophica ; the dropsical cases, " wet beriberi" or beriberia hydrops ; and those in which there is a combination of both conditions, "mixed beriberi." Sometimes the cases are classified according to the rapidity of development and gravity of symptoms into acute, sub- acute, and chronic. None of these classifications is good, seeing that they all refer to the same disease, and that one form may suddenly or more slowly merge into the other. ^Etiology.—Sex, age, occupation, etc.—Beriberi attacks both sexes. It occurs at all ages except early childhood and extreme old age, its favourite age being from about fifteen to thirty. It affects rich as well as poor. It is confined to no particular trade or occupa- tion ; if anything, it has a predilection for those who lead a sedentary life and are much indoors, as stu- dents, prisoners, and the inmates of asylums ; it is apt to attack pregnant or parturient females. It is quite as common in the strong and fulbblooded as in the weak and anaemic. Climatic conditions.—In countries in which there is a hot and cold season the epidemic outbreaks occur during the former, old cases improving and new .Etiology. 233 cases ceasing to crop up during the winter. In countries which are hot all the year round beriberi may appear at any time ; most frequently, however, in such climates it appears during the rains. _ Beriberi a place disease like malaria.—Everything points to beriberi being a disease of locality, in this respect resembling malaria. It further re- sembles malaria in being fostered by damp, by high temperature, and by its most often attacking those who sleep on or near the ground. As with malaria, though its explosion in any given individual residing in the endemic area may be solicited by fatigue, chill, privation, and other causes of physiological depres- sion, it is not actually caused by such circumstances. Influence of overcrowding.—Overcrowding seems to favour the outbreak of beriberi. This has, perhaps, a good deal to do with its frequency and virulence in such conglomerations of humanity as are found' in Oriental jails, schools, mining camps, plantation lines, armies, ships. Unlike malaria, it . is common enough in the middle of large cities as well as in villages and jungle land. Ship beriberi.—Unlike malaria, it is common in the native crews; more rarely, though occasionally, among the European officers and sailors of ships on the high seas and far away from any telluric influence. The crowding in the damp forecastle and the exposure in- cident to a sailor's life seem to be among, though not the only, reasons for ship beriberi. Thus this form of the disease is often seen at the Seamen's Hospitals at the Albert Docks and Greenwich among the lascars and sidi-boys of steamers trading to India, the disease appearing perhaps months after the ships had left the East, sometimes even months after they had been lying in the London docks. Some years ago a number of these cases were admitted to the Seamen's Hospital at the Albert dock. I had the curiosity to visit one of the ships from which several of the patients had been brought. I went into the forecastle. Although the weather was mild for Englishmen, it was evidently 234 Beriberi. very cold for the half-clothed lascars. They had a fire blazing in their quarters, every door, scuttle, window, and ventilator of which they had carefully closed. The place was suffocatingly hot, damp, and redolent of steaming humanity, and not very clean humanity either. I do not know how many men had stowed themselves away with their dirty rags in this place, but there was a crowd of them. Several had symptoms of beriberi, and were in their bunks. After seeing the forecastle I was taken to a little dark cell, an oblong den with a couple of bunks one on top of the other, located somewhere in the neighbourhood of the keel. There was no light, no means of ventilation, and barely standing room. There I found three men sitting on the lowermost bunk, all of them suffering from severe beriberi. One of them, I afterwards heard, died before morning; the others were sent to the hospital just in time to save their lives. The fact is that these epidemics of ship beriberi are fostered by the artificial conditions the ignorant lascars are allowed to bring about. They feel the cold of the English climate so much that, on entering British seas, they try to keep their quarters warm by lighting fires and stopping up all ventilators. By- these means they create a hot, steamy atmosphere and a sodden state of the place they live and sleep in, which is a very good imitation of the tropical con- ditions the germ of beriberi requires for its develop- ment. In other words, these lascar sailors create an incubator on a large scale, which, should it chance to contain a beriberi germ, quickly becomes extensively infected and lethal. Asylum beriberi.—Not very long ago exactly similar conditions, and with similar results, were produced by similar means in the Dublin lunatic asylum already alluded to. This asylum, built for 1,000 inmates, had 1,500 crowded into it. Any- one, who knows what the atmosphere of even a well-regulated and not overcrowded dormitory in a lunatic asylum is like, can imagine what it becomes .Etiology. 235 in warm weather, where three patients are lodged in a place barely sufficient for two. The heat, the breath- vapour condensed and streaming down the walls, the effluvia from the patients, the closed doors, the barred windows, the want of air, and the damp conspire to foster any germ of beriberi which evil chance may introduce into this incubator. These are just the conditions found in the tropics ; and when these conditions are reproduced elsewhere, even in temperate climates, on the beriberi germ being acci- dentally supplied from without the result will be just the same. Beriberi a germ disease, but probably not com- municable from man to man.—Beriberi is undoubtedly a germ disease, for, as not a few facts have shown, the cause can be transported from place to place and, on encountering suitable conditions, will multiply as only a living organism can. I do not think, however, that the germ lives as a parasite in the human body, or that it exercises its pathogenic powers in a direct way, or that it passes directly from one human being to another like the germ of the ordinary infectious or directly communicable diseases. Nurses and medical men in hospitals where, perhaps, there may be hundreds of beriberi patients, do not catch the disease; nor in hospitals located outside the endemic districts does it spread to other patients. Of course, if hospitals are themselves infective, are themselves beriberi centres, beriberi may in that case attack patients admitted for other diseases, particularly, I think I have observed, for surgical disease—operation cases; in these circumstances it may attack nurses and medical attendants. Beriberi seems to resemble yellow fever in some of these respects. Possibly caused by a toxin generated by a germ living in the patient's surroundings.—-It is often remarked that when patients are removed from the endemic spots they at once begin to improve, and may be out of danger in a few days ; whilst those who remain in the endemic area most probably go 236 Beriberi. from bad to worse, and very likely die. It is as if the place were infected by the germ, and not the in- dividual ; else, why should patients begin to mend so rapidly after they leave the locality ? It is as if some toxin were generated in the soil or surroundings, and, rising up, were absorbed constantly and day by day ; but when the spot in which the toxin is generated is quitted, and there is no longer a constant renewal of the poisoning going on, the effects, after a day or two, steadily and gradually wear out. This is not what happens where a germ is itself actually parasitic in the human body and the direct cause of disease; in such, disease and germ do not die out thus rapidly. Pekelharing and Winkler's views.-—Pekelharing and Winkler say that the beriberi germ is really introduced into the body, but as it can live there for a short time only, if beriberi disease is to be produced, fresh doses of the germ have to be con- stantly reintroduced. They have gone the length of saying that they have found the germ in question, a bacterium, in the blood; and that they have suc- ceeded in cultivating it, and in inducing in the lower animals, by repeated injections of their cultures, symptoms like those of beriberi. There are various sources of fallacy about Pekelharing and Winkler's experiments, and their conclusions have not been accepted as yet by many good authorities. Other germs.—Besides the bacilli and cocci of Pekelharing and Winkler, many other germs have been described as the cause of beriberi, but on evidence altogether insufficient. The latest I have heard of is one fathered by Glogner, who says that the germ is an amoeba—something like the malarial parasite in appearance and habits, and, like this, living in the red blood corpuscles. I have many times looked for bacteria and micro- scopic parasites in the blood of beriberics, hitherto without success. Nitrogen starvation theory.—A favourite theory ^Etiology. 237 some time ago was to the effect that beriberi was due to nitrogen starvation—to deficiency of nitro- genous elements in the dietary. In former years, beriberi used annually to attack quite one-fourth of the personnel of the Japanese navy. Now it is almost unknown in that service. This striking change coincided, in point of time, with the introduction into the Imperial navy of an improved ration, in accord- ance with a suggestion from Takaki who entertained this view about the influence of deficient nitrogen in food. It was inferred from the success following the change that the improvement in the health of the sailors was attributable to the increased amount of nitrogen in the new dietary. But the improve- ment could have been no more than coincidence; or, at most, the influence of the increased supply of nitrogen could only have been subsidiary. There were other hygienic reforms introduced about the same time as the improved dietary ; these, doubtless, had their favourable influence. If we examine all the circumstances, we shall find that the nitrogen starva- tion theory does not tally with the facts of the peculiar geographical distribution of beriberi, its peculiar local limitations, its affecting rich as well as poor, its appearing in some houses and not appearing in neighbouring houses, and many other facts. For example, during an epidemic of beriberi in Singapore jail the male side of the prison was decimated, whilst not a single inmate of the female side was attacked, although both classes of prisoners had the same food and drank the same water. The only hygienic differ- ence ascertainable between the two sides of the jail was, that whereas the male side was damp the female side was dry. Various erroneous theories as to the causation of beriberi.—At one time Indian writers seemed somehow to have lost hold of this disease. Probably this was owing to its disappearance from the army there. As a consequence, the nature, and even the clinical features, of the disease came to be misunderstood; so that in 238 Beriberi. several works on Indian diseases it is stated that beriberi is of the nature of an anaemia, in others that it is an expression of scorbutus, in'others, again, that it is a form of ankylostomiasis. These views are absolutely erroneous, and have been amply refuted in Burma, in the Straits Settlements, in Japan, and in many other places. Haemocytometric observations have shown that anaemia, if it should happen to be present in a case of beriberi, is in no relation, except an accidental one, to the disease ; so with scorbutus —a disease only too common in the underfed Oriental, and therefore likely enough to concur with beriberi in a certain proportion of cases; and so with the anky- lostomum duodenale and the trichocephalus dispar— intestinal parasites which are extensively distributed throughout warm countries, in beriberi districts and in non-beriberi districts alike. In fact, beriberi has been attributed to all sorts of causes—to damaged grain, damaged fish, to rain, to wind, to heat, to cold, to rheumatism, and to many other things, amongst others, of course, like every tropical pathological puzzle, to malaria. The germ viewed as a saprophyte.—My idea about the matter is, as I have said, that beriberi is a germ disease ; that the germ resides in the soil, in the houses and surroundings of beriberi spots ; that it there distils a poison which, on being absorbed by man, produces neuritis, much in the same way that alcohol does. The soil is the infected medium ; the man residing on it is poisoned, not infected. In the case of alcoholic neuritis—so like beriberi—the germ of the disease is the yeast plant; the culture medium, the saccharine solution ; the toxin, the alcohol. The alcohol germ may be swallowed with impunity; not so the toxin it generates. So with beriberi: its germ lives in the soil; it produces some kind of toxin there; and this toxin, being inhaled or swallowed by man, produces in him a specific neuritis; and, just as man can carry the yeast plant from one place to another, so may he carry the beriberi germ. So Pa thology. 239 far as I have been able to interpret them, this is the only hypothesis which fits in with all the facts of the case. Morbid anatomy and pathology.—There is very little to be said about the post-mortem appear- ances in beriberi which is not covered by the accepted descriptions of the lesions of peripheral neuritis. Central changes have not been made out with certainty, but there is a degeneration of the peri- pheral nerves—more especially of the distal nerves, and there is secondary atrophic degeneration of muscle, including that of the heart, which may be the subject of an acute fatty degeneration like that of diphtheria. If there is anything peculiar about the post-mortem appearances in beriberi, it arises from the somewhat special implication of the central and peripheral organs of the circulation—namely, dilata- tion of the heart, especially of the right side, and great accumulation of blood in the right heart and in the veins. In addition there is a marked liability in many cases to serous effusion into the pericardium, pleurae, peritoneum, and cellular tissue. This liability to serous effusion, and the tendency to cardiac dila- tation, may be said to be more or less distinctive of the beriberic neuritis as compared with other forms of multiple neuritis. It doubtless depends especially on vaso-motor disturbances, although car- diac weakness and partial suppression of urine may be contributory elements in its production. (Edema of the lungs is also not uncommon and has, probably, a similar pathology to the connective tissue oedema. There is no nephritis. Mode of death.—The most practically important point in the pathology of beriberi is that which relates to the modes of death. The paresis and the atrophy of the voluntary muscles, the oedema of the connective tissue, and the serous effusions are, as a rule, not -very serious matters—at all events as affecting life. But it is very different when paresis and degeneration seriously implicate the heart and the muscles of 240 Beriberi. respiration. In nearly all beriberics there is heart trouble arising, doubtless, from implication of the pneumogastric nerve and the cardiac plexus. In some patients the degree of implication is slight, but in others it is sufficient so to weaken the heart that death is in- evitable. We cannot be quite sure in what cases the pneumogastric implication is likely to be serious, or in what cases it is likely to be slight. Often the mildest cases of beriberi, as judged by the degree of voluntary muscle paresis, or by the amount of oedema, are in reality the most dangerous. There appears to be an element of chance determining the nerves which the poison picks out. Sometimes one may see a case which is completely paralysed so far as legs and arms are concerned, and perhaps wasted to a skeleton; and yet this same patient may never have a serious symptom referable to his heart, or in any way threatening life. On the other hand, one may see a patient with very little paresis, very little oedema, and yet in a short time the heart may become involved, and he will die in a few minutes or hours. I presume the dilatation of the heart, the usual cause of death in beriberi, is favoured or brought about by a concatenation of several conditions; by the degeneration of the muscle fibre following nerve destruction, by imperfect systole in consequence of an interrupted nerve supply, by obstruction to capillary circulation in consequence of vaso-motor paresis both in the pulmonary and in the general circulation. Once commenced, the cardiac dilatation tends to increase of itself; for the more the organ dilates, the more difficult does it become for it to contract, the greater the in- competency of the valves, and the more the blood stagnates in and over-distends it. The organ enters on a vicious pathological circle. Finally it becomes so distended that, like an overstretched bladder, it loses the power to contract altogether. The blood then rapidly accumulates in the great veins, the right auricle and ventricle are distended almost to bursting, and death is inevitable. This result is often Prognosis. 241 contributed to by the co-existence of pleural effusion, hydropericardium, paresis of the diaphragm, over- distension of the stomach by food or gas, and, above all, by oedema of the lungs. It can readily be under- stood how the establishment of any additional obstruc- tion of this description would still further tax the dilated, enfeebled heart, and determine the fatal issue. When we come to make a post-mortem in these cases we may find a heart slightly hypertrophied and enormously dilated, the right cavities distended with blood, the lungs and liver full of dark blood, and all the great veins engorged. Prognosis.—This tendency to dilatation of the heart is the dangerous element in beriberi; it should always be before our eyes, and dominate our plans of treatment. It is wonderful how rapidly it may come on, and how rapidly it may prove fatal. These sudden deaths, occurring sometimes from syncope—from in- stantaneous failure, as well as from the somewhat slower process of increasing over-distension—are con- stantly sprung on one in this disease. An absolutely favourable prognosis, therefore, ought never to be ventured on in even the mildest-looking case of beri- beri, or so long as the patient is in the endemic area, or so long as the disease appears to be active. That is a lesson which is often, and sometimes painfully, borne in on the practitioner in beriberi districts. Evidences of grave heart implication, such as pulsating cervical vessels, equal spacing of the intervals audible on auscultation, enlargement of cardiac dulness—especially to the right, epigastric pulsation, a rapid feeble pulse, cold extremities, cyan- osis, dyspnoea, are significant of danger. Paralysis of the diaphragm, of the intercostal muscles, extensive serous effusions, very scanty urine are also unfavour- able signs. Vomiting.—No one can say when or how soon fatal implication of the pneumogastric and other car- diac nerves may take place, but vomiting is always an ugly and threatening symptom in beriberi; it Q 242 Beriberi. probably indicates that the former important nerve is being attacked. The Japanese, who have much ex- perience of beriberi, regard the occurrence of vomiting as of fatal import. Prognosis is improved if the patient is early removed (that is before' the heart muscle, or the cardiac or respiratory nerves, are gravely degenerated) from the place in which the disease was contracted, to a healthy, non-beriberic, high-lying locality. Mortality.—The mortality in beriberi varies in different epidemics and in different localities. On the whole, it is greater in low than in high latitudes, in the dropsical than in the atrophic forms, in the acute than in the chronic. In some epidemics it is as high as 30 per cent, of those attacked; in others as low as 5 per cent. Diagnosis.—Usually the diagnosis of beriberi is not difficult. Multiple peripheral neuritis occurring as an epidemic, or in a place or ship on which the disease had occurred on some previous occasion, as a rule, may be set down as beriberi. Sporadic cases may be difficult to diagnose, more especi- ally if there is a history of alcoholism. The presence, actual or past, of oedema—especially of oedema over the shins—and palpitations and other evidences of cardiac implication, are significant of beriberi. It must be borne in mind that slighter degrees of beriberic poisoning, evidenced only by slight analgesia of the pretibial skin area, by slight oedema of the same region, by slight hyperaesthesia of the calf muscles, and, perhaps, by impairment or absence of knee-jerk, may be all the symptoms present. True rheumatism is rare in the tropics. Among natives, especially if their language is not understood, complaints of what may seem to be but rheumatic pains in the legs should always be carefully investigated, the knee-jerks tested, and signs of hyperaesthesia of the calf muscles sought for. The significance of these signs, of what may be described as larval beriberi, is too frequently Treatment. 243 overlooked until some sudden death, which, with earlier recognition of the disease, might have been avoided, puts the practitioner on his guard. All paretic affections, all cases of oedema, all cases of palpitation, and all cases of rheumatic-like pains occurring among the natives of warm climates, there- fore, should suggest the possibility of their being beriberi, and also the necessity for a detailed exami- nation with this possibility in view. Treatment.—The first and most important thing to be attended to in the treatment of a case of beri- beri is the removal of the patient from the building, camp, or ship in which the disease was contracted. His condition warranting transport, if possible the patient must be got out of the endemic district. To leave a patient suffering from beriberi in the spot where he contracted his disease, is to leave him to continue absorbing the toxin that caused it; it is like allowing the victim of alcoholic neuritis to go on drinking. It is hardly possible for him to get well in such circumstances; it is often—in bad epi- demics nearly always—tantamount to condemning him to death. He should be removed to some dry locality ; and, if such is available, sleep well off the ground in a thoroughly ventilated, sunny room situated in an upper storey. He ought to clothe sufficiently and feed well, taking care that the food is not of a bulky character, and that it contains a sufficiency of nitrogenous elements. Rice is found to be a bad food for beriberics ; it is too bulky. Wheat flour is better, so is oatmeal; beans of different kinds seem specially suitable for these cases, as they are cheap, and contain much nitro- genous matter in a small compass. Animal food must enter into the dietary in reasonable amount. Milk and eggs are beneficial. The worst cases, par- ticularly if there is any sign of serious cardiac implication, should remain in bed; jbut the mild cases had better spend the greater part of the 244 Beriberi. day in the open air- If the disease break out on shipboard, the crew—healthy and sick alike—should be kept out oE the forecastle, and, so far as possible, made to sleep on deck, properly protected from the weather by an awning. The seriously affected patients should take little fluid, and, with a view to diminish to some extent the bulk of blood in the vessels and heart, the bowels should be kept free by some saline aperient. In cardiac cases small doses of digitalis or of stro- phanthus seem to do good. Should signs of acute cardiac distress appear, full doses—three, four, or five drops of the 1 per cent, solution of nitro-glycerine— are indicated. This must be repeated every quarter or half hour, and kept up until the threatening symptoms pass away. In suddenly developed cardiac attacks inhalations of nitrite of amyl, pending the opera- tion of the nitro-glycerine, may be given. It is well that these two drugs be in the hands of properly instructed ward attendants, so as to meet cardiac complication on its earliest appearance. There is often no time to send for the doctor. Should, in spite of these means, signs of cardiac distension and failure persist and increase, there must be no hesitation in bleeding the patient, taking eight to ten ounces from the arm if it will flow, or, this failing for any reason, from the external jugular. Often, as the blood flows, rapid amelioration of the alarming condition sets in, and the patient is, for the time being, tided over an acute danger and given another chance. The bleeding should be re- peated if the alarming symptoms recur, as they are pretty sure to do. Oxygen inhalations, if available, are worth trying in cardiac attacks. Pleural and pericardial effusions should be sought for, and, if deemed to be interfering in the slightest degree with the circulation or respiration, drawn off with the aspirator. Provided the patient has been removed from the spot where he was being poisoned, and provided Treatment. 245 he can be tided over the first few days, he will probably recover; but in a serious case, should he remain in the place where his disease was acquired, though he may get over one or two cardiac attacks, the risk to life in bad epidemics is very great indeed, and he will almost surely die. For the atrophy of the muscles and anaesthesia of the skin, faradisation and massage are of great service, and should be employed so soon as the muscular hyperaesthesia has subsided—not before. Strychnine, arsenic, and nitrate of silver are in repute as tonics in these circumstances. Care should be taken that permanent deformity does not occur from contraction of muscles. Foot-drop should be counteracted by Phelps's talipes splint with an elastic accumulator, and any other threatening deformity appropriately met. Relapses must not be risked by a return to the original source of infection. A sea voyage has often a marvellously restorative effect. When beriberi breaks out in a school, jail, or similar institution the place should be emptied of its inmates as soon as possible ; at all events, those parts of the building in which the disease has appeared ought to be cleared out and not reoccupied until they have been thoroughly cleansed, disinfected, ventilated and dried. Overcrowding must be strictly avoided. Ventilation must be effective. The dietary should be revised and, if necessary, have rice eliminated from it as much as possible ; in the place of rice, meat, flour, or beans should be substituted. All the inmates should be obliged to pass a considerable time of every day in the open air ; their knee-jerks should be tested, and their legs examined for numbness, oedema, and muscular hyperaesthesia from time to time. Any suspicious case should be removed at once. Should beriberi appear on board ship, besides the precautions already indicated, special means of dis- infection must be employed. Rotten planking and bilge-water must be removed from the quarters of the crew ; the sound woodwork should be scraped and 246 Beriberi. painted; disinfectants should be freely and frequently employed; clothes and sea-chests washed, and every means necessary to destroy lurking germs vigorously practised. In beriberi countries low-lying, damp situations should be avoided as building sites. The sleeping quarters, especially, should be raised well off the ground, and located, if possible, in an upper storey ; all rooms should be so arranged as to be easily flushed with fresh air and flooded with light. 247 |CHAPTER XV. EPIDEMIC DROPSY. Definition and description.—A specific, epi- demic, communicable disease running its course in from three to six weeks, and characterised by the sudden appearance of anasarca, preceded in most instances by fever, vomiting, diarrhoea, or by irrita- tion of the skin ; and often accompanied by a rash, by fever of a mild, remitting type, by disorder of the bowels, and by pronounced anaemia. The case mortality varies from 2 to 40 per cent., death being sudden and depending upon oedema of the lungs, hydrothorax, hydropericardium, or other pulmonary and cardiac complications. History and geographical distribution.— The foregoing is a concise description, drawn princi- pally from McLeod's account (Trans. Epidem. Soc. Lon. N.S., vol. xii.) of a disease which appeared -in Calcutta, it is believed for the first time, in the cold weather of 1877-78, of 1878-79, and 1879-80. On each occasion it disappeared with the advent of the hot weather. The same disease broke out at Shillong, Assam, 5,000 feet above the level of the sea, in October, 1878 ; at Dacca in January, 1879 ; at south Sylhet, in the cold weather of 1878-79; and in Mauritius (Lovell and Davidson), having been im- ported from Calcutta, in November, 1878. There are no trustworthy accounts of its occurrence else- where, although certain vague statements seem to indicate that it appears at times in other parts of India. In Mauritius it prevailed until June, 1879, attacking about one-tenth part of the coolie popula- tion, of whom 729 died, a mortality of about 2 or 3 248 Epidemic Dropsy. per cent. At Sylhet there were no deaths ; at Shillong the mortality was also insignificant; but in Calcutta the death-rate in those attacked was estimated as high as 20 to 40 per cent. Coolies and natives were alone affected; Europeans enjoyed a complete immunity. In Calcutta the disease was confined to a particular quarter ; here it attacked families and groups of people, slowly extending its area, but at no time becoming generally epidemic throughout the city. The disease has not recurred in Calcutta since 1880 : at all events, if it has done so it has not been recognised. Special symptoms.—Dropsy was almost in- variably present. It usually appeared first in the legs, and in some instances was confined altogether to the lower extremities ; in others it spread and involved the entire body. Occasionally it was very persistent, lasting and recurring even after the patient was well in other respects. Fever was also a very constant symptom ; some- times it preceded, sometimes it accompanied, some- times it succeeded the dropsy. It was rarely high, ranging usually from 99° to 102° ; in a few cases —possibly from malarial complications—it reached 104°. Rigors were rare. Diarrhcea and vomiting generally ushered in the disease in the Mauritius epidemic. In Calcutta these symptoms were not so frequent, although they were by no means rare there, occurring at both the earlier and later stages. Dysentery was common in the Calcutta epidemic. Nervous symptoms—such as burning, pricking, itching, and feelings of distension of the skin, and sometimes limited to the soles and feet— often preceded the dropsy. Distressing aching of muscles, bones, and joints, worst at night, was usual. Anaesthesia of skin areas and paresis of muscles were never observed in Mauritius. Harvey re- marked two cases in Calcutta exhibiting doubtful paretic symptoms ; these are the only two recorded Symptoms. 249 in which there was anything resembling the paretic symptoms usually so prominent a feature in beriberi. An exanthem, erythematous on the face, rubeolar on the trunk and limbs, was frequently seen in Mauritius, less frequently in Calcutta. It appeared about a week after the oedema, and lasted from ten to twelve days. Circulation and respiration. — Disturbances of the heart and circulation were prominent features in nearly all the cases. The pulse was weak, often rapid and irregular; cardiac bruits were also noted. Breathlessness on exertion occurred in all cases; severe orthopnoea in many. Signs of pleural and peri- cardial effusion, of oedema of the lungs or pneumonia, and of cardiac dilatation were common in Calcutta. Anaimia was usually present and marked ; so were wasting and prostration. Scorbutic symptoms occasionally showed themselves. The liver, spleen and kidneys were not specially affected. The urine was rarely albuminous. Morbid anatomy.—Beyond general oedema and occasional pleural and pericardial effusion, nothing special was remarked post-mortem. .Etiology.—Both sexes were attacked; children under puberty were less liable than adults ; sucklings were seldom affected. The weak and the robust were equally susceptible. There are no observations on the germ of the disease ; there is distinct though indirect evidence, however, of its portability and of its com- municability. But as to whether it is directly com- municable from man to man, or whether it, or its pro- duct, is indirectly transmitted through some unknown medium, has not been determined. Evidence of its capacity for remaining latent for a considerable period is supplied by the history of the successive epidemics in Calcutta. The disease could not have been a very catching one, seeing that no medical man was attacked, and that, except in the case of Mauritius, it spread but slowly. Identification.—McLeod, after a careful analysis 25° Epidemic Dropsy. of all the available evidence, concludes that epidemic dropsy is a disease sui generis. At the time of its occurrence in Calcutta many of the physicians there looked upon it as a form of beriberi; and, indeed, in many respects it resembles very closely those cases of beriberi in which dropsy is a prominent symptom, and in which the nervous phenomena are slight or altogether absent. But in epidemics of beriberi such cases are the exception—in fact, are very rare, and always concur with others in which nerve symptoms are pronounced, and with purely atrophic cases; such were not seen in either the Calcutta or the Mauritius epidemics. In epidemic beriberi the mortality is much higher than it was in the Mauritius, the Shillong, or in the Sylhet epidemics. Furthermore, beriberi is a much more chronic disease, is not accom- panied by an eruption, and but seldom with well- marked fever. Treatment.—In the absence of anything like precise knowledge of the cause and pathology of epidemic dropsy, treatment must be entirely symp- tomatic. Mild purgatives, the exhibition of digitalis when there is evidence of cardiac weakness, and the occasional use of the nitrites in the fits of apnoea, might prove serviceable. During convalescence iron and arsenic are indicated. 25' CHAPTER XVI. NEGRO LETHARGY, OR THE SLEEPING SICKNESS OF THE CONGO. Definition.—A disease, so far as known, limited to tropical W'est Africa. It is characterised by a peculiar and slowly increasing lethargy, and by other morbid nervous phenomena. After a chronic course it probably invariably terminates in death. Geographical distribution.—In West Africa between Senegambia to the north, and the Portuguese territory to the south of the Congo, there occurs among the natives of certain districts a peculiar disease characterised by a gradually deepening lethargy and somnolence and other cerebral symptoms which culminate in death. Locally this disease is known as " the sleeping sickness." Its distribution in the endemic area is peculiar. In some limited districts it is extremely prevalent, whilst in neighbouring districts it may be completely absent. Recent accounts from the Lower Congo tell us of its extreme frequency in that district; we have also some meagre accounts of its occurrence in the upper reaches of that river. Corre tells us that in some parts of Senegambia it is equally common. It is said to be unknown on the lower part of the Niger (Crosse), at the mouth of the Congo, at Sierra Leone, and at a good many other places in the general endemic area. Its visitations seem to come and go. After decimating a village it may quite disappear for a time, migrating temporarily, as it were, to some neighbouring village. Accurate in- formation is wanting on this, as on many other matters relating to this interesting disease. This 252 Sleeping Sickness. much, however, is known—that it is an endemic which is liable to epidemic outbursts. So great is the terror of the natives, when the disease appears among them, that they may even abandon their villages. A peculiarity about sleeping sickness lies in the fact that, although it can be acquired in certain places only, the symptoms of the disease may appear for the first time in quite another country, and many years (up to seven the negroes say) after the endemic region has been quitted. For example, a native of the endemic area may leave his country, make a voyage to England or to the West Indies, reside there apparently in good health for several years, and then, at the end of this term, exhibit for the first time the characteristic symptoms, and ultimately die of the disease. In the days of the slave trade sleeping sickness was frequently seen among the negroes in the West Indies ; but it was never seen in negroes who were born in the West Indies and who had never visited Africa, being met with only in those who had come from, or had resided at one time in, the latter continent. Therefore although the symptoms may develop anywhere, the cause of the disease must be strictly endemic. Sleeping sick- ness is not exclusively confined to the negro race, but only to the negro country. It has been seen in mulattos and in Moors, possibly in Europeans. It is unknown as an endemic in the north, east and south of the African continent, being limited appar- ently, as already indicated, to the basins of the Senegal, the Niger, the Congo, and the minor inter- mediate rivers. Symptoms.—Sleeping sickness begins very in- sidiously. Those who are familiar with the disease are said to be able to recognise it in its earliest stages. The patient acquires a peculiar listless and morose manner, a somewhat melancholy expression of countenance, a certain fulness and puffiness about the face, a drooping of the upper eyelids ; he or she is liable to headache, to attacks of vertigo, to evanescent J Symptoms. 253 flashes of fever, sometimes to diarrhoea and other intestinal disturbances. By-and-by, after a variable period of weeks or months, he begins to experience feelings of excessive lassitude, and of disinclination or of inability for the daily task; generally, too, there is a desire and liability to fall asleep at unusual times. He may fall asleep while at work, while at his amusements, and even while he is eating. He is readily fatigued ; when he does speak, he complains of his weakness. He appears to feel chilly, for he likes to lie about in the sun. The lethargy and somnolence get better and worse; on the whole, they tend slowly to become aggravated. By-and-by, the patient seeks to seclude himself; he ceases to take a part in conversation, although, when obliged to speak or to answer a question, he may do so intelli- gently enough. Gradually he becomes more silent, more taciturn, and he sleeps, or, rather, appears to sleep, almost constantly. If he is forced to walk or move about, he does so as if half awake or as if intoxicated, staggering about. His temperature may be sometimes elevated during the attacks of irregular fever; at other times, and generally, it is distinctly subnormal. Limited patches of cutaneous anaesthesia may sometimes be discovered. A certain amount of muscular tremor is now observed, and muscular power diminishes. He takes to bed or lies about in a corner of his hut, indifferent to everything going on around him, though still able to speak and to take food when it is brought to him. At this more advanced stage, however, he never spontaneously enters into conversation or even asks for food. As torpor deepens he forgets even to chew his food, falling asleep, perhaps, in the act of conveying it to his mouth, or with the half-masticated bolus still in his cheek. In other respects his health seems good. When he can be got to eat, the food is digested and properly assimilated. There is no wasting at first, and faeces and urine are regularly voided. As time goes on, however, he begins to lose flesh ; muscular 254 Sleeping Sickness. tremor, in the hands and tongue especially, becomes very marked, and clioreic movements may occur in one or more limbs. He may be seized with localised or more general convulsions, which are apt to be followed by paralysis of the convulsed part. Later, bed sores begin to form, and the lips swell and saliva dribbles from the mouth. Gradually lethargy deepens, nutrition fails, the body wastes, bed sores extend, and, finally, the patient may become comatose and so die; or he may sink from slowly advancing asthenia. Possibly he is suddenly attacked with general and fatal convulsions. Such is the ordinary course of sleeping sickness ; but its manifestations are subject to considerable variation. Occasionally it seems to be arrested in its progress; though, very generally, once established, it proceeds to the fatal issue without material altera- tion for the better. Mania, occasionally noisy or violent, sometimes occurs; this, and other psychical and physical symptoms like those in the general paralysis of the insane, are not unusual in the earlier stages. There are one or two additional symptoms, not referable to the nervous system, which are frequently observed in sleeping sickness ; one is enlargement of the cervical glands; another is a papulo-vesicular eruption, especially pronounced in the chest, and attended with intense pruritus. The skin as a whole becomes dry, lustreless, and scurfy, and the hair is said to acquire a reddish tinge. In those instances in which the points have been investigated the fundus oculi has been found normal, the superficial reflexes active, the deep reflexes some- what exaggerated. The duration of sleeping sickness is very variable; it may be anything from four months to as many- years, a good deal depending on the way in which the patient is tended. Pathological anatomy.—Manifestly, sleeping sickness is a brain disease, although hitherto no /Etiology. 255 morbid appearances in connection with the nervous system, or with any organ, sufficient to account for the symptoms, have been discovered. .Etiology.—Sleeping sickness affects either sex and any age, and appears to be in no way influenced by occupation, temperament, food, or heredity. It has been attributed, on altogether insufficient grounds, to many things; but the true cause has not been definitely ascertained. Remarking the singular correspondence which seems to obtain in the distribution of this disease and that of filaria perstans, and the well-ascertained facts that the disease may declare itself, and that this parasite can remain alive, years after the endemic area has been quitted, I have suggested that filaria perstans may in some way be responsible for sleeping sickness. If this be really so, it is hard to say in what way the parasite operates. It is just possible, however, that by interfering with the nutrition of the brain, as by blocking the vessels, or by destroying some organ, such as the pituitary gland, necessary for the nutrition of the brain, the parasite, in un- known and peculiar circumstances, may bring about this singular disease. As a matter of fact, I have found filaria perstans in several cases of sleeping sickness, and the parasite is now known to be ex- ceedingly prevalent in a large proportion of the inhabitants of the endemic districts. The subject requires further investigation. Diagnosis.—Sleeping sickness has been con- founded with beriberi ; but if it be borne in mind that the former is a disease of the central nervous system, whereas the latter is a disease of the peri- pheral nerves, such a mistake is not likely to occur. Treatment.—Purging appears to do good tem- porarily. Arsenic in very large doses has also seemed to be followed by improvement, and even by arrest. Lately, I have heard from Dr. Sims, of Stanley Falls, that hypodermic injection of testicular fluid has cured several cases. On the supposition that disease of the 256 Sleeping Sickness. pituitary gland is responsible for the symptoms— which in many respects are like those resulting from pituitary gland disease—it might be worth while to try the administration of this body in some form, on the same principle as thyroidin is given in myxcedema. If filaria perstans be at the root of the disease, care in the matter of drinking-water is indicated as a prophylactic measure. 257 SECTION IIL-ABDOMINAL DISEASES. CHAPTER XVII. CHOLERA. Definition.—An acute, infectious, epidemic disease characterised by profuse purging and vomiting of a colourless serous material, muscular cramps, sup- pression of urine, algidity and collapse, the presence of a special bacterium in the intestine and intestinal discharges, and a high mortality. History and geographical distribution.— It is probable that from remotest antiquity cholera has been endemic in Lower Bengal,* and that thence, from time to time, it has spread as an epidemic over the rest of India. European physicians observed it there in the sixteenth, seventeenth, and eighteenth centuries, but it was not until the great epidemic extension of 1817 that the disease seriously attracted the attention of the profession in Europe. In that year cholera began to spread all over Asia, extending eastwards as far as Pekin and Japan, southwards to Mauritius, and westwards to Syria and the eastern shores of the Caspian. Stopping short at Astrakhan in 1825, it did not on that occasion invade Europe. European epidemics.—In 1830 cholera visited Europe for the first time. Advancing through Afghanistan and Persia, it entered by way of Russia, * Though it is customary to speak of Lower Bengal as the home of cholera, it is by no means certain that other eastern localities have not some claim to a similar distinction—Bankok, Canton, and Shanghai, for example. Dr. Henderson, in his health reports, indicates that the disease is rarely absent during the summer months from the latter city ; the same may be said of Bankok and of Canton. R 253 Cholera. and swept as an epidemic over nearly the entire continent, reaching Britain at the beginning of 1832. During the same summer it crossed the Atlantic to Canada and the United States. This epidemic did not die out in Europe till 1839. Since that time there have been at least five European epidemics—1848-51, 1851-55, 1865-74, 1884-86 and 1892-95. Great Britain has been seriously involved in four only of these epidemics— namely, in 1832, 1848, 1854-55, and in 1866. On the occasion of the last two European epidemics, although frequently imported, the disease did not spread in Britain. America has not been so for- tunate ; for, although the 1870-73 epidemic practically spared Great Britain, it crossed the Atlantic and, entering by way of Jamaica and New Orleans, raged for a time in the United States. From a study of the march of these various epidemics, it is to be concluded that cholera reaches Europe by three distinct routes :—First, via Afghanistan, Persia, the Caspian Sea, and the Volga valley; second, via, the Persian Gulf, Syria, Asia Minor, Turkey in Europe, and the Mediterranean ; and, third, via the Red Sea, Egypt, and the Mediter- ranean. With certain exceptions, hereafter to be mentioned, there is hardly an important country in the world which has not, at one time or another, been visited by cholera in the course of some of its pandemic extensions. .Etiology.—The disease is carried by man.— The study of the various epidemics shows that in its spread cholera follows the great routes of human intercourse, and that it is conveyed chiefly by man, probably, in its principal extensions, by man alone, from place to place. In Britain and the United States, for example, the places first attacked have b en invariably seaports in direct and active com- munication with other ports already infected. In India, although the problem is much more difficult /Etiology. 259 to unravel, the influence of human intercourse in diffusing the disease in certain instances can be distinctly traced. Thus the extensive pilgrimages, so frequent in that country, are a fruitful source of its rapid spread. During these gatherings hundreds of thousands of human beings are collected together in highly insanitary conditions—as at the Hurdwar and Mecca pilgrimages. Cholera breaks out among the devotees, who, when they separate, carry the dis- ease along with them as they proceed towards their homes, infecting the people of the places they pass through. Cholera never travels faster than a man can travel ; but in modern times, owing to the in- creased speed of locomotion and the increased amount of travel, epidemics advance more rapidly and pursue a more erratic course than they did sixty years ago. Isolation secures immunity. — In the case of isolated countries the absence of active and frequent intercourse with the outer world favours immunity, even during approximately pandemic extensions. Thus, though so near to the home of cholera, the Andaman Islands have never been visited by the disease. Similarly, Australia and New Zealand hitherto have enjoyed practical exemption. The same can be advanced of the Pacific islands, the Cape of Good Hope, the west coast of Africa, Orkney and Shetland, Iceland, the Faroe Islands, and many of the islands of the Atlantic. Its unequal diffusion in the endemic and epidemic areas.—Although cholera is always present in some part of the endemic area in Bengal, it is not equally diffused there, nor is it equally common at all seasons and every year. Thus, even within this area, there are places which enjoy an absolute or a relative immunity, and there are seasons and years of special prevalence. It has also to be remarked that the season of immunity for one place may be the season for prevalence in another place, and vice versd. The same observations apply to the areas of epidemic extension. When cholera extends as an epidemic, its course r 2 260 Cholera. is often singularly erratic. Some places, apparently in the direct line of advance, are passed over, to be attacked perhaps at a later period. Similarly, certain districts of a town may be spared, while other parts of the same town are ravaged by the disease. Local conditions favouring its presence.—On the whole, it may be said that low-lying districts, particularly those along the banks of rivers, are more subject to the disease than high and dry situations; and that overcrowding and unhygienic conditions generally conduce to its prevalence. The principal and special element, however, which deter- mines the diffusion of cholera is, undoubtedly, the character of the water supply. Cholera in the main a water-borne disease, entering by the stomach.—From time to time many theories of the cause and nature of cholera have been put forward, many of them very absurd and manifestly incorrect. Most of these have now been definitely abandoned in favour of the theory that the cause of cholera is a specific germ which, in the main, is water-borne. The evidence in favour of this view may be regarded as being almost conclusive, although there is still some room for doubting whether the germ itself has really been discovered. The earliest, and still one of the most telling pieces of evidence in favour of the water-borne theory of the diffusion of cholera, we owe to the late Dr. Snow. In August, 1854, cholera was epidemic in parts of London, notably in the neighbourhood of St. Anne's, Golden Square. A child at 40, Broad Street, after an illness of three or four days, died of the disease on the 2nd of September. The dis- charges had been thrown into a leaky cesspool which, as was subsequently discovered, drained into a well only three feet away. This well supplied the neigh- bourhood with drinking water. On the night of the 31st of August cholera broke out among those who used the water of this particular well, very few escap- ing an attack. On the 2nd of September a lady died /Etiology. 261 of cholera in Hampstead. Attention was specially called to this lady's case, as hitherto the disease had not been seen in that district. On inquiry it was found that this lady had been habitually supplied with drinking water from the Broad Street well re- ferred to. She had formerly resided in Broad Street and had retained a liking for the water from this particular well. She drank some of the water which had been procured on the 31st of August, both on that day and again on the 1st of September. On the latter day she was seized with cholera. A niece, on a visit to this lady, also drank some of the same water; she, too, was attacked by cholera and died. A servant also drank the water ; although she suffered to sorire extent, she recovered. So far as could be ascertained by careful inquiry, these people had had no connection whatever with the cholera districts except through the water fetched from this particular Broad Street well. Cholera, as mentioned, was not epidemic at Hampstead at the time. The inference that the germ had been conveyed in the polluted water is difficult to avoid. Another remarkable illustration of the diffusion of the cholera germ by water is supplied by the recent epidemic in Hamburg. At the time, the hygienic conditions under which the inhabitants of the con- tiguous cities of Hamburg, Altona, and Wandsbeck lived were practically identical, save in the matter of water supply. Hamburg and Altona both drew their water from the Elbe ; but, whereas the water distributed to the people of Altona was most carefully filtered, that supplied to the people of Hamburg was simply pumped up from the river and passed directly into the mains without filtration or purification of any description. The AVandsbeck water came from a lake and was filtered. In Hamburg, during the epidemic, there were 8,605 deaths from cholera, equal to 13-4 per thousand ; whereas in Altona tmly 328 deaths occurred, equal to 2-1 per thousand. The death- rate in Wandsbeck was similar to that of Altona. 262 Cholera. Hamburg and Altona are contiguous and practically one city. At one part a street forms the boundary between the municipalities. On one side of this street, the Hamburg side, there were numerous cases of cholera ; on the Altona side there were no cases. The houses on both sides of the street were of the same character, and occupied by the same class of people. The only difference, so far as could be ascer- tained, was in the water supply : the houses on the healthy side of the street received Altona water; those on the cholera-stricken side, Hamburg water. It was remarked that a certain group of houses on the Hamburg side remained free from the disease. On investigation it was found that, unlike the other houses on the same side, these houses derived their water supply from an Altona main. As regards its relation to the water supply this Hamburg epidemic is the exact counterpart of what happened in South London in 1854. Formerly this district was supplied with water by two companies— the Southwark and Vauxhall Company and the Lam- beth Company. Both companies drew their water from the Thames—-the latter from near Hungerford Bridge, the former from near Battersea Fields. The epidemic of cholera which visited London in 1849 was especially severe in South London. Subsequently, the Lambeth Company removed its intake higher up the river, to Thames Ditton, and consequently the water it supplied at the time of the 1854 epidemic had improved in quality. The Southwark and Vaux- hall Company did not change their intake, and in 1854 they were still drawing their supply from the river near Battersea Fields. When cholera visited London in that year the death-rate from the disease in the houses supplied by the Southwark and Vaux- hall Company amounted to 153 per 10,000 inhabitants; whereas that in houses supplied by the Lambeth Com- pany was only 26 per 10,000. The mains of the two companies ran side by side, some houses receiving the water of one company, some that of the other. .Etiology. 263 During the Hamburg epidemic it was also found that the incidence of cholera was three times greater among those who used the town water than among those who got their supplies from wells. These, and many similar facts which might be adduced, clearly point to water as a principal medium for the diffusion of the cholera germ. The virus contained in the dejecta, — Evidence, equally conclusive, tends to show that the germ on being swallowed by man multiplies in his ali- mentary canal, and, on being voided in the dejecta, subsequently finds its way by a route more or less direct to water again in which, under favourable conditions, it continues still further to multiply. An illustration, amounting almost to proof, of the fact that the germ of cholera is contained in the stools of cholera patients is supplied by Macnamara. Some of the characteristic rice-water discharge from a cholera patient got mixed accidentally with a few gallons of water. This was exposed to the sun for twelve hours. Early the following morning nineteen persons each drank about an ounce of the mixture. Within thirty- six hours, five of these nineteen persons were seized with cholera. Conditions of infection are complex.—It is evident that the ingestion of the germ is a necessary con- dition for the production of the disease, but there are many facts which render it equally evident that this is not the only condition. Were it the only con- dition, then every one of those individuals referred to by Macnamara would have sickened. What the other necessary conditions may be it is hard—in the present state of knowledge, impossible—to say. There is reason to believe that not only are these conditions complicated as regards the susceptibility of the individual, but also that they are equally com- plex as regards the germ itself in relation to its pathogenetic, proliferating, and diffusing properties. The germ of cholera.—Early views. Since European pathologists first directed their attention 264 Cholera. to the subject, many views have been entertained as to the exact nature of the cause of cholera. Some of these views were of the most fantastic description. Mysterious atmospheric and telluric conditions were invoked, and superstitious notions worthy of the Middle Ages, only a very few years ago were freely ventilated even in high places and by educated minds. Among those who ventured to formulate definite and more reasonable hypotheses some considered that cholera, like the more familiar exathematous fevers, was directly contagious. Others thought that it was not directly contagious, but that it was communicated by the evacuations of the sick after these evacuations had undergone some peculiar fermentative process out- side the human body. Others, again, as Von Petten- kofer, regarded the virus as a chemical ferment which developed in the soil under certain unknown epidemic conditions. Discovery of the comma bacillus.—Since the rise of the germ theory of infective disease most of these speculations have been definitely abandoned; or they have received more precise expression in the view that cholera is caused by a certain bacterium, known as the comma bacillus or cholera vibrio, which Koch discovered to be practically invariably present in the stools and intestinal contents of cholera patients. This bacterium Koch first discovered in Egypt in 1883. Believing in its importance, he afterwards proceeded to India on a special mission, and there, in Calcutta, in 1884, he found the same bacterium in the intestinal contents of forty-two fatal cases, and in the stools of thirty other cholera patients ; in fact, he found it in every case of the disease examined. More- over, he entirely failed to find it in any other disease or in healthy discharges. These observations, so far as they concern the presence of the comma bacillus in cholera stools, have been abundantly confirmed by many other workers; so that the presence or absence of this bacterium is now regarded as a trust- worthy and valuable practical test of the choleraic or /Etiology. 265 non-choleraic nature of any given case of intestinal flux ; and this even by the opponents of Koch's special view as to the nature of the relationship of the bacterium in question to the disease with which it is so intimately associated. If only on account of its diagnostic value the comma bacillus, therefore, is an organism of importance ; but as many high authorities regard it as a necessary concomitant and even as the actual germ and true cause of Asiatic cholera, the vibrio acquires an importance of the first rank. The comma bacillus; description,—The comma bacillus (Fig. 27) is a very minute organism, 1*5 to Fig. 27.—Cholera bacillus. Agar cult: 24 hours' growth. x 1000. (Muir and Ritchie.) 2 micromillimetres in length by o to '6 micromilli- metres in diameter—about half the length and twice the thickness of the tubercle bacillus. It is generally slightly curved, like a comma ; hence its name. After appropriate staining at each end, or at one end only, flagella can be distinguished ; sometimes one, some- times, though less frequently, two. These flagella are of considerable length—from one to five times that 266 Cholera. of the body of the bacterium; their extreme tenuity renders them difficult to see in ordinary preparations. The flagella are not always present during the entire life of the parasite. In virtue of this appendage, the bacillus exhibits very active spirillum-like movements. The individual bacilli, when stained, show darker parts at the ends or at the centre, suggesting the possibility of spore formation ; this point has not been definitely settled, however. Sometimes in cultivations two or more bacilli are united, in which case an S-shaped body is the result; or it may happen that several bacilli are thus united together, producing a spirillar appearance. The comma bacillus is easily stained by watery solution of fuchsin, or by Loffler's method, dried cover-glass films being used. Dilute solution of methyl violet mixed with the intestinal contents and placed on a slide suffices for partial staining. The bacillus grows best in alkaline media, at a temperature of from 30° to 40° Cent. Growth is arrested below 15", or above 42° Cent. ; a temperature over 50° Cent, kills the bacillus. Meat-broth, milk, blood serum, nutrient gelatine, or potato, are all suitable culture media. Nutrient gelatine and potato are the most convenient for diagnostic purposes. In gelatine plate-cultivations minute white points appear; around these the gelatine liquefies, and the colony of bacilli sink into a funnel or bubble-shaped depression. By the end of the second or third day, the cultivation is besprinkled with such depressions, liquefaction spreading peripherally until it involves the entire surface of the gelatine. The colonies are white or yellowish, very irregular in shape, granular, and shining like so many particles of ground-glass. Later they assume a peculiar roseate hue, said to be absolutely characteristic. In gelatine stab cultures the growth at first is most active near the surface; but later, the colony sinking, liquefaction advances most below the surface of the gelatine, so that a bubble-shaped appearance is /Etiology. 267 then produced. Later still, as growth proceeds along the needle track, a finger-shaped liquefaction results, which in time extends to the sides of the tube. At the bottom of the liquefied area there is an accumula- tion of a white mass of bacteria; at the top a scum of bacteria in various stages of degeneration is formed. These cultures may die after five or six weeks. Agar is not liquefied, and in it the cultivations retain their vitality longer. On potato, at 20° to 30° Cent., the culture appears as a thin, brownish, porcelain-like film. In broth, some of the bacilli form a scum on the surface ; others, falling in masses to the bottom, leave the body of the liquid clear. Although, taken together and in conjunction with the morphological appearances, these culture characters are fairly distinctive, nevertheless certain other bacteria, such as Finkler's spirillum, behave very similarly; and, as the microscopic features of these other bacteria in some instances are very much like those of the cholera vibrio, a mistake is easily made. The production of what is known as " cholera red " by the addition of pure sulphuric acid (indol reaction) to a culture in peptonised broth,, is also not quite distinctive of the cholera vibrio, for a similar reaction is produced by some other bacilli. In careful and practised hands, however, the diagnosis of cholera by the microscopic and cultural characters of the vibrio may be made with practical certainty. Is the comma bacillus the germ of cholera 'I— Although it may be safely asserted that cholera is intimately associated with the comma bacillus, it does not necessarily follow that this organism is the cause of cholera. Many attempts have been, and are being, made to establish such a relation- ship. Nevertheless, what may be considered as abso- lute proof is still wanting ; such proofs as alone can be afforded by the production in man, or in the lower animals, of a disease in every respect like cholera by the administration of pure cultures of the comma 268 Cholera. bacillus. Short of this the proof may be said to be almost complete; indeed, by many the causal relationship of the bacillus to the disease is considered as established. Since Koch first announced his discovery many facts having a bearing on the subject have been brought to light, some in favour of his views, some apparently militating against them. (1) It has been found that there are several bacilli with morphological and cultural characters closely resembling those of the cholera comma, notably the Finkler-Prior bacillus of cholera nostras, Lewis's saliva comma bacillus, many of the comma-shaped bacilli dis- covered by Cunningham, and certain species found in river water. Koch and others maintain that, though morphologically similar, those other bacilli behave so differently in culture media that, biologically, they may be considered as specifically distinct from the cholera vibrio. (2) Cultures of pure bacilli have many times been swallowed by way of experiment, yet, although in a few instances diarrhoea with comma bacilli in the stools has resulted, in perhaps no instance has true cholera, much less fatal cholera, been pro- duced. On this account, it is held by some that the comma bacillus cannot be regarded as the germ of cholera. Against this it is advanced that other factors must be present to insure the induction of cholera by such experiments ; for example, a suitable and peculiar condition of the body, possibly, as Buchner suggests, some second and as yet unknown micro-organism. Buchner therefore regards cholera as the result of a mixed infection. Moreover, the cholera vibrio, like other pathogenic bacteria, may lose through cultivation, or otherwise, its virulence while retaining its morphological and cultural qualities. (3) A few cases of what from a clinical point of view appears to be true cholera have been observed in which the most careful and most prolonged bacteriological examinations failed to detect the comma bacillus. /Etiology. 269 Therefore, it has been advanced, as cholera can occur without the comma bacillus, the comma bacillus cannot be the cause of cholera. Against this it has been said that these observations were defective ; that although the bacillus was not found, it by no means follows that the bacillus was not present at some time in the case. (4) The comma bacillus has been observed in the stools of individuals who did not at the time or afterwards suffer from cholera. To this it is answered that although one of the necessary con- ditions for the production of cholera was present, others, equally necessary, were absent. Possibly, as Pettenkofer remarked, for the production of an attack of cholera three things might be necessary, X, Y, and Z. The comma bacillus may be the X, but in the absence of the Y, certain local, and the Z, certain personal conditions, disease does not result. (5) It has been found impossible by the administra- tion of comma bacilli to produce in the lower animals true cholera, or any condition with clinical symptoms closely resembling cholera. Koch and others, in certain experiments on guinea-pigs, acting on the supposition that the acid in the stomach killed the bacillus, neutralised this by the administration of sodium carbonate, and paralysed the intestine by intra-peritoneal injections of tincture of opium. In this way they claim to have succeeded in killing guinea-pigs with symptoms to a certain extent like those of cholera. There are many sources of fallacy in this experiment,' as has been pointed out by Klein and others. Exactly similar results can be got by using the Finkler-Prior and other bacilli. The most promising experiments in this direction are those by Jablotny on the ground squirrel (spermophilus guttatus). By administering to this animal comma cultures in alkaline media, a disease in many respects like cholera was produced ; and, in the intestines and discharges of the animals experimented on, cholera-like pathological changes were found, as well as comma bacilli. 270 Cholera. Variability of the cholera microbe. — Bacterio- logical studies, always difficult, are extremely so in the case of the cholera microbe owing to its special liability to variation, both in its morpho- logical and in its pathogenic characters. On this subject Haft'kine remarks (Brit. Med. Jour., Dec. 21, 1895) : " When the cholera bacillus was first discovered its properties were described with extreme precision, which helped in concentrating for a long time all studies on well-defined and carefully, chosen specimens. Little by little, as the field of observa- tion grew larger, a number of varieties have been found with characteristics differing so largely as to annihilate almost completely the original description. When we open the intestine of deceased cholera patients and investigate the microbes there, the adopted methods will bring to the surface vibrios in which the external forms, instead of the characteristic comma or spirillum, will vary between a coccus and a straight thread ; the number and disposition of the cilia, the secretion of acids, the form of growth in broth, will vary; instead of giving in gelatine a discrete and well-defined figure of liquefaction, the variation will extend from the complete loss of this property to a rapid dissolution of the whole medium ; there will be varieties which grow luxuriantly in given media, and others which do not grow there at all; some will be phosphorescent in the dark, and others not; some will give the indol reaction, and others will be deprived of this property, and so on. The first thing to be done is to select carefully among these the most typical specimens, rejecting the others, and then to try their pathogenic power. WTe shall find such a divergence in strength that the extreme forms will not be believed to be the cholera species. There will be commas deprived of any virulence demonstrable on animals, and others which will kill the most resistent species. Some will be fatal to a guinea-pig at a dose of 1/100 of a culture tube, and others harmless in doses 500 times stronger. The average comma dies Symptoms. 271 out when introduced under the skin of an adult animal, others will spread in the system and give rise to a fatal septicaemia. The ordinary comma will be without effect on birds ; but several specimens have been isolated, and believed to be typical, which easily killed pigeons by hypodermic or intramuscular in- jection. I believe to be of great value the method worked out by Pfeiffer for comparing all such varie- ties with one selected as typical, which he employed for the preparation of an antitoxic serum. This method will be found of efficient help in distinguish- ing specimens of the greatest affinity with the average cholera comma. But once such specimens are selected and their particular properties studied they begin to change from the first day they are intro- duced into the laboratory, and no calculation based on these studies is possible. In a case quoted by M. Metchnikoff, the proportion of the initial power of the microbe, and the strength it showed at a later trial, was as 75 to 1, the microbe having gradually sunk to 1/75 of its initial virulence." These remarks, by so great a master of the subject, whilst they indicate a way of reconciling many apparent discrepancies in matters of fact and differences in the conclusions arrived at by different bacteriologists, and whilst they indicate a key to many of the clinical features of cholera, teach us caution in accepting as proved the causal relationship of the cholera vibrio to the disease with which it is so invariably associated. Symptoms.—An attack of cholera commences in one of two ways; either it may supervene in the course of what appears to be an ordinary case of diarrhoea, or it may come on suddenly and without any well-marked prodromal stage. During cholera epidemics, diarrhoea is unusually prevalent. It is a common observation that at such times an attack of this latter nature, after a day or two, may assume the characters of true cholera. The preliminary looseness in such cases is called the "premonitory diarrhoea." Whether this looseness is specifically related to the 272 Cholera. subsequent attack, or whether it is of an ordinary catarrhal or bilious type and acts simply by predis- posing to the specific disease, has not been determined. Possibly, owing to a catarrhal condition—in itself non-specific—the resisting power of the mucous mem- brane is impaired ; possibly, in diarrhoea, the large amount of fluid in the gut affords a favourable medium for the cholera germ to multiply in. Besides diarrhoea, other prodromota such as languor, depres- sion of spirits, noises in the ears, etc., are some- times noted. When true cholera sets in, profuse watery stools, painless or associated with griping, and at first faecal in character, pour, one after the other, from the patient. Quickly the stools lose their faecal character, becoming colourless or, rather, like thin rice water con- taining small white flocculi in suspension. Enormous quantities—pints —of this material are generally passed by the patient. Presently vomiting, also pro- fuse, at first perhaps of food, but very soon of the same rice-water description, supervenes. Cramps of an agonising character attack the extremities and abdomen ; the implicated muscles stand out like rigid bars, or are thrown into lumps from the violence of the contractions. The patient may rapidly pass into a state of collapse. In consequence principally of the loss of fluid by the diarrhoea and vomiting, the soft parts shrink, the cheeks fall in, the nose becomes pinched and thin, the eyes sunken, and the skin of the fingers shrivelled like a washerwoman's. The surface of the body becomes cold and livid, and is bedewed with a clammy sweat; the urine and bile are suppressed ; respiration is rapid and shallow ; the breath is cold and the voice is sunk to a hollow whisper. The pulse at the wrist soon becomes thready, weak, and rapid, and then, after coming and going and feebly fluttering, may disappear entirely. The surface temperature sinks several degrees below normal— 93° or 94°, whilst that in the rectum may be several degrees above normal—101° to 105°. The Symptoms. 273 patient is now restless, tossing about uneasily throwing his arms from side to side, feebly complain- ing of intense thirst and of a burning feeling in the chest, and racked with the cramps. Although apathetic, the mind generally remains clear. In other instances the patient may wander or pass into a comatose state. This, " the algide stage " of cholera, may termin- ate in one of three ways—in death, in rapid conval- escence, or in febrile reaction. When death from collapse supervenes, it may do so at any time from two to thirty hours from the com- mencement of the seizure, usually in from ten to twelve On the other hand, the gradual cessation of vomiting and purging, the reappearance of the pulse at the wrist, and the return of some warmth to the surface may herald convalescence. In such a case, after many hours, the secretion of urine returns, and in the course of a few days, the patient may be practically well again. Usually, however, on the cessation of the more acute symptoms of the algide stage, a condition, known as " the stage of reaction," is developed. When the patient enters on this stage the surface of the body becomes warmer, the pulse returns at the wrist, the face fills out, restlessness disappears, urine may be secreted, and the motions diminish in number and amount, becoming bilious at the same time. Coincidently, however, with the subsidence of the more urgent symptoms of the algide stage and this general improvement in the appearance of the patient, a febrile condition of greater or less severity may develop. Minor degrees of this reaction generally subside in a few hours ; but in more severe cases the febrile state becomes aggravated, and a con- dition in many respects closely resembling typhoid fever, " cholera typhoid," ensues. This febrile or possibly typhoid state may last from four or five days to perhaps a fortnight or even longer. In severe cases the face is flushed, the tongue brown and dry, and there may be a delirium of a low s 274 Cholera. typhoid character with tremor and subsultus; or the patient may sink into a peculiar torpid condition. The motions are now either greenish or like pea- soup, and may contain a larger or smaller amount of blood ; at the same time they are very offensive. The reappearance of urine may be delayed from two to six days ; at first scanty, high-coloured, cloudy, albuminous, and containing casts, it gradually be- comes more profuse, paler, and with less albumin. Though at first the urine is very deficient in urea, in uric acid, and in salts, later the quantity of these substances may exceed for a time the normal. During the stage of reaction death may occur from a variety of complications; from pneumonia, from enteritis and diarrhoea, from asthenia, or from such effects of uraemic poisoning as coma and convulsions. In cholera there is a considerable variety in the character of the symptoms and in their severity, both as regards individual cases and as regards different epidemics. It is generally stated that during an epidemic the earlier cases are the more severe, those occurring towards the end of the epidemic being on the whole milder. Ambulatory cases occur during all epidemics; such cases being characterised by diarrhoea and malaise merely, there is never complete suppression of urine, the diarrhoea never loses its bilious character and is unaccompanied by cramps ; the attack gradually subsides without developing a subsequent stage of reaction. In another set of cases, the diarrhoea may be somewhat more acute, and the stools assume the well-known rice-water appearance ; but the looseness soon ceases without leading to sup- pression of urine, or to algide symptoms, or even to very severe cramps, and without being followed by a stage of reaction. Such cases are sometimes desig- nated "choleraic diarrhoea" or "cholerine." A very fatal type is that known as " cholera sicca." In these cases, though there is no, or very little, diarrhoea and vomiting, collapse sets in so rapidly that the patient is quickly overpowered, as by an over- Pathology. 275 whelming dose of some poison, and dies in a few hours without purging or any attempt at reaction. At the post-mortem examination the rice-water material, so characteristic of cholera, though it may not have been voided during life, is found in abundance in the bowel. Other cases die suddenly from apnoea caused, apparently, either by coagula in the right heart, or by spasm of the pulmonary arterioles, the lungs refusing to transmit the thickened blood. In certain cases, after temporary improve- ment, relapse may occur and is nearly always fatal. Hyperpyrexia is an occasional though rare occurrence in cholera ; in such the axillary temperature may rise to 107°, the rectal temperature, perhaps to 109°; these cases also are almost invariably fatal. Cholera is apt to be followed by a variety of more or less important sequelae, such as anaemia, mental and physical debility, insomnia, pyretic conditions, chronic enterocolitis, nephritis, different forms of pulmonary inflammation, parotitis apt to end in abscess, ulcer- ation of the corneae, bed sores, or in gangrene of dif- ferent parts of the body. Jaundice occurs at times and is said to be of the gravest import. Pregnant women almost invariably miscarry, the foetus showing evidence of cholera. morbid anatomy and pathology.—Rigor mortis occurs early and persists for a considerable time. Curious movements of the limbs may take place in consequence of post-mortem muscular con- tractions. On dissection the most characteristic pathological appearances in cholera are those connected with the circulation and with the intestinal tract. If death have occurred during the algide stage, the surface presents the shrunken and livid appear- ance already described. On opening the body all the tissues are found to be abnormally dry. The muscles are dark and firm; sometimes one or more of them are discovered to be ruptured—evidently from the violence of the cramps during life. The right side of the heart and systemic veins are full of dark, thick, and s 2 276 Cholera. imperfectly coagulated blood, which tends to cling to the inner surface of the vessels. Fibrinous clots, extending into the vessels, may be found in the right heart. The lungs are usually anaemic, dry, and shrunken; occasionally they may be congested and oedematous. The pulmonary arteries are distended with blood, the pulmonary veins empty. The liver is generally loaded with blood; the gall bladder full of bile; the spleen small. Like all the other serous cavities, the peritoneum contains no fluid, its surface being dry and sticky. The outer surface of the bowel has generally a diffuse rosy red, occasionally an in- jected, appearance. On opening the bowel it is found to contain a larger or smaller amount of the charac- teristic rice-water material, occasionally blood. The mucous membrane of the stomach and intestine is generally pinkish from congestion, or there may be irregularly congested or arborescent patches of injection here and there throughout its extent. In addition, there may be seen smaller or larger points of ecchymosis in, or under, the mucous membrane. The changes in the alimentary canal are most marked at the lower end of the ileum, where Peyer's patches and the solitary glands may be seen to be congested and swollen. In some instances the bowel is pale throughout; in many the mucous membrane has a sodden, pulpy appearance from exfoliation of epi- thelium—possibly a post-mortem change ; occasionally, especially towards the lower end of the ileum, a croupous exudation is met with. The mesenteric glands are congested. The superficial veins of the kidneys are full; the medullary portion is much congested, the cortical portion less so; the tubules are filled with granular matter; the epithelium is cloudy, granular, or fatty, and, at a later stage, may be shed. The bladder is empty and contracted. Nothing special is to be noted in the nervous system. If death have occurred during the stage of re- action, the tissues are moist; the venous system is less congested: the lung probably congested and Pa thology. 277 oedematous, perhaps inflamed. Very probably there are evidences of extensive enteritis. Microscopical examination of the contents of the bowel during the acute stage of the disease discovers, in most instances, the comma bacillus. Usually it is in great abundance ; occasionally in what is almost a pure culture. Sections of the intestine show the bacillus lying on and between the epithelial cells of the villi and glands. In 110 other organ or tissue of the body is the bacterium to be found. Therefore, assuming that the comma bacillus is the cause of cholera, we must conclude that the clinical phenomena are not the result of a septicaemia ; but that they arise, either from a local irritation produced by the bacillus, or from some toxin which it generates in the bowel and which is absorbed, or from a combination of these factors. That the cholera vibrio is a powerful irritant is shown by the effect produced locally by a hypodermic injection of a virulent culture. When so injected, not only does it give rise to local oedema but, unless special precautions are taken, it causes necrosis of the tissues and extensive ulceration at the seat of injec- tion. It is conceivable, therefore, that when in the course of the naturally acquired disease the bacilli proliferate in the bowel, they or their products act as an irritant to the mucous membrane and so provoke the hypercatharsis, and the consequent dehydration of the tissues, which are the dominating features of the disease. On the other hand, the hypodermic injection of cholera vibrio cultures is followed by smart febrile movement lasting from one to three days, evidencing the presence of a febrogenetic toxin capable of pro- ducing constitutional symptoms. This fact, together with the rapid and intense prostration which, in some instances of natural cholera, appears to be out of all proportion to the amount of catharsis present, suggests that in a measure the lethal effects of the vibrio are attributable, not alone to the drain of fluid from the blood and tissues but also to the absorption of a 278 Cholera. cholera toxin from the intestine. It is somewhat strange, however, if this toxin be anything more than a subsidiary element in the production of the symptoms in most instances of the naturally acquired disease, that catharsis is not one of the effects of the hypodermic introduction of the vibrio, and that fever is not an earlier and more prominent symptom in natural cholera. The modern tendency is to regard the clinical phenomena as the result partly of local irritation and partly of a toxaemia; variation in the proportional intensities of the various clinical elements depending on the degree of virulence of the particular strain of microbe introduced, and on the circumstances and idiosyncrasy of the patient. Diagnosis.—During the height of an epidemic the diagnosis of cholera is generally an easy, matter; the profuse rice-water discharges, the collapse, the cold clammy skin, the cyanosis, the shrunken features, the shrivelled fingers and toes, the feeble, husky, hollow voice, the cold breath, the cramps and the suppression of urine, together with the high rate of mortality, are generally sufficiently distinctive. But in the first cases of some outbreak of diarrhoea, which may or may not turn out to be cholera and the true nature of which for obvious reasons it is of import- ance to determine, diagnosis may not be so easy. Symptoms resembling true cholera may supervene in the course of an ordinary severe diarrhoea, and are very usual in cholera nostras, in mushroom poisoning, in ptomaine poisoning, in the early stages of trichinosis, and in a certain type of pernicious malarial fever. In none of these, however, is the mortality so high as in cholera; it may be laid down, therefore, that epidemic diarrhoea attended by a case mortality of over 50 per cent, is cholera. In other forms of diarrhoea it is rare for the stools to be persistently so absolutely devoid of biliary colouring matter as they are in cholera. A careful inspection of the stools sometimes yields valu- able information in other ways. Thus in mushroom Diagnosis. 279 poisoning, fragments of the mushrooms which caused the catharsis may be seen ; in trichinosis, the micro- scope may detect the adult trichina. In choleraic malarial attacks the presence of the plasmodium in the blood, the periodicity of the symptoms, their amenability to quiuine, together with the character of the prevailing epidemic, generally combine to guide to a correct diagnosis. The detection of the comma bacillus in the stools is now regarded as a positive indication of cholera. It would be rash, however, to affirm that a negative result from bacteriological examination of a single case is conclusive against its being cholera. More- over, it must be borne in mind that such examinations to be trustworthy have to be made by a skilled bac- teriologist. According to Kanthack and Stephens, the following were the methods of bacteriological diag- nosis practised by Klein during the threatened epidemic in 1893 :—■ "Method 1.—A flake from the dejecta is placed in peptone broth and incubated at 37° Cent. In twenty- four hours an abundant crop of vibrios is found on the superficial layers of the broth. This pellicle consists of a practically pure culture, or, at any rate, is a culture which easily allows of pure sub-cultures being obtained. '■'•Method 2.—A flake is placed in sterile salt solution or broth; it is shaken up, and from this gelatine or agar tubes are inoculated, and plates are made. In agar plates incubated at 37° Cent, numerous colonies may be found in twenty to thirty hours. In the gelatine plates, after two to three days' incubation at 20° to 22D Cent, numerous typical colonies can be got. " Method 3.—A flake is placed directly into Dun- ham's peptone salt solution (1 per cent, peptone, 0-5 per cent, sodium chloride), or the Dunham's solution is inoculated after previous dilution of the material. The peptone solution, after six, eight, to ten hours' incubation at 37° Cent, shows a definite turbidity, due to the rapid growth of the comma bacilli; and the 280 Cholera. cholera-red reaction may be obtained. For speedy diagnosis this method is most valuable; in six to twelve hours, or, at latest, in sixteen hours, comma bacilli can be. found in the superficial layers of the peptone solution, so that in twenty-four hours pure cultures and the cholera-red reaction can be obtained in secondary peptone tubes. Also, a positive result may be obtained by this method in cases in which the microscopical examination has failed to give definite evidence of the presence of vibrios." The first two methods are applicable to those instances in which microscopical examination of the stools shows crowds of comma bacilli. Method 3 is specially applicable to those stools in which comma bacilli are in very small numbers. Mortality.—The average Case mortality in cholera amounts to about 50 per cent. Some epidemics are more deadly than others. The mortality is greater at the earlier stages than at the later stages of an epi- demic. To the old, the very young, the pregnant, the subjects of grave organic disease—particularly of the liver, kidneys, and heart—the dissipated, the under- fed, and the feeble, the danger is very great. Quarantine prevention.—Theoretically, quar- antine should be an efficient protection against the introduction of cholera into a community; practically, it has proved a failure. Unless they are stringent and thoroughly carried out, quarantine regulations can be of little use. Unfortunately, the temptation to evade such regulations is in proportion to their stringency. It is impossible to secure the absolute honesty and efficiency of every individual in a large body of men charged with the carrying out of the details of any system entailing great personal in- convenience and loss to travellers and merchants. Therefore, if the strength of the quarantine chain is to be measured by its weakest link, the chain must be weak indeed, as a very slight acquaintance with its working will prove. Even if the utmost care, intelligence, and honesty succeed in excluding Quarantine. 281 individuals actually suffering from cholera, or likely within a reasonable time to suffer from cholera, there is yet no guarantee that the germ of the disease may not be introduced. Koch and others have shown that sometimes the dejecta even of individuals ap- parently in good health and .who have not suffered, or who may not subsequently suffer, from choleraic disease, may yet contain, and for some time continue to contain, the cholera vibrio. If the cholera vibrio be the germ of cholera, then such healthy, vibrio- bearing individuals may well suffice to start an epi- demic. It is impossible, short of absolute and complete isolation, for any practicable system of quarantine to deal efficiently with such cases. So far from ordinary quarantine proving a defence against cholera, it may actually increase the risk of an epidemic. This it does by fostering a false sense of security, leading to the neglect of those well-proved guarantors of the public health—domestic, municipal, and personal cleanliness, and a pure water and food supply. The system to which Great Britain apparently owed her immunity during recent epidemics on the continent of Europe is a practicable one, and, in civilised conditions, seems to be an efficient one. Under this system only ships carrying, or which had recently carried, cholera patients were detained; and even these merely till they could be thoroughly dis- infected. Thus inconvenience and loss to travellers and merchants were small, and the temptation to con- ceal cases of the disease, or to evade regulations, was proportionately minimised. Any cholera cases were isolated in suitable hospitals, the rest of the crew and passengers, although supervised for a time, being given free pratique. At thasame time, attention was not diverted from the sanitation of towns, especially of seaports ; this was the measure mainly relied on. Suspicious cases occurring on shore were at once reported to the sanitary authorities and promptly dealt with, fomites being destroyed or disinfected at 282 Gholera. as little cost and inconvenience to individuals ns possible. Every endeavour was made to prevent faecal contamination of the public water supply. Of late years in India effort is being directed much on the same lines, attention being given to sanitation rather than to quarantine. During the great religious festivals the sanitary condition of the devotees is looked after so far as practicable, special care being given to provide them with good drinking and bathing water. Many of the large Indian towns now enjoy an abundant and pure water supply, and civilised systems of night soil conservancy and other important sanitary measures are being gradually introduced, in the case of more than one great city, with the most gratifying results. Among the troops in India, on the appearance of cholera in their neighbourhood special protective measures are promptly instituted, elaborate directions having been drawn up for the guidance of medical officers. For an account of these regulations the reader is referred to the Annual Report of the Sanitary Commissioner with the Government of India for 1895, Appendix, p. 189. Incubation period.—All quarantine and protective systems must take cognisance of the fact that although cholera may declare itself within a few hours of exposure to infection, it may also do so till as late as ten days. Three to six days may be set down as the usual duration of the incubation period. Anti-choleraic inoculations. — In 1885, during an epidemic of cholera in Spain, Ferran in- stituted a system of prophylactic inoculation. He injected hypodermically ordinary laboratory cultures of the cholera vibrio obtained directly from cholera corpses. No attempt was made to regulate or stand- ardise in any way the virulence of the cultures. The results were not encouraging. As accidents were frequent, the Government put a stop to the practice. In 1893 (Brit. Med. Jour., Feb. 11th, 1893) Haffkine, after elaborate experiments on the lower Anti-choleraic Inoculations. 283 animals, commenced a system of anti-choleraic vaccina- tions, using a pure virus of a fixed and known strength. This virus he prepared by passing the cholera vibrio through a series of guinea-pigs by means of intra- peritoneal injections. In this way the microbes were increased in toxicity to a definite point, beyond which their virulence could not be augmented. Cultures so prepared gave rise not only to a general but also to a local reaction, the latter being so severe that it generally ended in extensive sloughing and ulceration. To avoid this undesirable result, a milder vaccine was prepared by cultivating the strong vaccine in artificial media at a temperature of 39° Cent., and in an atmo- sphere kept constantly renewed. By first injecting under the skin of animals this milder vaccine, it was found that such a measure of protection was conferred that subsequent injection of the strong virus was no longer followed by a local reaction of such severity as to cause sloughing or ulceration. Having satisfied himself that the subcutaneous injection of these two vaccines conferred immunity against the cholera vibrio in the lower animals, Haff kine proceeded to use them in man on a large scale in India, and with the approval and aid of the Government. Up to 1895 70,000 injections of living cholera bacilli had been made in 43,179 individuals. In no instance did any bad result ensue. While admitting that the value of his method has not been fully proved, Haffkine claims that the results are sufficiently encouraging to justify a continuation of these in- oculations on a larger scale. The symptoms they produce are fever, transient oedema, and tenderness at the seat of injection, the first evidence of constitu- tional disturbance appearing from two to three hours after the injection is made. The fever and general indisposition last from twenty-four to thirty-six hours, the local symptoms gradually disappearing in from three to four days. The symptoms following the second injection—made from three to four days after the first—are generally more marked but of shorter 284 Cholera. duration. The microbes injected die. It is the substances set free at their death which confer the immunity ; for it is found that carbolised cultures—■ that is, dead vibrios—produce the same immunising and constitutional effect, though in a somewhat milder and probably less permanent degree. How long the immunity conferred by these injections endures has not been definitely settled. Full details of Haffkine's methods and technique are given in the Brit. Med. Jour, of Feb. 4th, 1893, and in the Indian Medical Gazette of Nov., 1896. Personal prophylaxis.—During cholera epi- demics great care should be exercised to preserve the general health ; at the same time, anything like panic or apprehension must be sedulously discouraged. Fatigue, chill, excess—particularly dietetic or alco- holic excess—are to be carefully avoided. Visits to cholera districts should be postponed if possible, seeing that the newcomer is specially liable to contract the disease. Unripe fruit, over-ripe fruit, shell-fish, food in a state of decomposition, and every- thing tending to upset the digestive organs and to cause intestinal catarrh are dangerous. Melons, cucumbers, and the like deserve the evil reputation they have acquired. Purgatives—particularly saline purgatives—unless very specially indicated, should never be taken at these times. All drinking water, and all water in which dishes and everything used in the preparation and serving of food are washed, should be boiled. Filters—except perhaps the Pas- teur-Chamberland filter—are not to be relied on; in most instances they are more likely to contaminate the water passed through them than to purify it. A good plan in a household, or in public institution, is to provide for drinking purposes an abundant supply of weak tea or lemon decoction, the supply being renewed daily ; such a plan insures that the water used in the preparation of the drink has been boiled. Diarrhoea occurring during cholera epidemics should be promptly and vigorously treated. Trea tment. 285 Treatment. — During cholera epidemics it is customary to establish depots where sedative and astringent remedies are dispensed gratuitously for the treatment of diarrhoea. Experience seems to encourage the belief that by such means incipient cholera may be aborted during the stage of pre- monitory diarrhoea. Of the various drugs used with this view, chlorodyne, or chlorodyne and brandy, is the most popular. Lead and opium pill; chalk, catechu and opium mixture ; compound kino powder ; aromatic powder of chalk and opium ; a pill of opium, asafoetida and black pepper; dilute sulphuric acid and laudanum are among the drugs more commonly em- ployed for this purpose. Whether true cholera can be cut short in this way or not, it is certainly in the highest degree advisable at such a time to neglect no case of diarrhoea ; but to insist on rest, warmth, and. the greatest prudence in feeding in all cases of intestinal catarrh or irritation. Many plans of treatment, based on theoretical considerations, have been advocated from time, to time ; so far, however, none of them has proved of material service in true cholera. The eliminative treatment advocated by Dr. George Johnson; the spinal ice-bag recommended by Chapman; various antiseptic methods directed to the destruction of the vibrio in the intestinal canal; drugs designed to counteract the physiological effects of the cholera toxins, as chloroform, atropine, nitrite of amy], and nitroglycerine may be mentioned as belonging to this category of remedies. Practically, the only treatment of any proved value in cholera is the purely symptomatic and expectant one. If our efforts have failed to counter- act the premonitory diarrlnca, attention should be given to maintaining the patient in as favourable a condition as possible to struggle against the poison of the disease. He should be kept strictly in the horizontal position, in a warm bed, and in a well- ventilated but not too cold room. His thirst should 286 Cholera. be treated by sips of iced-water or of soda-water, or champagne, or brandy and water; copious draughts provoke vomiting. Cramps may be relieved by gentle frictions with the hand or with ginger-root, by a small hypodermic injection of morphia, or, these failing, by short chloroform inhalations. The surface of the body should be kept dry by wiping it with warm dry cloths, and the surface heat maintained by hot-water bottles or warmed bricks placed about the feet, legs, and flanks. The patient must not be allowed to get up to pass his stools, a warmed bed-pan being pro- vided for this purpose. All food should be withheld while the disease is active. If the pulse fail or disappear at the wrist, stimu- lants by the mouth, or, if there is much vomiting and these do not appear to be absorbed, hypodermic injections of ether or brandy may be given. No improvement ensuing, intravenous injection of saline fluid may be had recourse to. A suitable injection may be quickly prepared of common salt sixty grains, carbonate of soda sixty grains, boiled water one quart. Of this, from one to three quarts at a temperature of 100° Fahr. may be slowly injected by gravitation into a vein, the effect being carefully watched. The pulse can generally be quickly restored temporarily by this means and life prolonged, possibly in a few instances saved; too often, however, the fluid so introduced rapidly escapes by the bowel and collapse once more sets in. Dr. Cox, of Shanghai, has had some en- couraging results from continuous, prolonged, slow, intravenous injection of saline fluid, the fluid gravi- tating from a vessel placed two and a half feet above the level of the patient's arm. The flow is kept up for several hours, and as long as it is deemed that there is any risk of collapse (China Med. Missionary Jour., June, 1897). During the stage of reaction, should purging persist, large doses of salicylate of bismuth with a little opium may prove of service. In these circum- stances massive rectal injections of tannin one ounce Treatment. 287 gum arabic one ounce, warm water one quart, are of use. If the secretion of urine is not quickly restored, large hot poultices over the loins, dry cupping of the same region, and the judicious use of bland diluents should be had recourse to. Stimulating diuretics are dangerous. Retention of urine must be inquired about, and the region of the bladder frequently ex- amined, and, if necessary, the catheter employed. In the event of constipation, purgatives must be eschewed and simple enemata alone used. In cholera convalescents the diet for a time must be of the simplest and most digestible nature—diluted milk, barley-water or rice-water, thin broths, meat juice, and so forth—the return to ordinary food being effected with the greatest circumspection. Cholera typhoid must be treated much as an ordinary enteric fever. 288 CHAPTER XVIII. DYSENTERY. Definition.—A term applied to what is probably a group of diseases whose principal pathological feature is inflammation of the mucous membrane of the colon, and whose leading symptoms are pain in the abdomen, tenesmus, and the passage of frequent small stcols containing mucus and blood. In some instances the disease is communicable. Geographical distribution.— From time to time forms of dysentery have extended as epidemics of great severity over vast tracts of country. These great epidemics, or such of them as have been re- corded, have been confined principally to temperate latitudes, and do not specially concern us here. In respect to geographical distribution and certain epidemiological points, tropical dysentery bears a close resemblance to malaria. Like malaria, although dysentery is found in temperate climates in them it is, with exceptions, a comparatively rare and mild affection. Like malaria, as we approach the Equator dysentery tends to become more common, and in type more severe. Like malaria, it is endemic in certain spots, where it often appears in sporadic form, and, at times, in limited local epidemics. Like malaria, it may extend beyond these endemic spots and involve more extensive tracts of country. Like malaria, it appears to have a predilection for low-lying, damp places ; and, like malaria, when occurring in temperate climates it is most prevalent in the late summer, or in early autumn. Like malaria, it tends to disappear on the cultivation, drainage, and improved sanitation of a Symptoms. 289 country. Furthermore, the two diseases often occur in the same places and at the same time. They may even concur in the same individual; and one disease seems to predispose to the other. To this extent these two diseases resemble each other ; nevertheless, though they have many points in their epidemiology and in their geographical distri- bution in common, they are pathologically totally distinct and independent affections, with different causes, different lesions, and requiring different treat- ment. Moreover, there are many places where dysen- tery is common and where malaria is unknown, and, though very much more rarely, vice versa. Symptoms. — In ordinary cases the leading symptoms of dysentery are those of inflammation of the great intestine—namely, griping, tenesmus, and the passage of frequent loose, scanty, niuco- sanguineous stools. It commences in various ways —insidiously, or suddenly; or it may be grafted, as it were, on some general affection such as scurvy or malaria, or on some chronic disease of the alimentary canal, as sprue. It may assume acute characters, or from the outset the symptoms may be subdued and of little urgency. As a rule, the symptoms are proportioned to the extent of the disease, but they are not necessarily so. In certain cases they may be extremely urgent and in apparent disproportion to the area of bowel affected; or they may be, in comparison to the extent and the degree of the anatomical lesion, disproportionately trifling ; or they may be altogether absent, even when the colon is extensively diseased. There is, therefore, endless variety in the character, urgency, and signifi- cance of the symptoms of dysentery. As a general rule, the nearer to the rectum the lesions, the more urgent the tenesmus ; the nearer to the caecum, the more urgent the griping. These two symptoms, together with the presence of points of localised tenderness, form, in the majority of cases, a fair guide to the location and extent of the lesions. T 2go Dysentery. Catarrhal dysentery.—A common history to re- ceive from a patient is that for some days he, or she, had suffered from what was supposed to be an attack of ordinary diarrhoea. The stools, at first copious, bilious and watery—perhaps to the number of four or five in the twenty-four hours—had latterly, and by degrees, become less copious and more frequent, less feculent and more mucoid, their passage being attended by a certain and increasing amount of straining and griping. On looking at what was passed, the patient had discovered that now there was very little in the pot except mucus tinged, or streaked, or dotted with blood ; a tablespoonful, or thereabouts, being passed at a time. By degrees the dysenteric element entirely supplanted the diarrhoea; so that when seen by the physician the desire to go to stool has become almost incessant, the effort to pass something being accom- panied by perhaps agonising griping and tenesmus. The patient has hardly left the stool before he has a call to return to it, and he may be groaning and sweating with pain and effort. The suffering is some- times very great; nevertheless, with all this suffering, there is very little fever, the thermometer showing a rise of only one or two degrees, rarely more. In another type of case the incidence of the dysenteric condition is much more abrupt. Within a few hours of its commencement the disease may be in full swing. The stools, at first feculent, soon come to consist of little save a yellowish, greenish, or dirty brown mucus—blood-tinged or streaked and dotted with little haemorrhages. Very soon the desire to stool becomes increased, the griping and tenesmus being accompanied, perhaps, with most distressing dysuria. The patient is glued, as it were, to the commode. Fever is absent or inconsiderable. The tongue soon becomes whice or yellow-coated; there may also be thirst; very generally anorexia is complete. In either case, after perhaps four, five, or six days, the urgency of the symptoms may gradually diminish Symptoms. 291 and the acute stage taper off into a subacute or chronic condition; or it may terminate more quickly in perfect recovery. Ulcerative dysentery.—Should, on the contrary, the disease advance, the urgency of the symptoms shows hardly any abatement; the stools become very offensive, and now contain, besides blood, large or small shreddy, ash-coloured, stinking sloughs. This may go on, better or worse, for days or weeks. Re- covery from this condition is a slow process, as the presence of sloughs in the stools indicates the ex- istence of deep ulceration which must necessarily take some time to cicatrise. Such a condition tends to drift into that most dangerous and most distressing complaint, chronic dysentery, relapsing and improving during many months or even years ; and causing, if severe and prolonged, great wasting, pain and misery. Gangrenous dysentery.—WThat is known as gan- grenous dysentery is, symptomatically, but an aggra- vated form of acute ulcerative dysentery. Instead of being mucoid, the stools come to consist of a sort of dirty water, like the washings of flesh. On stand- ing, they deposit a grumous, coffee-ground-looking material, and they stink abominably. Now and again sloughs of every shape, size, and colour, from ash- grey to black, are expelled. Sometimes tube-like pieces, evidently rings of mucous membrane which have been cast off en masse, are discharged. In such cases the patient' rapidly passes into a state of collapse. He sweats profusely; the features, the extremities, and even the whole body, are cold and pinched as in the algide stage of cholera; he may vomit from time to time, and the belly may become distressingly tympanitic. In this condition there is usually a persistent and worrying hiccough. Low muttering delirium sets in ; the pulse becomes small and running, and the patient rapidly sinks. Recovery is extremely improbable. Nevertheless, such cases have recovered, and must not necessarily be despaired of. t 2 292 Dysentery. Hemorrhage. — Whenever in dysentery sloughs separate, haemorrhage is always possible. Sudden collapse may occur from this cause, even in other- wise mild cases. As in typhoid, the occurrence of haemorrhage is more or less of the nature of an acci- dent, depending, as it does, on the position of the sloughing sore in relation to an artery ; of course, the more extensive and the deeper the sloughing, the greater the liability to haemorrhage. Perforation.—Another grave, though fortunately rare, accident in the course of dysentery, is the occurrence of perforation. Should this unhappily take place, and if the patient survive the shock of an extensive extravasation into the peritoneum, symptoms of peritonitis will supervene and rapidly prove fatal. Intussusception.—Intussusception is also an occa- sional occurrence, especially in children, not always readily recognised. A sudden increase of pain, in- creased straining, entire absence of faecal matter from the stools, vomiting, and perhaps the presence of a tumour in the rectum, might lead one to suspect this accident. Tenderness; thickening. — In most cases of dysentery there is a considerable amount of tender- ness of the abdomen; and! if the disease be of some standing a certain amount of thickening may be felt along the track of the colon, particularly over the sigmoid flexure. Hepatitis.—In acute dysentery the liver is usually distinctly enlarged and may be tender. It sometimes happens that attacks of hepatitis seem to alternate with attacks of dysentery ; or, rather, that hepatitis in- creasing, dysenteric symptoms decrease and vice versd. These are always very anxious cases, and too often eventuate in the formation of an abscess or multiple abscesses in the liver ; in the latter event they almost necessarily prove fatal. Pathognomonic symptoms.—No two cases of dysentery are exactly alike. In epidemic dysentery, Mortality. 293 which is usually of a more severe type than the sporadic form, the individual cases have a general resemblance to each other. In all varieties the leading symptoms are the same—frequent discharge of muco-sanguinolent stools, tenesmus, griping, and, usually, tender abdomen. In the presence of these symptoms, with or without fever, particularly if the disease be epidemic at the time, a diagnosis of dysentery is probably correct. mortality.—Although every now and again cases are met with which prove directly fatal from rapid exhaustion, from haemorrhage, or from perforation; and thoughsome epidemics exhibit a malignancy which, fortunately, is not very common, the direct and im- mediate mortality from this disease is, under modern methods of treatment, not very high. In India, the case mortality in dysentery among Europeans ranges from 3 to 22 per cent. ; among natives, about 37 per cent. In Egypt. Griesinger stated it at 36 to 40 per cent. In Japan, Scheube places it at 7 per cent. These figures are of little value, as so much depends on the place, the type of the epidemic, and the range of cases covered by the statistics. There was a time when. under a spoliative treatment by bleeding and calomel, dysentery proved a very fatal disease indeed. Even now, in the presence of scorbutus, famine, the stress of war, and similar conditions, whenever dysentery becomes epidemic in a community, it is apt to claim a large number of victims. Sequelai more dangerous than the disease.—As a rule, under modern treatment, it is the sequelae of the disease that we have to fear rather than the disease itself. The chronic ulceration, the scarring, thickening, and contractions of the gut, are con- ditions which cannot be remedied; and which too often, after months or years of suffering, lead to intestinal obstruction, or, very frequently to a general atrophy of the glandular system of the entire alimentary tract, wasting, and fatal asthenia. Such patients hardly ever pass a healthy motion; they 294 Dysenter y. are troubled with chronic indigestion; they pass their food unaltered ; they have recurring attacks of diarrhcea ; they are flatulent; their tongues are red, often ulcerated and tender; they develop the con- dition known as "sprue," and, sooner or later, almost invariably succumb. Liver abscess.—Much more frequent in its oc- currence than these, and much more rapidly fatal, sometimes accompanying or quickly ( following dysentery, more often showing itself after months of comparative good health and when dysenteric symp- toms had long ceased to trouble the patient, had perhaps been forgotten even, there is suddenly sprung on us the gravest of all the sequelae of this disease—the patient gets abscess of the liver. This important subject is specially dealt with elsewhere in this volume (p. 343). Morbid anatomy and pathology. — We were able to study the cognate subject of malaria to a certain extent scientifically ; at all events, we could point out its germ or cause, and, in a measure, indicate the way in which this germ produced pathological effects. Unfortunately, in the case of dysentery this cannot be done. Although in many instances the specific nature of the disease is not to be doubted, the specific body or germ has not been indicated with anything like certainty. Many bacteria have been incriminated—the bacillus coli commune, a bacillus dysenteria>, staphylococcus aureus and s. albus, etc. In one form of dysentery claims have been advanced for regarding the amceba coli as the germ. Up to the present all or any of these claims, whether for bacteria or for protozoa, are still very far from being established. In treating of the pathology of dysentery, there- fore, we cannot begin by describing the cause; we can describe the effects, and only speculate about their cause or causes. The term dysentery includes, probably, several diseases.—There is good reason to believe that the Pathology. 295 term " dysentery" includes not one but several distinct diseases. We know that the symptoms grouped under this word are apt to differ in intensity and character in different places and in different epidemics. Some forms of the disease run a more or less definite course, and then terminate for good. Other forms exhibit a remarkable disposition to relapse. The dysentery of certain tropical coun- tries, as the East Indies, is prone to eventuate in abscess of the liver; that of temperate climates and certain tropical countries, as the West Indies (ex- cepting one or two of those epidemics of which we have trustworthy accounts) is seldom succeeded or accompanied by hepatic suppuration. These and other circumstances seem to point to radical differ- ences in the several forms—differences of cause as well as differences of symptoms, course, and sequelae. It is well, therefore, to regard the term "dysentery" as but the name of a symptom or group of symptoms indi- cating an inflamed condition of the colon—much in the same way as we regard diarrhoea, cough, or fever as symptomatic merely of disease, and not as indi- cating a single and well-defined disease. Dysentery simply means inflammation of the colon. There may be many kinds of inflammation of the colon. Catarrhal dysentery.—It is unreasonable to sup- pose that those cases which, either spontaneously or in consequence of treatment, subside in a few days, advance further than a state of catarrhal inflamma- tion. In such cases it is reasonable to suppose that the pathological condition consists only, or mainly, in congestion or in catarrhal inflammation ; that here and there, or throughout its extent, the mucosa and, perhaps, submucosa are slightly swollen, red, injected ; and that the surface of the former is softened, perhaps eroded, and covered with a blood-streaked glairy mucus of the same character as that which appears in the stools. Ulcerating dysentery.—Cases of catarrhal dysen- tery rarely die; the exact conditions of the mucous 296 Dysentery. membrane, therefore, in these cases can only be conjectured. It is otherwise, however, in the severer forms of the disease. When such cases come to the post-mortem table, the mucous membrane of the large intestine and, very frequently, a foot or two of the lower end of the ileum are found to be thickened, congested, inflamed, speckled perhaps with ecchymoses, oedematous, and more or less riddled with ulcers of various sizes, shapes, and depths. It is found, as a rule, that the brunt of the disease has fallen on the sigmoid flexure and descending colon ; not infre- quently, however, the lesions are equally, if not more, advanced in the caecum and ascending colon. On the whole, the transverse colon, though often seriously involved, is so to a less extent than one or other of the parts mentioned, or than the hepatic and splenic flexures. The dysenteric ulcer varies in size from a punched- out-looking sore the size of a pea, or even less, to a patch several inches in diameter. As a rule, in the earlier part of the acute stage, the ulcers tend to follow the folds of the mucous membrane, the free borders of which are the parts most liable to implica- tion. The edges of the sores are ragged and under- mined, the floor is sloughy and grey. There may be considerable thickening of the edges and base of the ulcer, with peritoneal adhesions. The appearance of the ulcer suggests that it extends by a process of burrowing in the submucosa, the superjacent mucous membrane sloughing or disintegrating in consequence of the subjacent destruction of its nutrient vessels. This burrowing may extend for a considerable distance beyond the apparent margin of ulceration; so much so that long, suppurating, fistulous tunnels may con- nect one ulcer with another. In this way large patches of mucous membrane come to be undermined, and sub- sequently to slough away. Sores so formed are neces- sarily ragged and irregular in outline, and may even surround pieces of comparatively healthy mucous mem- brane. The floor of the active dysenteric ulcer may Pa thology. 297 be, and generally is, formed of a sloughy material lying on the muscular coat; but the sore may pene- trate deeper than this, and include the muscular coat itself, and even the serous membrane. The largest ulcers are generally found in the sigmoid flexure and descending colon; they are also frequently, though more rarely, found in the caecum, the magnitude of the lesions diminishing as we trace the bowel up- wards or downwards, as the case may be. Along with the ulceration there is intense con- gestion of the non-ulcerated parts of the mucous membrane. In places there may be oedema of the submucosa; there may be small abscesses even which elevate the mucous membrane; and there may also be distension of the solitary follicles by a mucoid or purulent material. In some instances a large portion of the mucous membrane may be seen to have died en masse and become gangrenous. In such, extensive sloughs may be thrown off as a sort of tube, apt to be mistaken during the lifetime of the patient for a diphtheritic cast of the bowel. The primary lesion.—Such, briefly, is a descrip- tion of the principal lesions found in the acute stage of fatal cases of dysentery. There is general agree- ment among pathologists about these; but there is very great discrepancy of opinion as to the exact nature of the primary and essential lesion. Some maintain that the starting-point of the disease is in the solitary follicles which, becoming distended by a specific exudation, afterwards slough, and form the starting-point for a spreading ulcer. Other patholo- gists regard the primary lesion as being altogether independent of the glandular structures of the mucous membrane. They hold that, in consequence of the irritation produced by the specific cause of dysentery, an exudation is thrown out on to and into the con- tinuity of the mucous membrane itself ; a dry eschar is formed of this, the implicated piece of tissue being subsequently got rid of, very much in the same way as the slough forming the core of an ordinary boil. 298 Dysentery. Another primary lesion described is the small abscess, already alluded to as elevating the mucous membrane and projecting into the lumen of the gut; these minute, pimple-like abscesses consist of a collection of a sort of gummy pus. After a time a minute opening forms at the apex of the little swellings, through which the con- tents may be expressed, and, as already stated, it is this opening which they say forms, on enlarging, the specific ulcer of dysentery. Assuming that there are several specific causes for dysentery, it is to be ex- pected that the corresponding primary lesions differ ; that whilst one causes a suppurative or gangrenous lesion, another may produce a croupous or diphtheritic one which, in time, may also end in ulceration. Healing process.—The dysenteric ulcer heals partly by contraction, partly by the formation of a very thin scar tissue—scar tissue which, besides con- tracting, is apt to become pigmented. Lost glandular structures are never reproduced. Owing to the con- stant peristaltic movement of the gut, and the passage of faeces over the face of the healing ulcer, cicatrisa- tion, as might be supposed, is a slow process, and one prone to interruption by recurring attacks of inflammation. lesions in chronic dysentery.—In chronic dysen- tery the ulcers are usually smaller and less numerous than in the acute disease. They are also less ragged in outline, tending to become circular in shape and to acquire thickened rather than undermined edges. Cicatricial bands and contractions may narrow the lumen of the gut, whose functions are still further hampered by thickening, or by adhesions which unite and bind it to neighbouring organs. Dilatation above the seat of cicatricial stricture is liable to ensue. In chronic dysentery large patches of the bowel, and even the ulcers themselves, may be pale and anaemic; whilst, at the same time, other patches of the gut are congested. Some parts may be thickened and con- tracted ; others, again, may be thinned and dilated, the glandular structures being atrophied. /Etiology. 299 Polypoid growth,—Some time ago I attended a case of chronic relapsing dysentery in which the mucous membrane—at all events of the rectum and descending colon—was covered with enormous numbers of polypoid growths of considerable magnitude, some of them at their free ends being as large as the tip of the little finger. The growths had pedicles one to two inches in length. During life these polypoid bodies appeared in the stools, often in great number, looking like so many mucilaginous seeds. Similar cases are occasionally met with. Liver ; mesenteric glands.—In by far the majority of cases of acute dysentery, the liver is hyperaemic and swollen. In about one-fifth of the cases of Indian dysentery which come to the post-mortem table, the liver is the seat of single or multiple abscess. In chronic dysentery this organ may be atrophied ; very generally it is the subject of fatty degeneration. In acute cases the mesenteric glands are enlarged, soft, and congested; in chronic cases they are en- larged, hard, and pale. None of the other viscera are characteristically affected. Abscess is sometimes dis- covered about the rectum. If perforation has occurred, there may be signs of commencing peritonitis. .Etiology.—Our knowledge of the cause of dysen- tery is of a most fragmentary and unsatisfactory character. Probably the several specific causes or germs of colitis have their action supplemented by the ordinary bacteria of suppuration and ulceration, which find their opportunity in a tissue weakened by, what may be regarded as, the more specific cause or causes of dysentery. It must be with the mucous membrane of the bowel, in this respect, as it is with the skin of the surface of the body. There are many causes for eczema and many secondary germs which proliferate on, and further irritate, an eczematous skin ; so with the intestinal mucosa. Amoeba coli.—Lately, certain observers—par- ticularly Kartulis, Councilman, Lafleur, Kruse, and Pasquale—have endeavoured to make out that there 300 , Dysenter y. is a distinct type of dysentery associated with the presence of the amoeba coli in the stools. According to these authors, this type of the disease is caused by the amoeba, and they designate it "amoebic dysentery." As distinguished from other forms of the disease, its principal clinical characteristics are said to be chroni- city, relapses alternating with periods of comparative quiescence, great liability to the formation of abscess Fig. 28.—Amoeba coli. a, Amoeba dysenteriae fixed and stained (Councilman); 6, a. dyseuteriae in stools (after Losch, Virchow's •' Archiv," Bd. 65). of the liver, and the presence of the amoeba in the stools. When present, the amoeba (Fig. 28) is generally easy to find. All the preparation necessary is to pick out a small fragment of stool shortly after it has been passed, preferably a piece of flocculent mucus, and then to lay this on the slide, and compress it suffi- ciently under the cover-glass to form a fairly transparent film. In warm weather a warm stage is not required; but in cold weather it is well, until the observer has become by practice familiar Amceba Coli. 301 with the appearance of the parasite in its passive condition, to warm the slide. This, in the absence of more elaborate apparatus, may be conveniently done by.placing the slide on a copper or tin plate with a hole cut in it to allow the transmission of light. Such a warm stage should be provided with a long arm to the end of which a spirit lamp is applied, care being taken not to raise the tempera- ture of the slide above blood heat. Search is then made with a half-inch objective. The amoeba, which is a clear body, having a very faint, often hardly perceptible, greenish tinge, some three to five times the diameter of a red blood-corpuscle, is recognised by its movements, which closely resemble those of the ordinary fresh-water amoeba. It consists of a somewhat granular endosarc surrounded, when active, by a very clear ectosarc. A nucleus may sometimes be detected in the endosarc, as well as one or two non-contractile vacuoles, and, generally, various extraneous bodies such as blood-corpuscles, bacteria, and so forth, which the amoeba has included. As the temperature of the slide approaches blood heat the amoeba sends out and retracts rounded pseudo- podia. These when first protruded consist of ectosarc only ; but when the clear protrusion of ectosarc has been extended a little way the endosarc is seen suddenly to burst, as it were, and flow into it. If the temperature of the slide be allowed to fall below 75° Fahr. the parasite assumes a sharply-outlined spherical form and remains quite passive until the slide is again warmed up, when the creeping move- ment may be resumed. In certain specimens heat fails to induce movement, the amoeba remaining spherical and passive as if encysted. The parasite will keep alive on the slide and exhibit movement for an hour or two. There can be no question as to the occurrence of this parasite in dysentery, but it is difficult to say what may be its exact significance in relation to the disease. It is found not only in the mucus lying on 302 Dysentery. or thrown off by the inflamed bowel, but also in the sloughs on the ulcerated surface and even, according to Kartulis, Councilman and Lafleur, in the tis- sues constituting the base- and sides of the ulcer, and in the still living and relatively healthy tissues for some distance around the sore. These circumstances constitute a good primd facie reason for regarding the parasite as the cause of the disease. On the other hand, there are many cases of dysentery in which the amoeba cannot be found, cases, too, of relapsing dysentery with clinical characters such as the American authors referred to describe as belonging to amo'bic dysentery. I have searched the stools in some such cases many times, but, though familiar with the appearance of the parasite, in a proportion of instances—just as has happened to other observers—have failed to find it, and this in well- marked dysenteries, acute, relapsing, and chronic. Moreover, as is well known, the amoeba, or an amoeba hitherto indistinguishable from amoeba dysenteriae, is found in perfectly healthy stools, in cases in which there is no reason whatever to suspect the existence of disease of the alimentary canal. Gasser (Arch, de Med, Experim. et dAnat. Path. No. 2, March, 1893), in material supplied by 153 cases of d}7sentery—principally soldiers from Oran— although he found amoeba coli in 45 out of 109 acute cases, observed no relationship whatever be- tween the number of amoebae present in the stools and the severity of the disease. In 34 chronic cases he found the amoeba in 13 ; and in 8 cases of chronic diarrhoea supervening on dysentery he found it in 5. In the stools of 20 healthy indi- viduals from Oran he found the amoeba in 4. He further states that he failed to find, or rather to recognise, the amoeba in stained sections of dysen- teric bowel. He concludes, therefore, against the amoeba having anything more than an accidental relationship to the disease; that, in place of the amoeba Amceba and Bacterium Coli. 303 causing the dysentery, it is, if anything, the dys- entery which causes or, rather, favours the amoeba; in other words, the amoeba finds in dysenteric dis- charges a favourable medium for multiplying in. Celli and Fiocca (Hygiene Institut..- Roman. Univ., Feb. 19, 1895) studied the parasitology of dysentery in material from 62 typical cases—some from Italy, some from Egypt. They, too, conclude that the amoeba coli is not the direct cause of dysentery, and for the following reasons :—(a) Epidemic, endemic, and sporadic dysentery may occur without amoebae in the stools. (b) Dysentery may be induced by the ingestion, or by the injection into the bowel, of dysenteric faeces which have been ascertained by microscopic examination to be quite free from amoebae. (c) Amoebae are very common in countries in which dysentery occurs, hence their frequency in the stools of dysenteries in these countries; they are there accidentally. They further point out that the amoeba coli is not the only amoeba to be found in the intes- tine ; amoeba guttula, diaphana, vermicularis, oblonga and reticularis, besides proteus, have all been found there. The amoeba coli has attracted attention, they consider, principally on account of its movements and size ; whereas the other amoebae, with perhaps quite as good a claim to be considered pathogenetic, inasmuch as they can be detected only in specially-prepared cultures, elude the eye, even of the sharpest observer, in stools prepared in the ordinary way. Bacterium coli commune.-—Celli and Fiocca be- lieve that dysentery is caused by the bacterium coli commune which, they assert, is always present in the stools in this disease. Generally non-pathogenetic, this bacterium, they and others believe, acquires in certain circumstances very virulent properties. They say that in the bowel it is often associated with a bacillus like that of typhoid, as well as with strepto- cocci ; and they assert that introduced by the mouth, or injected by the rectum, either or all of these, particularly when in combination and in certain not 3°4 Dysentery. understood circumstances, either singly or in combina- tion excite dysentery. They suppose that what they call the bacterium coli dysenteriae is but a variety of the bacterium coli commune, a variety brought about in some way by the presence of the other bacteria mentioned ; that in consequence of the presence of these other bacteria the bacterium coli commune ac- quires the power of secreting a specific toxin, which power it retains on being transferred from one human being to another. The toxin, they say, can be pre- cipitated by alcohol from cultures, and has the property of giving rise to dysentery when adminis- tered by the mouth, the anus, or hypodermically. These results require confirmation, more particu- larly as the writers experimented on the cat, an animal very subject to dysentery at all times and on the introduction of almost any irritant. Streptococci.—Zancarol considers that dysentery and dysenteric liver abscess are caused by streptococci. Significance of the concurrence of dysentery, liver ab- scess and amoeba coli, in connection ivith absence of pus bacteria in the liver abscess.—The intimate connection of abscess of the liver with dysentery, and the presence of the amoeba in the pus of a large proportion of liver abscesses, are now well-ascertained facts which, to my mind, constitute a powerful, though by no means a conclusive, argument for regarding the amoeba as an aetiological element, if not the probable cause, in at least one form of dysentery. The fact that the amoeba is found in liver pus proves that Councilman and Lafleur's statement about its presence in the tissues around the dysenteric ulcer is correct; for it is only by first pass- ing into the tissues that such an organism could get into the portal circulation and so arrive at the liver. There is yet another circumstance in connection with liver abscess which is not without a significance pointing in the same direction. In a large proportion of liver abscesses the usual pyogenetic bacteria are absent. This has been proved over and over again. Cultures made with such pus often remain sterile. It is a The Water-borne Germ. 305 very singular coincidence that it is just in those forms of suppurative hepatitis in which the usual pyogenetic organisms are absent that we find this other parasite present. Moreover, a liver abscess has no proper abscess wall. Liver pus is not like pus elsewhere ; it contains proportionately very few pus corpuscles; but it contains much debris of the tissues, many blood cells, and much granular matter. As an abscess, it is altogether peculiar. A peculiar effect suggests a peculiar cause. Anyone who has watched the movements of the amoeba coli on the warm stage can readily understand how such an organism might break down and separate the anatomical elements of an organ like the liver and so cause a softening—a cavity resemblino- an abscess. It feeds on the tissues, in fact, and to grow and multiply it must disintegrate their structures and consume their cells. I shall point out elsewhere that the amoeba coli occurs much more frequently in liver abscess than is generally supposed; thereby strengthen- ing the argument for regarding this parasite as'being in causal relationship to liver abscess and, therefore, pro tanto to dysentery. The germ of dysentery water-borne.—Notwith- standing the vast amount of speculation, and perhaps somewhat limited amount of work, expended in endeavouring to ascertain what the germ or germs of dysentery may be, it cannot be said that as yet we are even near the solution of the problem. One thing, however, is fairly well ascertained, and that is that these germs, whatever they may be, are often in- troduced by means of drinking water. The statistic- ally ascertained improvement in the public health in respect to dysentery in such large towns as Calcutta and Madras following so closely on the introduction of improved water supplies; the improvement in the health of the British Navy following the introduction of regulations requiring that, in all places in which the water supply is not above suspicion, the drink- ing water served out to the men should be distilled; u 306 Dysentery. constitute powerful testimony in favour of regarding dysentery as a water-borne disease. This conclusion receives additional support from the occurrence of epidemics of dysentery in the crews of ships which have watered at polluted sources; as well as by the occurrence of similar epidemics in large institutions in which, by some accident, surface water has leaked into the water supply. This, of course, does not exclude the possibility of other sources of infection, as by privies, and by vessels or instruments used by dysenteries ; but the water theory probably covers the vast majority of dysentery epidemics, as well as of sporadic cases. Predisposing and exciting causes. — It seems not improbable that, in conditions of sound health, the pathogenetic organisms of dysentery may exist in and pass through the alimentary canal without attacking the tissues and giving rise to the disease. So long as the mucous surface is sound and vigorous, it probably has the power of protecting itself against many such organisms. It is very probably the same in this respect with the dysentery germ or germs as with the cholera vibrio. It is probable that it is only on the establishment of some condition of lowered vitality, such as may be induced by catarrhal troubles, chill (a powerful excitant of dysentery), irritating food, bad food, constipation, malaria, scurvy, starva- tion, and so forth—all well-recognised exciting causes —that the dysentery germ can overpower the natural protective agencies and light up the specific lesions. It is a well-known fact that it is in such circum- stances that dysentery is most apt to declare itself. Hence the importance of avoiding these things in tropical climates, more especially in the presence of a bad water supply or of an epidemic. It seems probable that the well-known liability of lunatics to dysentery is associated with that lowering of the resistive powers which is so pronounced a feature in many forms of insanity. Influence of age, sex, and occupation.—All ages Diagnosis. 307 are subject to dysentery, children especially. Occu- pation has no special influence. Both sexes are liable. Pregnancy, miscarriage, and the puerperal state are grave complications. Diagnosis. — Provided reasonable care be exercised, diagnosis, especially in acute cases, is usually easy. In chronic cases the question of haemorrhoids, polypus, stricture, tubercle, malignant and specific disease, proctitis, abscess about the rectum, and tumour in the bowel, may require to be considered. Diagnosis must never be taken for granted. In every case stools must be inspected ; and in every case in which there is any probability of rectal disease digital or specular examination must be made. In African cases the possibility of bilharzia disease of the rectum must be borne in mind, and a microscopical examination made of the urinary sediments and of the faeces with a view t) the detection of any ova of bilharzia which may be present. In children especially, intussusception may occur independently, or as a complication, of dysen- tery ; the possibility of this must not be overlooked. Chronic dysentery is often diagnosed chronic diarrhoea. This error will be avoided by careful inquiry into the early history of the case, the detection of mucus or of blood corpuscles in the stools, and the occurrence of tenesmus. Careful inquiry for any history there may be of occasional exacerbations, in which straining, blood and mucus in the stools, are more or less prominent features, will often lead to a correct diagnosis. Treatment.—The treatment of dysentery re- quires much judgment and very careful supervision. In former days it was the fashion to bleed repeatedly and to large amount, and, at the same time, to ad- minister large doses of calomel—amounting in the aggregate to ounces—and opium. It is not to be wondered at, therefore, that in those days the mor- tality was excessive. Nowadays better and more rational methods u 2 3o8 Dysentery. prevail. There is less confidence in drugs, more in the self-recuperating powers of the body. A most important part of our modern plans has for its object to afford the diseased organs favourable conditions for repair; not so much to endeavour to heal them, as to give them the opportunity of healing themselves. If called on to treat a case of what appears to be dysentery, our first duty is to assure ourselves that diagnosis is correct. We must inspect the stools, and, until the case is quite recovered, we must inspect them daily. Their condition is the surest guide in the management of this disease. From them we can form a fairly accurate idea of what is going on in the bowel; and from them we can judge of the effects of diet and of drugs. Importance of rest. — It is with an inflamed bowel as with an inflamed joint; the first and all- portant indication to fulfil is, after removing the causes of irritation, to place the part at rest. Could these two indications, the removal of the cause of irritation and the repose of the organ affected, be fulfilled thoroughly, cure would at once set in. Un- fortunately, the affected surface being so inaccessible, we cannot always remove the irritant in the case of dysentery, nor can we place the parts involved at absolute rest. We can, however, partially meet these indications—quite sufficiently, as a rule, to insure recovery. The diagnosis of dysentery established, the patient should at once be sent to bed. This in itself has a marked influence on the bowel. Repose must be as nearly complete as possible. The patient must not be allowed to get out of bed ; when he has a call to stool he must use the bed-pan. To a certain extent this enforcement of rest is comparable to the placing of an inflamed leg in a splint and elevating it. It insures a certain amount of mechanical rest, and relieves the blood-vessels of the inflamed part of a certain amount of hydrostatic pressure. Food in acute dysentery.—The indication of rest Trea tment. 309 we further endeavour to meet by stopping all solid food. Were it possible, it would be well to stop all food. This, of course, is impossible, and so we make a compromise between the therapeutical indication and physiological necessity, by reducing the diet to a minimum and selecting only such foods as, while possessing considerable nutritive value, yield but a small fa'cal residue. The tongue is a fair index to the sort of food most likely to suit the case. When this organ is coated, indicating gastric catarrh, small quantities of thin chicken soup, egg albumin, thin barley or rice water, are better borne than milk; when the tongue is or has become clean, then milk, pure, diluted with barley- or rice-water, or peptonised, is the best diet. These foods should be taken in small quantities at a "time, a little every hour. They must be given neither hot nor cold, as food when either too hot or too cold is more apt to excite peristalsis and to cause colic and straining. Malaria and scorbutus.—If upon inquiry it is found that there is reason to suspect either a malarial or a scorbutic element in the case, treatment must be modified accordingly. Careful practitioners never forget to ascertain if these important complicating elements are present or not. If malaria be suspected, it would be well to make a careful microscopic examination of the blood for the plasmodium; if the parasite is found, then quinine must be freely administered either by the mouth or, if the bowels are very irritable, by hypodermic injection. The presence of scorbutus, of course, indicates fruit juices and fresh unboiled milk, in addition to the usual treatment for dysentery. Drug treatment.—The patient has been sent to bed; a diet has been prescribed, malarial or scorbutic complications, should they be present, have been provided for; attention must then be directed to en- deavour by one, or two, or three drugs to influence more directly the inflamed bowel. The drugs which have proved of most service in 3io Dysentery. the treatment of dysentery are ipecacuanha, one or other of the aperient sulphates—either of magnesia or of soda—opium, and calomel. It is difficult to prog- nosticate in any given case whether ipecacuanha is likely to prove the more effective drug, or whether the sulphates or calomel will answer better. In every case one or the other ought to be exhibited at once ; one failing after a fair trial, the other, unless manifestly contra-indicated, should get a chance. Ipecacuanha.—In English practice ipecacuanha is generally the first to be tried. It must be given on an empty stomach. The best plan is to interdict all food for three hours ; then to give fifteen or twenty drops of laudanum in a tablespoonful of water and, at the same time, to apply a mustard poultice to the epigastrium. About twenty minutes later, when the patient is coming under the influence of the laudanum, twenty to thirty—some give as much as sixty—grains of ipecacuanha in pill, bolus, keratine capsules, or in suspension in about half a wineglassful of water, are administered. With a view to prevent vomiting, the patient is directed to lie flat on his back—better with- out a pillow—and not to eat, drink, speak, nor move for at least three or four hours. Probably he will fall asleep. Should he feel nauseated, he must resist the desire to vomit as much as possible. With the same object in view, when saliva begins to collect in the mouth, as it is apt to do in such circumstances, it must not be swallowed; on a slight sign from the patient the nurse should remove the accumulating saliva with a handkerchief. If much saliva be swallowed, it is sure to provoke vomiting. In some instances these precautions suffice to avert emesis. Should, however, the ipecacuanha be brought up within an hour of its being swallowed, the dose had better be repeated so soon as the nausea has subsided, the same precautions against vomiting being observed. After three or four hours, and when all feeling of nausea has subsided, small quantities of food may be Trea tment. 3H given, and frequent and fractional feeding persisted in for six or eight hours, or until the following day, when the dose of ipecacuanha must be repeated. As a rule, one or two such doses abort the dysentery, and the acute symptoms rapidly subside. It may be necessary to go on with the ipecacuanha once or twice a day for three or four days. Aperient sulphates.—Should, however, this drug appear to be doing no good, sodium sulphate—which is less irritating than magnesium sulphate—may be tried (indeed, this may be preferred at the outset). These salts have the advantage over ipecacuanha of not causing nausea, and they are often quite as successful. They may be given in drachm doses in a little hot water every quarter of an hour until a purgative effect is produced, or they may be given in a large dose— half an ounce—to begin with, followed up by smaller doses if necessary. The purgative effect should be obtained once or twice daily, and for two or three days at least. The lessening of tenesmus and the production of copious, watery, feculent stools is the test of the successful action of the sulphates. Calomel. — Should these means fail to control the disease, and should the bloody mucoid stools persist, and the griping and tenesmus continue, recourse may be had to calomel in combination with opium and ipecacuanha—a grain of each every five or six hours, the effect being watched and salivation avoided. Some give calomel from the outset as a routine treatment in dysentery, either in five-grain doses every six or eight hours, or in fractional doses every hour. This method is most in vogue in Germany, and is probably best suited for the croupous forms of the disease. In France the sulphates are most in vogue; while British physicians, relying on Indian experience, place most confidence in ipecacuanha. Bismuth and opium,—As a result of either line of treatment, the dysenteric symptoms may subside rapidly —perhaps entirely. Sometimes, although the stools become faecal, and the mucus and blood disappear, 312 Dysentery. a sort of diarrhoea remains. This generally quickly yields to a salicylate of bismuth (grs. x-xx) and morphia (gr. T\,-) mixture. Other drugs.—Simaruba (ailanthus glandulosa) sometimes succeeds where other measures have failed. It is a drug which, though nowadays neglected in Europe, is still much used in the East by so-called " dysentery doctors." It seems to be specially ser- viceable when the case has become subacute or chronic. To be effective, it requires to be given in much larger doses than is directed in the Pharma- copoeias. One method of preparation I have seen employed is as follows :—Using an earthenware pot, boil half an ounce of simaruba in a pint and a half of water for three hours, and then strain it. Let the patient remain in bed and drink this decoction on an empty stomach every second morning for four times. Food must consist of milk and farinaceous stuffs. Another method is to boil an ounce of simaruba in twelve ounces of water until it is reduced to seven drachms; to this a drachm of spirit is added. This preparation, also, must be made in an earthenware or in an enamelled dish. For an adult this is a suitable dose ; a child may take a fourth part. It should be taken every night for four nights. Monsonia ovata,—Dr. John Maberly (Lancet, February 6th, 13th, 1897) reports very favourably on monsonia ovata — a South African plant — in dysentery. He uses a tincture of two and a half ounces of the dried plant to the pint of rectified spirit. It gave in his hands wonderful results, even in chronic cases and in acute cases which had resisted the ordinary remedies. Cinnamon sometimes does good in chronic dysen- tery, as also pomegranate; either may be combined with simaruba. I can offer no explanation of the action of any of these drugs in dysentery. We use them quite empirically. Ipecacuanha and simaruba really seem to have some .sort of specific action on the disease or Trea TMENT. 313 on its cause, but in what way it is impossible to indi- cate. Strange to say, ipecacuanha, which has been found so serviceable in India, Africa, the Brazils, and elsewhere, has a very poor reputation as an anti- dysenteric in the United States (Osier); it has also signally failed in some English epidemics (Clouston) ; facts pointing to specific differences in the dysenteries of different countries. Relief of pain. — During the attack the patient may suffer much from griping and tenesmus. These are generally relieved by hot fomentations, turpentine stupes, or by a hot bath. An excellent application is the Japanese hot-box, a small tin box containing a slowly-burning cartridge of powdered charcoal. Three or four of these hot boxes may be roughly sewn into a piece of flannel and laid on the abdomen. This appli- cation has the advantage of being very light, of not wetting the clothes, and of keeping warm for many hours. Tenesmus and dysuria are best relieved by morphia hypodermically ; or by an enema of a wine- glassful of thin starch containing forty or fifty drops of laudanum ; or by suppositories of morphia and cocaine. Washing out the rectum with a pint of very hot water, with or without boracic acid, is sometimes effectual in removing for a time or, at all events, of mitigating the incessant desire to go to stool and to strain. Two drachms of bismuth with laudanum, thirty minims, and thin starch, two ounces, is also a good sedative enema (Davidson). Treatment should be energetic and thorough at the outset of dysentery. Every effort must be made to prevent it from becoming chronic, as in this stage the disease is very difficult to treat successfully, and is prone to terminate in permanent invalidism. Treatment of chronic dysentery. Nitrate of silver injections. — The most effective treatment of certain types of chronic dysentery is undoubtedly massive injections of large quantities of nitrate of silver solution of a strength of from half a grain to one grain to the ounce of distilled water. There is 3H Dysentery. a right and there is a wrong way of using this splendid remedy. If employed in the wrong way, it is useless, perhaps worse than useless. It must never be prac- tised when acute symptoms are present. These must first be got rid of by ipecacuanha, by the sulphates, by calomel, and by rest and diet. The patient should be prepared for a week at least in this way. Then the bowel is to be cleared by a minute dose of castor oil, followed by a large enema of three or four pints of warm water to which two or three tea^- spoonfuls of carbonate of soda have been added. The whole of this injection having escaped, and when the bowel is quite empty, two to three pints of the nitrate of silver solution are thrown in by means of a long tube passed slowly and carefully into the bowel as far as it will go without kinking. It is better to fill the bowel by gravitation, using a funnel and tube, rather than by a syringe. The patient should be encouraged to retain the injection as long as he can, to lie flat on his belly, and to roll from side to side so as to secure that the injection comes in contact with every portion of the large intestine. If it seems to be doing good, this injection may be used every few days and kept up for some time. Im- provement in suitable cases generally sets in at once. The nitrate must not be persevered with if it causes any marked irritation or increase of symptoms. In the mild chronic dysenteries which are seen in Great Britain, and which originally had been contracted in the tropics, and also in the more acute relapses of tropical dysenteries, ipecacuanha should always be tried. Other methods of treating chronic dysentery which succeed at times are the systematic washing out of the bowel daily with boracic water, with linseed in- fusion, with mangosteen rind decoctions, with weak alum water solutions, with tannin ; systematic dosing with minute quantities of castor oil, with or with out morphia; ten to twenty drops of turpentine three times a day ; the daily consumption of some Trea tment. 315 preparation of fresh bael fruit; a course of Carlsbad, of Kissingen, or of Vichy water; a diet of grapes only, of milk only, or of beef only; cold water com- presses to the abdomen. Post-dysenteric constipation. — After the subsi- dence of a dysentery constipation and balling of the stools is by no means an uncommon event. This complication is best prevented, or met, by enemata of warm water to which a little salt has been added—a teaspoonful to the pint—or, if the bowel is very irritable, of linseed tea or of thin rice-water. An occasional dose of castor oil, half to one teaspoonful, once or twice a week or oftener, and kept up so long as the motions are not quite healthy, is an excellent routine practice ; its action may be sup- plemented by a glycerine suppository. A course of Carlsbad waters or salts often gives excellent results. Food and clothing.—In chronic dysentery much attention should be given to clothing and food. The former should be very warm. Dysenteries ought never to feel cold. Cold bathing is very dangerous for them ; so are alcoholic drinks of all sorts. Food should be simple in the extreme. Beef, mutton, cheese, bread, coarse fruit or coarse vegetables, nuts, pickles, and such-like are, as a rule, not well borne. Fruit and fine well-cooked vegetables in moderation are neces- sary and often beneficial. In obstinate chronic dysentery it is often a good thing to change the diet from slops to solids, from a meagre to a more liberal one. Wonderful results are sometimes got from a sea voyage. Hepatitis. — During the whole course of an attack of dysentery, and for months thereafter, the con- dition of the liver must receive the most careful attention. We may not be able to prevent abscess of this organ; but if pain and swelling seem to suggest it as threatening we can try, by means of saline aperients, ipecacuanha, rest, low diet, fomentations, dry cupping, and such-like measures, to avert what, to say the least, is a very grave complication. 316 Dysentery. Prophylaxis.—The prophylaxis of dysentery consists principally in securing a pure water supply, in avoiding unwholesome food, in temperance, in clothing warmly and avoiding chill, in correcting con- stipation and stopping diarrhoea. 3i 7 CHAPTER XIX. EPIDEMIC GANGRENOUS RECTITIS. So far as known, this very fatal, disease seems to be confined to the natives of the low-lying, hot, damp regions in the north of South America and, perhaps, to the natives of Fiji and other islands of the South' Pacific. In Guiana it is known as " Caribi " or Indian sickness, in Venezuela as " Bicho " or " El Becho." It is said to be very contagious, and appears to be a form of rapidly.spreading phagedena, which starts from the neighbourhood of the anus. Occasionally it may begin higher up—in the colon. In this case it is called the " high " form ; in the other, the " low " or rectal form. Animals, as well as men, are attacked. I am indebted to Dr. Ackers of Curagoa, formerly of Venezuela, for the following information on the subject:—" I have only seen cases of the disease in animals, principally fowls, though also in dogs and calves; but I have been told by medical men, who themselves attended the cases, of its occurrence in children of the poorer classes. The disease commences by an itching in the anus, which produces an inclina- tion to frequent defaecation. This stage continues for a few days, when a severe inflammation of the mucous membrane of the rectum sets in, giving rise to symptoms of acute dysentery. There are frequent stools of a mucous, bloody substance, accompanied sometimes by bile or excrement ; at the same time, there is much straining, considerable elevation of temperature, anorexia, and great thirst. At this period, if the animal or child is not attended to, the above symptoms become more alarming ; a constant flow of a slimy, foetid, semi-liquid substance streaked with blood appears. Sometimes the discharge is of a 318 Epidemic Gangrenous Rectitis. bright green colour, such as might be obtained by crushing tender stalks of grass. When this occurs the patients refuse all food, but the thirst is still intense. The affected animal remains standing in one place, with drooping head, as if overcome by fever and weakness. For a day or so it continues like this, until at last, unwilling to move, eat, or even drink, it suddenly dies in convulsions. Sometimes, however, this stage is not fatal, but is followed by prolapsus of the rectum, which is in a very inflamed state and ulcerated; rapidly gangrene sets in and is quickly fatal. The Venezuelan peasants state that this disease arises in children from chewing the green tender stalks of unripe maize, of which they are very fond on account of its sweetness. In children pro- lapsus of the rectum is very frequent; in fatal cases they may die, like the animals, in convulsions, though in children convulsions are not necessarily a fatal symptom. The treatment employed by the natives for animals consists in an enema of strong lemon juice, mixed with a weak dilution of white rum and water (aguardiente), two or three times a day ; at the same time, the anus is freely dusted with wood ashes, some of which are also introduced into the rectum. A purgative of oil is generally administered also. In some cases I have known this treatment prove very successful. On the other hand, when the disease is too far advanced, or when the ulceration of the bowel appears at an early date, it seems to be of little or no avail. Another treatment employed, especially for children, consists in an enema of the juice obtained by crushing the stalks and leaves of spigelia anthel- mintica (pasote). A decoction of the same herb is also given by the mouth three or four times a day. This decoction is very frequently administered by the peasants as an anthelmintic. In cases of children suffering from ' bicho,' one of the quarters of a lemon is roasted and introduced into the rectum as a suppository once or twice a day, and I have heard that it gives very satisfactory results." 3^9 CHAPTER XX. HILL DIARRHOEA. Definition.—A form of morning diarrhoea accom- panied by flatulent dyspepsia and the passage of copious, liquid, pale, frothy stools. It occurs princi- pally in Europeans on their visiting the hills after residing for some time in the hot lowlands of tropical countries. Geographical and seasonal distribution. Crombie, who gives an excellent account of this disease (Ind. Med. Gaz., Dec. 1880; May, 1892), points out that a similar affection may show itself in the highlands of Europe as well as in those of India. It is said also to occur in corresponding circum- stances in South Africa. There is no reason, therefore, to suppose that hill diarrhoea is special to India, although, owing to the large European population frequenting the hill sanitaria in that country, it has been particularly noticed there. An elevation of 6,000 feet or over, if combined with an atmosphere saturated with watery vapour, is particularly favourable to its development. In India it is found to begin and end with the rains, during which, in certain years and places, it is apt to assume almost epidemic characters. Thus, during the wet season of 1880 in Simla, an epidemic of hill diarrhoea affected from 50 to 75 per cent, of the population, three-fourths of the cases happening within a week of each other. In some years hill diarrhoea is less prevalent than in others ; but at the proper season few of the various hill sanitaria of India are without examples. Symptoms.—Without very obvious cause the patient, who in other respects may be in good health, 320 Hill Diarrhosa. soon after arrival at a hill sanitarium becomes subject to a daily recurring diarrhoea, the looseness coming on regularly every morning some time between 3 and 5 a.m. The calls to stool are often sudden and impera- tive ; the motions passed being remarkably copious, very watery in some instances, pasty in others, pale, frothy, and looking like recently stirred whitewash—■ so devoid are they of biliary colouring matter. Their passage is attended with little or no pain, often with a sense of relief. From one to half a dozen, or more, such stools may be voided in the morning before 11 a.m. After that hour, at all events in ordinary cases, the diarrhoea is in abeyance for the rest of the day, and the patient may then go about his duties or pleasures without fear of inconvenience. The distinctive features of this form of diarrhoea are, therefore, the regularity of its recurrence every morning and its cessation after a certain hour in the forenoon; the absence of bile in the stools; and the attendant flatulence. The abdomen is sometimes blown out like a drum, the patient being conscious of unpleasant borborygmi, associated with a feeling as of some boiling or chemical operation proceeding in his inside. Occasionally cases are met with in which the stools are very pale, but in which there is no diarrhoea. Under treatment, or spontaneously, or, according to Crombie, on acclimatisation occurring, after some days or weeks the diarrhoea may subside. In other instances it persists, in defiance of treatment, until the return of the patient to the warm plains, when it at once spontaneously subsides. Crombie in- stances a case in which the patient was regularly attacked with hill diarrhoea whenever he visited Simla—twelve occasions—recovery invariably taking place on his return to the plains. If the looseness is not only considerable, but also protracted, there neces- sarily ensue debility, wasting, and anaemia, and the disease may lapse into confirmed sprue—an affection having, apparently, close affinities with hill diarrhoea. Trea tment. 321 JEtiology and pathology—It is difficult to say what may be the precise factors determining this disease. Low barometric pressure, associated with great elevation above the sea-level, may be a favouring circumstance. Damp seems to be indicated by the fact that the disease occurs principally during the rains. Chill after exposure to the high temperature of the plains has possibly an important share. Manifestly there is a suspension of the functions of the liver and, considering the dyspepsia and looseness, most probably of those of the pancreas and of the other glandular structures subserving digestion. Hill diarrhoea is certainly something more than an intestinal catarrh. As Crombie points out, it is more of the nature of dyspepsia. There are no adequate grounds for connecting it with either the water or the food supply. The question of micro-organisms has, ap- parently, not been studied. Treatment.—The treatment recommended by Crombie, and endorsed by other medical men of experience in India, consists in a pure milk diet, rest, warm clothing, a teaspoonful of liquor hydrargyri perchloridi in water about fifteen minutes after food, and twelve grains of pepsine, or a corresponding quantity of lactopeptine or ingluvin, two hours after food. If, in spite of treatment, the disease persists, the patient must return to the low country. v 322 CHAPTER XXI. SPRUE (PSILOSIS). Definition.—By the term "sprue" is understood a peculiar and very dangerous form of chronic catarrhal inflammation of the whole or part of the mucous membrane of the alimentary canal, generally asso- ciated with suppression of the chologenic function of the liver and, probably, of that of the other glandular organs subserving digestion. It is frequently met with in tropical countries, particularly in European residents. The same disease may develop for the first time in temperate climates ; only, however, in individuals who have previously resided in the tropics or subtropics. Sprue is characterised by irregularly alternating periods of exacerbation and of compara- tive quiescence ; by an inflamed, bare, and eroded condition of the mucous membrane of the tongue and mouth ; by flatulent dyspepsia ; by pale, copious and generally loose, frothy, fermenting stools; by wasting and anaemia; and by a tendency to relapse. It may occur as a primary disease, or it may super- vene on other affections of the bowels. It is very slow in its progress; and, unless properly treated, tends to terminate in atrophy of the intestinal mucosa, which usually, sooner or later, proves fatal. Nomenclature.—Sprue has been more or less recognised by writers on tropical medicine for many years. It has been called "tropical diarrhoea," " diarrhoea alba," " aphthae tropicae," " Ceylon sore mouth," " psilosis linguae" (Thin), besides a variety of other names. The term " sprue " is an adaptation from the Dutch word "spruw" infuse in Java, where the disease is very common. /Etiology. 323 Geographical distribution.—It is probable that sprue, although more common in certain warm countries than in others, is found throughout the greater part of the tropical and many parts of the subtropical world. It is especially common in South China, Manila, Cochin China, Java, the Straits Settlements, Ceylon, India, tropical Africa, and the West Indies (Hillary). Apparently it is most prevalent in those countries in which high tempera- ture is combined with a moist atmosphere. It is common, however, in certain subtropical countries, as North China, and, occasionally, even in Japan; countries where, although the summer is hot and damp, the winter is dry and bracing. ^Etiology.—Prolonged residence in the endemic area is perhaps the most potent predisposing influence; cases, however, do occur in which the disease shows itself after a residence of one or two years only. Exhausting diseases, particularly those involving the alimentary canal, as dysentery, hill diarrhoea, morning diarrhoea, haemorrhoids, and fistula, are apt to terminate in sprue. Frequent childbearing, miscarriages, uterine haemorrhages, exhausting discharges, and prolonged lactation also predispose to the disease; so may syphilis, courses of mercury or of iodide of potassium, bad food, bad water, anxiety, chills, and so forth—in fact, any depressing influence, particularly if it is combined with intestinal irritation. Malaria does not seem to be specially responsible. At one time the anguillula stercoralis (p. 550), a parasite very common in the stools of cases of chronic intestinal flux, particularly in Cochin China, was put forward as the cause of the chronic entero-colitis (for the most part sprue) of that country. Subsequent investigations have disproved this. Like the anguillula, the amoeba coli may be present in the stools in these cases; but, similarly, it is in no way responsible for the disease. Neither has any bacterium which can be regarded with any degree of certainty as special to sprue, been separated from the characteristic stools. In searching for the v 2 324 Spr ue. fundamental cause of this affection, the latency which the disease occasionally exhibits, and the fact that the first symptoms may not appear until months or even years have elapsed since the patient quitted the tropics, must be kept in view. Symptoms. — Variability. — There is infinite variety in the combination and in the severity of the various symptoms of sprue, as well as in the rate of progress of the disease. In some instances it may be almost a subacute process running its course in a year or two ; in others, again, it may drag on intermit- tingly for ten or fifteen years. Much depends in this respect on the circumstances, the character, the care, the treatment, and the intelligence of the patient. General symptoms in a typical case. — In an ordinary fully developed case the patient—who is generally dark or muddy in complexion and much emaciated—complains of three principal symptoms :— soreness of the mouth, dyspeptic distension of the abdomen, looseness of the bowels ; the last being par- ticularly urgent during the morning and earlier part of the forenoon. The patient may also complain of feeling physically weak, of loss of memory, and of inability to take exercise or to apply his mind. His friends will probably volunteer the information that his temper is irritable and unreasonable. Mouth lesions.—If the mouth is examined, the soreness will be found to depend on a variety of lesions of the mucous membrane, which, though painful, seem to be of a very superficial character. These lesions vary considerably in intensity from day to day. During an exacerbation the tongue looks red and angry; superficial erosions, patches of conges- tion, and perhaps minute vesicles appear on its surface, particularly about the tip. Sometimes, from the folding consequent on swelling of the mucous membrane, the sides of the organ have the appear- ance of being fissured. The filiform papillae cannot be made out, although here and there the fungiform papillae may stand up, pink and swollen. If the Symptoms. 325 patient be made to turn up the tip of the tongue, very likely red patches of superficial erosion, some- times covered with an aphthous-looking pellicle, may be seen on either side of the fraenum. On everting the.lips, similar patches and erosions are visible; and if the cheek be separated from the teeth the same may be seen on the buccal mucous membrane. Occasionally the palate is similarly affected; very often in this situation the mucous follicles are enlarged, shotty, and prominent. The gullet and uvula may also be raw and sore. In consequence of the irritation caused by these superficial and exceedingly sensitive lesions, the mouth tends to fill with a watery saliva which may dribble from the corners. If the patient attempts to take any sapid food, strong wine, or anything but the very blandest diet, the pain and burning in the mouth are intolerable ; so much so that, although perhaps ravenously hungry, he shirks eating. Not in- frequently swallowing is accompanied and followed by a feeling of soreness and burning under the sternum ; suggesting that the gullet, like the tongue, is also in an irritated, raw, and tender condition. During exacerbations of the disease the condition of the mouth becomes greatly aggravated. Although during the temporary and occasional improvements it becomes much less painful, even then salt, spices, strong wines, and all kinds of sapid food sting un- pleasantly ; and the tongue, particularly along its centre, is seen to be bare and polished as if brushed over with a coating of varnish. At all times the tongue is abnormally clean and devoid of fur; during the exacerbations it is swollen, but during the remis- sions, and when not inflamed, it is small, pointed, and, owing to the probably anaemic condition of the patient, yellowish like a piece of cartilage. Dyspepsia.—Dyspepsia is usually much complained of, the feelings of weight, oppression, and gaseous distension after eating being sometimes excessive. Very likely the abdomen swells out like a drum, 326 Spr ue. and unpleasant borborygmi roll through the bowel. Occasionally, though not often, there may be vomit- ing, the vomiting sometimes being sudden and not always accompanied by feelings of nausea. Diarrhoea.—The diarrhoea associated with sprue is of two kinds; one chronic and habitual, the other more acute and, in the early stages, evanescent. The former is characterised by one or more daily dis- charges of a copious, pale, greyish, pasty, fermenting, mawkish, evil-smelling material. The latter is of a watery character, also pale and fermenting, the dejecta perhaps containing undigested food. In these latter circumstances the diarrhoea usually brings with it considerable relief to the dyspeptic distension, at all events for a time. When the mouth is inflamed the diarrhoea is usually more active. The stools during periods of quiescence may be confined to one or two in the early morning or forenoon ; during the later part of the day the patient is not disturbed. The stools, however, even in this quiescent phase, are always extraordinarily copious; patients remark their phenomenal abundance. They are passed almost, or altogether, without pain. Not infrequently during exacerbations there may be a, tender excoriated con- dition of the anus, and sometime3, in women, a similar condition of the vagina. The stools in sprue are acid. (Thin.) Types, history, course, and termination. Proto- pathic sprue.—There is a striking uniformity in the history of most cases of sprue. On inquiry, we shall probably learn that the patient has been suffering for months, or perhaps years, from irregularity of the bowels. This, we may be told, began soon after arrival in the tropics as a bilious morning diarrhoea. For a long time this morning diarrhoea went on, without interfering in any way with the general health. Later the mouth, now and again, became tender, little blisters or excoriations appearing for a day or two at a time about the tip of the tongue or inside the lips. These sore spots would come and Symptoms. 327 go. Perhaps, from time to time, exacerbations of the mouth symptoms would be associated with a little increase of diarrhoea. Cradually the stools lost their bilious character and became pale and frothy; dyspep- tic symptoms, particularly distension after meals, now appeared. As time went on, these symptoms would recur more frequently and in a more pronounced form, following, almost inevitably, any little impru- dence as regards food or exposure. The general condition now began to deteriorate; emaciation, languor, lassitude, and inability to get through the day's work satisfactorily, becoming more pronounced each summer until, finally, a condition of permanent invalidism was established. Should the disease con- tinue to progress, the emaciation advances slowly but surely. Diarrhoea- may be almost constant, and now no longer confined to the morning hours; the com- plexion becomes dark, sometimes very dark ; the appetite, sometimes in abeyance, is more frequently ravenous ; unusual indulgence in this respect being followed by increased discomfort, temporarily relieved by smart diarrhoea. Finally the patient is confined to the house, perhaps to bed. The feet now become (edematous, and the integuments hang like an ill- fitting garment, the details of the bony anatomy showing distinctly through the dry, scurfy, earthy skin. Finally, the patient dies in a semi-choleraic attack ; or from inanition ; or from some intercurrent disease. Such is the history of an ordinary, mis- managed case of sprue. Sprue secondary to dysentery.—When the disease has supervened on dysentery, we shall learn that the motions characteristic of the original dysen- teric attack gradually changed in character; from being scanty, mucoid, bloody, and accompanied with pain and tenesmus, they became diarrhoetic, pale, frothy, their discharge being followed by a feel- ing of relief rather than of pain. The mouth at the same time became sore, exhibiting the char- acters already described. Gradually a condition of 328 Sprue. confirmed sprue was established, which ultimately, unless properly treated, will almost certainly prove fatal. Sprue secondary to acute entero-colitis.—Another type of case commences as an acute entero-colitis with sudden and profuse colicky diarrhoea, vomiting perhaps, and a certain amount of fever. The acute symptoms do not subside completely, but gradually have the typical symptoms of sprue grafted on to those of an acute intestinal catarrh. Incomplete sprue, (a) Gastric cases.—Occasion- ally we meet with cases of confirmed sprue in which, at first, the morbid process, judging from the existing clinical symptoms and subsequent history, is confined to a limited part of the alimentary canal. Thus we sometimes get sprue without diarrhoea, the principal symptoms being sore mouth, dyspeptic dis- tension, pale but solid stools, and wasting. (b) Intestinal cases.—On the other hand, we may get cases in which the mouth is not ulcerated, and in which there is little or no distension or dyspepsia, but in which the stools are liquid, copious, pale, and frothy. Sometimes a patient may have suffered at an earlier period, or on a former occasion, from the first type of the disease, who, later, acquires the diarrhoetic form ; and vice versa. (c) Sprue without diarrhoea.—It sometimes hap- pens that under treatment the sore mouth, the dyspepsia, and the diarrhoea completely subside; nevertheless the wasting continues, the stools re- maining phenomenally copious—so much so that the patient may declare that more is passed than has been eaten. In this case wasting is progressive, and the patient gradually dies of inanition. Intestinal atrophy consequent on sprue.—In cer- tain instances, under treatment the symptoms proper to sprue subside; but the patient's digestive and assimilative faculties are permanently impaired. Slight irregularities either in the quality or the amount of food, chill, fatigue, depressing emotions, Morbid Anatomy. 329 and other trifling causes suffice to bring on dyspepsia accompanied by flatulence and diarrhoea. These cases may linger for years; usually they improve during the summer in England, getting worse during the winter and spring, or during cold damp weather. Ultimately they die from general atrophy, diarrhoea, or some intercurrent disease. Morbid anatomy—Post mortem the tissues in sprue are abnormally dry; fat is almost com- pletely absent; the muscles and the thoracic and the abdominal viscera are anaemic and wasted. With these exceptions, and certain important changes in the alimentary tract, so far as known there are no special lesions which are invariably associated with this disease. According to Bertrand and Fontan, occasionally certain changes are present in the pan- creas—namely, fatty or granular degeneration of the cells, with softening of isolated acini and slight inflammatory infiltration of the connective tissue. These, however, are not constant, any more than are certain other and similar changes occasionally found in the liver and kidneys. Lesions of the alimentary tract.—The principal and characteristic lesions are found in the alimentary tract. The bowel is thinned to such an extent as to be almost diaphanous. The serous coat is gener- ally healthy, the muscular coat atrophied. The submucosa in places has undergone hypertrophic fibrous changes; and the mucous membrane from mouth to anus, either in patches or universally, is eroded and atrophied. The internal surface of the bowel is coated with a layer of dirty grey, tenacious mucus which conceals patches of congestion, of erosion, or even of ulceration, besides such evidences of similar antecedent disease as pigmented areas and thin-scarred, cicatricial patches. The villi and glands are eroded and in many places completely destroyed. Here and there minute spherical indurations, about the size of a pin's head and surrounded by a dark pigmented or congested areola, can be felt in the 33° Sprue. mucous membrane. On cutting into these, they are found to be minute cyst-like dilatations of the follicles filled with a gummy muco-purulent material. Sections of the diseased bowel show under the micro- scope corresponding changes ; such as varying degrees of erosion or ulceration of the surface of the mucous membrane ; degenerations of villi, glands, and follicles ; the small mucous cysts referred to ; sometimes small abscesses; and, also, infiltration by leucocytes of the basement membrane and submucous layer; and, in the latter, fibro-cirrhotic changes. The mesenteric glands are generally large and pigmented, perhaps fibrotic. The ulceration lesions are usually most marked towards the end of the ileum and in the colon; but they may be present in greater or lesser degree universally, or in patches throughout the entire alimentary tract from mouth to anus. Pathology.—In attempting an explanation of the phenomena of sprue, two features of the disease have to be considered—the catarrhal condition of the alimentary canal, and the absence of the normal colouring matter of the faeces. Possibly one of these is the consequence of the other; possibly the two conditions are concurrent but independent conse- quences of the same cause. What that cause may be is quite unknown. Whether the first pathological step originates in physiological exhaustion of the digestive functions, brought about by tropical condi- tions abnormal to the European constitution; or whether the disease depends upon a specific organism ; or whether there is a combination of these, has still to be settled. In view of the occurrence of morning diarrhoea of dark bilious stools as a frequent first step in the development of sprue,. hyperactivity of the liver might be assumed to be a first step in the development of the disease, an activity which in time ends in exhaustion of the chologenic functions of the gland. It might be further suggested that, con- currently with this hepatic disturbance, there is a similar initial hyperactivity of all the other glands Pathology. 33i appertaining to digestion, a hyperactivity which also ends in a corresponding exhaustion. Chemical changes in the ingested food would then follow on these apep- tic conditions, and ultimately, from the formation of acrid chemical bodies, lead to the chronic catarrhal changes found post mortem. An analysis by Wynter Blyth of the stools in sprue resulted in ascertaining the presence of the ordinary elements of bile, notwithstanding their apparent absence so far as absence of colour would indicate. On the other hand, Bertrand and Fontan, in a similar analysis, failed completely to find bile acids. Until a decision is arrived at on this point it is useless to speculate further on the subject. Micro-organisms, of course, abound in the fer- menting stools of sprue; but hitherto no bacterium or protozoon which must be regarded as specific has been found in association with the disease. Personally, I incline to regard sprue as an ex- pression of exhaustion of the glandular structures subserving digestion, the result of over-stimulation by certain meteorological conditions which are found in tropical countries, and which are unsuited to the European constitution. The remarkable effect of phy- siological rest, as supplied by " the milk treatment," in curing sprue seems to support this hypothesis. Diagnosis.—The condition of the tongue, the character of the stools, and the history are sufficiently distinctive, one would suppose, to render diagnosis an easy matter. Nevertheless, I have known of cases in which the disease has been diagnosed and treated as syphilis, the condition of the mouth being at- tributed to this disease, and the character of the stools and other symptoms being ignored. Prognosis is good for recent cases, provided proper treatment is carried out. It is bad for patients over fifty, for long-standing cases, for care- less and injudicious patients, and for those who cannot or will not take a pure milk diet. Treatment.—Importance of early and thorough 332 Spr ue. treatment.—If treatment be undertaken sufficiently early in sprue, and be thoroughly and intelligently carried out, it is generally marvellously successful. Should, however, it be undertaken at too late a period, when the glands and the absorbing surface of the ali- mentary canal have been hopelessly destroyed, do what we will, the case is sure to end fatally. In prescribing a treatment, therefore, the first thing for the physician to do is to get his patient thoroughly convinced of the deadly nature of his complaint; for, unless he receives the hearty and complete co-operation of his patient, the physician must not expect to cure a well-established case. To be successful, treatment must be thorough, sustained, and prolonged, and .all predisposing causes, as uterine or other discharges, syphilis, scurvy, and the like, must first be dealt with and, so far as possible, removed. The milk cure.—By far the most successful treatment is what is known as the " milk cure." In carrying this out it is well to commence with a dose of some aperient—castor oil or pulvis rhei composita. Pending the action of the drug, all food, including milk, should be withheld. The patient should be sent to bed in order to economise strength and main- tain an equable warm temperature of the skin. He should also be directed to clothe warmly, to encircle the abdomen with a broad flannel binder, to cover his arms and shoulders with a warm jacket, and to live in a warm room. When the purgative has acted the milk is begun. At first sixty ounces, at most, are allowed in the twenty-four hours, small quantities being given every hour. When the patient is very weak, the feeding must be continued during the night. The milk should not be drunk but sipped with a teaspoon, or taken through a straw or fine glass tube, or from an ordinary child's feeding bottle. As a rule, on this regimen, in the course of two or three days the patient's condition is very much im- proved. The stools have increased in consistency— are solid perhaps—the distension of the abdomen has Trea tment. 333 subsided, dyspeptic symptoms have vanished, and the mouth is much less tender and inflamed. The quan- tity of milk should now be increased at the rate of half a pint a day or every second day, until 100 ounces, or thereabouts, are taken in the twenty-four hours. It is well to keep at this quantity for ten days at least, when, everything going well, a gradual increase to six or seven pints may be sanctioned. Up to this point the patient should keep to bed ; but when he has reached this quantity he may get up and, if he feels strong enough and the weather is mild, go out of doors. For six weeks, dating from the time the stools become solid and the mouth free from irritation, no other food or drink whatever should be permitted. A raw egg, if it is found to agree, may now be added to the milk; later, some artificial malted food; next, small quantities of well-boiled arrowroot, thin bread (stale) and butter, or other digestible form of starchy food; later still, chicken broth, a little fruit; and, by-and-by, fish and chicken may be gradually introduced. Importance of prompt treatment of threatened relapses.—Should, however, the slightest sign of dyspepsia or flatulence, especially of diarrhoea, or of sore mouth show itself, then the extra food must be immediately suspended, a dose of compound rhubarb powder administered, and the patient be sent back to bed and placed once more at absolute rest and on a pure milk diet. In convalescents, no matter how long the acute symptoms have been in abeyance, this prompt recognition and treatment of threatened relapse should be rigorously observed This is a rule of the utmost value and importance. Procrastination in treatment, under these conditions, is exceedingly dangerous. Promptitude in recognising and treating relapse not only saves time, but it may avert hopeless intestinal atrophy. Symptoms persisting.—In commencing this treat- ment, if the patient after two or three days be found unable to digest and assimilate so much as 334 Spr ue. three pints of milk in the twenty-four hours, the daily allowance must be reduced by half a pint a day until thirty ounces or thereabouts only are taken. If now the motions become solid, the quantity of milk must be gradually increased by five or ten ounces a day, so that in the course of a few weeks the full allowance—six or seven pints—is consumed. How to meet inadequate assimilation.—It some- times happens that the quantity of milk can be raised to seventy or eighty ounces per diem, but no higher, further increase bringing on sore mouth, distension, and diarrhoea. In some of these cases the difficulty appears to depend not so much on digestion as on inability to absorb a large quantity of fluid. Occasionally, in such cases, one may succeed in getting the necessary amount of nutriment introduced by thickening the milk with condensed milk; or by slowly evaporating fresh cow's milk so as to reduce its bulk without diminishing the solids (Thin). The evaporation is best done in a vessel like a glue-pot, in which the milk is not boiled, but is surrounded by a jacket of boiling water; the milk during the process must be constantly stirred to prevent the formation of a scum. Or the milk diet may be supplemented by an adequate allowance of raw or underdone meat. Other forms of giving milk.—Digestion is some- times aided by peptonising the milk; or by mixing it with lime water or a little salt; or by aerating it in a soda water syphon (Goldsmith, Brit. Med. Jour., July 1, 1893). Koumiss sometimes agrees for a time when ordinary milk fails, and, if necessary, should be tried. Similarly, white wine whey is occasionally digested when milk is not; it is often of great service, especially when an alcoholic stimu- lant is indicated. Treatment with meat juice and underdone meat.— Occasionally, notwithstanding the utmost care and perseverance, symptoms persist or become aggravated under this system of treatment, and one is forced to conclude that milk does not suit the patient. Trea tment. 335 In my experience such cases are rare—very rare, but undoubtedly they do occur. In such circum- stances raw meat juice will often prove an efficient substitute for milk. The juice of four or five pounds of fresh lean meat, and a little water to allay thirst, may be taken in small quantities at short intervals daily. After a time, when the stools are reduced in number and quantity, although perhaps not quite solid, scraped meat, or very much underdone meat, and by-and-by a little charred toast, a plain rusk or biscuit, and so forth, may be gradually added to the diet, Meat and warm water diet.—Not infrequently, after the stools have become solid under a care- fully regulated pure milk diet, it is found that any attempt to return to ordinary food, or to take anything beyond the most simple farinaceous dishes, is quickly followed by a recurrence of diarrhoea and the familiar flatulent dyspepsia. Such cases are sometimes successfully treated by a complete aban- donment of milk, fish, and farinaceous stuffs for a time, and placing the patient on what is known as the " Salisbury cure." This is a diet consisting only cf meat and warm water. Commencing with smaller quantities, in time the allowance of meat is gradually raised to about three pounds per diem, taken at equi- distant intervals in three or four meals. The meat must be of good quality, free from fat, coarse fibre, and gristle; it may be prepared as mince, or in the form of steak or chop, not too much cooked. Warm water, amounting in all to four pints in the twenty- four hours, is drunk before going to bed and on rising in the morning, and also about two hours before meals —never at meals. This course must be persisted in for six weeks, when ordinary food is gradually attempted again. Nutrient enemata or suppositories.—In all grave cases of sprue nutrient enemata or suppositories should be steadily administered every four or six hours. If tolerated they are most valuable aids to 336 Sprue. nutrition. It is well, when using them, to wash out the rectum once a day with cold water. These methods of treatment—milk and meat juice combined with rest—are the two most successful methods of treating sprue; should they fail, the chances are poor indeed. When to send the patient to Europe. — When sprue develops in the tropics, if feasible, the patient should be sent to Europe as soon as possible. It is a mistake, however, to ship an invalid with his disease active on him, or if his end is manifestly not very far off. Diarrhoea should not be active when the patient is put on board ship. In every case pro- vision, such as a cow or an abundant supply of sterilised milk, should be made for carrying on treatment during the voyage. The clothing and general management. — Sprue patients who return to Europe ought to be especially careful in their clothing, and they ought to get out their warm clothes before the ship leaves the tropics. If their return is during the winter, they should arrange to remain in the South of Europe till at least late spring. Next to an unsuitable dietary, perhaps cold is the most prejudicial influence to which a sprue case can be exposed. A sprue patient ought never to feel cold ; he ought always to wear thick flannels, thick stockings, and, when up and about, thick boots. In winter a chamois leather waistcoat, provided with sleeves, is of great service. His rooms ought to be warm. He ought never to be fatigued; he ought to go to bed early and rise late; in fact, he ought to do everything in his power to avoid irri- tating the bowel, to guard against chill, physiological depression, and the necessity for copious eating. During the summer England is suitable enough as a residence ; but during the cold winter and spring months some milder, drier, and more sunny climate must be sought out. Drugs in sprue.—Experience soon teaches one to distrust medicines in sprue. Occasionally a gentle Trea tment. 337 aperient or, if diarrhoea is watery and excessive, a few drops of laudanum are of service; but active drugging of all sorts is, as a rule, in the highest degree pre- judicial. If the mouth is A-ery painful, cocaine—five grains to the ounce—brushed on before eating will deaden sensibility and, for a time at all events, relieve suffering. Constipation must be carefully avoided, and a simple enema used if necessary. I think it right to state that two methods of drug treatment seem, in some cases, to have been followed by good results. One, advocated by Dr. Begg, lately of Hankow, consists in the administration of re- peated doses of yellow santonin. He recommends one or two doses of castor oil to commence with, and, thereafter, five grains of santonin in a teaspoonful of olive oil once or twice a day for a week, diet being at the same time attended to. The other method has gained for an irregular practitioner in Shanghai some reputation; it consists in the repeatedad ministration of purgatives alternately with or before the exhibition of large quantities—twoteaspoonfuls ata time—of some form of carbonate of lime, believed to be powdered cuttlefish bone or powdered crabs' eyes. I have tried the santonin treatment without benefit to patients. I have also used cuttlefish bone; in one case with the result of permanently stopping the diarrhoea but not of arresting the progress of the disease. In this case, although diarrhoea was most effectively checked, yet massive solid stools continued to pass. After a few weeks the patient died from asthenia, notwithstand- ing a liberal diet which, apparently, was digested but not absorbed. The sprue patient, if possible, ought not to return to the tropics. If compelled by circumstances to go back, he must exercise the utmost care with regard to his health, and avoid exposure, fatigue, cold bath, alcohol, and all excesses; take a minimum of, or avoid alto- gether, red meat ; purge gently and go on absolute milk diet on the slightest sign of relapse. w 338 CHAPTER XXII. TROPICAL LIVER. The subject of liver disease is everywhere a difficult and complicated one. It is especially difficult in tropical countries ; for not only is the resident there liable to all the forms found in temperate climates, but he is exposed, in addition, to various potent predisposing and exciting causes of liver disease not present, or only present in a very mild degree, in more temperate latitudes. These additional causes of liver disease, inseparable from the tropics, are heat, malaria, and especially dysentery. To these, too often, have to be added injudicious personal habits, a tendency to over-full and over-rich feeding, to over- stimulation by alcohol, and deficiency of muscular exercise. The young European who finds himself in the tropics for the first time is surrounded very often by luxuries in the shape of food, wine, carriages, serv- ants, luxuries to which he had not been accustomed perhaps in his home. At first the change, the excite- ment of novelty, and the high temperature act as stimulants to appetite, and the excessive loss of fluid by cutaneous transpiration creates a powerful thirst. Little wonder, therefore, that in such circum- stances the youth, having the appetite and the oppor- tunity of gratifying it, is apt to indulge in food and drink beyond safe physiological limits. He is made lazy by the heat; he cannot exercise during the day, and when evening comes he prefers lounging on the verandah or hanging about the club bar to walk- ing, or riding, or games. Very likely he sits up late at night, drinking and smoking, so that in the Symptoms. 339 morning he is too sleepy to ride out or take any other form of exercise. And so it comes about, what with a surcharge of aliment and alcohol, and the diminished activity of lung metabolism and excretion incident to high temperature and muscular inactivity, that a very large and unusual amount of physiological work is thrown on the liver. Writh this large amount of work there is a corresponding hyperaemia. This may be considered the first stage of tropical liver— hyperaemia from functional activity; up to this point it is a purely physiological condition. Pushed a step farther, however, this physiological hyperaemia passes into congestion with blood stasis and consequent diminished functional activity. Hyperaemia of a physiological character will be evidenced by increase of functional activity, and there will be a copious flow of bile, sometimes causing diarrhoea of a bilious character, particularly morning diarrhoea. But when the limits of physiological hyperaemia are passed, and congestion of a pathological character sets in, the consequent arrest of function will be evidenced by pale stools, perhaps diarrhoea of a pale, watery, frothy, fermenting character; in the latter case the diarrhoea doubtless depending, in part at least, on fermentative processes set up in the con- tents of an alimentary canal no longer kept relatively aseptic by an adequate supply of healthy bile. Other symptoms of this condition are headache, furred tongue, scanty, high-coloured, loaded urine, a feeling of weight or fulness, or even of pain in the region of the liver, and, probably, enlargement of the percus- sion area and other physical signs of enlargement of the organ. One step farther, and such a condition may pass into actual hepatitis attended with fever, smart pain in the liver, tenderness on percussion, and still more marked increase of the hepatic area. A functionally very active hyperaemic organ is prone to inflammation even on slight cause. In the case of the hyperaemic liver a common cause is chill, such as may arise from a cold bath, a wetting, or w 2 34° Tropical Liver. from lying uncovered on a warm night in a current of air. The experienced resident knows this very well, and is at great pains to guard against such an occurrence. He very likely wears what is known as a cholera belt; he sleeps, even on the warmest night, in flannel pyjamas, and with a thin blanket drawn over his abdomen; during the day he wears a woollen singlet and very likely serge or thin tweed clothes. lie does not sit down in damp clothes, and he has a great respect for a shower of rain. Besides chill, there are other causes which may convert the hyperaemia into congestion or inflammation ; a blow may operate in the same way, so may a surfeit of eating or drinking, so may exposure to the sun, so may an attack of malarial fever or of dysentery. Treatment.—Nature sometimes effects a cure in these cases of hepatic congestion by establishing a smart diarrhoea. In the treatment of such cases we cannot do better than to imitate Nature, and even to supplement her efforts. A few doses of the sulphates, in the shape of some kind of bitter water or of Carlsbad salts, generally give prompt relief. But if the subject of such attacks does not profit by experience and mend his ways, very likely his liver, in time, will become chronically hyperaemic and extremely liable to intercurrent attacks of congestion of a character more or less acute. The subjects of this type of " liver" ought to be most careful in their habits. They must not lie abed too long ; they must not take cold baths; they must not take cold drinks, nor expose themselves to cold in any form ; they must clothe warmly ; and they must eschew alcohol in every shape. Animal food they must partake of but sparingly ; and they should give the preference to fowl and fish over beef and mutton. Fruit and farinaceous food may be more freely partaken of, but over-eating in every form must be avoided. Exercise should be taken at least twice a day ; and, at least once in twenty-four hours, the exercise should be of such a character as to provoke perspiration. A gallop on Trea tment. 34i horseback, a smart game of tennis or rackets, are excellent hepatic stimulants. Occasionally, once a week or not so often, particularly when a sense of fulness or aching in the right side seems to indicate that all is not right with the liver, a dose of Carls- bad salts or bitter water, preceded perhaps by a few grains of calomel, may avert more serious trouble. When hyperaemia becomes chronic, when the patient is continually suffering with "liver," he should leave the tropics for a time. Nothin'o- re- lieves these cases of chronic congestion so quickly or so effectively as a visit to Carlsbad and a thorough course of the waters there, and of the dietetic restric- tions imposed in the Carlsbad cure. This should be followed up by country life in England and the active pursuit of country sports ; the usual precautions in the shape of warm clothing, avoidance of cold baths, chills, alcohol, and high living being scrupulously observed and a weekly saline purge taken. A serviceable imitation of the natural Carlsbad water may be made by dissolving fifty-three grains of the powdered salt in a pint of boiling water.* This may be divided into three equal portions, which are to be sipped as hot as possible, at intervals of twenty minutes, on an empty stomach, first thing in the morning. While taking the solution gentle exercise, as moving about the room, should be indulged in! Breakfast must not be taken till an hour after the last dose. If the bowels are not gently acted on an increased quantity of the salts should be taken. During the course, which should be persevered in for three weeks, the diet must be carefully regulated ; butter, fat, nuts, fruits, pastry, preserves, tinned foods, cheese, salads, wines, spirits, and beer are to be avoided. Too much meat must not be taken ; a small meat meal once a day must suffice. The quantity of food, too, should be restricted, and clothing, exercise, and bathing be carefully attended to. Much excellent * A good substitute for Carlsbad salts consists of sod. sulph. 2 parts, sod. bicarb. 1 part, sod. chlorid. 1 part. 342 Tropical Liver. advice on the subject of the Carlsbad treatment will be found in Surgeon-Major Young's book, "The Carlsbad Treatment for Tropical Ailments," published by Thacker, Spink & Co., Calcutta. During severe attacks of acute congestion, or of severe hepatitis attended with fever and much local distress, the patient must be kept in bed and placed on a very low diet of thin broths, barley water, or rice water, or milk and water. He should be purged freely and often with salines. A large hot poultice, two feet or more in length by one foot in breadth, should be laid over the region of the liver ; such a poultice to be effective should pass from the centre of the back to well over the epigastrium. Dry cupping sometimes gives marked relief. Muriate of ammonia has a certain reputation in these cases; it should be prescribed in twenty-grain doses every six or eight hours. I have often used it, but I cannot vouch for its virtues ; it does no harm. When such a hepatitis is associated with dysen- tery, should it resist these milder measures, thirty to sixty grains of ipecac, often give marked relief. This dose should be repeated every twelve or twenty-four hours for two or three times. When the hepatitis is associated with malarial fever, full doses of quinine, in addition to the purging and to the other measures already mentioned, are indicated. Whether hepatitis, unless associated with dysen- tery, ever passes on to suppuration is a moot point. Some say that it may; others resolutely deny that there is such a thing as " tropical abscess," unasso- ciated with dysentery. This subject is discussed in the following chapter. Malarial hepatitis has already been considered (p. 92). 343 CHAPTER XXIII. ABSCESS OF THE LIVER. Definition.—A form of suppuration in the liver, occurring especially in warm climates, and principally in male Europeans and in association with dysentery. Geographical distribution.—Abscess of the liver, of the type known as tropical abscess, is, for the most part, a disease of warm climates. Usually a sequel, or, it may be, a concomitant of dysentery, it is rare or altogether absent in countries where dysen- tery is also rare or absent. Its geographical distri- bution, therefore, is in the main regulated by that of dysentery. It has to be noted, however, that liver abscess is not a sequel or concomitant of the dysentery of all countries and at all times. Thus it is rare as an indigenous disease in temperate climates, even in those temperate climates in which dysentery is at times common enough. Again, in tropical climates the dysentery and liver abscess curves do not every- where and at all times maintain a constant and definite relation to each other; for, even in hot countries, the dysentery of some places is more apt to be followed by liver abscess than is the dysentery of other places ; and, even as regards dysentery in the same place, some epidemics are more apt to be asso- ciated with liver abscess than others are. Neverthe- less, on the whole, it may be laid down as a fairly general law that in the tropics and sub-tropics the liver abscess curve follows in the main the dysentery curve; and that the geographical range of liver abscess in these climates is the same as that of dysentery. In Great Britain the liver abscesses met with 344 Abscess of the Liver. occur most frequently in individuals who manifestly had contracted the disease in the tropics. As a disease of indigenous origin, notwithstanding the considerable amount of dysentery at times in some of the lunatic asylums and similar large public institutions in Great Britain, it is distinctly rare, though not so uncommon as is usually supposed. Of course this remark does not apply to those suppurations which are connected with ordinary pyaemia, with gall-stones, hydatids, pylephlebitis, and the like; it applies only to dysenteric and, possibly, if there be such a disease, to idiopathic abscess. 'In northern and central Europe it is much the same in this respect as in Britain. The disease is more frequent in southern Europe— in Italy, Greece, the Balkan peninsula, and south Russia; it is said to be particularly common in Roumania. In eastern Asia, even outside the tropical belt, it is far from rare : thus it is not un- common in Japan, and it is a very notable feature in the morbidity of Shanghai and the coast of South China. In Africa it is common enough; indeed, some of the best modern studies of the disease have been made in Egypt and in the Algerian province of Oran. In the western hemisphere there is a corresponding distribution; fairly common in the tropics, it becomes progressively rarer as we proceed north and south. It is apparently less common in the West Indies than in India and the East generally. In the southern hemisphere, although Australia seems to enjoy a practical immunity, the European in the neighbouring island of New Cale- donia is said to be specially subject to this disease. Etiology.—Relation to dysentery.—There can be no question as to the existence of an intimate relationship between dysentery and liver abscess. Numerous and well-authenticated statistics, as well as everyday experience attest this. In 3,680 dysen- tery autopsies made in various tropical countries, and collated by Woodward, 779 (21 per cent.) revealed abscesses of the liver. To quote recent Indian /Etiology. 345 experience:—According to the Annual Report of the Sanitary Commissioner with the Government of India for 1894, out of 465 European soldiers who died from dysentery in India during the period 1888-94, 161 (35 per cent.) had, in addition to dysenteric lesions, abscess of the liver. Conversely, in Egypt, Kartulis, in an experience of over 500 cases of liver abscess, elicited a history of dysentery in from 55 to 60 per cent. ; Zancarol, also in Egypt, in 444 cases, elicited a similar history in 59 per cent. ; and Edwards and Waterman, in 699 collated cases, elicited a like history in 72-1 per cent. During the period 1870-95, of 45 cases of liver abscess treated at the Seamen's Hospital, Greenwich, and collated by Mr. Johnson Smith, post- mortem evidence, or a distinct history, of dysentery was obtained in 38 (84-4 per cent.). These figures are conclusive as to the existence of an intimate relationship between dysentery and liver abscess. There is good reason, however, for believing that, while they represent the truth, they do not represent the whole truth, and that the association is even more frequent than they indicate. As has been pointed out by Dr. Neil Macleod and others, the occurrence of antecedent dysentery in cases of liver abscess is very often overlooked ; for, without a post- mortem examination, it may be impossible to pro- nounce definitely on this point in every instance. It is also well known that extensive dysenteric ulcera- tion may be present and yet give rise to no active subjective symptoms whatever. Moreover, it must be borne in mind that many patients suffering from liver abscess forget, or fail to mention, the occurrence of a previous dysenteric attack, and that they may mislead the physician by describing such an attack as " diarrhoea." Further, at post-mortem examinations, dysenteric lesions of a superficial and apparently trifling character are often either not sought for or they are overlooked. Consequently, although the evidence of antecedent dysentery may not be forth- coming in a proportion of cases of liver abscess, it 346 Abscess of the Liver. must not be concluded from this that there had been no dysentery. In a masterly paper (British Medical Journal, October 26th, 1895) Macleod, after a very careful and critical analysis of certain figures bearing on this subject, concludes that dysentery is a factor in nearly every case of tropical liver abscess. In forty cases of the disease observed in Shanghai he had positive evidence of dysentery in all except one ; and even in this case, as recovery ensued, there was no certainty that dysenteric lesions had not been present in it also. Perhaps Macleod's conclusions are somewhat too sweeping ; I confess, however, that they are, in the main, in harmony with my own experience. Doubt- less they apply to liver abscess as met with in Shanghai and, probably, in many other places. It is just possible, however, that what holds good for one place may not hold good for all places, and that Bombay, for example, may differ in this respect from Shanghai. In the Sanitary Commissioner's Report, above referred to, it is stated that in 2 (3 per cent.)- instances only, out of 74 cases of liver abscess occur- ring in the Bombay Presidency in the period 1888-94, were there dysenteric associations. It is difficult to believe that, did it always exist, so important and evident a circumstance as dysentery had been over- looked 72 times in 74 cases. It is equally difficult to believe that the liver abscess of Bombay is associated with dysentery in only 3 per cent, of cases, whilst, according to the same authority, in the whole of India it is certainly so associated in at least 30 per cent, of the total cases. Manifestly, the statistical aspect of this important question requires re-study in the light of more careful clinical and post-mortem observation. Another important point, yet to be definitely settled, is the exact relationship in point of time of the dysentery to the liver abscess. In the great majority of cases the dysentery antedates the abscess. But many clinicians have held that in some instances /Etiology. 34 7 the relationship is reversed; that in others the two diseases are from the commencement concurrent; whilst in others, again, hepatitis, presumably of a kind which may eventuate in abscess, alternates with active dysenteric symptoms. If the abscess antedate the dysentery, then the dysentery cannot be the cause of the abscess. On these grounds some pathol- ogists have regarded liver abscess and dysentery as but different expressions of one morbid condition; reacting to some extent on each other, but not directly related the one to the other as cause and effect. Here, again, the latency as regards symptoms of some dysenteries has to be discounted in attempt- ing to settle the question. Race and sex.—Besides this matter of its re- lationship to dysentery, there are several well- ascertained facts to be reckoned with before we can arrive at sound views on the subject of the aetiology of liver abscess. (1) Though common in Europeans in the tropics, liver abscess is rare among the natives. Thus, in the native army of India the proportion of deaths from liver abscess to the total mortality in 1894 was only 0 6 per cent., whereas in the European army it was 7-4 per cent. Man for man the relative liability of the European soldier and the native soldier was as 95-2 to 4-8. (2) This disproportion is in spite of the fact tlrnt the native is more liable to dysentery than the European. Thus, in 1894, in the Indian army the admission rate among the native troops for dysentery was 43 -8 per thousand, whereas in the European troops it was only 28-6 ; and in every hundred deaths in the native army 4 7 were from dysentery, against only 3-8 in the European army. (3) European women in the tropics, though quite as subject to dysentery as European men, rarely suffer from liver abscess; children hardly ever. (4) The rarity of liver abscess in temperate climates. 348 Abscess of the Liver. Predisposing conditions.-—The foregoing considera- tions seem to indicate that for the production of liver abscess at least two things are necessary—a pre- disposing cause, and an exciting cause. Dysentery is certainly not always and alone both the exciting and predisposing cause. Were it so the native soldiers, and the European women and children, in India would suffer as frequently from liver abscess as do the European males there. Some additional factor evidently complicates the problem. As liver abscess is developed principally in tropical climates and in European visitors there, and much more rarely in the native, it would seem that tropical conditions in those unaccustomed to them are in some way bound up with this predisposing element; and as liver abscess is rare in European women and children, it would seem that these conditions are in some way specially operative on European men. We have therefore grounds for concluding that, in addition to general tropical conditions, it must be the greater amount of exposure to which men, as compared with women and children, are subjected in the course of their business and amusements; or some other con- dition, especially that one which is relatively more common in men than in women and children—over- indulgence in stimulating food and alcoholic drinks— that constitutes this predisposing cause. Intemperate habits and exposure, doubtless, lead to a special liability in men to a hyperaemia and congestion of the liver tissue by which its resistive faculty to patho- logical influences is impaired. In these circumstances pathological influences, which in the healthier condi- tion of the organ—such as we assume to exist more generally in natives and in European women and children—would have been successfully overcome, gain the upper hand, and lead to suppurative disinte- gration of the organ. In support of this view we have the statement of Waring, that 65 per cent, of liver abscesses observed by him were in alcoholics; and it is also said, that when the native takes to /Etiology. 349 European habits in the matter of eating and drinking, his liability to liver abscess is greatly and proportion- ately enhanced. I conclude, therefore, that in the vast majority of instances the exciting cause of liver abscess is dysen- tery ; the predisposing cause hyperaemic, congestive, or degenerative conditions incidental to tropical life, supplemented by such things as exposure and un- physiological habits in eating and drinking. Supplementary causes.—It is conceivable that in a highly predisposed liver exciting causes other than dysentery, such as a blow or sudden aggravation of chronic congestion by chill or excess, may suffice at times to determine suppuration. Liver abscess is most prone to develop at the commencement of the cold season. Further, one can conceive that in a hyperaemic liver struggling to resist dysenteric sup- purative influences some third condition, such as the blow, chill, or surfeit referred to, may contribute to or determine the formation of abscess which, in their absence, might have been averted. Briefly stated, the causes of liver abscess are, first, predisposing—hyperaemic and degenerative conditions of the liver; second, exciting—dysentery, or dysentery combined with chill, dietetic excess, or traumatism. Influence of age and length of residence.—Liver abscess may occur at any age after childhood, but is most common between twenty and forty. It is most prone to show itself during the earlier years of residence in the tropics (40 per cent, in the first three years), although the older resident is by no means exempt. Influence of malaria.—Malaria, by causing fre- quent attacks of hepatic congestion and by lowering the general vitality, may have some predisposing influence ; but, as already pointed out, malarial hepa- titis is essentially of a plastic and not of a suppurative nature. It is a common mistake to suppose that malaria causes the suppurative liver disease of the tropics ; the two concur geographically, but are in no way aetiologically identical. 35° Abscess of the Liver. Organisms concerned.—The questions of the organisms concerned in liver abscess will be dis- cussed in the section on pathology. Symptoms.—There is great variety in the grouping of symptoms in liver abscess. The follow- ing is a common history. The patient, after residing for some time in the tropics, during which he enjoyed good general health and lived freely, was attacked by dysentery. In due course he appeared to recover, aud resumed work. Several weeks or months elapsed when, after a wetting, or some such incident, he began to feel out of sorts, to suffer from headache, foul tongue, want of appetite, irregularity of the bowels, disturbed nights, excessive and unaccountable languor, irritability of temper, and depression of spirits. About the same time he began to be conscious of a sense of weight and fulness in the right hypochondrium. Later, he became feverish, par- ticularly towards evening, the oncoming of the febrile distress being sometimes preceded by a sense of chilli- ness. At times he had sharp stabbing pain in the right side in the region of the liver, perhaps a dry cough and, possibly, a gnawing, uncomfortable sen- sation or pain in the right shoulder. His friends observed that his face had become muddy and haggard. He was uneasy if he lay on his left side. The quo- tidian rise of temperature now became a regular feature, the thermometer every evening touching 102°—sometimes more, sometimes less—and sink- ing to near normal by morning. He now began to perspire profusely at night, and even during the day should he chance to fall asleep. He had to change his sleeping clothes once or even twice every night on account of the drenching sweats. On examination it is found that the patient is somewhat emaciated ; his complexion thick and muddy; his pulse 80 to 100; his tongue is furred and yellowish; the palms of his hands and soles of his feet are cold and el am my. As he lies on his back it is obvious, on in- spection, that the epigastrium is too full for one so Symptoms. 35' emaciated ; and it is seen that the breathing is shallow and mainly thoracic. The right rectus muscle is found to be rigid. Considerable discomfort, if not pain, is elicited by attempts at palpation and percussion over the right hypochondrium. The liver dulness extends an inch too high, and an inch or more beyond the costal border in the nipple line; posteriorly, it rises to about the eighth rib in the line of the angle of the scapula. It is further observed that the line of dul- ness is arched along its upper border; and that it is not materially altered by changes of position, unless it be on standing, when the lower margin descends markedly in the epigastrium. Percussion below the right costal border, on deep inspiration, gives rise to much uneasiness or even to acute pain. Very likely one or two tender spots can be discovered on firm pressure being made with the finger tips in some of the lower right intercostal spaces, or below the right costal margin. The spleen is not enlarged. Auscul- tation may detect pleuritic friction somewhere over the base of the right lung, or peritoneal friction over the liver itself. The urine, free from albumin, is scanty, high-coloured, and deposits copious urates on cooling. As the case progresses emaciation increases ; hectic with drenching nocturnal sweats continues; the liver dulness and pain may further increase; or the general enlargement may somewhat subside, and percussion may reveal a pronounced local bulging, upwards or downwards. If the abscess which has now formed is not relieved by operation, after months of illness the patient may die worn out; or the abscess, which has now attained enormous dimensions, may burst into the right lung or pleura, or elsewhere, and be discharged, and either recovery or death from con- tinued hectic and exhaustion, or from some inter- current complication, ensue. The great variety in the urgency of symptoms.— Although the foregoing is a fairly common history in liver abscess, there are many instances in which the 352 Abscess of the Liver. initial symptoms are much more urgent, and in which the disease progresses much more rapidly. In other instances subjective symptoms are almost entirely absent; or so subdued that the true nature of the case may be entirely misapprehended until the abscess bursts through the lung or bowel, or a fluctuating tumour appears in the neighbourhood of the liver; or, perhaps, not until after death, when the unsuspected abscess is discovered on the post-mortem table. Eever.—In an acute sthenic case the initial in- flammatory fever may run fairly high and persist for some time. Later, when it may be assumed that pus has formed, the fever becomes distinctly quotidian and intermittent in type, the morning temperatures being normal, or only slightly above normal, the evening rising to 101° or 102°, or a little over or under this. Sometimes evening temperatures of 103°, rarely of 104°, are registered. In the asthenic and insidious type, at first there may be short flashes of feverishness at more considerable intervals, to be followed later by a steadier fever of a hectic type, as in the suppurative stage of the sthenic cases. In either type there may be afebrile intervals of several days' duration ; and in either there may also occur, concurrently with aggravations of the local conditions, spells of continued high temperature. Occasionally, though very rarely, liver abscess may be unattended by fever of any description whatever. Rigors.—In the classical descriptions of liver abscess the occurrence of violent rigor is generally mentioned as a notable sign of the formation of pus. Undoubtedly such a rigor does at times signalise this event; but it is by no means constant, and its absence is no guarantee that abscess has not formed. Gener- ally the evening rise of temperature is preceded by a sense of chilliness, sometimes by a more marked rigor simulating, in the regularity of its recurrences and in its severity, the rigor of a quotidian malarial fever. Sweating, particularly nocturnal sweating, and Symptoms. 353 of a very profuse character, is an almost invariable accompaniment of liver abscess. The patient's clothes may be literally drenched with perspiration. Even during the day—particularly, as already men- tioned, if he chance to fall asleep—the sweat may stand in beads upon the forehead and around the neck. This, like most of the other symptoms, may be temporarily absent, or, in a small proportion of cases, trifling. The complexion is generally muddy, cachectic, and slightly icteric-looking; marked jaundice, how- ever, is uncommon. Wasting is generally decided and progressive. Rheumatic-like pains and swelling of the hands and feet, such as occur in chronic septic affections, are sometimes to be noted. They usually disappear rapidly when the abscess bursts or is opened, and free drainage is established. Pain of some description is rarely absent. In a few exceptional cases there is no pain ; such a patient may declare that he does not know that he has a liver. There are several types of pain—local and sym- pathetic—associated with liver abscess. Complaint is almost invariably made of a sense of fulness and of a sense of weight in the region of the liver, not infrequently referred to the infra-scapular region. Stabbing, stitch-like pain, increased by pressure, and especially by deep inspiration, coughing, and all sudden jarring movements, is very common, and pro- bably indicates peri-hepatitis from proximity of the abscess to the surface of the organ. Percussion or firm palpation, especially if practised during deep inspiration and below the ribs in front, generally causes smart pain and decided shrinking, the rectus muscle starting up as if to protect the subjacent inflamed parts. Pain on swallowing, at the moment the bolus of food traverses the lower end of the (esophagus, was mentioned to me by a medical man, himself the subject of hepatic abscess, as being a x 354 Abscess of the Liver. marked symptom in his own case. Pain on firm pressure with the finger tips in an intercostal space, and over a limited area, is a common and valuable localising sign. Among the sympathetic pains may be mentioned shooting pains radiating over the chest and down the right flank and hypochohdrium. Pain in the right shoulder.—This symptom is present in about one-sixth of the cases. It may be persistent, or it may intermit; it may radiate to the side of the neck or to the region of the scapula, or down the arm ; or it may be limited to the shoulder tip and clavicular region. In some instances it is of a dull, gnawing, aching character; in some it is more acute ; and in some it may be represented by a burning sensation, as if the surface of the skin had been flayed by a blister. This symptom is a reflex transmitted from the hepatic terminals of the phrenic through the fourth cervical to the branches of the cervical and brachial plexuses. Cough, of a dry, hacking character, doubtless also a reflex from irritation of the diaphragm, or from an inflamed condition of lung or pleura over the seat of abscess, is not uncommon. When the abscess dis- charges through the lung, cough is sometimes very severe, and may cause vomiting. The respiration is generally shallow and propor- tionately rapid. This is partly symptomatic of the attendant fever; but it is often owing to the fact that fuller inspiration is attended with stitch. Sometimes the breathing is entirely thoracic, the lower part of the chest seeming to be fixed— especially the right side—and the diaphragm almost motionless. The decubitus is usually dorsal or right dorsal, the body being somewhat bent towards the right side and the right leg perhaps slightly drawn up. When the patient stands, a stoop to the right may be notice- able. Lying on the left side generally causes pain from dragging on adhesions, or discomfort from the pressure of the enlarged liver on the heart and Symptoms. 355 stomach. Occasionally the decubitus is indifferent, or even on the left side. The digestive organs are usually disturbed. The tongue is generally coated; vomiting may occur from time to time, arising either from pressure on the stomach by the swollen liver or as an expression of gastric catarrh ; appetite, as a rule, is poor; flatulence may be troublesome; the bowels are confined or ir- regular, or there may be diarrhoea or dysentery. In the case of concurrent dysentery, it may be noted sometimes that the hepatic and dysenteric symptoms alternate in severity. The area of hepatic percussion dulness is usually extended upwards and downwards, and sometimes horizontally. The extension may be general, especially in the earlier stages; later, careful outlining of the upper and lower boundaries may discover a limited and dome-like increase in one direction, most signifi- cant if upwards. The upper line of dulness is not, as a rule, horizontal, as in hydrothorax; almost invari- ably, on approaching the spine, it trends downwards more markedly than in hydrothorax or empyema. Variations in the extent of the dulness may take place from time to time, and sometimes very rapidly, de- pending on fluctuations—not in the size of the liver abscess, but on the varying and relative amounts of local and general hepatic congestion. One sometimes finds even a narrow hepatic dulness in the nipple line with a great increase in the axillary or scapular lines. In one case the lower border of the liver may be as low as the umbilicus; in another, especially in front, it may be well inside the costal margin. _ Diagnosis in the latter type of case is difficult, and depends rather on the nature of the fever, and on the history and general condition, than on local signs. Splenic enlargement may be present even when there is no malarial complication. This is rare, how- ever, and, in uncomplicated cases, is seldom great. I have seen splenic tumour closely simulated by abscess in the left lobe of the liver. x2 356 Abscess of the L^er. Varicosity of the epigastric and hcemorrhoidal veins —one or both of them—is sometimes discoverable. OJJdema of the feet and ascites are rare in the earlier stages ; but the former is very usual towards the termination of long-standing cases. Local oedema over one or more intercostal spaces, or more extensive and involving the whole or part of the hepatic area, is sometimes apparent. When limited it is a useful locating symptom. Local bulging, if attended with fluctuation, in- dicates the presence of pus near the surface and the pointing of the abscess. Usually this, when it occurs, is in the epigastrium; but pus may burrow and find its way down the flank, or among the muscles of the abdominal wall, and open perhaps at a point remote from the abscess cavity in the liver. Friction, both pleuritic and peritoneal, is some- times to be made out, and is not without its value as a localising symptom. Pneumonia, generally limited to the base of the right lung, and of a sub-acute and persistent character, indicates contiguity of the abscess to the diaphragm. It is especially common in those cases in which the abscess subsequently ruptures through the lung. This form of chronic pneumonia is a fruitful source of error in diagnosis. Chronological relation of the hepatitis to the dysenteric attack.—This is most irregular and un- certain. In many cases of dysentery a concurrent hepatitis is manifest almost from the commencement of the attack; this hepatitis may not subside, but pass directly to abscess formation. Or the initial hepatitis and dysentery may both subside apparently, but the former may recur weeks, months, or even years afterwards when, perhaps, the attack of dysen- tery is almost forgotten. Or there may be no active hepatic symptoms with the dysentery, hepatitis supervening only long after all bowel trouble has passed away. In a few cases no dysenteric history can be elicited; it is seldom, however, as has already Termina tions. 357 been insisted on, that careful inquiry fails to bring- out some story of previous bowel disturbance more or less urgent. In a few instances liver abscess of tropical origin does not declare itself until the patient has been several years resident in a temperate climate and quite outside the endemic area. The incidence of the symptoms is equally variable. Some cases commence with marked sthenic fever, much local pain, great tenderness and hepatic en- largement, signs of suppuration as rigor, hectic, and local bulging, rapidly supervening. Others, again, commence so insidiously that the patient can hardly say when he first began to feel ill; perhaps there may be a history of slow deterioration of the general health during a year or longer before definite hepatic symptoms show themselves. The former type seems to be the more common in the young and robust newcomer to the tropics; the latter, in the more or less cachectic and old resident. Between these extremes there is endless variety. Duration of the disease.—Liver abscess may run its course in three weeks. Generally it is an affair of several months. Sometimes it may run on for a year or even longer ; particularly so if it burst through the lung and drainage be imperfect, in which event the cavity may keep on bursting and refilling at intervals for almost an indefinite period. Terminations.—Apart from operative inter- ference, liver abscess may terminate in various ways. It may end in spontaneous rupture leading to death or recovery. Death may also be brought about in other ways: by the severity of the local disease; by prolonged hectic and exhaustion ; by concurrent dysentery, or by intercurrent disease as pneumonia, pulmonary abscess, empyema, peritonitis. Recovery may also ensue on the abscess becoming encysted, or, possibly, absorbed. Rupture of the abscess.—Rendu in a series of 563 instances of abscess of the liver, compiled from various sources, gives an interesting table showing the direction of rupture in 159 (28 per cent.) of the cases which 358 Abscess of the Liver. 31 , , 5-5 59 , , 10-5 39 , , 69 6 , , 1 8 ,, , 1-4 4 ,: , 0-7 3 ,, , 0-5 2 , . 0-3 opened spontaneously. This table may be summarised as follows :— Rupture occurred into the pericardium in 1 case 0-13 per cent. ,, pleura >, lung „ peritoneum „ colon ,, stomach, and duodenum ,, bile ducts „ vena cava ,, kidney ,, lumbo-iliac region 6 ,, 1 „ From this it will be seen that about 28 per cent, of liver abscesses rupture spontaneously, most generally into the lung or pleura. Rupture into the lung.—-If rupture takes place into the lung the abscess contents may be sud- denly discharged, mouthful after mouthful of pus mixed with blood welling up or being coughed up. In a few instances, in such circumstances, death has occurred suddenly from the flooding of the lungs with pus. More commonly the discharge is effected gradually, a few drachms being brought up with each cough; in the aggregate this discharge may amount perhaps to five or ten ounces in the twenty-four hours. In favourable cases the daily amount expectorated gradually diminishes until all discharge ceases and the patient recovers. Frequently, however, a deceptive arrest of discharge and cessation of cough are followed by a rise of temperature, which had become normal on the occurrence of rupture. With this there may be a reappearance of the night sweats. In a few days cough and expectoration return as before and fever once more subsides. This process of alternate emptying and refilling of the abscess cavity may recur many times before recovery finally takes place. In some cases it continues for months, and may finally wear out the patient. In some, expec- toration never altogether ceases; if accompanied by fever this persistency indicates imperfect drainage, Mortality. 359 or, possibly, the presence of a second and unruptured abscess. Characters of the expectorated liver pus.-^-The appearance of expectorated liver pus is almost patho- gnomonic. In colour it is chocolate brown; in con- sistence it is viscid and jelly-like. It may be streaked with blood; sometimes the expectoration may be almost entirely pure blood. Not infrequently these haemorrhagic cases are regarded and treated as ex- amples of ordinary haemoptysis. Presumably this blood comes from the wall of an abscess jarred and torn by the succussion of the harassing cough. Under the microscope expectorated liver pus exhibits the appearance to be presently described (p. 361). Rupture into the pleura leads to sudden develop- ment of evidences of pleural effusion, which, unless relieved by drainage, may, in its turn, give rise to all the signs of empyema, and terminate in death, or in rupture through the lung or chest wall. Rupture into the stomach is generally signalised by vomiting of the characteristic pus and, at all events temporarily, by cessation of local symptoms and fever. Rupture into the bowel may cause diarrhoea, the pus more or less altered appearing in the "stool. This is an occurrence that is frequently overlooked. Rupture into pericardium, into peritoneum, or into a blood-vessel is almost necessarily and rapidly fatal. Rupture through the skin is said to be the most favourable, though a rare, termination of liver abscess. Mortality. — Rouis (203 cases), in Algiers, observed a mortality of 80 per cent. ; Castro (125 cases), in Egypt, a mortality of 72-5 per cent, or, excluding cases operated on, of 76 per cent. In the Indian army, during the period 1891-94 (prior to which abscess of the liver, in the statistical returns, is not separated from hepatitis), and, presumably, including cases operated on, the mortality was 57-7 per cent. Causes of death.—In Rouis's 162 fatal cases, the 360 Abscess of the Liver. causes of death are stated as follows :—Severity of the local disease, or through the associated dysen- tery, 12"5 ; bursting of the abscess into the peritoneal cavity, 12 ; into the pleura, 11 ; gangrene of abscess wall, 3 ; peritonitis, 3 ; pneumonia from effusion of liver pus into the lung, 3 ; rupture of adhesions, 2 ; pneumonia, 2; rupture into the pericardium, 1. ITIorbid anatomy.—It may be inferred from the symptoms that in the early stages of suppurative hepatitis there is general congestion and enlargement of the liver; in some instances this condition may be more or less confined to one lobe or even part of a lobe. Later, as we know more especially from obser- vations in cases that have died from the attendant dysentery, one or more greyish, ill-defined, anaemic, circular patches, half to one inch or thereabouts in diameter, in which the lobular structure of the gland cannot be made out, are formed. These grey spots are very evident on section of the organ. A drop or two of a reddish, gummy pus may be expressed from the necrotic patches—for such they are. Still later, the centres of the patches liquefy and distinct but ragged abscess cavities are formed. An abscess thus commenced extends partly by molecular breaking down, partly by more massive necrosis of portions of its wall; partly by the formation of additional foci of softening in the neighbourhood and subsequent breaking down of the intervening septa. The walls of such an abscess have a ragged and rotten appearance. Spherical on the whole, there may be one or more diverticula extending from the main cavity ; or contiguous abscesses may break into each other and communicate by a sinus. Occasionally a thickened blood-vessel is met with stretching across the cavity. Though the pus and detritus lying on the abscess wall are viscid and adhesive, there is no notable exudation of lymph either lining the cavity, or in the still living liver tissue beyond. There is a peripheral zone of hyperaemia ; beyond this zone the gland may appear normal or simply congested. Morbid Anatomy. 361 Number and size of abscesses.—Liver abscess may be single or multiple. If multiple, there may be two, three, or many abscesses. Zancarol's statistics, apply- ing to 562 cases, give the proportion of single to multiple abscess cases as three of the former to two of the latter. W hen single the abscess sometimes attains a great size. Frequently it is as large as a cocoanut or even larger ; it has happened that the entire liver, with the exception of a narrow zone of hepatic tissue, has been converted into a huge abscess sac. When multiple the individual abscesses are generally smaller, ranging in size from a filbert to an orange. As might be expected, from considerations of the relative size of the parts, abscess is more common in the right than in the left and smaller lobes. Roux gives the proportions in 639 cases as 70'85 per cent. right lobe, 3 per cent, left lobe, and 0-3 per cent. lobus spigelii.' Adhesions to surrounding organs are frequently, though not invariably, formed as the abscess ap- proaches the surface of the liver. In this way the danger of intra-peritoneal extravasation is usually averted. Pulmonary inflammation and abscess from escape of liver pus into the lungs are sometimes discovered post-mortem. Generally the pulmonary abscess com- municates with the mother abscess in the liver by means of a small opening in the diaphragm. Liver pus. — As already mentioned, the naked- eye appearance of liver pus is peculiar. When newly evacuated it is usually chocolate-coloured and streaked with, or mixed with larger or smaller clots or streaks of blood, and here and there with streaks of a clear mucoid material. It is so thick and viscid that it will hardly soak into the dressings, but lies on the surface of the gauze like treacle on bread; spreading out between the skin and the dressing, and finding its way past the edge of the latter rather than penetrat- ing it. When quite fresh, here and there little islands 362 Abscess of the Liver. of yellowish, what may be described as, laudable pus may be made out in the brown mass. Sometimes it contains considerable pieces of necrotic tissue. Occa- sionally, from admixture of bile, the abscess contents are green-tinged. Liver purulage has always a peculiar mawkish odour ; it is rarely offensive, unless the abscess lie near the colon, in which case it may have a faecal odour. Under the microscope many blood corpuscles are discoverable, besides much broken- down liver tissue, large granular pigmented spherical cells, debris, oil globules, haematoidin crystals and, occasionally, Charcot-Leyden crystals, amoebae, and the ordinary pyogenic bacteria. Amoeba coli and pyogenic organisms.—According to my experience of tropical abscess of the liver seen in England, amoeba coli can be detected in about half the cases. This is fairly in harmony with Kartulis's experience in Egypt, and that of others elsewhere. I have observed in a good many instances in which I have failed to detect the amoeba in the aspirated liver pus, or in the pus which escaped at the time of operation, that the parasite appeared, often in great profusion, four or five days later in the discharge from the drainage-tube. I have seen them in these circumstances in strings of eight or ten, the string-like arrangement suggesting that they had developed in some tube, such as a blood-vessel. The amoebae per- sist in the discharge until the abscess has healed. It is justifiable to infer from the absence of amoebae in the pus constituting what might be called the body of the abscess, and their appearance in the pus coining from the walls of the abscess a few days later, that the habitat of the parasite is not so much the pus occupy- ing the general abscess cavity as that immediately in contact with the wall and the breaking-down tissues themselves. This is an inference entirely in harmony with Councilman and Lafleur's demonstration of the parasite in the still living tissues around the abscess. In my experience the presence of the amoeba does not affect prognosis unfavourably ; Lafleur (" System of Morbid Anatomy. 363 Medicine," Allbutt, vol. ix., 1897) says it does, but I cannot agree with him, as I have many times seen amoebic liver abscess cases recover completely and rapidly after operation. Other protozoa have been found in liver pus. Thus both Grimm and Berndt have found numerous active flagella therein. Some time ago, in the ex- pectorated pus from a liver abscess discharging through the right lung, I found a ciliated infusorium resembling balantidium coli. In the pus of a large proportion of liver abscesses, both microscopic examination and culture may fail to detect the usual pyogenic micro-organisms. To har- monise this well-established fact with modern views on the cause and nature of the suppurative process, it has been suggested that, though in these sterile abscesses micro-organisms had originally been present, they had subsequently died out. This view receives a measure of support from the fact that in a proportion of instances there is no difficulty in demonstrating in the pus the ordinary pyogenic bacteria, and sometimes the bacterium coli communis. It by no means follows from this, however, that bacteria are a necessary factor for the production of all liver abscesses. Encystment.—Ju rare instances the pus of liver abscess, instead of possessing the chocolate colour and viscid consistency described above, is yellow and creamy. This is particularly the case when the abscess becomes encysted—an occasional event. The walls of these encysted abscesses are thick, smooth, resistant, and fibrous. In time their contents become cheesey, and ultimately cretified; in the latter event the cyst shrivels up and contracts to a small size. Pathology.—The pathology of liver abscess has been a fruitful source of speculation and controversy. Much confusion has crept into the question from attempts to separate, aetiologically and pathologically, multiple from single liver abscess. The former is often called " pyaemic abscess " or " dysenteric abscess," and has been set down as being the peculiar 364 Abscess of the Liver. sequel of dysentery; the latter has been called and considered the " tropical abscess " par excellence, and regarded as idiopathic and entirely unconnected with dysentery. As already pointed out, a careful examination of cases and statistics shows that both forms of abscess, single and multiple alike, are, in the vast majority of instances, clearly associated with dysentery. The dysenteric association, therefore, will not hold as a basis of classification and distinction. In their respective clinical histories, in their symptoms, in the characters of their walls and contents, in the frequent presence of amoeba coli, single and multiple abscesses are practically identical. The only difference between them is a numerical one; also a circumstance quite in- adequate to base a doctrine of specific distinction on. The view which I incline to hold on this subject has already been partly indicated in the section on aetiology. There are two factors which are princi- pally concerned in the production of liver abscess : (1) the predisposing — weakening of the resistive faculty of the liver by chronic congestion or tissue degeneration, and, perhaps, other subtle changes brought about by a combination of climatic, dietetic, and other tropical conditions; (2) the exciting—some micro-organism, streptococcus, staphylococcus, bac- terium coli communis, amoeba, or other parasite which, coming from the ulcerated dysenteric colon, or by way of the portal circulation, gains access to the liver and proliferates in the weakened tissues. In at least 90 per cent, of cases the pyogenic micro-organism is derived from dysenteric processes in the colon. Whether the resulting abscess be single or multiple is more or less a matter of accident. If the weakened liver is efficiently inoculated at one point only, there is only one abscess ; if at many points, then there is multiple abscess. This is virtually, in a sense, Budd's theory expressed in modern terms. An apparently weighty objection to this view is sometimes urged. Why, it is asked, if liver abscess Pa thology. 365 be the result of septic absorption from a dysenteric ulcer, is it not a common sequel of typhoidal or of tuberculous ulceration in the tropics? Macleod has met this objection very ingeniously and, I believe, to a certain extent, correctly. He points to the fact that typhoidal and tuberculous ulcerations are surface lesions unattended with abscess formation in the wall of the bowel. In their case there is free escape of the products and germs of ulceration; whereas in dysenteric lesions, in addition to the superficial ulcer- ation, there is often what is really abscess formation with burrowing and retention of pus below the mucous membrane, and therefore great liability to entrance of micro-organisms into the radicles of the portal vein. Liver abscess, therefore, according to this view, is a pyaemic process. Often, however, it must be con- fessed, the dysentery preceding liver abscess appears, judging from the symptoms, to be of the catarrhal rather than of a more severe type. To what extent amoeba coli is concerned as an occasional, or even common, cause of liver abscess it is as yet impossible to state. But if we watch the movements of this animal on the warm stage; and if we reflect that it lives and wanders about in the same very active way among the structures forming the walls of the liver abscess, and even in what are com- paratively sound tissues, preceding, as it were, the suppuration ; and consider that it lives at the expense of these tissues, it is hard to resist the conclusion that the amoeba operates as a disintegrating and irritating agency. Kartulis suggests that it may act merely as a carrier of pus-forming bacteria. Others maintain that it is a harmless epiphenomenon, incapable in any way of inducing pus-formation. Calmette, in view of the frequency with which he and others have found liver abscess to be sterile, suggests that the exciting agency is of a chemical nature, some irritating liquefying body derived from the decomposition processes going on on the surface of the dysenteric ulcer. 366 Abscess of the Liver. Diagnosis.—Of all the grave tropical diseases, none is so frequently overlooked as abscess of the liver. Acute sthenic cases are readily enough recog- nised ; not so the insidious asthenic cases. The novice in tropical practice is some time in realising that grave disease of so important an organ as the liver may, for a long time, be unattended with urgent symptoms, whether local or constitutional, or both. The most common mistakes in diagnosis are : (1) Failure to recognise the presence of disease of any de- scription, even when an enormous abscess may occupy the liver. (2) Misinterpretation of the significance and nature of a basic pneumonia—a condition so often accompanying suppurative hepatitis. (3) At- tributing the fever symptomatic of liver abscess to malaria. (4) Mistaking other diseases for abscess of the liver and vice versd—for example, hepatitis of a non-suppurative nature, such as that attending malarial attacks; suppurative hepatitis before the formation of abscess ; syphilitic disease of the liver— softening gummata, which are often attended with fever of a hectic type ; pylephlebitis; suppurating hydatid; gall-stone and inflammation of the gall- bladder; subphrenic abscess ; abscess of the abdominal or thoracic wall; pleurisy ; encysted empyema; pye- litis of the right kidney; pernicious anaemia; leucocythaemia; scurvy and similar blood diseases associated with enlargement of the liver; ulcerative endocarditis. Any of these may be attended with fever of a hectic type, increased area of hepatic percussion dulness, and pain in or about the liver. Many times a correct diagnosis can be arrived at only by repeated and careful study of the case in all its aspects. Golden rules in tropical practice are to think of hepatic abscess in all cases of progressive deteriora- tion of health; and to suspect liver abscess in all obscure abdominal cases associated with evening rise of temperature, and this particularly if there be en- largement or pain in the liver and a history of dysentery — not necessarily recent dysentery. If Diagnosis. 367 doubt exists, there should be no hesitation in having early recourse to the aspirator to clear up diagnosis.* As bearing on prognosis, apart from the risk from sudden rupture in some untoward direction, to over- look abscess of the liver is a much graver error than to mistake some other disease for liver abscess; for the chances of recovery from operation are pro- portionately prejudiced by every day's delay. Low pneumonia of the right base in a tropical patient should always be regarded with suspicion; in most instances it means abscess of the subjacent liver. Perhaps the most common error is to regard the hectic of liver abscess as attributable to malaria. The regularity with which the daily fever recurs, the daily chilliness or even rigor coming on about the same hour, the profuse sweating, and other circum- stances so compatible with a diagnosis of malaria, all contribute to this mistake. So common is the error that Osier says he hardly ever meets with a case of liver abscess which has not been drenched with quinine. My experience is the same. I have seen medical men make this mistake, not only in their patients, but in their own persons. If carefully con- sidered, there are several circumstances which should obviate so serious an error. (1) No uncomplicated ague resists quinine in full doses. (2) In malaria, if the liver be enlarged the spleen is still more so; the reverse is the case in liver abscess. (3) The plasmodium cannot be found in the blood in non- malarial hepatitis. (4) In liver abscess the fever is almost invariably an evening one ; in malaria it most frequently comes on earlier in the day. (5) Quoti- dian periodicity, contrary to what is the case with tertian or quartan periodicity, is by no means pathognomonic of, nor peculiar to, malaria. (6) The almost invariable history of antecedent dysentery, or, at least, of bowel complaint in liver abscess. To mistake other forms of suppuration for liver abscess is of no great moment, because in many of 368 Abscess of the Liver. the suppurative diseases just enumerated the treat- ment is the same as for liver absfcess, and no bad result need be looked for if diagnosis is not quite accurate. A more serious error, however, is to over- look the presence of leucocythaemia, pernicious anaemia, or scurvy, and to proceed to aspirate an enlarged liver on the supposition that the symptoms arise from abscess. Fatal intra-peritoneal haemorrhage from the puncture has been known to ensue in such circum- stances. If any doubt exists on this point, a micro- scopic examination of the blood should be made before proceeding to explore. A point to note in exploring is, that when the instrument enters the liver, an up-and-down pendulum- like movement will be communicated to the outer extremity of the needle in harmony with the rising and falling of the organ in respiration. If the needle does not exhibit this movement, its point may be in an abscess cavity but this abscess is not in the liver. Treatment.—Hepatitis which has not proceeded to abscess formation should be treated, in the absence of dysentery, with free purging by the sulphates, massive hot poultices, low diet, and rest in bed. It there be much pain, relief may be afforded by either wet or dry cupping over the liver, or by leeches around the anus. Ammonium chloride, in twenty-grain doses three times a day, is usually prescribed. If dysentery be present, the case should be treated with full doses of ipecacuanha, repeated once or twice a day for two or three days, or by a cautious use of the purga- tive sulphates, and by poultices, rest, and low diet. When the occurrence of rigor, or the development of hectic, or the appearance of local bulging, or the persistency of the fever and of the local symptoms, gives grounds for suspecting that abscess has formed, active medication must be suspended, a somewhat improved dietary prescribed, and measures taken without unnecessary delay to locate by means of the aspirator the position of the pus. Trea tment. 369 When he proceeds to use the aspirator, the surgeon must be prepared to open and drain the abscess if ous be discovered; once diagnosis is established, nothing is gained by delay. By proceeding to open the abscess at once the shock of a double operation is avoided and only one administration of the anasthetic is required. To facilitate aspiration, as well as the subsequent operation if such should be found to be necesearv the patient ought invariably to be placed under an anaesthetic. Unless in very special and excep- tional circumstances, it is a mistake to attempt exploration without this, for the surgeon ou^ht to proceed with deliberation and to feel himself at liberty to make as many punctures as he may think necessary. A medium- or full-sized aspirator needle should be used, as, owing to the nature of the pus, it may not flow through a cannula of small bore. If there are localising signs, such as a tender spot, a fixed pain, localised bulging, localised pneu- monic crepitus, pleuritic or peritoneal friction, these should be taken as indicating, with some probability, the seat of the abscess and the most promising spot for the exploratory puncture. If none of these localising signs are present, then, considering the fact that the majority of liver abscesses are situated in the upper and back part of the right lobe, the needle should, in the first instance, be inserted in the axillary line in the eighth or ninth interspace, about an inch or an inch and a half from the costal margin and well below the limit of the pleura. The instrument should be carried in a direction inwards and slightly upwards and backwards, and, if found necessary, to its full extent. If pus be not struck, the needle must be slowly withdrawn, a good vacuum being maintained the while in case the abscess has been transfixed and the point of the needle lodged in the sound tissue beyond. No pus appearing in the aspirator, the remainder of the dull hepatic area must be system- atically explored, both in front and behind, regard 370 Abscess of the Liver. being had for the lung and pleura on the one hand, and for the gall-bladder, large vessels, and intestine on the other. The peculiar colour—often like dirty brown thick blood—of liver pus must not be allowed to deceive the operator into thinking that he has failed to strike the abscess. At least six punctures should be made before the attempt to find pus is abandoned. Provided there is complete absence of breath sounds, of vocal fremitus and resonance over the lower part of the right lung, and pus has not been reached from lower down, then the pleura or lung may be disregarded and puncture made anywhere below the line of the nipple and angle of the scapula, or wherever the physical signs suggest. The surgeon should be encouraged to make early use of the aspirator by the fact that its employment, even where no pus is discovered, is not infrequently followed by rapid improvement in all the symptoms ; many such cases are on record. Hepatic phlebotomy, as Dr. George Harley designated the removal from the liver of a few ounces of blood by the aspirator needle, is a measure of proved value in hepatitis. With due care, risk from haemorrhage is small ; it is very small indeed in comparison with the risk of allowing a hepatic abscess to remain undiscovered and unopened. It is hardly necessary to add that strict aseptic precautions, in the way of purifying the patient's skin, the surgeon's hands, and all instruments, must be carefully observed. Operations for abscess of the liver.—The following is the operation usually practised by English surgeons. It is substantially that described by Mr. Godlee in the British Medical Journal of January 11th, 1890, to which the reader is referred for many valuable details and practical hints. If pus is struck below the costal border, the aspirator needle being left in situ as a guide, the abdominal wall is incised down to the peritoneum. A three-inch incision will give plenty of room. If firm adhesions be discovered, a sinus forceps is at once Trea tment. 37i run along the needle, and pushed through the inter- vening liver tissue and into the abscess. The aspirator cannula is now removed, and the blades of the forceps opened sufficiently, as it is being withdrawn, to make a wound in the liver large enough to admit the fore- finger, which must now be inserted and moved about so as to enlarge the wound and to gain some idea as to the size and direction of the cavity of the abscess. A rubber drainage-tube, about as large as the finger, and provided with a flange, is cut to a suitable length, and carried by means of the forceps to the back of the abscess. The abscess is then allowed to empty itself. When pus no longer flows freely, a massive antiseptic dressing is applied and firmly secured by a broad binder or many-tailed bandage. If after division of the abdominal wall no reliable adhesions be discovered between this and the liver, the capsule of the latter must be securely attached to the former by a double circle of stitches. The abscess is then to be opened, as above described, with sinus forceps. After stitching, some surgeons prefer before opening the abscess, first to stuff the wound in the abdominal wall with iodoform gauze, and to wait for a day or two for adhesions to form. Should the abscess be struck through an inter- costal space, and if the latter be not deemed suffi- ciently wide to admit of manipulation and free drainage, a couple of inches of rib had better be excised. The diaphragm may then be stitched to the thoracic wall or, better, to the skin as well, when the abscess may be opened with forceps. To stitch the capsule of the liver to the diaphragm is a some- what difficult proceeding; but if there are no reliable adhesions it had better be attempted, especially if the opening is to be made through a part of the liver covered by peritoneum. If, by any chance, the pleura is opened during the operation pneumo- thorax will result, an unfortunate, but not necessarily a serious, contingency. In this case the hole in the pleura must be carefully stitched in such a way that y 2 372 Abscess of the Liver. the pleural cavity is completely cut off before the diaphragm is divided and the abscess opened. Pus must not on any account be allowed to enter the pleural cavity; this, owing to the aspirating in- fluence of inspiration, it would readily do if the smallest hole should remain patent. The young surgeon would do well to practise these operations on the dead body, and familiarise himself with the relations of the various structures they involve. Some operators of experience completely ignore the absence of peritoneal adhesions, and, even in these circumstances, open the abscess without pre- vious stitching of peritoneal surfaces. The risk and danger of escape of pus into the peritoneal cavity, they hold, is very small if free drainage to the out- side is secured. Dr. Neil Macleod considers that, in the circumstances, stitches will not hold in the soft and inflamed liver tissue; he also considers that, in the event of the incision having to be made in the thoracic wall, removal of part of a rib is unnecessary. On account of the liability of the rubber drainage- tube to become nipped wben the emptying sac causes a want of correspondence between the wound in the abdominal or thoracic wall and that in the liver, and, also, on account of facility of introduction during the subsequent dressings, this operator uses metal drainage-tubes of suitable lengths—four, three and a quarter, two and a half, and one and three-quarter inches—with an oval lumen of four-tenths by three- tenths of an inch. These tubes he introduces by means of a special guide (Brit. Med. Jour., December 26th, 1891). The author's method.—The following easy, rapid, and efficient method of operating on abscess of the liver I have frequently practised, and can recom- mend. The necessary apparatus (Fig. 29), which can be made by native workmen, consists of a large trocar and cannula (a), four to five inches long, by three-eighths of an inch in diameter; a steel stilette (b) at least fourteen inches in length; two metal buttons (c, d) \ inch at their Trea tment 373 greatest diameter, with long (half-inch), hollow, rough- ened necks into which the ends of the stilette fit loosely; six inches of half-inch stout drainage tubing (e). While the ends of the drainage tubing are held and well stretched by an assistant, they are firmly lashed to the stem of the buttons, over the ends of the shorter (d) of which, for additional security, the Fij?. 29.-Apparatus for operation for Abscess of the Liver, a and 6 reduced. tubing is also tied (e). Two large holes, to provide for free drainage, are then cut close to one end of the drainage-tube. The tube is then mounted on the stilette by inserting one end of the latter through one of the drainage holes and lodging it in the hollow neck of the distal button (d,e), and thereafter so stretch- ing the rubber that the other end of the stilette can be inserted into the neck of the other button (c). When thus stretched, the drainage-tube should be capable of 374 Abscess of the Liver. passing easily through the cannula. The apparatus being thus prepared and rendered thoroughly aseptic by soaking in carbolic lotion, and the position and depth of the abscess having been carefully ascertained by means of the aspirator and noted, the aspirator is withdrawn and an incision about an inch in length made with a scalpel through the skin at the site of the puncture. The trocar and cannula are then thrust into the abscess and the trocar is withdrawn. After allowing a small quantity of pus to escape, so as to relieve any tension that may be present in the abscess sac, the stretched drainage-tube, perforated end first, is slipped into the cannula and carried to the back of the abscess. Holding the stretched drainage-tube firmly, and maintaining it carefully in contact with the back of the abscess with one hand, the cannula is withdrawn with the other. Still grasping the drainage-tube firmly, the button on the free end of the apparatus is slipped off the stilette, the end of which is made to perforate the drainage-tube close to the button. This it readily does, and the drainage- tube is allowed slowly to resile towards the fixed end, still held in contact with the back of the abscess. When the drainage-tube has completely contracted, the stilette is withdrawn. The drainage-tube is now transfixed with a safety-pin inserted close to the skin, and the superfluous tubing cut off. Pus flows freely from the tube, which now firmly plugs the wound in the abdominal wall and liver, and bridges the peritoneal cavity. When the abscess has nearly emptied itself the usual antiseptic dressing is applied. In operating through the thoracic wall, if deemed desirable, part of a rib may be excised before the trocar is introduced. I claim for this operation that it is easily done, and that it may be undertaken by the merest tyro in surgery and in the absence of skilled assistance"; that there is no risk from bleeding ; that, the peritoneum being bridged across by the drainage-tube which is securely grasped by the liver tissue, there is no risk Treatment. 375 of escape of pus into the peritoneal cavity; that in a very short time lymph is effused around the tube, giving additional security when, after a time, the tube has become loose ; that, if deemed necessary, a larger drainage-tube, by stretching it on the stilette in the same way as described, can be substituted for the half-inch tube; that an abscess deep in the liver can be as readily opened, and with as little risk, as one lying near the surface; that the shock is much less than in the cutting and tearing operation; that there is no risk of pneumothorax should the pleural cavity be traversed ; and that the drainage obtained is equal to that secured by any other method of operating. Several of my surgical friends have adopted this method of operating, and have expressed great satisfaction with the ease with which it is per- formed, and with the results. Other operations. — Some Continental surgeons recommend extensive incision of the liver, using a Paquelin's knife with the view of minimising bleeding. Zancarol, for example, advises that the hepatic and integumental incisions should extend the whole breadth of the abscess cavity, which he mops out, and stuffs with iodoform gauze. Certain French surgeons recommend scraping the abscess cavity ; most of them practise irrigation with some antiseptic fluid. These methods do not find favour with English or Indian surgeons. The method of opening the abscess by caustics, formerly much in.vogue, is now abandoned; equally so another method, also formerly employed—namely, that of leaving a rigid trocar in the wound. Treatment after operation.—For the first few days after a liver abscess has been opened the discharge is considerable, and the dressing may have to be changed frequently. Very soon, however, should the case do well, the discharge rapidly diminishes, and the dressing requires renewal only every other day or every three or four days. During the first week the drainage- tube, provided it be acting efficiently, should not be 376 Abscess of the Liver. disturbed, more particularly as it may be difficult to replace. Later, it may be removed and cleaned, and when discharge has practically ceased, cautiously shortened ; it is a great mistake, however, to begin shortening the tube before it is being pushed out, or so long as there is any appreciable discharge. If there is the slightest indication, such as rise of tem- perature, that pus is being retained, the sinus must be dilated with forceps and finger, and a full-sized drainage-tube introduced as far as it will go. If this does not suffice, a counter opening may have to be made. Delay in remedying imperfect drainage is a serious error. Should an abscess on being opened be found to be septic, or should it become so, it must be flushed out daily, or twice a day, with a weak non-mercurial antiseptic, and a counter opening made if necessary. After liver abscess has been opened and is drain- ing well, temperature rapidly falls and, in a few days or almost at once, becomes normal. Should fever persist, it is to be inferred either that the drainage is inefficient, or that there are more abscesses in the liver, or that there is some complication. If it be deemed that there is another abscess, this should be sought for with the aspirator, and, if found, opened and drained. I have seen a patient recover after three abscesses had been so treated. Treatment of abscess discharging through the lung.—In the case of abscess discharging through the lung, and not progressing favourably, the question of obtaining by surgical means more efficient drainage must be considered. There are two possibilities which render interference desirable. (a) Continued discharge of pus and blood, with or without attendant hectic ; a condition which, if it persists, in all probability will in the end kill the patient. (6) Not; infrequently prolonged dis- charge through the lung may induce fibrotic changes in that organ, or may give rise to pneumonia, or to abscess of the lung with all its attendant dangers. Treatment. 377 In these circumstances it is sometimes difficult to arrive at a decision as to whether an attempt should be made to open and drain the abscess, or to leave it alone. A large proportion of the cases recover, but at least an equally large number die. Of the latter, by timely surgical interference, a proportion may certainly be saved. In all cases of abscess discharging through the lung a careful register should be kept of three things —body temperature, daily amount and character of expectoration, and, once a week, the weight of the patient. If temperature keeps up, if the amount of pus continues the same or increases, or if the patient continues to lose weight, an attempt should be made at all risks to reach and drain the abscess from the outside. If temperature keeps normal, if pus gradually or intermittingly decreases, and if the body-weight be maintained or increases, operation is unnecessary, or, at all events, should be deferred. In exploring the liver in such cases, it must be borne in mind that most likely the abscess cavity is collapsed, and that the sides of the abscess are in contact. Such an abscess is not likely to be discovered unless the needle be thrust in to its full extent, and, whilst a good vacuum is being maintained in the aspirator, slowly withdrawn. If by good fortune the abscess has been traversed, then, when the end of the needle crosses the cavity, a small amount of pus will be seen to flow. Great care must now be exercised to keep the needle in position so as to serve as a guide in opening the abscess. Recovery has been known to follow the introduction of a drainage- tube in the presumed direction of such an abscess, even although the abscess cavity was not entered, much less drained by the tube. Treatment of abscess rupturing into a serous cavity.—When there is evidence that an abscess of the liver has ruptured into the peritoneum, into the pleura, or into the pericardium, the particular serous cavity involved must be opened at once and treated 378 Abscess of the Liver. on general surgical principles ; otherwise, the patient will almost surely die. In the circumstances the surgeon will be justified in assuming great risks. The prognosis in early operations on single abscess of the liver, provided there is no dysentery or other complication, is good. In multiple abscess, or in single abscess if there is active dysentery or other serious complication, prognosis is bad. In multiple abscess, if there are more than two or three abscesses it is necessarily hopeless. The question of return to the tropics after recovery from liver abscess frequently crops up. If feasible, and if the patient has not to make too great a sacrifice, he ought to remain in a temperate and healthy climate. There are many instances, however, of individuals who have enjoyed permanent good health in the tropics after recovery from liver abscess. 379 CHAPTER XXIV. INFANTILE BILIARY CIRRHOSIS. Within the last fifteen or sixteen years, a peculiar disease of the liver has been noticed in children in Calcutta and, to a less extent, in other large towns of India. It is found to be more prevalent in Hindoo than in Mahomedan children. Thus in Calcutta, from 1891 to 1893 inclusive, infantile biliary cir- rhosis, the name given to this disease, caused 1,718 deaths. Although the Hindoo and Mahomedan popu- lations of that city are about equal, yet as many as 1,616 of the deaths occurred in Hindoos, whilst only 80 occurred among Mahomedans, the balance of the mortality being among the Eurasians and other races. The disease occurs principally in children under one year, rarely attacking those over three years. As a rule, it commences during dentition, or about the seventh or eighth month, running a fatal course in from three to eight months. In rare cases it may commence within a few days of birth. Instead of lasting several months, its progress may be much more rapid, and terminate in death in from two to three weeks. The cause of infantile biliary cirrhosis is quite un- known. Neither alcohol, syphilis, nor malaria has anything to do with it. The children of the well-to-do are relatively more frequently attacked than those of the poor. It has also been observed that it tends to run in families, child after child of the same parents succumbing within a year or two of birth. In 400 cases, Ghose had only six recoveries, and in some of these recoveries the diagnosis was doubtful. Symptoms.—Commencing insidiously, the cha- 380 Lnfaxtile Biliary Cirrhosis. racteristic initial enlargement of the liver may have made considerable progress before the disease is suspected. Nausea, occasional vomiting, sallowness, feverishness, constipation, anorexia, irritability of temper, thirst, and languor call attention to the child's condition. On examination, the liver is found to be enormously enlarged, extending perhaps to the um- bilicus or even lower. The surface of the organ is smooth ; the edge, at first rounded and prominent, as the liver begins to contract becomes sharp and distinct and can be readily grasped between the fingers, the swollen organ feeling hard and resistant. Fever of a low type sets in ; the sallowness deepens into profound jaundice ; the stools are pale, the urine is dark; and there may be ascites, with puffiness of the feet and hands. Sooner or later, death from cholaemia ensues. Pathological anatomy and pathology.— Surgeon-Major Gibbons, who has given an elaborate and most careful account of the pathological anatomy of this disease, concludes that it is a peculiar form of biliary cirrhosis, the consequence of the action on the liver cells of some irritant of gastric origin, which leads to degeneration of the cells in the first instance, with subsequent increase of intercellular connective tissue and, later, of the portal sheaths. The forma- tion of new bile ducts between the hepatic cells, which is a well-marked feature, he regards as evidence of a natural curative effort having for its object a regene- ration of the liver cells. Treatment.—Hitherto, in this disease, treatment has been of little avail. There is some ground, how- ever, for thinking that early removal from the endemic locality, and a complete change of wet-nurse and food might have a beneficial effect. (Trans. First Calcutta Med, Cong.) 3»i CHAPTER XXV. PONOS. Under the name "Ponos" Karamitsas (Gaz. des Hbpit., 1880) and Stephanos (Gaz. Heb. de Med., 1881) have described a peculiar disease endemic in the islands of Spezzia and Hydra in the Grecian Archipelago. Ponos, in a sense, is analogous to the infantile biliary cirrhosis of Indian cities. Like the latter, it is confined to very young children, it is endemic in particular districts, tends to run in par- ticular families, to pursue a more or less chronic course, and is invariably associated with disease of an abdominal viscus—in this case the spleen. Though not invariably so, it is usually fatal. Symptoms.— Commencing somewhat suddenly and. commonly, during the first year of life, the earliest symptoms to attract the attention of the parents are languor and a pallor which rapidly acquires a sallow tint. Fever of an irregular character sets in ; the spleen enlarges; prostration is very marked ; and, it is said, the urine exhales a peculiarly disagreeable odour. Emaciation becomes progressive. Although the digestion is enfeebled and constipation is nearly- always present at first, the appetite is fairly preserved and may be perverted or excessive. The spleen gradually attains a great size, and is tender— hence the name, " ponos" (pain). The associated fever is of an irregular character, tending to become remittent, the thermometer rising during the exacer- bations to 39° oi- 40° Cent. ; towards the end it acquires hectic characters. Complications in the form of bronchitis, pneumonia, diarrhoea, dysentery, peri- tonitis, or meningitis may show themselves. WThen 382 Ponos. the disease has been established for some time oedema and ascites may occur, and there may be haemorrhages in or from various organs, especially the gums. In certain cases boils, and even patches of superficial gangrene, are met with. The progress of the disease is very variable ; it may last from one or two months to one or two years. Pathological anatomy and pathology.— Of these nothing is known further than that ponos exhibits none of the characteristic lesions of tuber- culosis, of leukaemia, or of malaria. Its cause is quite unknown. It has been remarked, however, that it is prone to occur in the children of those who have themselves suffered in infancy in the same way. It is said that in the case of the disease attacking the child of a tuberculous mother, recovery will very promptly set in if the child be supplied with a healthy wet-nurse. It has been suggested that ponos is an expression of malaria, but the post-mortem evidences are altogether against this supposition ; moreover, malaria is said to be unknown in the two islands in which this peculiar disease is endemic. The tendency to bleeding from the gums, cutaneous ecchymoses, and liability to haemorrhages suggest a scorbutic element. Ponos affects the children of rich and poor alike, and those living in good as well as those living in dirty, unhygienic houses. Treatment.—No specific is known. Quinine, tonics, fruit juices, careful management of the food, and early change of residence would seem to be indicated. 383 SECTION IV.-INFECTIVE GRANU- LOMATOUS DISEASES. CHAPTER XXVI. LEPROSY. Definition.—A chronic infective granulomatous disease, produced by a specific bacterium, and cha- racterised by lesions of the skin, nerves, and viscera eventuating in local anaesthesia, ulceration, and a great variety of trophic lesions. After a long course it is almost invariably fatal. History.—The many allusions in the oldest Chinese, Indian, Syrian, and Egyptian writings to a chronic, disfiguring, and fatal affection possessing well-marked and characteristic skin lesions, warrant us in concluding that the disease now known as leprosy was as common and familiar in the East in times of remotest antiquity as it is at the present day. There is some evidence—necessarily of a negative character—that leprosy is of comparatively recent introduction into Europe. The earlier Greek and Latin writers do not mention the disease. Hippo- crates, who, had he been practically acquainted with leprosy, would undoubtedly have described it accu- rately and fully, makes but brief allusion to the subject. Aristotle is the first of the Greek writers to give an unequivocal description. We may infer, therefore, that the introduction of leprosy into Greece probably took place between the time of Hippocrates and that of Aristotle—that is to say, between 400 B.C. and 345 b.c. Most likely it came from Egypt. In the time of Celsus—53 B.C. to a.d. 7—it was still a rare disease in Italy ; but, during the earlier centuries 384 Leprosy. of our era it increased there, and, probably extending in the wake of the Roman conquests, it appears to have spread thence over the greater part, if not over the whole, of Europe. By the end of the seventh century it was well known in Spain, France, and Lombardy. There is a notice of its occurrence in Ireland in 432. As regards England, the first allu- sion to leprosy refers to about the year 950. The popular idea that it was brought to this country from the East by the returning Crusaders (circa 1098) is therefore incorrect ; though, doubtless, the Crusaders, and the multiplicity of pilgrimages so much the fashion in the Middle Ages, and the destitution arising from the many wars of the period, had something to do with its rapid diffusion and great increase about this time. So common was leprosy during the Middle Ages that the rulers and clergy of nearly all European States, becoming alarmed at its rapid extension and terrible ravages, took measures, by instituting leper asylums and enacting stringent laws for the segrega- tion and isolation of lepers, to restrict the spread of what was speedily becoming almost a general calamity. These measures, based on what we now know to be a correct appreciation of the infectious nature of the disease, were ultimately crowned, in the case of most European countries, by almost complete success. Reaching its acme during the fourteenth century, leprosy then began gradually to decline, although as re- gards Great Britain it did not finally disappear as an indigenous disease until the end of last century. It died out first in England, later in Scotland—the last British leper dying in Shetland in 1798. In Italy, France, Spain, Germany, and Russia the repressive measures were almost equally successful, although in these countries, in Greece, and in the Greek islands leprosy of indigenous origin is still occasionally to be seen. The only country in Northern Europe in which at the present day it may be said to linger to any extent is Norway, where, in places, it is still by no Geographical Distribution. . 385 means uncommon (in 1890 there were 1,100 known lepers) ; but even here, under a system of segregation and comparative isolation—more humane perhaps in its application than that practised by our ancestors, although identical with it in principle—the disease is rapidly dying out. Apart from Egypt, we know nothing of the early history of leprosy in Africa. We are equally igno- rant as regards aboriginal America. The historians of the Spanish conquest do not allude to it as a native disease ; we appear, therefore, to be justified from this circumstance in concluding that the introduction of leprosy into the New World was probably effected through the negroes in the days of the slave trade. Rise of modern knowledge of leprosy.—The more important landmarks in our modern knowledge of leprosy are, first, the publication in 1848 of Danielssen and Boeck's Traite de la Spedalskhed, in which, for the first time, the clinical features of the disease were carefully and critically described ; second, the descriptions of the macroscopic and microscopic lesions—the leproma, the nerve lesions, and the lepra cell—by Virchow, Vandyke Carter, and many others ; and last, the discovery in 1874 by Arinauer Hansen of the specific cause of leprosy—the bacillus leprae—a discovery which brings this disease into line with tubercle, and which has given a much-needed pre- cision to our ideas on the important subjects of heredity and contagion, and on other practical points bearing on the question of the leper as a source of public danger and on his treatment and management. Geographical distribution.—Whatever may have been the case formerly, at the present day, with unimportant exceptions, leprosy is a disease more particularly of tropical and sub-tropical countries. So generally is it diffused in these that it would be more easy to specify the tropical countries in which leprosy has not, than to enumerate those in which it has, been ascertained to exist. Moreover, it is probable that in many of the countries not yet z 386 Leprosy. positively known to harbour the disease it does really exist; for experience shows that the endemic area of leprosy enlarges as our knowledge of the natives of the uncivilised regions of the earth becomes more intimate. It may be safely concluded, there- fore, that with the exception of a few insignificant islands, leprosy is an element, and often an impor- tant element, in the pathology of nearly all warm countries. The only tropical country of any magnitude about which we have anything like accurate leprosy sta- tistics is Tndia ; and even in this instance the figures, for many reasons—principally errors in diagnosis and concealment—are untrustworthy. According to the census of 1891, after making allowance for error, it is estimated that in British India there were 105,000 lepers in a population of 210,000,000—a ratio of about 5 in 10,000. Respecting China, of all countries probably the one in which there is the largest number of lepers, we have no figures to go by ; but, judging from what is seen in the coast towns and treaty ports, the number of lepers there is even greater than in India. In Japan, in the Philippines, in Cochin China, in the Malay peninsula, in the islands of the Eastern Archipelago, and in several of the South Pacific islands, in Persia, Arabia, and Africa, the disease is common enough. The same may be said of the West Indies and of the tropical regions of America. As regards more temperate countries, we know that there is a considerable number of lepers at the Cape, a few in Australia (principally Chinese but also a few Europeans), a few in San Francisco (Chinese). In Canada and in the United States there are also a few lepers of European blood, but their number is quite insignificant. In New Zealand, where leprosy was at one time common among the Maoris, it has died out. There are a good many lepers in Iceland. It is also reported as existing among the aborigines of the Aleutian pen- insula and Kamschkatka. In Great Britain and Geographical Distribution. 387 other European countries, particularly in the capital cities, lepers are not infrequently exhibited at medi- cal societies ; but, with rare exceptions, these cases are not of indigenous origin, most of them having con- tracted the disease abroad. Though thus extensively diffused, leprosy is by no means equally prevalent throughout the wide area indicated. Thus in China it is comparatively rare in the northern provinces, excessively common in the southern. In India a similar caprice of distribution is noted ; in Burdwan, for example, the proportion of lepers in 10,000 of the population is as high as 19-5, whereas in several other districts it is as Fow as 1 •;">,' or even lower. This caprice of distribution does not seem to depend on climate, geological formation, or suchlike physical conditions; leprosy is found in mountainous districts, on the plains, on the coast, in the interior, in all varieties of climate, and on'all kinds of geological strata. Social conditions, it would seem, have most to do in determining distribution ; its endemic prevalence appearing to be bound up in some way with uncleanly habits, squalor, dirt, and poverty —not, be it noted, directly caused by these things, but associated with them. Recent introduction.—An interesting and, from the aetiological standpoint, an important circumstance about the geographical distribution of leprosy is its appearance in recent times and rapid spread in certain islands whose inhabitants, there is good reason to believe, had previously been exempt. This modern introduction of leprosy into virgin soil, so to speak, has taken place in two islands at least—the Sand- wich Islands and New Caledonia. Sandwich Islands.— In the case of the Sandwich Islands leprosy was noted among the aborigines for the first time in 1859. After the most painstaking investigation Dr. Hildebrand failed to trace it farther back than 1848. Soon after its presence was recog- nised the disease spread so rapidly that by the year 1865 there were 230 known lepers in a population z 2 388 Leprosy. of 67,000. By 1891 the native population, from various causes, had diminished to 44,232 ; of these 1,500 were lepers—about 1 in 30. New Caledonia.—In New Caledonia (Grail, Arch. de Med. Navale, Oct., Nov., Dec, 1894) leprosy was unknown until 1865. It is supposed to have been introduced about that time by a Chinese ; the man was well known. Its rapid diffusion throughout the island can be, and has been, traced step by step. In 1888 the lepers numbered 4,000. Isles of Pines.—Similarly, in the Isles of Pines it was introduced in 1878, and has since spread. In the Loyalty Islands the first case was seen in 1882; in the island of Mare alone in 1888 there were 70 lepeis. Symptoms.—Although, as will afterwards be explained, the bacillus leprae is the cause of all leprosy, the clinical manifestations of its presence are far from being identical in every case; indeed, they are almost as varied as are those of syphilis or of tubercle. Our early conceptions of the disease, derived for the most part from the Bible or poetical literature, in which the leper is symbolical of all that is loathsome and hopeless, are apt to mislead. Asa matter of fact, in its earlier stages leprosy is far from being always, or even generally, a striking disease. Often for years the only visible evidence of its existence may be two or three small blotches, or perhaps one or two patches of pale or pigmented skin about trunk or limbs—very likely concealed by the clothes and perhaps disregarded by the patient him- self—whose true significance and nature can be appreciated only by the expert. It is generally not until the later stages that we see the disfiguring and extensive lesions on which the popular conception is founded. As a rule, leprosy is a disease of very slow development. Sometimes, it is true, it is suddenly and frankly declared from the outset, and progresses rapidly ; but, in the vast majority of cases, the early lesions are trifling and are apt to be misinterpreted and overlooked, and years elapse before serious Symptoms. 389 mutilation or deformity is produced. The student must bear this important practical fact in mind in the study and diagnosis of all equivocal skin lesions in persons residing in, or coming from, the endemic haunts of leprosy. To facilitate description, it seems advisable to divide the evolution of leprosy into stages, premising, however, that the division proposed is in great measure an artificial one. What are here designated stages are not, all of them, in nature and in every in- stance, abruptly separated or even present ; for the most part they merge imperceptibly into each other and, in not a few instances, some of them cannot be recognised. 1. The primary infection. 2. The period of incubation. 3. The prodromata. 4. The primary exanthem or macular stage. 5. The period of specific deposit. 6. The sequelae — ulceration, paresis, trophic lesions. 7. Terminations. 1. The primary infection.—Seeing that leprosy is caused by a specific germ, there must have been a time in the history of every leper when the infecting germ entered the body. In the case of many specific diseases, such as syphilis, the site of the primary infection is indicated by a well-marked local lesion and the time of infection can usually be ascer- tained. So far as present knowledge goes, this much cannot be affirmed of leprosy ; in this disease we know of nothing that indicates either the seat or, with rare exceptions, the time of primary infection. In this respect leprosy resembles tuberculosis. We are equally ignorant as to the condition of the infecting germ, whether it enters the organ or organs through which it gains access as spore or as bacillus ; and, also, as to the medium in or by which it is conveyed. We cannot say whether it enters in food, in water, in air; 39° Leprosy. whether it passes in through the unbroken epithelium, or whether it is inoculated on some accidental breach of surface, or, perhaps, introduced by some insect bite. But though we are in absolute ignorance as to the process of infection, we may be quite sure that in leprosy there is an act of infection, and that the in- fective material comes from another leper. Leprosy has never been shown to arise de novo. There are many facts and arguments to support this statement ; their discussion is deferred until the important practical subjects of heredity, contagion, and the hygienic questions connected therewith come to be considered. 2. The period of incubation.—This is generally, possibly always, long, and has to be reckoned usually in years—two or three at least. There are cases on record in which the period of incubation must have been longer even than this. Danielssen mentions one in which the period was ten years. Leloir describes another in which fourteen years or more, and Hbegh one in which twenty-seven years, elapsed between the time at which infection was pre- sumed to have occurred and the first manifestations of the disease. On the other hand, cases are on record in which the incubation period was set down at three months or even at a few weeks. 3. Prodromata. — Fever of greater or less in- tensity, and occurring more or less frequently is, almost invariably, a feature of the prodromal stage of leprosy. Febrile attacks may recur off and on during one or two years. It is well to bear in mind that in tropical countries such attacks are apt to be looked on as malarial. Another very common pro- dromal feature is an unaccountable feeling of weak- ness, accompanied usually by a sensation of heaviness and a tendency, it may be irresistible, to fall asleep at unusual times. Dyspeptic troubles, associated with diarrhoea in some cases, with constipation in others, and usually attributed to " liver," are also common. Epistaxis and dryness of the nostrils, Symptoms. 39i corresponding to the epistaxis in the prodromal stage of typhoid, tuberculosis, and such as is sometimes met with in early syphilis, are noted by Leloir. This epistaxis must not be looked upon as resulting from actual leprous rhinitis, which is a feature of a later stage of the disease. Headache ; vertigo ; perversions of sensation—such as localised pruritus, hyperaesthesia, "pins and needles," neuralgic pains—intermittent for the most part, and perhaps very severe and especially common in the limbs and face; general aching, rheumatic-like pains in loins, back, and elsewhere; all or any of these for months before may herald the explosion of leprosy. They point to a direct and early implication of the nervous system, by the lepra bacillus, or to a toxin poisoning by its products. Another curious feature in early leprosy, also noted by Leloir, is the liability in many instances to excessive sweating, which comes on without apparent, or on very slight, provocation. I had once under observation an Englishman who subsequently de- veloped leprosy, in whom this prodromal symptom was particularly pronounced, so pronounced that he had remarked it himself. This gentleman for many years kept a diary in which, among other things, he recorded very carefully matters relating to his health ; so that it was easy to trace from this diary the gradual evolution of his leprosy. The first unequi- vocal manifestation of the disease, an extensive erythematous patch on the ulnar side of the left arm and hand, which afterwards became anaesthetic, and two or three pigmented spots on the cheek, back, and leg, was noted on March 3rd, 1894. Five years before this there is an entry in his diary, under date June 4th, 1889, of the first of a long series of severe head- aches, transient febrile attacks, and progressive deterioration of health and vigour. Under date of June 9th, 1892,' is the first mention of the profuse perspiration which, occurring without obvious cause, continued to be a prominent feature until several months after the appearance of the skin lesions 392 Leprosy. referred to. In the diary such entries as the following frequently occur: "Nov. 20th, 1892. -—Feel poorly and sweating inordinately ; wondering what is coming over me. I am very ill." " Dec. 5th to 19th, 1892.—111 in bed. 1 had furious sweats during this time, and had dreadful pains in the back, lower part." And again, "Dec. 21st, 22nd—Feeling very ill; awful sweats ; weak ; done up." As pointed out by Leloir, this hyperidrosis may be general or it may be confined to particular parts, generally the trunk, the limbs being unaffected or even being the subject of anidrosis. A still more limited anidrosis is sometimes noted ; it usually happens that these non-sweating spots become anaesthetic at a later period of the disease. It is well to bear in mind that, just as in syiihilis, in a very small proportion of cases of leprosy there is a complete absence of constitutional symptoms prior to the appearance of the specific skin eruption. Such cases do occur, although they are distinctly rare. 4. The primary exanihem..— After a longer or shorter period of indifferent health, and being some- times preluded by an outburst more severe than usual of fever and other prodromic phenomena, an eruption appears on the skin. The occurrence of this generally coincides with, or is soon followed by, an improvement in the general health. Although strictly macular, this eruption—the primary exanthem of leprosy—varies in different cases both as to the size of the spots, their number, duration, and other characteristics. They may be no larger than a millet seed, or they may occupy surfaces many inches in diameter ; they may be numerous, or there may be only two or three. The earlier spots are usually purely erythematous, disappearing on pressure, and being darkest in the centre and shading off towards the periphery. But in some cases they may be pigmented from the outset; or they may be mere vitiliginous patches ; or all three forms of macula may concur in the same individual- erythematous, Symptoms. 393 pigmented, and vitiliginous. In not a few lepers what in the first instance was an erythematous patch may in time become pigmented, or it may become pale ; in the latter case the loss of pigment is usually associated with a certain degree of atrophy of the cutis. Or it may be that the centre of an erythe- matous patch clears up, the periphery of the patch remaining red and perhaps becoming pigmented; so that the affected spot comes to present the appearance of a red or dark ring, or portion of a ring, enclosing a patch of pale, usually anaesthetic skin. In certain instances the eruption of the various forms of maculae may be preceded by local paraesthesiae, such as a sense of burning, tingling, pricking, and so forth. At first the maculae may be evanescent and may fade wholly or in part in the course of a few days, weeks, or months; but as the disease progresses, and fresh spots appear, they tend to greater permanency, to be more liable to pigmentation, and are partially or wholly anaesthetic from the outset, or subsequently become so. A striking feature in this and in all leprous eruptions is the loss of the hair in the affected areas. Another striking circumstance in this connection is the fact that the most hairy part of the body, the scalp, is never affected either with leprous eruptions or with what could be considered leprous alopecia. As the face, particularly the superciliary region, is prone to all forms of leprous eruption, falling of the eyebrows is a very usual, very early, and very characteristic phenomenon. The beard, too, is apt to be patchy, particularly in nodular leprosy. In many instances, before they drop out, the individual hairs become white, or downy, or splintered, or nionillated. The most frequent seats of the primary macular eruption are the face, especially the superciliary region, the nose, cheeks, and ears; the extensor surfaces of the limbs; the backs of the hands; the back, buttocks, abdomen, and chest. The palms of the hands and the soles of the feet are rarely if ever 394 Leprosy. attacked; the scalp never. At this stage of the dis- ease the mucous membranes are very rarely affected. In the distribution of the maculae a rough symmetry may or may not be discernible. 5. The period of specific deposit.—During the stage just described, if there be any thickening of the skin or other evidence of new growth, it is barely per- ceptible to sight and but slightly to touch. Sooner or later, however, another stage is entered on, a stage characterised by the deposit or, rather, growth of a tissue possessing well-marked specific characters. This deposit occurs either in the skin, or in the continuity of the peripheral nerve trunks, or in both. If in the first situation, nodular or, as it is sometimes called, tuberculous leprosy is the result; if in the second, we have nerve or anaesthetic leprosy ; if in both of these situations, then what is known as " mixed leprosy " is produced. These three forms of the completely developed disease, though having much in common, are, as a rule, clinically fairly distinguishable. It is customary, therefore, to describe them separately. NODULAR LEPROSY. This form of leprosy often appears without a preliminary well-marked macular stage, being ushered in, after a longer or shorter prodromic stage, by a smart attack of fever and the rapid development on the face or elsewhere of the specific lesion. In other instances a well-defined but, in comparison with nerve leprosy, short macular stage precedes the appearance of the characteristic lepromata (Fig 30). The essential element in nodular leprosy is the leproma. The dimensions, the combinations, the situations, the growth, and the decay of this give rise to the more manifest symptoms of the earlier stages, at all events, of the disease. The leproma, which will be more fully described in the section on the pathological anatomy of leprosy, is formed by in- filtration of the deeper layers of the derma with what Fig. 30.—Nodular Leprosy (Leloir). 396 Leprosy. at first is a small-celled, somewhat dense neoplasm. As this slowly or more rapidly increases it forms a prominent, rounded boss or protuberance covered with unbroken epidermis. In size it ranges from the dimensions of a split pea, or of a bean, to a great plaque many inches across. In colour it is different according to its age and condition, and according to the natural hue of the skin of the leper ; it varies from red to dirty pink in the earlier and congestive active stage, to dark brown or dirty yellow in the later stages. It is generally, though not always, especially at first, anaesthetic to some degree, if not absolutely so; it is devoid of hair, usually somewhat greasy-looking and, perhaps, stippled with gaping follicles. Though not so hard as keloid growth, it is fairly firm to the touch, and, unless very extensive, can be readily raised up and freely moved over sub- jacent structures. Isolated lepromata are usually round or oval; when contiguous they may coalesce, forming patches of irregular outline. When many lepromata run together, or are closely set, the growth causes the natural folds of the skin to be exaggerated ; and thus great disfigurement, especi- ally of the face, may ensue. Thus the skin of the forehead and eyebrows—an early and favourite site of leprous infiltration—is thrown into massive folds and overhangs the eyes; the fleshy parts of the nose broaden out; the cheeks become massive; the lips are thickened and protrude; the chin is swollen and heavy ; the external ears are thick and pendulous; and the bloated, dusky, wrinkled, greasy, passive countenance acquires the repulsive appearance very appropriately designated " leontiasis." Nodules may appear in greater or less profusion on the limbs and body; favourite sites being the backs of the hands, the external surfaces of the arms, wrists, thighs, and the groins. On the trunk they may occupy very large areas, forming extensive plaques. As a rule, in the latter situation they are not so prominent as on the face and arms. The same remark Nodular Form. 397 applies to the legs, where the infiltration is usually dusky, diffuse, ill-defined, and prone to ulcerate. From time to time, and at longer or shorter intervals, fresh tubercles appear, their formation generally concurring with an outburst of leprous fever. Occasionally, and this is very often observed during an intercurrent attack of some acute disease —such as an exanthematous fever, or erysipelas, or even of some exhausting disease like phthisis—all or a proportion of the nodules are temporarily absorbed, leaving only slight traces behind. But the normal and usual fate of the nodule is either first to soften in the centre and then to be absorbed, leaving a smooth circular patch of scar tissue; or, after soften- ing, to ulcerate and discharge a sticky, yellowish pus. This discharge tends to dry up into crusts, ulceration proceeding underneath. . Finally the ulcer may heal, leaving an irregular, depressed scar. When the mucous membrane of the nose is affected, as it usually is in time, the cartilage of the septum breaks down, the tip of the organ becoming depressed, and a stinking discharge escapes from the nostrils. In such circumstances breathing is very much inter- fered with, more especially if, at the same time, leprous deposit occurs or ulcerates in or about the glottis, the epiglottis, pharynx, tongue, or mouth generally. The senses of smell and taste are then lost for ever. The eyes, also, are sooner or later attacked, lepro- matous growth spreading from the conjunctiva on to the cornea or into the anterior chamber, or originating in the iris or ciliary body. Ultimately this organ also is destroyed, and with it the sense of sight. Thus, in time, with the exception of that of hear- ing, one sense after another disappears. Ulcers form everywhere from the breaking-down of the nodules or from injuries to the insensitive skin. The cervical and inguinal glands, owing to leprous infiltration, swell and perhaps suppurate and become fistulous ; the abdomen enlarges from leprous, perhaps combined with amyloid, infiltration of the liver, and there 398 Leprosy. may be diarrhoea from amyloid disease of the in- testine. In addition to these troubles, if the patient live, the nerve trunks are attacked, and then the neuralgic, paretic, and trophic lesions of nerve leprosy are superadded. The fingers and toes ulcerate and drop off, or they become distorted and atrophied ; or the phalanges are absorbed, the hands and feet becoming reduced to useless stumps. A peculiar goat-like smell is emitted by the ulcerating, decay- ing body. Altogether, the blind, lame, unhappy wretch—still retaining his intellect but devoid of every sense except that of hearing, breathing with difficulty through a stenosed larynx, and racked by neuralgic pains and irregular outbursts of fever- comes to present, before the inevitable death from exhaustion occurs, a sadder, more loathsome, and more repulsive picture than imagination could conceive. Fortunately, in a large proportion of cases, the leper is mercifully carried off by phthisis, pneumonia, or some intercurrent, affection at an earlier period, and before his disease could be said to have run its full course. NERVE LEPROSY. Just as in nodular leprosy, in nerve leprosy the prodromic and macular stages may be severe, or slight, or altogether absent. Usually, however, in nerve leprosy, much more frequently than in nodular leprosy, the ulterior and more distinctive lesions are preluded by a long and well-marked macular stage, during which large areas of skin are occupied by erythematous (Fig. 31), by pigmented, or by vitiliginous patches. The ringed form of eruption is a very usual one ; a red, congested, slightly elevated and, perhaps, hyperaesthetic border enclosing a larger or smaller area of pale, anaesthetic, non-sweating in- tegument—the whole resembling somewhat one of those extensive body-ringworms so common in natives of hot, damp climates, for which these rings are sometimes mistaken. Such eruptions may come and ^^mm^^fsgr% 'U< ':* A.--;A*w«- ^ Fig. 31.—Nerve Leprosy (Leloir). 400 Leprosy. go, or they may be permanent, or they may spread and multiply during many years before the more distinctive and graver signs of nerve leprosy are evolved. A frequent and very distinctive symptom of this type of the disease, occurring often about this time, is the sudden appearance of bullae (pemphigus leprosus) —one or more or a series of them—on the hands, feet, knees, backs of thighs, or elsewhere. These bullae vary in size from a pea to an egg. After a few days they rupture, exposing a reddish surface which presently crusts over, exfoliates, and finally turns into a pale, perhaps anaesthetic, spot with a sharply defined, pigmented border. More rarely the site of the bulla ulcerates. Should similar bullae be formed in the neighbourhood of the first, the resulting ulcera- tions may unite into an extensive, probably superficial, serpiginous-looking sore. A time comes when evidence of profound implica- tion of the nervous system, in the shape of severe neuralgic pains, formication, hyperaesthesia, or anaes- thesia, becomes more accentuated. The lymphatic glands enlarge, and there is often considerable fever and general distress. Hitherto, the most prominent symptoms have been the skin lesions. These may remain or even increase ; on the other hand, they may in part or entirely disappear. But whether the skin lesions increase or retrograde, evidences of pro- found implication of the peripheral nervous system now distinctly show themselves; the neuralgic pains still further increase, and hyperaesthesia, anaesthesia, and various paraesthesiae, along with trophic changes in skin, muscle, and bone, the results of nerve de- struction, become the dominating elements in the case. If at this stage the ulnar nerve where it passes round the internal condyle of the humerus be examined, generally it will be found to be the seat of a fusiform swelling perhaps as thick as the little finger. Other nerves, such as the anterior tibial, the peroneal, more Nerve Form. 401 rarely the median, radial, brachial, and cervical nerves, especially where they pass over a bone and lie close under the skin, can be felt to be similarly swollen. Occasionally even the smaller nerves, where superficial, can also be detected hard and cord-like. At first these thickened nerves are tender on pres- sure, and the parts they supply may be the seats of hyperaesthesia and acute neuralgia. By degrees, however, the great thickening of the nerve trunks decreases somewhat, the hyperaesthesia and neuralgia subside, and anaesthesia and muscular atrophy and other trophic changes, with paresis, take their place. For a time the condition may fluctuate; the neuritis apparently may come and go with corresponding changes in the condition of the area subserved by the affected nerves. Sooner or later, however, fibrotic changes ensue in the neural leprous deposits, the nerve tubules ultimately atrophying and disappearing. The nerve tissue is now irreparably damaged, and trophic changes steadily advance. In other instances, anaesthesia comes on without neuralgic pains, without hyperaesthesia, without constitutional symptoms, with- out discoloration of the skin, the patient discovering its existence by accident. In nerve leprosy, the anaesthesia begins most com- monly in the feet, the thighs, hands, arms, forearms, and face. Later, and more rarely, it affects the trunk. The anaesthesia, though associated with well-marked lesions of the larger nerves, does not always, or even as a rule, coincide accurately with the anatomical distribution of their terminals; a circumstance which tends to show that the anaes- thesia is not always and simply the result of lesion of nerve trunks, but that it may be the effect of the destruction by the bacillus of the nerve ter- minals themselves; a suggestion which is strength- ened by Gerlach's discovery that in anaesthetic leprosy the bacilli appear first in the skin around the nerve terminals, and only subsequently extend upwards to the nerve trunks. Another, and sometimes a A A 402 Leprosy. very striking, fact in nerve leprosy is the symmetry observed in the distribution of some of the anaesthetic areas. This symmetry is by no means invariable ; in not a few cases, however, it is very perfect and remarkable. At the outset the anaesthesia in the affected patches may not be absolute; it may also come and go ; and it may be very superficial, deep pressure being for a long time appreciable. But when the anaesthesia becomes, as it were, settled in a part, it seems gradually to extend deeper into the tissues; so that after a time it is absolute, and the parts may be pinched, incised, and even seared with fire, and the leper be absolutely unconscious of pain or even of being touched. Step by step with the progress of the anaesthesia, atrophy of the subjacent muscles supplied by the thickened nerves proceeds. Along with the atrophy there is a corresponding distortion and a corresponding loss of power. There is no ataxia or inco-ordination of movement—simply feebleness. Thus the forearm wastes, the grasp is weakened, the thenar and hypo- thenar eminences, and the interossei melt away, and the main-eu-griffe or some such deformity is gradually produced (Fig. 32). Similar changes occur in the legs and feet, so that the power of walking is much impaired. The muscles of the thighs and upper arms, the pectorals, and the muscles of the face follow suit; very much as in progressive muscular atrophy, only in the latter there is no superjacent anaesthesia. In the affected nerve areas all the muscles are not simultaneously or equally attacked, so that, especially in the. face, curious distortions may ensue. These facial atrophies, whether symmetrical or one-sided, in time produce a facies as characteristic of nerve leprosy as leontiasis is of nodular leprosy. From muscular atrophy the eyes after a time can no longer be closed; the upper lid droops, the lower lid becomes everted, and the eye itself may become fixed. At first, owing 1 4*/.->/\,fc-,.rc # Fig. 32.--Nerve Leprosy: Main-en-ckiffe (Leloir). 4°4 Leprosy. to exposure of the organ, there is lachrymation ; but by-and-by the secretion of tears dries up, the con- gested conjunctiva becomes cornified, the cornea ulcerates or turns leucomatous, and in the end sight is entirely lost. Ulceration often occurs in the mucous membrane of the nose, the septum being destroyed as in the nodular form ; the tip of the nose may then be lost or it falls down. The lips, too, may become paralysed, interfering with articula- tion and permitting the saliva to dribble from the mouth in a constant stream. Changes occur, too, in the mucous membrane of the mouth ; the gums may retract, exposing the maxillary bone, the teeth ultimately dropping out. Anaesthesia of the tongue and buccal mucous membrane, and implication of the muscles of mastication may render eating and articulation very difficult. In time the skin of anaesthetic patches on the limbs tends to atrophy ; it loses its glands and hairs, and, in the end, may become so thinned and tense that it may actually burst into long cracks. The nails are not generally shed, but they become rough or thinned or atrophied info minute, hook-like appendages. Ulcers form over exposed parts of the hands and feet. They may penetrate and disorganise the joints, and thus often cause fingers and toes to drop off, one after another. Or, perhaps, an abscess forms around a phalanx, destroys the periosteum, and ultimately leads to loss of the bone. Or a sort of dry gangrene may amputate finger or toe. Or there may be a curious interstitial absorption of one or more phalanges, the shaft of the phalanx wasting more rapidly than the articulating surfaces. In any of these ways the fingers and toes are distorted or destroyed. It is no unusual thing to see on a leper's hand a finger in which one or more of the phalanges have been thus got rid of without destruction of the fleshy part, or with only a general shrinking of this. Thus it comes about that a distorted, talon-like nail may crown a finger which is a mere stump; or, the finger Mixed Form. 405 having been entirely absorbed, the nail springs, as it were directly, from the knuckle. Perforating ulcer of the sole of the foot, as might be expected, usually under the ball of the great toe or the heel, is a very common lesion in nerve leprosy. On the whole, the advance of this form of leprosy is much slower than that of the nodular variety. The average duration of the latter is from eight to nine years, of nerve leprosy about eighteen years. Often such lepers live much longer—twenty, thirty, or even forty years. As can readily be understood, the end of these cases is quite as sad and repulsive as it is in nodular leprosy. Death seldom results directly from the disease itself ; diarrhoea, chronic nephritis, phthisis, pneumonia, or bronchitis being, one or other of them, usually the immediate cause of death. MIXED LEPROSY. As already explained, in most cases of nodular leprosy, trophic changes from implication of nerve trunks ultimately supervene. Similarly, though not so frequently, nodular infiltration of the skin may appear in the course of what originally seemed to be a case of pure nerve leprosy. In yet other cases nodular and nerve lesions concur from the outset of the disease. In one or other of these ways what is known as mixed leprosy is produced. The lesions are in no way different from those already mentioned, and therefore this form of the disease does not call for more detailed description. Pathological anatomy. — Bacillus leprce. — The lesions of leprosy are the result, direct or in- direct, of the proliferation of the bacillus leprae in the tissues. This parasite (Fig. 33) in size, shape, and staining reactions closely resembles the bacillus of tubercle. In length it is from half to two-thirds, and in breadth about one-sixteenth the diameter of a blood-corpuscle. The ends of the rod—which is always straight—are in many specimens somewhat 406 Leprosy. attenuated; and in many instances — presumably in old bacilli — a nioniliform arrangement of the protoplasm, as if from spore formation or, accord- ing to Hansen, from disintegration, can be detected. By some authorities it is said to possess a gelatinous capsule. From bacillus tuberculosis it may be dis- tinguished by the somewhat greater difficulty with which the stained specimen is decolourised by acids; by the impossibility hitherto experienced of growing Fig. 33.—Bacillus leprae, x 1000 (Muir and Ritchie). it on the usual, or on any. culture media, and of inocu- lating it in man and the lower animals; by its tendency to occur in dense clusters; and by its very generally being found inside cells or, according to Unna, in zooglcea masses in the lymphatic spaces. Specimens of the bacillus can be procured readily by excising a portion of a leproma—a proceeding, in consequence of the absence of sensation in most tubercles, not usually much objected to by lepers; or they may be obtained by including a succulent leproma in a pile clamp, slowly screwing up the jaws of the instrument so as to drive out the blood, Pathological Anatomy. 407 pricking the now pallid leproma, and then collecting on a cover-glass the droplet of "leper juice" which exudes from the puncture. The juice may be spread out on the cover-glass, fixed, stained, and decolourised as for the demonstration of tubercle bacilli, or it may be examined fresh. If examined fresh, or if a morsel of leproma be teased up in water, the bacilli may be seen both inside and outside the cells and in active motion. Whether this motion is simply molecular, or whether it is vital, it is hard to say ; probably the former, for, whilst osmic acid does not stop it, it is immediately arrested by the addition of viscid fluids, such as glycerine or albumin water. The bacillus is found in all primary leprous de- posits ; in the skin leproma—-where it occurs in prodigious numbers; in the meagre infiltration of the macular eruptions—where it is much more sparsely distributed ; in the early stage of leprous neuritis— where, also, it is present only in small numbers; in the specific lesions of the liver, spleen, testes, and lymphatic glands. In the blood-vessels it has been found in the endothelium and, occasionally, free in the blood or enclosed in leucocytes. It is abundant in the purulent discharges from ulcerating lepromata or other forms of primary leprous infiltration. It has very rarely been found in the spinal cord or in the lungs. It is doubtful if it occurs in the brain, the intestinal tract, or in the kidneys, although the latter are prone to inflammation in leprosy. It is not found in muscle, in bone, or in cartilage ; and it is not neces- sarily present in the secondary trophic lesions of nerve leprosy, or in secondary inflammatory effusions. The leproma.—The young leproma presents a smooth, white, glistening section. Wdien the leproma is older the cut surface has a brown tint, and the morbid tissue may become, from fibrotic changes, harder, or, from degeneration, softer. The specific lesion of leprosy differs from that of tubercle, inasmuch as it is well supplied with blood-vessels, contains no giant cells 408 Leprosy. (Hansen), and never undergoes caseation. It har- dened, cut, stained, decolourised, and examined under the microscope, the leproma is found to consist princi- pally of small round cells about the size of a leucocyte, epithelioid cells, and fusiform cells—the two latter in increasing numbers with the age of the leproma. It can be seen that these cells have infiltrated and partially dissociated all but the most superficial layer of the derma. It may be further observed that the cells are arranged for the most part in groups, generally around and near blood-vessels ; and that a very large proportion of them contain bacilli, some cells having only a few, whilst others are literally crammed with the parasites. Isolated bacilli are also found scattered through the preparation, apparently free in the lymph spaces. The bacilli are never seen inside the nuclei of the implicated cells. In addition to the bacilli-bearing cells, and in- creasing in number with the age of the lesion, a number of brown granular bodies, larger and smaller, which have been named "globi," are to be found. These Hansen holds to be cells in which the bacilli have perished and become granular. It is to them that the brown colour of old lepromata is due. There has been considerable discussion as to the exact position of the bacilli as regards the lepra cells —whether they lie inside the cells or whether they are free. On the one hand, Unna holds that they lie free in the lymph spaces, and that they are never in the cells, the appearance of cell inclusion being produced by the zoogloea arrangement so common with bacteria. On the other hand, Leloir maintains that some of the bacilli are free, whilst others are inside the cells. A third set of observers, following Hansen, hold that the bacilli are almost invariably included within cells the nuclei of which can readily be demonstrated surrounded by the parasites. Other lesions.—The histology of the infiltrated macula is practically the same as that of the leproma, the number of bacilli, lepra cells, and globi being Pathological Anatomy. 409 proportionately fewer. In old maculae, as in very old lepromata, the bacilli may be hard to find or entirely absent. In the anaesthetic maculae the terminal nerve fibres are degenerated. As the fusiform thickening of the larger nerve trunks in nerve leprosy is a secondary inflammation, bacilli may not always be found in it, although at the very commencement of the nerve disease bacilli, both in cells and, according to Leloir, free between the nerve tubules, are present and may even lie in the nerve tubules themselves. In time the affected nerves become mere fibrous cords destitute of nerve tubules. The anatomy and histology of the various trophic lesions are such as are found in other examples of destructive neuritis, and are in no way peculiar to leprosy; they do not, therefore, cal 1 for description here. In nodular leprosy the liver and spleen are the subjects, in many instances, of a peculiar infiltration which, in well-marked examples, may be visible to the naked eye. Fine yellowish-white dots and streaks are seen to occur in the acini of the former. These dots and streaks consist of new growth in which bacilli abound ; according to Leloir, the parasites are never found in the hepatic cells themselves. In all cases of nodular leprosy the testes atrophy and undergo fibrotic changes, bacilli and globi being found both in and around the tubules, free and in cells. In all forms of leprosy the lymphatic glands ap- pertaining to parts in which leprous deposit is present are characteristically affected. They are swollen and hard, and on section the gland tissue is seen to have a yellowish tinge from an infiltration which contains numerous bacilli and globi. Albuminoid disease of the alimentary canal, liver, and spleen, and nephritis occur in a large proportion of the cases of nodular leprosy. Diagnosis___The touchstone in all doubtful cases is the presence or absence of anaesthesia in some skin 4io Leprosy. lesion or in some skin area. Anaesthesia is rarely absent in leprosy ; generally, in the implicated spots, it is complete, or nearly so. It should be particularly sought for towards the centre of maculae, in the pale patches left after the fading of former maculae, in the hands and feet, and in nodules of some standing. In no other skin disease is definite anaesthesia a symptom. Vitiligo, or leucoderma—sometimes called white lep- rosy, and by the vulgar very generally regarded as true leprosy—bears a certain resemblance to the pale post-macular patches referred to ; not to mention other features, the absence of anaesthesia in leucoderma at once settles diagnosis. Further assistance may sometimes be got in doubt- ful cases from the fact that leprous spots rarely perspire. A hypodermic injection of pilocarpine is of use in bringing out this point. The sensory and trophic lesions of syringo-myelia might be mistaken for nerve leprosy ; but the general history of the case, the history or presence of macular eruption, of thickened nerve trunks, and of enlarged lymphatic glands in leprosy, and their absence in syringo-myelia, are mostly sufficient to establish a diagnosis. It is hardly necessary to point out the diagnostic marks of leprosy as against syphilis, erythema multi- forme, erythema nodosum, lupus vulgaris, lupus erythematosus, psoriasis, eczema, lichen planus, keloid, body-ringworm, erythrasma, pityriasis versi- color, elephantiasis Arabum, etc. Mistakes can scarcely be made unless from carelessness, or by some one completely ignorant of the nature, history, and symptoms of these diseases. In approaching the diagnosis of skin eruptions, localised pareses, muscular atrophies, and anaesthesia in patients living in, or coming from, a country in which leprosy is endemic, the possibility of their being attributable to this disease must be borne in mind. If doubt exist, and it be found feasible, search should be made in eruptions or in thickened nerves I /Etiology. 411 for the bacillus. If this is found the diagnosis of leprosy is infallibly established. Prognosis.—Complete recovery is an event so rare in leprosy that, though it may be hoped for, it must not be expected. Recovery from the actual disease itself—that is, in the sense that fresh leprous infiltra- tion may cease to occur, and old infiltration may be absorbed, and that the bacilli may die out—is perhaps the rule in nerve leprosy ; but the effects of the leprous process are permanent, the trophic lesions resulting from nerve destruction being irremediable. Such cases may live, however, for many years—thirty or forty—and die of some other disease; at best, they are but mutilated specimens of humanity. Nodular leprosy is usually a much more acute disease than nerve leprosy, sapping the strength and general health much more effectually and quickly. It rarely runs its full course, death being brought about by some intercurrent disease, such as, and especially, phthisis, nephritis, albuminoid degeneration of the alimentary tract, dysentery, stenosis of the larynx, and pneumonia. It may prove fatal as a sort of galloping leprosy within a year even of its first declaring itself. .Etiology.—Age.—It is open to question if leprosy has ever been seen in the foetus. It has once or twice been reported in the newly-born. Cases are also on record of its occurrence as early as the first and second years of life; such, however, are quite ex- ceptional. Leprosy is extremely rare before the fifth or sixth year. In the great majority of instances the disease begins between the tenth and thirtieth years. It rarely commences after forty, although it has been known to begin up to, and even after, seventy. Sex ; occupation ; social and hygienic conditions.— Sex, apart from the- associated social conditions as affording opportunity for contagion, seems to have little bearing on the liability to leprosy. The same may be said of occupation, and social and hygienic 4T2 Leprosy. conditions in general. Yrery probably bad food and bad hygienic circumstances have in this, as in most germ diseases, a predisposing influence; but they certainly cannot create a lepra bacillus and leprosy any more than they can create an acarus scabiei and itch. This is abundantly demonstrated by the absence of leprosy at an earlier period in countries in which, without alteration in the food or other hygienic con- ditions, the susceptibility of the natives to the disease was subsequently proved by its rapid spread on being introduced from without, e.g. the Sandwich Islands and New Caledonia ; and, also, by the disappearance of the disease, in other instances, under the influence of the segregation and isolation of lepers, without any concurrent material alteration in food or other circum- stances, e.g. Scotland and Ireland and many other European countries. Climate.—Climate can in no way be considered a cause of leprosy, for leprosy exists in all climates and in all latitudes. But it does seem to have some influ- ence in determining, to a certain extent, the type the disease assumes. It would appear that the nodular form is more common in cold, damp climates ; the nerve form in warm or dry climates. The lepra bacillus.—Hansen remarks, " There is hardly anything on earth, or between it and heaven, which has not been regarded as the cause of leprosy." However true this remark may be as regards times prior to Hansen's discovery, we are now practically certain that the lepra bacillus is the cause of leprosy. The only gap in the evidence, otherwise conclusive, lies in our present inability to cultivate the bacillus, or to convey it by inoculation or otherwise to the lower animals, or, perhaps, to man himself. Many attempts have been made to communicate leprosy to man by inoculation, but hitherto, with one questionable exception, all have failed. A Sandwich Islander, apparently at the time free from leprosy, was inoculated from a lepra tubercle. Within a month he had symptoms of leprous neuritis; two .Etiology. 4'3 years later he was a confirmed leper; and in six years from the date of the inoculation he died of leprosy. Unfortunately the subject of the experiment was a native of a country in which leprosy was extensively endemic; and besides, he had lived among lepers, in fact, members of his family were lepers. However possible it may be that the bacillus in this instance had been communicated by the inoculation, the circum- stances in which the exjjeriment was made, and the unusual shortness of the incubation period, are against its being regarded as conclusive evidence of the inoculability of the disease. To bridge over temporarily this important gap in the evidence, we have to fall back on the close analogy that exists between the lepra bacillus and the bacillus tuberculosis, the leproma and the tubercle, leprosy and tuberculosis. In consideration of this and other cir- cumstances, it is generally conceded nowadays that the bacillus leprae is the true cause of leprosy, just as bacillus tuberculosis is the cause of tubercle. Authori- ties differ, however, as to the way in which the bacillus is acquired. How acquired.—It is aburd to suppose that an organism of any sort, no matter how humble in the scale of life, can originate de novo; such an hypo- thesis may be at once dismissed. Disregarding this we have to consider two principal views entertained as to the way in which the bacillus is acquired— heredity and contagion. Heredity.-—From the fact that it tends to run in families and that it assumes the appearance of atavism in certain instances, leprosy, until the bacillus leprae was discovered, was almost universally—as it still is by some—believed to be a hereditary disease. That this belief, in the same sense as that tubercle may be said to be hereditary, was well founded is quite possible; that is to say, that certain physio-patho- logical qualities predisposing to the disease may be inherited. But since the discovery of the bacillus it is impossible any longer, if we properly consider it, 414 Leprosy. to believe that the bacillus itself, and therefore the disease it causes, can be hereditary in the scientific sense of the word " hereditary." Physiological peculiarities and susceptibilities may, but parasites cannot, be inherited. It is true the ovum may be infected by a germ, as in syphilis ; but infection is not heredity. That the ovum can be infected at some stage of its existence by the lepra bacillus is proved if it be true that children have been born with the lesions of leprosy on them. But because leprosy is common in the descendants and blood collaterals of lepers, this is no proof of ovum infection in every, or, perhaps, in any case; for family liability is quite as explicable by an hypothesis of contagion or outside infection as by an hypothesis of inherited infection. Not only may the individuals of a family inherit a family predisposition of susceptibility to the bacillus, but, as a family, the members of it are generally at one time or another closely associated, exposed to the same hygienic influences, liable to communicate by contact with each other each other's parasites, or to acquire the parasites latent in their common surround- ings. Because the members of a family simultaneously, or one after another, contract scabies, or ringworm, or typhoid, no one supposes on this account that any of these diseases is hereditary. Without absolutely denying the possibility of ovum infection, the probability is that such an event is very rare. The age at which leprosy usually appears is against such a supposition. The latency of a germ for twenty, thirty, forty, or even seventy years is an extremely improbable thing and without parallel in pathology. Atavism, or, rather, the appearance of atavism, frequently met with in leprosy, is also against such a supposition ; for, although we can understand infection of an ovum by a leper parent, we cannot understand the transmission of a germ from a grandparent to a grandchild through a parent who is not, never was, and who may never become, a leper. Such a thing would imply J /Etiology. 4i5 proliferation of the bacillus in the parent without pathological evidence of its presence. Even admitting that leprosy is sometimes trans- mitted by ovum infection, this method of transmission cannot be the only one, or even a common one, for many lepers have no leper ancestors; and, as is well known, the healthy European, coming from a country in which leprosy has not been seen for generations, may acquire leprosy on visiting a country in which the disease is endemic. If leprosy be communicated generally, or even sometimes, by parent to child by heredity, how explain the striking fact, brought out by Hansen, that of the numerous offspring of 160 Norwegian lepers who emigrated to America not one has become a leper? Or, again, the equally well attested fact that children sometimes become lepers first, their parents afterwards 1 Another powerful argument against the doctrine of heredity is the circumstance that lepers become sterile early in the disease. From this it is evident that unless the ranks of leprosy are recruited in some other way than by heredity the disease would in- evitably die out in one, or at most, two generations. From considerations such as these the view that leprosy is a hereditary disease has now few adherents among the well informed. Contagion. — The best authorities believe that leprosy is propagated by contagion and only by contagion. The same unanimity of opinion does not obtain as to the particular way in which, or medium by which, the contagium is applied ; but that it passes directly or indirectly from the infecting leper to the infected, nearly all are agreed to regard as being practically proved. The principal facts and considera- tions on which this important conclusion is founded are as follows :— Leprosy is a germ disease, and therefore it cannot originate de novo. It must come from a pre-existing germ whose habitat may be air, soil, water, plant, 416 Leprosy. beast, food, or man. That the habitat of the infect- ing germ is man is rendered in the highest degree probable by the fact that the germ is found in the human tissues and hitherto nowhere else; and by the fact that leprosy has never been known to appear on virgin soil independently of the prior advent of a leper. When a leper settles down in virgin country, after a time cases of the disease crop up among his companions and immediate neighbours. Some of these new-made lepers, proceeding to a different part of the country, in time become centres for other groups of cases. Thus in the early history of the introduction of leprosy into a virgin country—as New Caledonia—the spread of the disease from in- dividual to individual, and from place to place, can be, and has been traced. In further proof it can be advanced that not only may a native of a non-leper country acquire the disease on visiting a leper country, but he may also communicate the disease to others, his countrymen, on his return to his own country. There is at least one well-authenticated example of this on record. Dr. Haw trey Benson, in 1872, showed at the Medical Society of Dublin a leper, an Irishman, who had ac- quired his disease in the West Indies. After his return to Ireland he slept in the same bed as his brother, who, moreover, sometimes wore the leper's clothes. In time the brother., who had never been out of the United Kingdom, became a leper and was shown to the same medical society in 1877. In this case there can be no question of fact or of diagnosis. Such a case can only be explained by contagion. Many similar, though not quite so well authenticated and conclusive, instances of the communication of leprosy by contagion are on record ; but the case just mentioned is alone almost conclusive, for if leprosy is proved to be communicable by contagion in one case, the probabilities are that it is so acquired in every case. It has been advanced against the contagiousness of leprosy, that it attacks a very small proportion Prevention. 417 only of the attendants, nurses, and doctors in leper asylums. But might not a similar objection be raised to the contagiousness of scabies or of ringworm 1 The conditions for successful contagion are known and can be easily avoided in the latter diseases ; they are not known, and are therefore not invariably avoided in leprosy. All contagious diseases demand certain conditions for their diffusion. In some diseases these conditions are easily complied with and often concur; in other diseases they are with difficulty complied with and rarely concur. Leprosy belongs to the latter category. Probably intimate personal contact, and certain concurrences in the phases of the disease with special conditions in the health or physiological state of the recipient—conditions which are as yet unknown, and which, for all we know, may concur only at long in- tervals in the intercourse of any two individuals— are necessary for the successful communication and acquisition of leprosy. The simple implantation of the bacillus does not suffice; for, as already pointed out, of the many inoculations that have been made only one has any claim to be regarded as having been successful. Articles of diet—such as fish—have been incrimi- nated as media for infection. The data on which it is sought to establish this and similar speculations are altogether insufficient, and do not bear investi- gation. Prevention.—If it be conceded that leprosy is caused by a germ, that it is contagious directly or in- directly, that it never breaks fresh ground unless first introduced from without and by a leper, then the leper must be regarded as a source of danger, and, qua. leprosy, the only source of danger to any com- munity he may live amongst; and that a sure, and the most effectual way of suppressing the disease is the thorough isolation of existing lepers. There are many difficulties, however, in such countries as India, in giving practical expression to what appears to be a B B 4i8 Leprosy. perfectly logical conclusion—difficulties springing from the rights of the individual, finance difficulties, diffi- culties arising from concealment or incorrect diagnosis, as well as from the continued introduction of fresh cases from without. These and other obvious obstacles, incident to an}^ attempt at a wholesale system of thorough isolation, are so great that the most that can be hoped for at the present time, and in the pre- sent state of public opinion, is some modified system of segregation and isolation, such as has worked so successfully in recent years in Norway. Where possible, therefore, lepers should be segre- gated in isolated asylums which should be so conducted as to prove attractive. Those who cannot be made, or persuaded, to enter these asylums should be isolated as much as possible from their families and the public; scrupulous cleanliness of their persons and houses should also be insisted on. Lepers ought not to be allowed to beg in the streets—as is often the case in Eastern cities, to keep shops, or to handle food or clothes intended for sale, to wander about the country as pedlars or mendicants, to hire themselves out as servants or prostitutes, or to frequent fairs and public places. All lepers in the ulcerative stage of the disease, when it is to be presumed that myriads of bacilli are being constantly given off from their sores, should be still more scrupulously isolated, their discharges, clothes, and dressings being systematically destroyed or disinfected. A child born of a leper should at once be removed from the diseased parent, and, if necessary, cared for at the public expense. If laws were enacted to give effect to such common- sense precautions, and if these laws were faithfully carried out, the best results might be looked for. Leprosy is feebly contagious, or rather, the conditions for successful contagion rarely recur; so rarely, that it is more than probable that under such a modified system of segregation and isolation as that indicated, they would recur so seldom that the disease would rapidly die out. Trea tment. 419 Vaccination.—It has not been actually proved that leprosy can be communicated by vaccination, although there is some evidence in favour of such a supposition. But, although this has not been proved, it is an obvious and very desirable precaution in countries in which the disease is endemic to take care that the vaccinifer is not only not the subject of actual leprous eruption, but, also, that he or she comes from a family and community free from leprosy. An apparently healthy vaccinifer may contain lepra bacilli in a latent state, be a potential leper, in fact, capable of communicating the disease. Treatment.—Scrupulous and systematic atten- tion to personal and domestic hygiene and cleanliness; frequent bathing and the free use of soap ; frequent changes of underclothing; good food ; fresh air; light work; the avoidance of over-strain, fatigue, and of exposure to bad weather ; these things are all of prime importance in the treatment of leprosy, and should be insisted on. It has been found that most lepers on being placed in favourable hygienic conditions improve, at all events for a time, and that in a small proportion the disease by these means may sometimes be actually arrested. Europeans, who have contracted leprosy in the tropics, almost invariably undergo temporary improvement on return to the more bracing climate and more nutritious diet of their native lands. Many drugs have been regarded, from time to time, as being more or less of the nature of specifics in the treatment of leprosy. But, though some of these drugs appear for a time to do good, and in con- sequence acquire a certain degree of popularity, hitherto all of them, one after another, have sooner or later fallen into disfavour. There is no good reason to think that any known medicinal substance is really a specific for leprosy, in anything approach- ing the sense that mercury and iodide of potassium are specific in syphilis. One is very apt to be deceived in estimating the value of a drug in leprosy. B B 2 420 Leprosy. The leper applies for treatment generally during, or soon after, one of the periodical exacerbations of the disease, and when the nodules and other eruptions are active and well pronounced. In the natural course of events, and without treatment of any description, especially if the patient be placed under favourable hygienic conditions, these acute manifesta- tions tend to become quiescent, and the disease tem- porarily to ameliorate. Observers are too apt to attribute this natural and temporary amelioration to whatever drug the patient may happen to be taking at the time. Moreover, in judging of the value of any drug in leprosy, it must be remembered that the disease may be arrested spontaneously, or even be recovered from, and that without the use of any drug whatever. Chaulmoogra oil, in doses of from two to ten up to forty drops or more, according to tolerance, three times a day, together with inunction of the same drug mixed with some oil, is a favourite remedy with English practitioners. Gurjun oil, once in favour, seems to have been abandoned. Unna claims to have cured several cases by the internal administration of ichthyol in increasing doses, combining the internal medication with vigorous rubbing of the arms and legs twice a day with pyro- gallic acid (10 per cent.) in lanolin, and the cheeks and trunk with chrysophanic acid (10 per cent.) in lanolin; at the same time applying to the forehead and chin a plaster of chrysophanic and salicylic acids with creasote, changing the plaster every day. The treatment is continued for a month, and is then followed by a course of warm baths before being resumed. Tuberculin has also been tried. It produces a local and a general reaction, which is sometimes curiously delayed for one or two days. So far from doing good it seems to aggravate the disease, causing fresh eruptions, and, also, causing bacilli to appear in the blood. Trea tment. 421 Dr. Badcliffe Crocker has recorded (Lancet, August 8th, 1896) two cases of leprosy in which great im- provement followed weekly hypodermic injections of one-fifth of a grain of perchloride of mercury. Iodide of potassium aggravates leprosy if given in full doses ; it not only affects the general health prejudicially, but it causes fresh eruptions to appear. Danielssen regards salicylate of soda, combined with cod-liver oil, quinine and iron, good food, and good hygiene, as the best treatment for leprosy. He claims for the salicylate, if commenced within the first few months from the appearance of the disease, that it sometimes effects a cure. He begins with fifteen grains, four times a day, and gradually increases the dose during six months or a year. I have lately tried thyroidin in a case of nerve leprosy. The patient has improved marvellously since taking it during three years. Hydroxylaniin, europhen, naphthol, salol, methy- lene blue, and aristol have also been tried recently; the results have not proved encouraging. Nerve stretching, with or without nerve splitting, has been strongly advocated (McLeod) for the cure of leprous neuralgia, anaesthesia, muscular atrophy, and other trophic lesions. At the best they can benefit the local lesion alone, and that but tempo- rarily, and only in the earlier stages of the leprous neuritis before the nerve has undergone fibrous transformation. In the case, of leprous nodules spreading on to the cornea and threatening to interfere with the line of vision, Broeckmann has shown that the extension of the leproma may be arrested by division of the cornea on the pupillary side of the lesion; it is found that the bacilli do not traverse the cicatrix. Tarso- rhaphy for ectropion of the lower lid; iridectomy for iritis, or synechia;; tracheotomy for laryngeal stenosis ; and necrotomy for bone disease, may sometimes have to be performed. The existence of leprosy does not materially interfere with the success of surgical 422 Leprosy. operations. I once removed an enormous elephan- tiasis of the scrotum from a confirmed leper ; the presence of the leprosy did not prevent sound heal ing of the extensive operation wound, the man making a good recovery so far as the operation was concerned. If only one tubercle, or one limited lepra macula is present, and there have been no constitutional signs of a general invasion, it is advisable to excise freely the affected spot. It is just possible that in this spot we may be dealing with the primary lesion of leprosy—the point of invasion—and that as yet the disease is limited to this. At all events, to excise this can do no harm ; and in face of the terrible fate which is otherwise in store for the victim of this infection, it would be wrong to withhold any possible chance of escape, however small, such a trifling operation might afford. A case has been recorded (Arch, de Med. ecper., 1st Jan., 1895) in which a child, twenty-seven months old, presented on one temple a minute, red, anaesthetic spot which, on microscopic examination, proved to contain lepra bacilli. The child's brother was a confirmed leper. Six months after the discovery of the spot it was excised and the wound cauterised. This was done in October, 1893; in April, 1894, the child showed no signs of leprosy. As already mentioned, the occurrence of acute disease may cause absorption of leprous deposit. This has been more particularly observed after erysipelas. It has accordingly been proposed to treat leprosy by inoculations of the erysipelas streptococcus, or by injections of the filtered toxin obtained from cultures of that organism (Impey). 423 CHAPTER XXVII. YAWS (FRAMBCESIA). Definition.—Yaws—a word of very uncertain ety- mology—is the name usually employed in English to designate a certain contagious, inoculable disease characterised by an indefinite incubation period, fol- lowed usually by fever, by rheumatic-like pains, and by the appearance of a papular rash which usually develops into a fungating, granulomatous, encrusted eruption. It runs a chronic course; is mostly pro- tective against a second attack; and, to a certain extent, is influenced by mercury and potassium iodide. Geographical distribution.—Yaws is widely diffused throughout the greater part of the tropical world. In certain places it is very common—as in tropical Africa, particularly on the west coast; in many of the West India islands; in Ceylon, where it is one of perhaps several obscure diseases included under the term parangi ; in Fiji, where it is known as coko; in Java ; in Samoa ; and in many of the islands of the South Pacific. It is difficult to say to what extent it exists in India; some deny its presence there altogether, but recent observations show that it does occur there to a limited extent. Mr. Arthur Powell (Ind. Med. Gaz., Sept., 1894, the Brit. Jour. of Dermat., No. 98, Dec, 1896) has recognised and described it as occurring in Assam. Possibly some of the skin diseases of the Eastern peninsula, as that described by Dr. W. C. Brown (Brit. Jour, of Dermat., No. 56, Vol. v.), under the name of purru, as being common in parts of the Malay peninsula, are of this nature. If it occurs in China, it is certainly rare there—at all events on the coast. In some of the 424 Yaws. West India islands, and in Fiji, almost every child passes through an attack. In the latter, according to Dr. Daniels, those children who do not acquire the disease in the ordinary way are inoculated with it by their parents, who regard an attack of yaws as an occurrence more or less necessary and sanitary. Dr. Nicholls (Report on Yaws, Blue Book, 1894) has made a careful and admirable study of West Indian yaws. His inclination is to look upon parangi, coko, and similar Asiatic and Pacific island diseases as specifically different from the African and West Indian disease. Dr. Daniels, however—a most accu- rate observer, who has had extensive experience both in Fiji and in British Guiana—shows very clearly that in both places the diseases are identical. Probably the view that certain forms of the parangi of Ceylon are not yaws is likewise incorrect. It is impossible at the present day to settle the point, but it seems probable that yaws was originally an African disease, and, so far as America and the West Indies are concerned, that it was introduced by negro slaves. In the days of West Indian slavery the specific and infectious nature of yaws was thoroughly recognised. The planters from com- mercial, apart from other, considerations, by institut- ing yaws houses and other repressive measures, took much trouble to keep the disease under. Since emancipation has permitted the West Indian negro to revert to some extent to the state of savagery from which he had partly emerged, yaws has again become very prevalent, and is now a principal and loathsome feature in the morbidity of these islands. Symptoms.—The initial fever.—In yaws there is an incubation stage of very variable duration—two weeks to six months*—the appearance of the charac- * Paulet, who inoculated fourteen healthy persons with yaws, found the first lesion in from twelve to twenty days ; Chariouis, in twenty-eight inoculations in thirty-two indi- viduals, observed a papule at the site of inoculation after fourteen days. Naturally acquired yaws seems to have a longer incu- bation period than the inoculated disease. Symptoms. 425 teristic eruptions being preceded by a certain amount of constitutional disturbance. The intensity of the general symptoms varies within wide limits. Some- times, they are hardly perceptible, and are not com- plained of ; usually there is well-marked malaise with rheumatic pains. Occasionally there is severe consti- tutional disturbance, lasting for about a week, with rigor, smart fever—100° to 103°—persistent head- ache, pains—worst at night—in the long bones, joints and loins, and sometimes gastric disturbance and diarrhoea. During the decline of these constitutional symptoms the eruption appears. Stage of furfuraceous desquamation.—The skin becomes harsh and dry, loses its natural gloss, and here and there patches of light-coloured, very fine furfuraceous desquamation, best appreciated with the aid of a lens, are formed. These patches are usually small and circular; occasionally they are oval, irre- gular, or form rings encircling islets of healthy skin. Their extent and number are very uncertain. They are mostly scattered irregularly over limbs and trunk ; but occasionally they may be almost confluent, the patches coalescing and giving rise to an appearance as if the entire skin had been dusted over with flour. On the other hand, this furfuraceous desquamation may be so slight as to be overlooked. In other in- stances it may be very marked; the heaping up of desquamating epidermic scales producing white marks, very evident on the dark skin of a negro or Oriental. This patchy, furfuraceous condition of the skin occurs not only at the early stage of yaws, but it may persist throughout the attack, or reappear as a fresh eruption at any period of the disease. The yaw.—When the furfuraceous patches have been in existence for a few days minute papules ap- pear in them. Describing these papules, Dr. Nicholls remarks that, in examining them with a lens, "they are seen to be apparently pushed up from the rete malpighii through the horny epidermis, which breaks 426 Ya ws. over their summits and splits in lines radiating from the centre, the necrosed segments curling away from the increasing papule. When the papules become about a millimetre in height and breadth, a yellow point may be observed on the summits.....con- sisting not of a drop of pus under the epidermis . . . but of a naked, cheesy-looking substance, which cannot be wiped away unless undue force be used. Frequently a hair will be observed issuing from this yellow sub- stance, thereby indicating that the hair follicles are the centres of the change going on." This eruption may persist during the entire attack, or it may appear at any time during the course of the disease. When extensive and occurring late, it indicates a protracted attack. The papule, having arrived at this stage, may either cease to grow, the apex becoming depressed, cupped, and lined with the yellow cheesy material alluded to; or it may go on, increasing in size, to the formation of the typical yaw. In the latter case the lesion gradually grows into a rounded excrescence, the yellow material at the top widening out so as to form a complete cap encrusting the little tumour. The yaw so formed may be no larger than a split pea ; or it may attain the breadth of a crown piece. The smaller tumours are hemispherical; the larger are more flattened or even depressed at the centre, possess- ing everted, somewhat overhanging, rounded edges. Occasionally, though rarely, a big yaw may include an area of sound skin. Several yaws may coalesce, and together cover a large and irregular surface, as an entire cheek, a popliteal space, or the dorsum of a foot. In the case of these large yaws, the surface of the growth is apt to be irregular and fissured. The neighbourhood of the mouth and anus are favourable sites for coalescent yaws; in such situations the moisture of the parts softens and removes the crust wholly or in part, so that the surface, in addition to being fissured, may be more or less bare, sodden, and fungoid. Symptoms. 427 The crust which caps and encloses an uninjured yaw is yellowish, granular, blotched with blood stains and encrusted dirt. At first the crust is somewhat moist, but gradually it becomes dry, brown, and black even. The crusts are firmly adherent, requiring some force to remove them ; a proceeding which, though painless, may entail a little oozing of blood. Deprived of its crust, the little swelling is seen to be red in colour, and generally smooth and rounded on the surface. According to size, it stands out anything from one- eighth to six-eighths of an inch above the surrounding healthy skin. Immediately after removal of the crust, the exposed surface begins to pour out a pale, yellowish- grey, viscid fluid, which soon becomes inspissated, rapidly forming a fresh cap to the yaw. Pus, unless as a consequence of irritation, is not, as a rule, found under the crust. Although the formation of the papules and yaws is attended with much itching, the yaw itself is not at all sensitive. Tearing off the crust therefore, as stated, gives no pain ; the tumour may be touched with acid even with impunity:—a diagnostic point of some importance. The yaw usually attains its maximum develop- ment in two weeks; for several weeks longer it remains stationary, and then begins to shrink. The crust then thins, shrinks, darkens, separates at the periphery, and at last falls off, disclosing at the site of the former fungating mass a slightly thickened (pale—Nicholls, hyperpigmented—Daniels) spot of fairly sound skin. Ulceration.—Such is the normal process of evo- lution and involution of a yaw. But it sometimes happens that the tumours, in place of becoming absorbed, break down and ulcerate, the ulceration, however, being confined to the yaw itself. In other instances ulceration goes deeper and extends laterally, giving rise to extensive sores with subsequent cica- tricial contractions. Such ulcerations may or may not be encrusted. With the development of the 428 Yaws. deeper and wider forms of ulceration, the typical lesions of yaws may disappear for a time, or perhaps permanently. In the latter case the ulcers are said not to be infective, and do not communicate yaws ; they are, therefore, to be regarded rather as compli- cations or, it may be. sequelae. Such ulcers may persist for years. Ulceration, according to Dr. Nicholls, occurs in about 8 per cent, of cases. Onychia.—Yaws may occur around or under a nail and give rise to a troublesome form of onychia. Foot yaws.—When a yaw develops on the sole of a foot, in consequence of being bound down by the dense and thick epidermis, it causes much suffering. Spreading laterally under the thick, leathery, and unyielding epidermis, it may attain a large size. After a time, however, the epidermis over the growth gives way, splitting in a radiating fashion ; pressure being thus removed the yaw fungates, and, at the same time, suffering diminishes. A cracked scaly condition of the hands and feet, sometimes persisting for years, is not unusual in negroes and must not be confounded with yaws, although not infrequently the two conditions co- exist.* Distribution.—The tumours may be scattered over * In the course of time the West Indian negroes have adopted a peculiar jargon—a mixture of French, English, and Spanish— to designate the various manifestations of yaws. The scaly patches ■ are known in some of the islands as " pian dartres," in Jamaica as "yaws caeca"; the papular stage of eruption as "pian gratelle " ; when the papular eruption occurs as a late symptom, it may be called "pian charaib," or " guinea-com yaws." The developed yaw is sometimes known as " bouton pian." "Tubboes," "tubba," "crabs," "crappox," "crabes," are expressions applied to the painful manifestations on the soles of the feet. Forms of chronic dermatitis on hands and feet are called "dartres," "tubboe," "crabs," " dry tubboes " ; or where exudation goes on between cracks in soles or palms, " running crab yaws." A large persistent yaw is sometimes known as the "mother," or "grandmother," or "mama-pian" ; smaller yaws as "daughter" or " grand-daughter " yaws. Yaws which show themselves some time after the disease appears to have subsided are called "memba " (remember) yaws. Yaws coalescing in the form of a ring are called "ringworm " yaws. Symptoms. 429 the whole body; or the crop may be limited to one or two growths; or they may be confined to a circum- scribed region of the skin. They are commonest on exposed parts, on the anterior surface of the body, and on parts much exposed to injury, as the feet and legs. They are most frequently found on the lower extremities ; rarely on the scalp, and still more rarely in the axillae. They are hardly ever seen on mucous surfaces unless about the lips, around the angles of the mouth, and in the nostrils, where they often form clusters. Duration and recurrences.—"Y aws lasts for weeks, months or years, its duration depending on the general health, on idiosyncrasy, hygienic conditions, and the treatment employed. Mild cases in healthy sub- jects finish in about six weeks. In other instances, especially in the debilitated, the disease runs on for months, successive crops of eruption being evolved. Sometimes these recurrences may stop short at the stage of desquamation, or at the papular stage, or they may proceed to the formation of typical yaws. The recurrences are usually preceded by fever- ishness, pains in the bones and joints; and the suc- cessive crops may either be limited and partial in their distribution, or they may be general. In Fiji, Daniels states, the average duration of an attack of yaws is about one year. The general health.—With the exception of during the initial fever, or during one of the recurring febrile relapses, the general health is not as a rule affected. Occasionally there is debility and cachexia; or there may be enlargement and tenderness of the lymphatic glands. In other instances the rheumatic pains are a principal feature and may be very severe. Persistent yaws.—That yaws sometimes effects a permanent hold is shown by the persistency with which they occasionally continue to recur during many years. In such cases the lesion has always the characters of a true yaw, and cannot be regarded as a " secondary " or " tertiary " manifestation in the sense 430 Yaws. in which these terms are applied to the late lesions of syphilis. Question of sequela;.—Mention is often made of nodes, of gummatous-like thickenings, and of punched out and serpiginous ulcerations in connection with yaws. Most recent authorities, however-, regard all such phenomena as essentially the results of an independent, though concurrent, syphilitic infection. It sometimes happens that an individual who years previously passed through an attack of yaws is affected with destructive ulceration of the soft palate, or of the mucous membrane and cartilage of the nose. Opinions differ as to the true re- lationship between this ulceration and the antecedent yaws; some holding that it is a later manifesta- tion of yaws, others regarding it as purely the result of an independent syphilitic taint. As regards the West Indies the question is one which, considering the great frequency of both acquired and congenital syphilis there, it is hard to decide. Daniels, however, says that in Fiji, where syphilis is unknown among the natives, these destructive ulcerations of palate and nose, together with a skin affection like lupus vulgaris—all of which he says are amenable to potas- sium iodide—are not uncommon ; he is inclined, therefore, to regard them as true sequelae of yaws. (Question of a primary sore.—Another point in the symptomatology of yaws is the question of the occurrence of a primary sore, as in syphilis. Numa Rat says there is such a sore, but that it is usually overlooked. He describes it as a papule with a pale yellow material at its apex, which may remain a papule, or which, after seven days, may ulcerate and subsequently cicatrise. Other observers do not agree with this. They say that though yaws virus applied to a pre-existing ulcer may render it unhealthy-looking and cause it to fungate like an ordinary yaw, yet successful puncture inoculations, although they some- times give rise to a yaw at the point of inoculation, do not by any means always produce a local lesion, /Etiology. 431 much less an ulcer. The lower animals appear not to be susceptible to yaws ; this, and other interesting points, therefore, cannot be settled by experiment on them. Mortality—Although in the literature of the subject reference is made to deaths from yaws, yet, judging from the statistics collected by Nicholls, the mortality must be very small indeed, in 7,157 West Indian cases, treated in various yaws hospitals, there were only 185 deaths—a mortality of 25 8 per thou- sand, a death-rate, as Nicholls points out, less than the average annual death-rate in one of the islands —Antigua. Doubtless, however, although yaws itself rarely directly proves fatal, intercurrent diseases, such as sloughing phagedaena and phagedaenic ulcera- tion, predisposed to by the skin lesions, occasionally do so. If the verruga of Peru be yaws, then, under cer- tain conditions, yaws becomes a very dangerous disease. /Etiology.—Contagion and heredity.—As yaws is highly contagious, all circumstances favouring contact with the subject of the disease favour its occurrence. Simple skin contact does not suffice for infection ; a breach of surface is necessary. Prob- ably the virus is often conveyed by insect bites, or by insects acting as go-betweens and carrying it from a yaws sore to an ordinary ulcer. Thus the disease often commences in a pre-existing ulcer. Cases are prone to originate in certain dirty houses, the virus from previous yaws patients seemingly impregnating the floors and walls of the filthy huts in which the latter had resided. In this way the disease may be acquired without direct transference from an existing case. Yaws is neither hereditary nor con- genital. A pregnant mother suffering from yaws does not give birth to a child suffering from the same disease; or one which will subsequently develop yaws, unless the virus be introduced after birth directly through a breach of surface. It is not conveyed by the milk ; nor does a suckling suffering from yaws necessarily infect its nurse. 432 Yaws. Age, Sex, Occupation, Race.—Although two-thirds of the cases in the West Indies occur before puberty, no age is exempt. Three males are infected to every female attacked. Occupation has no manifest in- fluence. In the West Indies, Europeans, Chinese, and Indians catch the disease if exposed to the contagion. iloiiixl anatomy and pathology. —No vfs- ceral changes have been found in yaws, although, of course, when yaws concurs with syphilis, gummata, etc., may be found ; but in this case the concurrent gummata belong to the syphilitic and not to the yaws infection. The tumours on the skin are granulomata made up of round or spindle-shaped cells, held together by a small amount of connective tissue and abundant blood-vessels. The focus of the circumscribed cell proliferation is the papillae which become very much swollen, and the malpighian layer. The cause of the proliferation is probably some micro-organism ; what this may be has not been satisfactorily determined. Both Pierez and Nicholls found a micrococcus in great profusion in the growth and exudation. This they succeeded in cultivating; but the causal relation- ship of the bacterium to the disease has not been established, inoculations of cultures into the lower animals proving negative. Diagnosis.—A painless, insensitive, larger or smaller, circular, encrusted, red granulomatous ex- crescence, occurring in the endemic district, is almost certainly yaws. The most important point in con- nection with yaws, both as regards diagnosis and aetiology, is its relationship to syphilis. It has been, and is still, held by some distinguished authorities, Hutchinson for example-, that yaws is possibly syphilis modified by race and climate; and certain features which the two diseases have in common are pointed to in support of the contention. The dis- cussion is bound to continue until the respective germs of yaws and syphilis have been separated, cultivated, and inoculated. So far as clinical and Diagnosis. 433 microscopical evidence goes, it is decidedly in favour of, not to say conclusive for, regarding the two diseases as specifically distinct. There are many points of contrast in their clinical features. I may mention the primary sore, the infection of the foetus, the adenitis, the exanthem, the alopecia, the absence of itching, the iritis, the affection of the permanent teeth, the bone and eye affections, the congenital lesions, the polymorphism of the eruptions, the nerve lesions and the gummata of syphilis. All these are wanting in yaws. Moreover, both diseases may concur in the same individual (Powell cites two cases, and Charlouis two, of syphilis supervening on yaws); and antecedent syphilis certainly does not confer im- munity as against yaws. Yaws may die out in a com- munity, as in British Guiana (Daniels, Brit. Jour, of Dermat., November, 1896), yet syphilis remain ; yaws may be universal in a community, as in Fiji, and yet true syphilis, whether as an acquired or congenital disease, be unknown. Finally, syphilis has never been shown to give rise to yaws, nor yaws to syphilis; neither, so far as known, has yaws been evolved in any community from syphilis, or appeared independently where the possibility of its having been introduced from a recognised yaws centre could be excluded with certainty. The therapeutical argument for the identity of the two diseases is a very fallacious one. Sulphur will cure scabies and pityriasis versicolor ; yet from this circumstance we may not conclude that these diseases are identical. The same may be said in respect of the influence of mercury and iodine on syphilis and on yaws. Prophylaxis.—This resolves itself into the adop- tion of measures to prevent contagion. These are, the isolation and segregation of the affected ; the dressing and treating of wounds in the hitherto unaffected ; the application of antiseptic ointments to yaws sores so as to obviate the diffusion of germs; the purifying or destruction by fire of houses or huts notoriously c c 434 Yaws. infected ; the prevention of pollution of bathing water by yaws discharges. Treatment. —All are agreed as to the propriety of endeavouring by good food, tonics, and occasional aperients to improve the general health. Most are agreed as to the propriety of endeavouring to procure a copious eruption by stimulating the functions of the skin by warm demulcent drinks ; by a daily warm bath with plenty of-soap; and, during the outcoming of the eruption, by such diaphoretics as liquor am- monite acetatis, guaiacum, etc. Confection of sulphur is also recommended as a suitable aperient; it may be taken frequently in the early stages of the disease. All are agreed as to the propriety of avoiding everything—such as chill—tending to repress the, eruption ; warm clothing is therefore indicated. Many use mercury or potassium iodide, or both, after the eruption is fully developed. These drugs have undoubtedly the power of causing the eruption in yaws to resolve. Some practitioners rarely use them or, if they use them, do so only at the latest stages of the disease, considering that relapses are more prone to occur after their too early employment Mercury, owing to its proneness to cause anaemia, is less frequently employed than potassium iodide. Where the eruption is persistently squamous, or papular, arsenic is frequently prescribed. Some touch the yaws with sulphate of copper; some apply nitrate of mercury ointment; others iodoform oint- ment ; others leave them alone, confining their local measures to the enforcement of cleanliness. When the soles of the feet are attacked, the feet ought to be soaked in warm water to soften the epidermis, which should then be cut away sufficiently to liberate the subjacent yaw. Ulceration must be treated on ordinary principles. During convalescence, iron, arsenic, and quinine are indicated. 435 CHAPTER XXVIII. VERRUGA PERUAXA. Ix certain narrow valleys of the Andes, between the ninth and sixteenth parallels of south latitude, and at an elevation of from 3,000 to 10,000 feet, an aggra- vated form of a disease closely allied or identical with yaws, and locally known as " verruga," is endemic. The peculiar initial rheumatic-like pains and fever are apparently identical with those of yaws, only they are more severe. Just as in yaws, one attack of verruga confers immunity. The constitutional symp- toms, likewise, subside on the appearance of the skin lesion which, judging by the published descriptions, is a granuloma macroscopically and microscopically identical with that of yaws. Just as in the latter disease, the eruption may be sparse or abun- dant, discrete or confluent. As in yaws, individual granulomata may fail to erupt; others may subside rapidly ; others again may continue to increase, and then, after remaining stationary for a time, gradually wither, shrink, and drop off without leaving a scar. If difference there be between verruga and yaws, apparently it is more one of degree than of kind. In verruga the initial fever may continue for weeks, or even for months. It is very severe in many instances. Often it exhibits features like those of a malarial infection, including intermittency, profound anaemia, and sometimes enlargement of the spleen and liver. Very probably in such cases it is the outcome of a compound infection—verruga attacking a malarial subject. Not infrequently in the endemic district a certain type of fever, believed to be verruga CC 2 436 Verruga Peruana. fever, proves fatal before the appearance of definite skin manifestations such as would justify a positive diagnosis. This was apparently the case with a medical student, hamed Carrion, who inoculated himself with blood from a verruga granuloma. The symptoms in his case closely resembled those of the very deadly fever referred to, which is known locally as Oroya fever. In addition to the severity of the fever and rheumatic pains, the Peruvian disease is remarkable for the tendency to spontaneous haemorrhage exhibited by the skin lesions. Apparently this peculiarity is attributable, like the haemorrhages in the affection known as "mountain fever," to the diminished atmo- spheric pressure at great altitudes; for when the patients descend to the lower valleys, or to the sea level, the tendency to bleeding ceases. Doubtless, the unusual vascularity of the swellings, which are sometimes permeated by a network of cavernous sinuses, also arises from the same circumstance. In yaws we find no mention made of the occur- rence of fungating granulomata in any situation but the skin. In verruga it would seem that the tumours may develop on mucous surfaces—in the (esophagus, the stomach, intestine, bladder, uterus, and vagina. Hence the dysphagia—a common symptom—and the occasional occurrence of haematemesis, melaena, haemat- uria, and bleeding from the vagina in the last-named disease. The geographical distribution of verruga, so far as known, is singularly limited ; it is confined to certain valleys, the inhabitants of neighbouring places being exempt. It is said that the disease may be acquired in merely passing through the endemic districts; and that, unlike yaws, the domestic animals in these districts, as well as the human inhabitants, are sub- ject to the disease. Treatment.—It appears that cold tends to re- press the development of the eruption, and that until this appears fever and pain persist. For this reason Trea tment. 437 as well as to avoid the haemorrhage from the desions when they do erupt, the patients should quit the heights and descend to near the sea level. External haemorrhages, when they do occur, must be treated by graduated pressure; otherwise, the local as well as the general treatment is the same as in yaws. 438 CHAPTER XXIX. ULCERATING GRANULOMA OP THE PUDENDA. Geographieal distribution.—Drs. Neal, Ozzard, Conyers and Daniels (Brit. Guiana Med. Ann., 1896) describe a peculiar form of ulcerating granuloma affecting the pudenda in dark-skinned races. Their observations were made in British Guiana and, principally, on West Indian negroes. Daniels believes that he bas seen a similar, or the same disease, in Fijians. If it be the case that this affection occurs in places so far apart as Fiji and Guiana, the prob- ability is that, although hitherto overlooked, it occurs in other tropical countries also. Age and sex.—This form of groin ulceration has not been observed before puberty; it has been found only after thirteen or fourteen and up to forty or fifty. It occurs in both sexes, but particularly in women. Symptoms.—The disease commences somewhere on the genitals or groins as an insignificant, circum- scribed, nodular thickening and elevation of the skin. The affected area, being covered with a very deli- cate, pinkish, easily-rubbed-off" epithelium, excoriates readily, exposing a surface prone to bleed and break down, although rarely ulcerating deeply. The disease advances in two ways ; by continuous eccentric peri- pheral extension and by auto-infection of an oppos- ing surface. In its extension it exhibits a predilection for warm and moist surfaces ; particularly the folds be- tween the scrotum and thighs, the labia, and the flexures of the thighs (Fig. 34). Its extension is very slow, years elapsing before it covers a large area. Concurrently with peripheral extension a dense, contracting, uneven, readily-breaking-down scar forms on the surface tra- velled over by the coarsely or finely nodulated active Symptoms. 439 new-growth which constitutes the peripheral part of the diseased area. Occasionally islands of active disease spring up in this scar tissue; but it is at the margin of the implicated patch that the special features of the affection are to be observed. In a case of some stand- ing there is found a large area of white or irregularly pigmented, perhaps excoriated, unsound, contracting, Fig. 34.—Ulcerating granuloma of the pudenda in the male. folded, and dense cicatrix ; surrounded by a narrow, serpiginous, irregular border of nodulated, somewhat raised, red, glazed, delicately skinned or pinkish, superficially ulcerated or cracked new-growth. In the case of the female (Fig. 35) the disease may extend into the vagina, over the labia, and along the flexures of the thighs. In the male it may spread over the penis, involve the glans, scrotum, and upper part of the thighs. In either sex it may spread in the course of years to the pubes, over the perineum, and as far back as the region of the coccyx. At times a profuse watery discharge exudes and even drips from the surface of the new-growth, soiling the clothes, soddening the skin, and emitting a peculiarly offensive odour. In this condition the disease, slowly extending, 44° Ulcerating Granuloma. continues for years, giving rise to inconvenience and perhaps seriously implicating the urethra, vagina, or anus, but not otherwise materially impairing the health. Histology.—On microscopical examination the new growth at the margins of the sore is found to be made up of nodules, or masses of nodules, con- sisting of round cells having large and, usually, Fig. 35.—Ulcerating granuloma of the pudenda in the female. badly-staining nuclei. These cells are imbedded in a delicate fibrous reticulum. The nodular masses are, for the most part, covered by epithelium, their under surfaces merging gradually into a dense fibrous stroma in which small clusters of similar round cells are here and there embedded. The growths, though very vascular, contain no haemorrhages ; and there are no signs of suppuration or of caseation, no giant cells, and no tubercle bacilli. In a section of one of the small nodules the round cell mass will be found to be wedge- shaped, the base of the wedge being towards the skin, the deep-lying apex usually pierced by a hair or two. The growth is found around sebaceous follicles, blood- Diagnosis. 441 vessels, lymphatics, and sudoriporous glands ; but it is specially abundant, and most deeply situated, around the hair follicles. No characteristic micro- organism has hitherto been discovered. For a detailed description of the histology the reader should consult an elaborate article by Dr. James Galloway, in the British Journal of Dermatology, April, 1897. Diagnosis—In British Guiana, as elsewhere, malignant and syphilitic ulcerations of the groin are common enough; the disease under notice, however, differs widely from these both clinically, histologically, and therapeutically. It is characterised by extreme chronicity—ten or more years—by absence of cachexia or of any tendency to cause death, by non-implication of the lymphatic system, and by non-amenability to mercury and iodide of potassium. The disease which it most resembles is lupus vulgaris. From this it differs inasmuch as it is practically confined to the pudendal region, affects mucous as well as cutaneous surfaces, tends to follow in its extension the fold of the skin, is not associated with the tubercle bacillus, giant cells, caseation, or other evidences of tuberculous disease. Treatment.—This disease is very rebellious to treatment. Scraping and caustics, including the actual cautery, have been freely employed ; but, although some improvement may be effected by these means, new nodules almost invariably spring up in the resulting cicatrix. Complete excision, where practicable, offers the best chance of permanent cure ; of course, such a proceeding must be undertaken before large areas and important passages have become involved. Drs. Conyers and Daniels have found that camphor and carbolic acid in equal parts, and salicylic acid in unguentum creasoti, thirty to forty grains to the ounce, give the best results ; although in no instance have they succeeded in effecting a complete cure, the growth invariably recurring in the scars soon after discontinuance of treatment. Mercury and iodide of potassium are useless. 442 CHAPTER XXX. ORIENTAL SORE. Definition. — A specific ulcerating granuloma of the skin, endemic within certain limited areas in many warm countries. It is characterised by an initial papule which, after scaling and crusting over, breaks down into a slowly extending and very indolent ulcer. Healing after many months, it leaves a depressed scar. The sore is inoculable and, to a considerable degree, protective against recurrence. Geographical and seasonal distribution.— Among the endemic places may be named Morocco, the Sahara (Biskra, Gafsa), Egypt, Crete, Cyprus, Asia Minor, Syria (Aleppo), Mesopotamia (Bagdad), Arabia, Persia, the Caucasus, Turkestan, India (Lahore, Multan, Delhi, etc.). Locally, Oriental sore is often called after some town or district in which it is specially prevalent; thus we have Delhi boil, Bagdad boil, and so forth. It is much more common in cities than in the country. In Bagdad few escape an attack ; visitors, even of a few days only, are almost certain, at particular times of the year, to contract it. Juliano describes (Jour, des Mai. Cut. et Syph., Oct., 1890) the disease as being common in Bahia, Brazil ; the name Oriental sore, suggested by Tilbury Fox, is therefore no longer quite appropriate. According to Hirsch, in the tropics this form of ulceration is specially prevalent about the commence- ment of the cool season, in temperate climates towards the end of summer or beginning of autumn. Years of prevalence may be succeeded by years of Symptoms. 443 comparative rarity ; possibly in harmony with altered sanitary conditions. In Delhi, for example, in 1864 from 40 to 70 per cent, of the resident Europeans were affected with the local sore; on certain sanitary improvements being effected, the frequency of the disease was immediately materially reduced. Symptoms. — Oriental sore commences as a minute, itching papule which tends to expand some- what as a shotty, congested infiltration of the derma. After a few days the surface of the papule becomes covered with fine, papery scales. At first these scales are dry and white ; later they are moister, thicker, browner, and adherent. In this way a crust is formed which, on falling off, or on being scratched off, uncovers a shallow ulcer. The sore now slowly extends, discharging a scanty ichorous material which, from time to time, may become inspissated and crust over the sore which continues to spread underneath. The ulcer extends by the erosion of its perpendicular, sharp-cut, and jagged edge, which is surrounded by a slight or more considerable areola of congestion. The surface of the ulcer is irregular. Any granula- tions which form speedily break down. Subsidiary sores may arise around the parent ulcer, into which they ultimately merge. These sores, usually about an inch or so in diameter, in process of time may come, in some instances, to occupy an area several inches across. After a variable period, ranging from two, or three to twelve, or even more months, healing sets in. Granulation is slow and frequently interrupted. Often it commences at the centre whilst the ulcer may be still extending at the edge;. often it is effected under a crust. Ultimately a depressed, white, or pinkish cicatrix is formed. Contraction of the scar, particularly if it happens to be on the face, may cause considerable and unsightly deformity. Oriental sore may be single or multiple. Two or three are not uncommon; in rare instances as many 444 Oriental Sore. as forty have been counted on the same patient. They are mostly situated on uncovered parts—hands, feet, arms, legs, and, especially in young children, on the face ; rarely on the trunk ; never on tlie palms, soles, or hairy scalp. In a very few instances the initial papule does not proceed to ulceration but persists as a scaling or scabbing, non-ulcerating, flattened plaque—just as sometimes happens in the case of the primary chancre of syphilis. Occasionally, from contamination with the virus of erysipelas, of sloughing phagedaena, or of some other infectious acute inflammatory skin disease, the primary lesion may become complicated and correspondingly modified and, perhaps, a source of serious danger. Otherwise, Oriental sore is more troublesome and unsightly than painful or dangerous. Histology; aetiology.—Section of the papule displays an infiltration of the derma by a mass of small round granulation cells. They lie between the elements of the tissues, particularly about blood- vessels, lympathics, and sweat glands; towards the centre of the lesion they completely replace the normal structures. Various micro-organisms have been described in association with Oriental sore. By staining sections in gentian violet and afterwards partly decolorising in spirit, Cunningham and Firth found certain violet-stained bodies, varying in size and grouping, in a proportion of the infiltrating cells. These bodies Cunningham was inclined to regard as parasites. Riehl, however, looks upon them as the result of a hyaline degeneration of protoplasm, and advances a claim for certain micrococci which he found in great profusion in the granulation cells. Other observers have likewise found micrococci in the tissues ; but, so far, inoculations from cultures have failed to produce the sores. As the disease has been proved to be communicable to the lower animals (as well as to man) by inoculation of the discharge from the surface of the ulcers, there can be little doubt that in Oriental sore the discharges contain the Treatment. 445 specific germ ; and, as Riehl's micrococcus did not communicate the true type of sore, it is probable that ■the germ has yet to be discovered. In what way, under natural conditions, the para- site enters the tissues it is as yet impossible to state definitely. Not improbably it is conveyed by flies or other biting insects, and by them either inserted into the skin or applied to some pre-existing wound or sore. As a rule, second attacks do not occur. Observing this, the Jews of Bagdad at one time practised on their young children Oriental sore inoculation, select- ing for the purpose some part of- the body habitually covered by the clothes. They designedly forestalled the infection by natural agencies, which experience had taught them to regard as inevitable ; and thereby avoided an ugly scar on the faces, hands or arms of their children. Neither race, sex, age, occupation, nor social con- dition influences susceptibility. Treatment.—Some have advocated destruction of the primary papule, and even of the ulcer, by caustics or by the actual cautery. It is doubtful if such a measure would prove effective. A knowledge of the nature and natural progress of the disease suggests a protective and soothing, rather than an irritating line of treatment. A dressing with some mild antiseptic ointment, as of iodoform, boracic or salicylic acid, is indicated. Tonics when the patient is anaemic or debilitated, attention to the general health, change of climate should the disease persist beyond the usual time for cicatrisation, are also indicated. 4*6 SECTION V.-ANIMAL PAKASITES AND ASSOCIATED DISEASES. CHAPTER XXXI. FILARIASIS. He who would properly qualify himself for medical work, in warm countries especially, must acquire something more than a smattering of helminthology. The conditions of life in the tropics are such, that not only are the careless natives extremely subject to verminous invasions of many descriptions, but the more carefully living and fastidious European is also constantly exposed to being victimised in the same way. Obscure diseases are very often the expression of some form of helminthiasis, and many diseases which formerly were mysterious and inexplicable can now with confidence be referred to " worms." The ability to recognise the presence of these parasites has, in some instances, enormously enhanced our powers of diagnosis, treatment, and prophylaxis. The physician, therefore, cannot afford any longer to ignore what, not many years ago, was regarded as but an unimportant department of natural history. I. PARASITES OF THE CIRCULATORY AND LYMPHATIC SYSTEMS. THE FILARLE SANGUINIS AND FILARIASIS. History*—Our knowledge of this subject dates from the discovery by Demarquay, in 1863, of an embryo nematode—filaria nocturna—in the milky fluid from a case of chylous dropsy of the tunica vaginalis (p. 464). Later, in 1866, Wiicherer found the same organism in the urine of a number of cases of History. 447 chyluria. In 1870 Lewis made a similar observation in India. Two years later, in 1872, the latter observer discovered that the blood of man was the normal habitat of this embryo parasite which he named, accordingly, filaria sanguinis hominis. Since that date the subject has rapidly expanded, and its great practical importance in tropical pathology is now slowly becoming recognised. Recently the writer has pointed out that Lewis's filaria is not the only bloodworm in man, and that the human circulation is the habitat of the embryos of no fewer than four, possibly of five or even more, distinct species of nematodes. Nomenclature.—In consequence of the discovery of so many additional and similar blood parasites, it has been deemed advisable to modify the original name of Lewis's filaria. This I have proposed to call filaria nocturna. The other filariae of the blood I have named filaria diurna, filaria perstans, filaria Demarquaii, filaria Ozzardi, and a sixth, which may or may not be connected with one of the two last, has been called filaria Maga/hdesi, after its describer. Their pathological importance.—Only two of these parasites, so far as we know at present, appear to have important pathological bearings—-filaria noc- turna, the embryonic form of filaria Bancrofti, a mature parasite inhabiting the lymphatics of man; and filaria perstans, probably the embryo of a para- site which lias but recently been discovered. The pathological significance of the latter is still doubtful. There can be no question of the importance in tropical pathology of filaria nocturna and of its parental form ; there is abundant reason to believe that it is the cause of endemic chyluria, of various forms of lymphatic varix, of tropical elephantiasis Arabum, and probably of other obscure tropical diseases. filaria nocturna (filaria Bancrofti). Geographical distribution and preval ence.—The geographical distribution of filaria noc- 448 Filariasis. turna is very extensive. It has been found as an indigenous parasite in almost every country throughout the tropical and subtropical world, as far north as Spain, in Europe, and Charleston, in the United States of America; and as far south as Brisbane, in Australia. In many places quite 10 per cent., and in other places half, of the population harbour it. I have ascertained that it is probable that one-third of the inhabitants of at least one district in India—-Cochin —carry blood filariae. I also find that in some of the South Sea islands, Samoa, for example, fully one-half of the people are affected in this way. Thorpe has shown (Brit. Med. Jour., Oct. 3rd, 1896) that in the Friendly Islands 32 per cent, of the people harbour the filaria. The table on p. 449, drawn up from a number of observations on the blood of the natives of certain tropical countries, will convey some idea of the wide area over which this and the other blood filariae are distributed, and of the degree of their prevalence in the countries mentioned. Demonstration of blood filariae.—Whoever would investigate the subject of filariasis will find that, in order practically to comprehend the subject and provide himself with abundant material for observation, it is advisable to make a systematic examination of the blood of the inhabitants of some district in which elephantiasis is endemic. If this be done, the observer is sure to come across, sooner or later, cases in which filaria nocturna abounds, and also of the diseases to which it gives rise. I commend the following procedure as likely to supply the investigator not only with material but, also, with much useful information. Let him visit late in the evening some hospital or prison, or other establishment where he can have an opportunity of examining the inmates, and let him procure slides of the blood of, say, 100 individuals. The slides are conveniently prepared by pricking the finger of each individual in turn, transferring large drops of the blood so obtained to ordinary microscope slips by Distribution of Blood Filarle. 449 £■4 F-i Eh 1 MM I I I 1 1 1 1 MM i?t vra 1 1 1 1 1 i 1 I'll 1 1 1 1 1 1 1 1 1 1 1 -f >ra 1 1 1 1 1. E| rt ilar per tans O 02 Ift lO W H 1 r 1 1 1 1 1 l 1 1 1 1 1 1 1 1 1 1 cc CO ^ 1 1 1 1 1 1 1 MM 1 1 1 1 1 1 1 fa w c8 i . 1|| 1 MM 1 1 1 1 1 1 1 i MM 1 1 12 1 M Epi ~ =5 t" ilar; urn i i rs 1 1 1 1 i 1 1 i MM 1 1 1 1 1 l 1 i.:g _« - t rt rt 0 P 1 •-< CO ~^ — -r Tc3 ■^ ~ ^ 0 0 ^c 3=2 A 25 s; .* ^ - ^ =5ffl^ £ ^ Wtt^ \ T. f. ■* —, -i^MO: —1 0 t)< cc CD X >o O ii'fOOC (M -j: r-H C^l 00 O " u S ^i Cr-i £ X S S -5 O « J S O H H in HH ^ 7: M ; S . i, 0 c 1 5^ ? !S e a j !3'|r< -s ^ X 0 « x -5 0 ? t- > £ 03 h .E S -; s | > W "5 h5 5 ^- ^ ^S _• A M3 X rH x v___^ ^ __'• —,——■" c . c He 'E s c 0 5 '5 . —Elephantiasis of the vulva (Fig. 51) and mammae (Fig. 52) is still rarer. Where growth has be- come inconveniently large the diseased tissues should be removed. Instances are on record in which the integuments of the mammae have become so thickened, heavy and elongated, that the organ has descended to the pubes and even to the knee. One such tumour weighed twenty-one pounds after removal. Tumours of the labia or of the clitoris, similarly, may attain a great size—eight or ten pounds, or even more. Elephantiasis of limited skin areas.— Dr. Corney, of Fiji (Lancet, April 6th, 1889), states that pedunculated elephantoid tumours, springing froni the groin or from the anterior surface of the thigh, are not uncommon in Fiji. One such tumour which he removed weighed twenty pounds. Dr. Daniels (Brit. Guiana Med. Ann,, 1896) has seen, both in Fiji and in Demerara, several cases of this description. (Fig. 53.) Dr. Silcock (Indian Med. Gaz., July, 1895) de- scribes a pedunculated tumour of this nature which he removed from the neck of an East Indian, and which weighed, after removal, thirty pounds. I have often seen limited areas of elephantoid thickening of the skin, particularly on the thighs. These conditions are easily dealt with by simple operations. Chylous dropsy of the tunica vaginalis, and of the peritoneum; chylous diiirrlura.— Chylous dropsy of the tunica vaginalis is not an unusual occurrence in the tropics. A fluctuating swelling of the tunica vaginalis, which does not transmit light, and which is associated possibly with Fig. 52.—Elephantiasis of mamma : left leg and foot also affected. {From a photograph by Dr. Davies, Samoa.) Prophylaxis. 491 lymph scrotum, with varicose groin glands, with chy- luria, or with filariae in the blood, would suggest a diagnosis of this condition. These collections of chylous fluid in the tunica vaginalis generally contain ——— r | sg? — Fig. 53.—Pedunculated groin elephantiasis. (From a photograph by Dr. Daniels, Demerara.) enormous numbers of filaria embryos. They may be treated as ordinary hydroceles, either by aseptic incision or by injection. Chylous dropsy of the peritoneum, and chylous diarrhoea of filarial origin are very rare. Prophylaxis of filarial disease; a pure water supply.—The prevention of filarial disease resolves itself into securing a water supply uncon- taminated by mosquitoes. With this in view, shallow and unprotected wells and tanks must not be used as sources of drinking water; tanks and buckets for 492 Filariasis. storing domestic water (the influence of these in spreading filarial disease has been ably demonstrated by Daniels in Demerara, loc. cit.) should be covered with fine wire netting and regularly emptied and cleaned every three or four days. Water that is not absolutely beyond suspicion should be boiled or filtered. The subjects of filariasis should be regarded as dangers to the community, and be compelled to sleep under mosquito nets. FILARIA DIURXA. (Fig. 30, b.) I have twice encountered in negroes a blood worm with - the same dimensions and anatomical characters, so far as these have been made out, as filaria nocturna, but differing from this latter parasite inasmuch as it comes into the blood during the day and disappears from it during the night. One of these patients came from Old Calabar, the other from the Congo. The periodicity observed by the parasite was thoroughly made out by prolonged observation in one of the cases. As the man was in good health at the time, and was observing ordinary habits as regards the hours of sleeping and waking, there can be little doubt that the parasite was not filaria nocturna. Some years previously this patient had a filaria loa in one of his eyes; it is just possible, therefore, that filaria diurna, as I name this blood worm, is the embryonic form of the sexually mature filaria loa (p. 517). Nothing further. is known about its life history, or pathological significance. From recent observa- tions I believe it to be very common (1 in 4) in the natives of the lower Niger region, where it seems to take the place of the f. perstans of the Congo negroes. FILARIA DEMARQUAII. (Fig. 36, c.) In examining blood, sent me by Dr. Newsam, from natives of St. Vincent, West Indies, I found this blood worm in several individuals—in 10 out of 152 examined. It resembles filaria nocturna and Filaria Ozzardi. 493 filaria diurna so far as shape is concerned, but differs from them in size. I have had no oppor- tunity of making trustworthy measurements of living specimens in suitably prepared slides, but, judging from rough preparations, filaria Demarquaii ap- pears to be about half the size of filaria nocturna and f. diurna. It is sharp-tailed like these, but, in addition to the size, it differs from them inasmuch as it observes no periodicity, being present in the peripheral circulation both by day and by night. I do not think—though of this I cannot be quite sure —that it possesses a sheath. Nothing is known of its life-history, minute anatomy, or pathological bearings. Possibly it is the embryonic form of filaria Magalhaesi—also a tropical American blood parasite. I have recently met with, apparently, the same para- site in the blood of natives of St. Lucia, W.I., and of New Guinea. It is quite possible that the sharp- tailed filaria (f. Ozzardi) of British Guiana is the same species. FILARIA OZZARDI. (Fig. 36, c/.)- Some time ago I received from Dr. Ozzard, of the Colonial Medical Service, British Guiana, a number of blood films prepared from aboriginal Carib Indians inhabiting the back-country of that colony. Although the negroes and other inhabitants of the littoral and settled districts of British Guiana are very subject to filaria nocturna and to elephantiasis, in none of the con- siderable number of slides of Carib blood which I have from time to time received from Dr. Ozzard and Dr. Daniels have I once encountered filaria nocturna. I am assured by Dr. Ozzard that elephantiasis, also, is unknown amongst these people. On examining the blood slides referred to, I discovered certain nematode embryos with characters so peculiar that I suspect they may represent at least one new species of blood worm, which I call, provisionally, filaria Ozzardi. At least half of the slides examined con- tained these parasites, some slides only one or two, 494 Filariasis, other slides as many as forty or fifty. In size and shape five out of six resemble very closely filaria perstans (p. 495)—that is to say, they are blunt-tailed, have no sheath, and are very minute (-173 to ■240 mm. by -0043 to -005 mm., Daniels). But along with the blunt-tailed filariae and on the same slides there occurs a sharp-tailed form, also very minute and resembling, though perhaps more slender, filaria Demarquaii. There are about five blunt-tailed para- sites to every sharp-tailed parasite. Drs. Ozzard ami Daniels (Brit. Guiana, Med, Ann,, 1897) have con- firmed this discovery. Both of these observers have had abundant opportunity of examining filaria Ozzardi alive, and state in letters to me that they regard the sharp- and blunt-tailed worms as phases of the same parasite. Dr. Ozzard considers that the worm when alive has the power of retracting the tip of its tail; Dr. Daniels, ajiparently, is of opinion that the sharp appearance of the tail in some specimens is produced in the act of dying. Filaria Ozzardi is sheathless. It is present at all times of the day and night in the peripheral blood, and possesses distinct powers of locomotion, similar to those of filaria perstans. It is possible that the blunt-tailed and the shaip- tailed parasites belong to different species. If such be the case, then it is also possible that the sharp- tailed species is f. Demarquaii, and the blunt-tailed f. perstans, or that both, or either, may be entirely new species Adopting the view of Ozzard and Daniels, that the blunt-tailed and the sharp-tailed are but phases of the same embryo, it follows that it must belong to an entirely new species; for. in that case, filaria Ozzardi cannot be filaria perstans, because in a large number of slides from Africa containing filaria perstans which I examined with this point in view, I did not once encounter a sharp-tailed filaria. Similarly, in a considerable number of slides from St. Vincent, West Indies, containing filaria Demar- quaii, I did not encounter one blunt-tailed parasite ; Filaria Perstans. 495 filaria Ozzardi, therefore, cannot be filaria Demarquaii. Further observations are required before this point can be considered as settled. Recently, having- found one case in which sharp-tailed filariae were alone present, Daniels inclined to regard the two forms as the young of distinct species, f. perstans being one of them. I incline to this view. I do not know as yet of any pathological condition attributable to these new and interesting blood worms. Parental form.—In a letter Dr. Daniels tells me that he has recently found parental filariae—male and female—at the post-mortem examination of two Demerara Indians whose blood, during life, contained both blunt- and sharp-tailed embryos. The mature worms, apparently numerous, were about three inches in length and very slender—about one-third the dia- meter of f. Bancrofti. They were, therefore, not f. Magalhaesi. The head is somewhat club shaped and shows no papillae. The tail of the male is much coiled and carries at least one long protruding spicule. These worms were found in the mesentery, and fat at the base of the mesentery, in one case ; in the other " not only in the mesentery and abdominal fat, but also in the subpericardial fat." The embryos in utero, Dr. Daniels states, were all blunt-tailed. Pos- sibly he has found the mature form of f. perstans. (Brit. Med, Journ., April, 1898.) FILARIA PERSIANS. (Fig. 36, e.) Geographical range.—This parasite is very common in the blood of the natives of large districts in West Africa. I have found it in natives from Old Calabar and from the Congo—both in the coast negroes and in those from the interior. In the endemic dis- tricts it occurs in about half the population. Prof. Firket, of Liege, has confirmed this observation as regards the Congo district. Sometimes it occurs along with f. diurna and f. nocturna in the same indi- vidual. I have never found it in West Indian negroes, nor, in fact, in natives of any country except 496 Filariasis. West tropical Africa, and, possibly, in Demerara Caribs. Its characters. — Filaria perstans observes no periodicity, being present in the blood both by day and by night. Tn this respect it resembles filaria Demarquaii and f. Ozzardi; and, like these, in size, shape, and anatomical detail it differs very materially from filaria nocturna and f. diurna. It measures, on an average, T^T inch in length by •g-gVo inch in breadth ; but, as it possesses to a remark- able degree the power to elongate and to shorten itself, these measurements do not always apply. On the whole, however, it is manifestly much smaller than filaria nocturna and diurna. It is further distin- guished from these filariae by the entire absence of a sheath, and by the characters of its caudal end, which is invariably truncated and abruptly rounded-off. The taper terminating in the tail extends through quite two-thirds of the entire length of the animal. Further if the head be carefully observed with a high power, a fang can generally be easily seen—much more easily than the corresponding structure in filaria nocturna —in constant play, shot out and retracted. From indications in stained specimens I judge that it pos- sesses a V- and a tail-spot; this point, however, I have not carefully studied. No hooked cephalic prepuce can be made out. Its movements also differ from those of filaria nocturna, for it not only wriggles about, just as that parasite does, but it indulges from time to time in long excursions through the blood, moving freely all over the slide, "locomoting," in fact, very much in the same way as filaria nocturna does in the mosquito's stomach after it has cast its sheath. Parental form and pathology.—The parental form and the life-history of filaria perstans are quite un- known. What pathological r61e it may play is still uncertain. I have conjectured, for reasons stated elsewhere (p. 255), that it may in some way be the cause of negro lethargy and of one of the forms of African craw-craw (p. 520). Filaria Magalhaesi. 497 FILARIA MAGALHAESI. Professor Magalhaes describes (Rev. des Cursos theoricos e prat, da Fac. de Med. de R, de Janeiro, No. 3, An. III., 1886) two sexually mature filarial haematozoa, male and female, which were found lying in the left ventricle of the heart of a child who died in Rio de Janeiro. No information was received as to the nature of the disease of which the child died, nor had any examination of the blood been made during life. The parasites were cylindrical, capillary, opalescent, white, uniform in thickness except where the body tapered towards the tail and at the club- shaped oral end. The mouth was simple, circular, unarmed; the cuticle marked with fine transparent striations. The female worm measured 155 mm. in length by 7 mm. in diameter, the male 83 mm. in length by 4 mm. in diameter. The tail of the latter was provided with four pairs of pre-anal and four pairs of post-anal papillae, and two spicules. Manifestly this parasite is specifically distinct from filaria Bancrofti. The fact that it occurred in the Western hemisphere would suggest the possibility that it may be the parental form either of filaria Demarquaii or of filaria Ozzardi. Nothing is known of its life-history, nor of the associated pathology. G G 498 CHAPTER XXXII. ENDEMIC HEMATURIA (BILHARZIA DISEASE). Definition.—A form of haematuria caused by bilharzia haematobia (distomum haematobium), and characterised by the presence of the ova of that parasite in the urine. History and geographical distribution.— The frequency of haematuria in the natives of Egypt, and in visitors to that country, has long been re- marked. The explanation of this peculiar circum- stance was supplied by Bilharz, who, in 1851, dis- covered the cause in a peculiar trematode, sub- sequently named by Cobbold, in honour of its discoverer, Bilharzia haematobia. The geographical distribution of this parasite is limited to Africa and its island dependencies. Dr. John Harley discovered, in 1864, the characteristic ova in cases of haematuria from Natal. It has many times been found in patients from Mauritius. It has been found on the Gold Coast, in Tunis, and it probably exists in many other parts of Africa, more particu- larly along the eastern side of the continent. Egypt, however, is its favourite haunt; there, judging from Bilharz's, Griesinger's, and Sonsino's post-mortein records, it is present in quite one-half of the popula- tion. /Etiology.—The parasite (Fig. 54). — Bilharzia haematobia belongs to the distomidae; but, unlike the majority of distomes, which are nearly all of them her- maphrodite, bilharzia presents the peculiarity of being bisexual. The male is white, cylindroid, measuring 15 mm. in length by 1 mm. in breadth. It possesses an oral and a ventral sucker placed close together. sEtiology. 499 The cylindrical appearance of the worm is produced by the lateral infolding of the two sides of what would otherwise be a flat body. By this infolding a gynaecophoric canal is formed, in which the female is partially enclosed. The female is rather darker in colour than the male, con- siderably longer (20 mm.), more filiform, her middle being embraced by the gynaecophoric canal referred to, whilst her anterior and posterior portions remain free. The genital openings of the sexes face each other, and are placed immediately posterior to the ventral sucker. These parasites are found in the blood of the portal vein, in its mesenteric and splenic branches, and in the vesical, uterine, and haemorrhoidal veins. They have also been found in the vena cava; Sonsino considers that, if searched for, they would prob- ably be found elsewhere in the circulation. Their numbers -p\ vary considerably. Sonsino reports finding in one case forty ; in another case Kar- tulis found 300 in the portal vein and its branches. The ovam(Fig. 55).—On microscopical examination, the uterus of the female bilharzia is found to be stuffed with ova of a peculiar and characteristic shape. They are oval, each egg on an average measuring about 0-16 mm. in length by 0-06 mm. in breadth, one end of the ovum being provided with a short, stout, and very definite spine. In certain instances, hereafter to be mentioned, this spine is not terminal but is placed laterally. g g 2 54. Bilharzia hsematobia, male and female, the latter in the gynsecophoriccanal of the former. (After Leuckart.) 500 Bilharzia Disease. Fig-. 55.—Ova of Bilharzia. The exact nature of the process by which the ova leave the body of the human host has not been satisfactorily explained. Apparently, the female worm migrates from time to time from the larger veins to their smaller radicles, and in these deposits her ova. The walls of the bladder and rectum are the favourite situations for this pur- pose. Afterwards the eggs are somehow carried, possibly aided by the spine with which they are provided, towards the surface of the mucous membrane, and then, falling into the lumen of the bowel or into the bladder, are voided in the faeces or urine, a certain amount of blood escaping at the same time. The free embryo (Fig. 56).—In newly voided urine the ovum presents a somewhat brownish appearance, and generally contains a ciliated embryo. After a time the embryo may escape through a longitudinal rupture in the shell. It then swims about; but, unless supplied with fresh water, soon perishes. If, how- ever, the urine be freely diluted with water, the embryo not only escapes more quickly from the shell but also continues to live, swimming and gyrating about very actively for a considerable time. While swimming, the body of the little animal under- goes many changes of shape. For the most part, when advancing, it is oblong, tapering somewhat posteriorly; when more stationary it tends to assume a circular form. It moves by means of the cilia which, with the exception of the minute papillary beak, thickly cover the entire body. On carefully examining the embryo, a canal may be traced from the beak into what looks like a rudimentary stomach ; on both sides of this two much smaller^gland-like organs can be seen, Fig. 56.—Free em- bryo of Bilharzia. - Etiology. 5°l and from each of these a delicate tube passes forward and opens, apparently, somewhere in the neighbour- hood of the beak. The bulk of the embryo is occupied by a number of sarcode globules. A care- ful description of the embryo is given by Dr. G. S. Brock in the Lancet of Sept. 9th, 1893, p. 625, to which the reader is referred for further details. Life-history.—Beyond its first stage of free swim- ming ciliated embryo the extra-corporeal life of bilharzia is quite unknown, notwithstanding the many attempts that have been made to trace its future progress. Sonsino believed at one time that he had discovered its intermediate host in a fresh water arthropode ; this view he afterwards abandoned. Judging from analogy, the embryo bilharzia probably passes into the body of some fresh-water mollusc, into some crustacean, or into some larval arthropode ; there, it is conjectured, it undergoes the developmental changes into redia and cercaria usually exhibited by the distomes. Later, it probably becomes encysted and then, either free or still in the body of the inter- mediate host, it gains access to man in drinking water and so, through the stomach, passes to the veins of the portal system. Symptoms.—The symptoms produced by bil- harzia vary in degree within very wide limits. Some- times the patient experiences no trouble whatever; in other instances the suffering is very great. In- directly, from the serious nature of the lesions of the urinary organs to which it may give rise, bilharzia is not an infrequent cause of death. The most characteristic symptom of its presence in the wall of the bladder is the passage of blood at the end of micturition, with or without a sense of urinary irritation. The amount of blood so passed varies from a few drops of slightly tinged urine, to a considerable quantity of pure blood. The quantity of blood passed and the degree of irritation are increased by exercise, by dietetic indiscretions, and by all such causes as are calculated to aggravate cystitis. As a 502 Bilharzia Disease. rule, it is only the last few drops of urine that contain blood; sometimes, however, the hiuniorrhage is more extensive, and then the entire bulk of the urine may be blood tinged. Occasionally, clots even are passed. If in a case of moderate bilharzia infection the urine be passed into a glass and held up to the light, minute flocculi, or coiled-up mucoid-looking threads will be seen floating about in the fluid. If it be allowed to stand, the flocculi, and perhaps minute clots, will sub- side to the bottom of the vessel ; these, on being taken up with a pipette and placed under the micro- scope, will be found to contain, besides blood corpuscles and the usual catarrhal products, large numbers of the characteristic spined ova. In doubtful cases, where ova are few, the best way to find them is to get the patient to empty the bladder and to catch in a watch-glass the last few drops of urine which the patient can force out by straining ; these invariably contain ova. A low power of the microscope suffices and is best for diagnosis. Endemic haematuria lasts for months or years. Recovery is rarely complete. In ordinary cases, pro- vided no reinfection take place, the haematuria tends to decrease, although ova may continue for years to be found in the last few drops of urine passed. In severe cases, sooner or later, signs of cystitis super- vene, and give rise to a great deal of suffering. Not infrequently the ova become the nuclei for stone, and then, of course, the symptoms are those of urinary calculus. Sometimes the pathological changes induced by the presence of the parasite in the bladder lead to the development of new growth, in which event the symptoms become more urgent and the haematuria perhaps excessive. Hypertrophy, contraction, or even dilatation of the bladder, are not unusual. Besides the bladder symptoms there may be signs of prostatic disease, or of disease of the vesiculae seminales causing spermatorrhoea. In the latter case, ova may be detected in the semen. In other instances the ureters and kidneys become involved, and grave disease of Symptoms. 5°3 these organs ultimately ensues. In consequence of the continued suffering which these aggravated forms of infection produce, the patients become anaemic, wasted, debilitated, and a ready prey to any intercurrent disease. When the rectum is involved, dysenteric-like symptoms may supervene, mucus with blood being passed from time to time, the stools becoming frequent and their passage being attended with tenesmus. In such cases small, soft growths are to be felt inside the sphincter ani. On removing one of these and break- ing it up with needles, the spined ova can be readily made out in the debris. In the female, vaginitis and cervicitis have been known to be produced by this parasite. The ova have also been found in the liver and in the lungs ; but, so far as known, their presence in the latter organs gives rise to no active symptoms. Pathological anatomy.—The character of the changes brought about by bilharzia varies very much according to the degree and the duration of the infection. In almost every case the walls of the urinary bladder are early affected. All that may be apparent to the naked eye at this stage of the disease is a certain amount of injection of the small vessels of the mucosa vesicae, and, according to Sonsino, certain exceedingly minute vesicular or papular eleva- tions of the surface of this membrane. When these minute elevations are examined microscopically they are found to contain ova. Ova are also to be found in the dilated minute blood-vessels. Later, especially in the trigone of the bladder, there are found rounded patches of inflammatory thickening which project somewhat, are granular on the surface and dense in consistence ; on section they creak under the knife as if they contained many gritty particles. It is evident that these elevated, thickened patches are the result of an inflammatory process provoked by the clusters of ova which the microscope reveals scattered through- out their entire extent. The ova are principally 504 Bilharzia Disease. deposited in the submucosa, less extensively in the mucous membrane itself, still less in the muscular walls of the organ or in its sub-serous connective tissue. They tend to occur in groups, each of which is invested by a sort of connective tissue capsule ; or they may be lying in small blood-vessels which they occlude. Some ova are seen to have undergone calci- fication; others are still fresh, either segmenting, or already containing a ciliated embryo. On the surface of the rounded patches, already mentioned, phosphatic deposits, also containing ova, are not uncommon; sometimes the patches present minute sloughs. In addition to these indurated patches, various forms of polypoid excrescence—sometimes ulcerated—may pro- trude from the mucous surface into the cavity of the bladder. These various hyperplasias frequently contain the adult parasite as well as ova. In addition to what may be called the specific changes in the mucosa, the muscular coats of the bladder are generally hypertrophied. In consequence of this, as well as of the ingrowth of villosities and different forms of new growth, the capacity of the organ may be much diminished. Its mucous surface is generally coated with a sanguineous mucus con- taining myriads of ova. Gravel or small stones are sometimes found either imbedded in lacunae in the hypertrophied and roughened bladder wall, or free in the cavity. Not infrequently, a similar hyperplasia occurs in the ureters, particularly towards their lower ends. In rare instances, the pelvis of the kidney itself is affected. Obliteration of the ureter, both from small stones and, also, from thickening of the mucous membrane, has sometimes been met with; it leads to dilatation of the pelvis and atrophy of the parenchyma of the kidney. It is easy to understand how, in time, these changes of the bladder and ureters may give rise to hydronephrosis, pyelitis, abscess of the kidney, and similar secondary affections. Hyperplasia from bilharzia infection may also occur in the vesiculae seminales, in the walls of the Pathological Anatomy. 505 vagina, and in the cervix of the uterus, leading to corresponding bloody, ova-containing discharges. Next to bilharzial infection of the bladder and consequent kidney changes, that occurring in the large intestine, particularly in the lower part of the rectum, is of the greatest practical importance. In this situa- tion polypoid growths, apt to be mistaken for piles, are frequent. Large extravasations of blood under the mucous coat may also occur. Strange to say, in ova found in the bowel, accord- ing to Sonsino and Mackie, the spine is generally placed laterally ; whereas in ova coming from the walls of the bladder the spine is invariably terminal. This lateral situation of the spine has been explained in various ways, the most probable suggestion being that it is a consequence of the compression exer- cised by the muscular coat of the intestine on the parent worm while the ova are passing the shell glands; the relations of certain of the reproduc- tive organs are supposed to be altered by this compression. It may be mentioned that ova in small numbers have been found in the liver, in gall-stones, in the lungs, in the heart, and in the kidneys. We have no knowledge of any definite pathological change entailed by their presence in these organs. Diagnosis.—The diagnosis of bilharzia disease is easy ; the presence of ova in the urine is decisive. In countries like Egypt, where the disease must often concur with chyluria, with stone, with vesical tumour, with gonorrhceal cystitis, and with pyelitis, as well as with prostatic disease, care must be exercised in each particular case to separate the special factors to which the different symptoms are attributable. Thus in chyluria concurring with bilharzia disease there will be chyle in the urine in addition to blood ; in such a combination the clot which forms will be large, will contain oil granules and globules and, very probably, filaria embryos in addition to bilharzia ova ; moreover, the filaria will generally be detectable in the finger 506 Bilharzia Disease. blood if looked for at night. Stone in the bladder, when suspected, has to be searched for with the sound. In gonorrhceal cystitis the history of gonorrhoea will be forthcoming. In prostatic disease, enlargement of this organ may be made out; and so on. Difficulty may sometimes arise when ova are few in number, or when they have ceased altogether to come away, the parent worm or worms having died. The mischief wrought by the parasite remains, although the ova —the most certain evidence of the parasite's previous presence—may be discharged no longer. But, even if ova are very few, they may still be found in the last drop or two of urine passed, as has been men- tioned. If they are no longer to be found in the urine, sometimes, by scratching the surface of the bladder with a sound and examining the shreds of mucus so obtained, a few, calcified it may be, but presenting the characteristic spine, may be seen with the microscope. In rectal disease, if bilharzia be suspected, the mucus and the fasces, or, failing these, one of the polypoid growths after removal by finger or forceps, as well as the urine, should be examined for ova. Prognosis.—An important element to be con- sidered in venturing on a prognosis is the long life of the parasite. Sonsino mentions a case in which living ova were still being passed nine years after their first appearance, and after all chance of reinfection had ceased. Another important element in prognosis is the degree of infection ; the greater the number of worms the more severe and the more extensive the disease they produce. As with filarial infection, the greater the number of cases in a district the greater will be the probability of severe infections being met with. The prognosis is practically that of a chronic cystitis depending on an irremediable, but not in itself fatal, cause. Much suffering may often be looked for and, as a consequence, anaemia and debility; possibly calculus may be foriued ; possibly grave renal disease may ensue. In the milder degrees of infection, which Trea tment. 5°7 fortunately are the commonest, the patient seems to be in no way inconvenienced by the parasite, and generally escapes all serious consequences. In any case, mild or severe, there may be attacks of haemat- uria from time to time ; as a rule, the quantity of blood lost is insignificant. Treatment.—Our knowledge of the situations occupied by the parasite indicates the futility of attempting a radical cure by means of poisonous sub- stances, whether introduced by the bladder, by the rectum, or by the stomach. As yet, we know of no direct, or other, means by which the bilharzia can be destroyed. Harm only can result from attempts at a radical cure of endemic haematuria on such lines. Our efforts must, therefore, be confined to palliating the effects of the presence of the parasite. Prac- tically, the treatment resolves itself into that of chronic cystitis. The diet should be bland, but fairly nutritious; stimulants and spices are to be avoided. Excess of all kinds, violent muscular efforts, cold and other causes of catarrh must also be guarded against. During exacerbations of haematuria, or of cystitis, rest should be enjoined and diluents freely partaken of. Pain may demand anodynes. Excessive catarrh of the bladder suggests washing out with weak boric acid lotion, and the internal administration of uva ursi, buchu, perhaps small doses of cubebs, copaiba, or sandalwood oil, salol, benzoic acid, and so forth. Stone, and troublesome new growths, are to be removed by operation. Where distress is extreme, Mackie has had good results from cystotomy. Poly- poid growths in the rectum, where accessible, should be removed. Hyperplasia in the vagina and cervix are best treated by scraping. Prevention.—Since analogy justifies the belief that the embryo of bilharzia, on obtaining access to fresh water, enters a fresh-water animal and by it obtains access to another human host, it is evident that if the embryo be kept from getting into the water, or, if drinking water be boiled or filtered, the 508 Bilharzia Disease. spread of the disease from man to man would be effectually prevented. In the endemic districts, children, in particular, should be carefully and repeatedly warned against drinking the water of ponds and canals. Provided reinfection be avoided by the exercise of prudence in the matter of drinking water, there is no neces- sity for sending the patient with bilharzia disease away from the country in which the parasite was acquired. 5°9 CHAPTER XXXIII. II. PARASITES OF THE CONNECTIVE TISSUE. GUINEA WORM (FILARIA MEDINENSIS). Geographical distribution.— This important parasite is found in certain parts of India — the Deccan, Scinde, etc.—in Persia, Turkestan, Arabia, tropical Africa—particularly on the west coast, and in a very limited part of Brazil (Feira de Santa Anna). Formerly it was supposed to be endemic in Curacoa, Demerara, and Surinam; ap- parently it has now disappeared from these places. Guinea worm is not equally diffused throughout this extensive area; it tends to special prevalence in limited districts, in some of which it is excessively common. In parts of the Deccan, for example, at certain seasons of the year, nearly half the popula- tion is affected ; and in places on the West Coast of Africa nearly every negro has one or more specimens about him. Although guinea worm is sometimes seen in Europe, it is only in natives of, or recent visitors to, the endemic area. Though frequently introduced in this way it has not become acclimatised either in Europe or in North America. We have no account of the parasite as endemic in any part of Asia east of Hindustan, in the Eastern Archipelago, Australia, or in the Pacific Islands. Guinea worm occurs occasionally in the lower animals—horse, dog, ox, etc. Possibly, some of the parasites in the lower animals, described as guinea worm, may belong to quite a different species. The parasite (Fig. 57).—Anatomical features. —The female guinea worm alone is known ; the male has not been recognised with certainty. She 510 Guinea IForm. is reputed to attain in some instances enormous dimensions ; it is probable, however, that worms of five or six feet in length owe their size to errors of observation, two worms, or their fragments, having been regarded as one. According to Ewart, in forty carefully measured specimens, the shortest was 12| inches, the largest 40 inches in length ; 30 inches is probably an average length. The diameter of the worm is about one-tenth of an inch. The body is cylindrical, milky-white, smooth, and without markings. The tip of the tail is abruptly bent, forming a sort of blunted hook, perhaps func- tioning as a "holdfast." The head end is rounded off', terminating in what is known as the cephalic shield. The mouth is triangular, very small, and surrounded by six papillae—two large and four small. The alimentary canal is relatively small, being compressed and thrust to one side by the uterus; it is probably cascal, for it has not been traced to an anus. The vagina, which must have existed at an early stage, at maturity has also become ob- literated by the growth of the enormous uterus which, filled with coiled-up embryos (Fig. 58), extends from the head to the tail of the worm. Habits.—The habitat of the female guinea worm is the connective tissue of the limbs and trunk. When mature, in obedience to instinct, she proceeds to bore her way through this tissue, and, finally, travelling downwards, reaches a leg or foot. In 85 per cent, of cases she presents in some part of the lower extremities; occasion- ally in the scrotum ; rarely in the arms; very Fig. 57.—Guinea worm. (Reduced.) (Leuckart.) Habits of Parasite. 511 exceptionally in other parts of the body, or even in the head. Arrived at her destination she pierces the derma. Probably in consequence of some irritating secretion, a small blister now forms and elevates the Fig. 58.—Section of guinea worm. (Leuckart.) epidermis over the site of the hole in the derma. By- and-by the blister ruptures, disclosing a small super- ficial ulcer half to three-quarters of an inch in diameter. At the centre of the ulcer, which sometimes quickly heals spontaneously, a minute hole, large enough to admit an ordinary probe, can be seen. Some- times when the blister ruptures the head of the worm is seen protruding from this hole; as a rule, however, at first the worm does not show herself. If now we douche the neighbourhood of the ulcer with a stream of cold water expressed from a sponge and, as the \^ater falls, watch the little hole in the centre of the ulcer, we shall see in a few seconds a droplet of fluid—at first clear, later milky—well up through the hole and flow over the ulcer. Sometimes,' instead of this fluid, a small, beautifully pellucid tube, about y1^ of an inch in diameter, doubtless the uterus of the worm prolapsed through her mouth, is projected 5" Guinea Worm. through the hole in response to the stimulus of the cold water. When this tube has been extruded an inch or thereabouts, it suddenly fills with an opaque whitish material, ruptures and collapses, the fluid Fig. 59.—Embryos of guinea worm. (From a photogram by Mr. H. B. Bristow.) spreading over the surface of the ulcer. If a little of the fluid, either that which has welled up through the hole, or'that which has escaped from the ruptured tube, is placed under the microscope, it is seen to contain myriads of embryo guinea worms lying coiled up, almost motionless, with their tails projecting The Embryo. 5i3 in a very characteristic manner (Fio\ 59). If now a drop of water be instilled below the cover-glass the embryos may be observed to unroll themselves and, in a very short time, to swim about, more suo, with great activity. Manifestly these em- bryos come from a guinea worm lying in a tissues and communi- cating with the surface through the little hole in the derma. The embryo (Fig. 60).—The em- bryos are not cylindrical; they are distinctly flattened. In swimming they move by a sort of side to side lashing of the tail, and tadpole-like motion of the body. The movements are intermittent; sudden, short swims alternating with brief pauses. When progressing the longer transverse axis of the body is perpendicular to the plane travelled over ; but when, from time to time, the little worms pause they gradually roll over on to their flat surfaces. As soon as they come to rest on the flat they suddenly recover themselves with a jerk, and turn quickly on to their edges and begin swimming about again. This series of movements is constantly repeated. The embryo of the guinea worm measures about -J^ of an inch in length, by T^M of an inch at its greatest breadth. The head is some- what tapered and then abruptly rounded off. The tail is long, slender, and sharp-pointed. The alimentary Fig. 60.—Embryos of canal can be readily detected. To- guinea worm. , ,. » ., , .1 , a, Side view ;&, front wards the root of the tail two view. 1x250.) h 5'4 Guinea Worm. peculiar gland-like organs, placed opposite to each other, can be made out. The cuticle is very distinctly transversely striated. In clean water the embryo remains alive for six days; in muddy water, or in moist earth, it will Fig. 61.—Embryos of guinea worm in body-cavity of cyclops. The cyclops lias been slightly compressed so as to force out some of the worms, which can be seen escaping from ruptures at the head and tail. (From aphotogram by Mr. Andrei'.' Pringle.) live from two to three weeks. If slowly desiccated it does not die ; it may be resuscitated by placing it again in a little water. Intermediate host.—If, by way of experiment, we place some guinea worm embryos along with cyclops quadricornis in a watch-glass we shall find that, after a few hours, the embryos have transferred themselves to the interior of the body-cavity of the cyclops, where Treatment. 5*5 they can be seen moving about, coiling and uncoiling themselves, with great activity (Fig. 61). As many as fifteen or twenty young guinea worms may be counted in each of the little crustaceans, which, unless the infection is excessive, seem in no way inconvenienced. After a time, the embryos so transferred undergo a metamorphosis. They cast their skins two or three times, get rid of their long swimming tails, acquire a cylindrical shape and, ultimately, along with increased size, develop a tripartite arrangement of the extreme posterior end, which recalls a similar arrangement in the tail of filaria nocturna towards the termination of that nematode in the mosquito. Mode of infection.—The metamorphosis of guinea worm in cyclops was discovered by Fedschenko in Turkestan. His observations I have been able to con- firm in England; but, in the colder climate of the latter country, in English cyclops the metamorphosis takes somewhat longer to complete; eight or nine weeks, instead of five weeks as in Turkestan. Fedschenko supposed that the cyclops containing the embryo guinea worm, on being swallowed by man in drinking water, was digested; and that the parasite, being then set free, worked its way into the tissues of its new and definitive host. It is possible, however, that the embryo may have to undergo further changes before it is fitted for life in man. Considering the peculiar geographical limitations of this helminthiasis, and the very general distribution of cyclops, such an arrange- ment seems likely enough. However this may be, Fedschenko's discovery makes it certain that it is in drinking water that the guinea worm is acquired. The male worm.—Nothing certain is known, as already stated, about the male worm; nor as to when or where impregnation of the female is effected. Im- pregnation probably occurs at an early stage of parasitic life, and long before the female worm has grown to the great length which she subsequently attains. The male worm, his function fulfilled, probably dies and is absorbed. u 11 2 5'6 Guinea Worm Biological peculiarities explained.—The little we now know of the life-history of the guinea worm explains many things that were formerly mysterious. We now understand why the parasite, on attaining maturity, makes for the legs and feet; these are the parts of the human body most likely, in tropical countries, to come in contact with puddles of water, the medium in which cyclops—the intermediate host—lives. We can understand, also, why it is that the contact of water with the skin of the host causes the guinea worm to extrude her young ; and we can understand the rationale of the douching, so much practised by the natives of certain of the endemic districts, in their attempts at extraction. Premature death of parasite.—Occasionally the guinea worm fails to pierce the integument of her host; sometimes she dies before arriving at maturity. In either case she may give rise to abscess; or she may become cretified, and in this condition may be felt, years afterwards, as a hard convoluted cord under the skin of the leg, or be discovered only on dissection. Treatment.—Formerly it was the custom, so soon as a guinea worm showed herself, to attach the protruding part to a piece of wood and endeavour to wind her out by making a turn or two of this daily. Sometimes these attempts succeeded ; but, just as often, the worm snapped under the strain. The consequences of this accident were often disastrous. Myriads of young escaped from- the ruptured ends into the tissues, and violent inflammation and fever, followed by abscess and sloughing, ensued ; weeks, or months, perhaps, elapsed before the unhappy victims of this rough surgery were able to get about. Too often serious contractions and ankyloses, from loss of tissue and inflammation, and even death from septic trouble, resulted. If a guinea worm be protected from injury, and the part she occupies frequently douched with water, her uterus will be gradually and naturally emptied of embryos. Until this process is completed she resists extraction; possibly the hook at the end of her tail Trea tment. 5*7 assists her to maintain her hold. But when par- turition, in from fifteen to twenty days, is completed, the worm tends to emerge spontaneously. A little traction or winding out if practised then may aid extrusion. Traction, however, must not be employed so long as the embryos are being emitted. The com- pletion of parturition can be easily ascertained by the douching experiment already described. Lately Emily, a French naval surgeon, has intro- duced a system of managing guinea worm cases which bids fair to shorten treatment and obviate the serious risks of the old winding out system. By means of a Pravaz's syringe he injects the body of the worm, if she chances to be protruding, with solution of bichloride of mercury, 1 in 1,000. This kills the parasite ; after twenty-four hours, extraction is generally easily effected. If the worm has not shown herself externally, but can be felt coiled up under the skin, he injects as near the coil as possible, and through several punctures, a few drops of the same solution. This, too, kills the parasite. Her body is then absorbed, as a piece of aseptic catgut would be, without inflammation or reaction of any descrip- tion ; or she may be cut down on, and easily extracted. Others have confirmed the value of Emily's method, which saves much time and suffering and with due care is devoid of risk. FILARIA LOA (Fig. 62). This parasite is peculiar to the West Coast of Africa where, in many parts, it is not uncommon—in Old Calabar, for example. The male worm measures about 25 to 30 mm. /yf^ in length by 03 mm. in breadth, the U y _ female 30 to 40 mm. in length by 0-5 „. C1 „.. mm. in breadth. Both sexes are filiform, loa. (Nat. size.) cylindrical, colourless, like fine fishing {Pr- Argyll •> .' ' ° Robertson.) gut, tapering slightly at the head, more decidedly at the tail. The body is dotted over with minute chitinous bosses. The anus is subterminal. The 5*8 Filaria Loa. tail of the male (Fig. 63) is markedly incurvated and provided with five large papillae on each side of the anus, and two rather short, unequal spicules. The mouth is simple, punctiform, and without armature. The habitat of filaria loa appears to be the subcutane- ous connective tissue, which it traverses freely. When, in the course of its wanderings, it crosses the subconjunctival connective tissue, and the delicate integuments about the orbit, it becomes distinctly visible. When passing under such thin structures as the skin of the eyelids, or that ,,j., ;f over the bridge of the nose, „.„„..„ . './ . . or when moving about under Fig. 63.—Tail of male filaria loa. ^ the skin of the fingers, the slight elevations it gives rise to, as well as its move- ments, are sometimes appreciable, and may be both seen and felt. From the circumstance that this parasite has occasionally been seen in individuals who have been ten or more years away from the endemic area in which alone it can be contracted, we may conclude that the loa is long-lived. The female produces sheathed embryos closely re- sembling filaria nocturna and filaria diurna. At one time I had a negro patient under my care in whose blood filaria diurna abounded. This man remembered that, when a lad, he had a loa in his eve. I have thought, therefore, that filaria diurna may be the embryonic form of filaria loa. On the otber hand, Dr. Argyll Robertson has placed on record a remark- able case of filaria loa in which the parasites, a male and a pregnant female, were removed from the eye. The patient's blood was frequently examined, but no embryos were found. Lately I had an opportunity of examining the blood of another patient known to Symptoms. 5i9 be the subject of loa infection, but failed to find any hsematozoal embryos. AVe do not know in what way the embryo escapes from the human body, nor do we know anything about its life history outside the human body. Notwithstanding the failures to find the embryo in the peripheral blood, analogy suggests that it probably circulates for a time in this fluid and, like filaria nocturna, that it is removed from this medium by some suctorial insect which acts as intermediate host. Filaria loa, as stated, is very active in wandering about the body, but it seems to have a predilection for the eyes and neighbourhood. It comes and goes there at irregular intervals of clays, weeks, or months, traversing the subconjunctival tissue, and moving across the bridge of the nose from one eye to another. Warmth seems to solicit its presence near the surface. The sexes appear to hunt each other about; at all events, in Dr. Argyll Robertson's case (Trans, of the Ophthalmalogical Soc., 1895) a male worm was re- moved from the eye, and not long afterwards a female worm appeared about the same situation and was also removed. The worm gives rise to pricking, itching, creeping sensations and, occasionally, transient ^edematous swellings in different parts of the body. When it appears under the conjunctiva, it may cause a con- siderable amount of irritation and congestion. There may be actual pain even, associated with swelling and inability to use the eye and, perhaps, tumefaction of the eyelids. Treatment.—The negroes treat filaria loa in two ways—either by dropping a grain of common salt into the conjunctival sac, which has the effect of driving the filaria away, for a time at least; or they extract it with a sharp thorn, or by some other rude surgical means. With proper in- struments there is no difficulty in removing the parasite from under the conjunctiva or from the eyelid—that is, if the operator is possessed of 520 Fila ria Vol vul us. the requisite deftness in operating. All that is necessary, on the parasite showing itself, is, after cocainising the eye, to seize the conjunctiva with a pair of forceps, taking care to include the worm and the subconjunctival connective tissue in the grasp of the instrument. Having fixed the parasite in this way, the conjunctiva maybe snipped through with scissors; when, with the aid of another pair of forceps, and after releasing the first pair, the parasite may be withdrawn. In the case of the parasite showing itself elsewhere, I would suggest that it might be killed, as in the case of the guinea worm, by local hypodermic injection of bichloride of mercury solution (1 in 1,000). FILARIA VOLVULUS. A medical missionary transmitted to Professor Leuckart two tumours, the size of a pigeon's egg, which had been removed, one from the scalp, the other from the chest, of Gold Coast negroes. Each of the tumours contained several male and female filaria', the former 60 to 70 centimetres, the latter 30 to 35 centimetres in length. The worms were coiled up in the form of a ball, and weue bathed in a fluid full of embryos re- sembling filaria nocturna and filaria diurna; no sheath, however, was visible. Nothing further is known of these parasites and the diseases, if any, to which they may give rise. CRAW-CRAW. Most itching papular and pustular eruptions are termed kra-kra by the natives of the West Coast of Africa. Dr. John O'Neil describes (Lancet, Feb., 1875) under this name a pustular affection which he says is common in certain parts of the West Coast, and which he found to be associated with the pres- ence of a filariform parasite in the papules. O'Neil says that this form of craw-craw resembles scabies; but he adds that symptoms subside in a cooler climate, to return, however, when the negro revisits the hot and damp atmosphere of his native country. Cra iv- Cra w. 52t The papules occur all over the limbs and body, either singly or in rings. In two days from its appearance the papule, he says, becomes a vesicle, and in two more a pustule. On paring off the top of the papule with a sharp knife, and teasing up the little piece of integument in water, he found a number of minute filaria-like organisms wriggling about with great activity. Their activity speedily slowed down, and in a short time the worms died. These organisms, according to O'Neil's drawings and description, resemble somewhat filaria nocturna. The measurements do not quite correspond however, the craw-craw filaria being shorter and broader (tICINE NATK ) ~6 f" ■ S C%s o Aavaan ivnoiivn snid j a \ T l ' CINE NATIONAL LIBRARY OF MEDICINE NATIONAL LIBRARY OF MEDICINE ' -o II1VN 3NIDIQ3W dO AMVaaiT IVNOIIVN 3NIDI03W do Aavaan ivnoiivn 3ni: o ! S I ^ CINE NATIONAL LIBRARY OF MEDICINE NATIONAL LIBRARY OF MEDICINE NATI )iivn sNiDiasw do Aavaan ivnoiivn 3Noia3w do Aavaan IVNOIIVN sni: CINE NATIONAL LIBRARY OF MEDICINE NATIONAL LIBRARY OF MEDICINE NAT m IDG 1 7 1# mo Aavaan ivnoiivn .. snidiqsw do Aavaan ivnoiivn ^ bni 3NI 5 WC 680 M289m 1898 35210980R NLM D517DT27 b NATIONAL LIBRARY OF MEDICINE NLM051709276