Reprinted from the New York Medical Journal 
for March 10, 189. 
ACUTE LACUNAR 
DIPHTHERIA OF THE TONSILS, 
WITH STUDIES ON THE RELATION OE THE REAL TO THE PSEUDO 
BACILLUS DIPHTHERIA. 
ATTENDING PHYSICIAN TO THE GOOD SAMARITAN DISPENSARY ; 
ASSISTANT ATTENDING TO THE MOUNT SINAI HOSPITAL (CHILDREN’S WARD), 
NEW YORK. 
HENRY KOPLIK, M. D., 
The class of cases forming the subject of this paper 
are those in which diphtheria either begins or runs its en- 
tire course with the local picture of: a lacunar or follicular 
amygdalitis. These cases, whose clinical study has been 
the subject of much difference of opinion, are becoming 
more important daily. It is through the avenue of these 
cases that diphtheria, sometimes of a fatal character, is un- 
suspectingly spread broadcast. If we are to advance in 
the prophylaxis of diphtheria we must do this not through 
means of the pronounced cases, in which the membrane is 
apparent even to the lay observer, but through the cases 
which in every way simulate the ordinary “ sore throat,” 
or tonsillitis, or lacunar or follicular amygdalitis. In my 
first paper upon diphtheria published in this journal I made 
a study of the doubtful cases of diphtheria. In those cases 
the diphtheria began or persisted as a simple angina or 
was manifest in the form of minute doubtful specks 
Copyright, 18£4. by D. Appleton and Company/ 2 
ACUTE LACUNAR DIPHTHERIA OF THE TONSILS. 
ndate, “ punctate membrane ” upon the tonsils or soft 
palate, or was found to begin or run its course as an 
amygdalitis, or, beginning as a lacunar amygdalitis, would 
terminate in a descending diphtheria with stenotic symp- 
toms. For the sake of unity the writer has confined him- 
self in the present paper to the study only of those cases 
of diphtheria which begin or run their entire course with 
the clinical picture of a typical lacunar amygdalitis. 
Anatomically the assumption of a form of diphtheria 
which may present a lacunar distribution can be more 
easily understood if we study what transpires in the nor- 
mal tonsil as well as in the inflamed structure. Stohr 
proved conclusively that in the tonsils there is normally a 
constant diapedesis of leucocytes from the central follicles 
of the organ through the several layers of flat epithelium 
on the surface of the tonsil. These leucocytes reach the 
surface of the tonsil and are found in small masses between 
the epithelial cells of the external layer of the tonsil. They 
are thrown thus into the cavity of the mouth and are found 
also in the lumen of the lacunae. 
Heubner, studying the abnormal conditions that are 
found in diphtheria, states that this normal lymph current, 
if we may so call it, is replaced by an abnormal exudate of 
lymph and fibrin from the vessels in the interior of the 
tonsil. This fluid is exuded through the several layers of 
surface epithelium, and when it reaches the surface of the 
tonsil it coagulates. Its youngest form is in the shape of 
a coagulated network of fibrinous exudate, containing in 
its meshes the flattened horny epithelium of the uppermost 
layer on the tonsil. Thus for the first few days in the his- 
tory of diphtheria we may have this coagulated exudate 
manifest itself in streaks or spots on the surface of the 
tonsil, indicating the situation of the lacunae, follicles, or 
crypts, and the irregularities of surface between these ACUTE LACUNAR DIPHTHERIA OF THE TONSILS. 
3 
structures. It is foreign to the purpose of this study to 
enter the pathological field dealing with the structure of 
the forms of diphtheritic exudate or membrane. 
Modes of Investigation.—The cases studied in this 
paper have been investigated both from a clinical and bac- 
teriological standpoint. As to the latter mode of study, 
the methods pursued in all cases were exactly those utilized 
in the first paper of the writer which appeared in this jour- 
nal August 27, 1892. Special stress is laid upon the ani- 
mal experiment as the only positive proof of the virulence 
of the Loetfler Bacillus diphtherice. From the ordinary 
crude clinical, diagnostic, or hygienic standpoint it can be 
said that an adept can easily identify the Loefiler bacillus 
by its form, lack of motion, growth on media, and bouillon 
reaction (Roux, Yersin, Escherich), without going through 
the tedious animal tests. Yet this method, moderately cer- 
tain for rapid diagnosis, is scarcely available for permanent 
and reliable scientific work. 
The cases in this paper have thus been subjected to the 
above mentioned test and the number is limited. After 
proving certain theses the further accumulation of material 
has no additional scientific value. 
Clinical Course.—The cases collected in this study 
divide themselves quite distinctly into three leading 
groups. 
The first group of cases are those whose course is an 
exceedingly mild one—so much so that the patients show 
little or no constitutional disturbance. The appetite is 
good ; the children are up and about; they complain of slight 
uneasiness in the throat; sometimes these throat symptoms 
are absent. Examination of the fauces shows a general 
hypersemia ; the tonsils are enlarged. When the patient 
gags, the tonsils become still more prominent and reveal the 
enlarged open lacuna?. There is absolutely no membrane 4 
ACUTE LACUNAR DIPHTHERIA OF THE TONSILS. 
to be seen on the surface of the tonsil, but there is a 
yellow spot here and there which, on investigation, will 
be shown to be the opening of a lacuna or follicle or 
crypt. The lymph nodes at the angle of the jaw may or 
may not be enlarged. The above-described local symptoms 
are so mild that they may have improved or even disap- 
peared the following day. The patient then is to all in- 
tents recovered from this so-called attack. We will show 
the fallaciousness of this assumption in our cases. 
Case I.—Boy, aged six years, has been ill only for twenty- 
four hours; complains of soreness in his throat. Inspection 
shows the lacunas filled with a fibrinous material on the right 
side, which can be scooped out of the tonsillar lacuna without 
difficulty. There is on the surface at the anterior border of the 
tonsil a minute fibrinous streak. Lymph nodes at the angle of 
the jaw on the right side enlarged. Temperature 101-8° in the 
axilla ; the boy’s condition is excellent and he does not feel ill. 
Bacteriological examination of the fibrinous plug removed 
from the lacuna of the right tonsil and spread upon blood serum 
and subsequently isolated shows Loeffler bacilli virulent to gui- 
nea-pigs in dosage of 0-5 c. c. of bouillon culture within forty- 
eight hours. On the following day the tonsils still large, but 
the fibrinous streaks of exudate had disappeared. 
A week subsequent to the above, the boy had completely 
recovered and the tonsils had returned almost to the normal 
size and appearances; they were still a little large and slightly 
red. A minute scoop was entered into the lacuna of the right 
tonsil as near as possible in the same situation as the first plug. 
This tonsil had this lacuna near the anterior border. 
Diphtheria bacilli found virulent in same dosage as above. 
Two tceeks after the onset of the disease a similar plug re- 
moved from the same tonsil in the same locality. 
Diphtheria bacilli still virulent in dose of 0-5 c. c. of bouil- 
lon culture forty-eight hours old. 
At this time the appearance of the fauces was absolutely 
normal; no lacunar plugs to be seen. The above fibrin plug ACUTE LACUNAR DIPHTHERIA OF THE TONSILS. 
5 
was extracted from the depths of the lacuna of the right tonsil. 
The case is continued in Part II of this paper. 
Case ll.—Sister of the preceding, aged eleven years, had 
absolutely no subjective symptoms yet tonsils were enlarged 
and swollen, lacunse open and wide, no elevation of tempera- 
ture; child denies even soreness of the throat or any feeling of 
ill ness. Examination of the contents of the lacunas scooped 
out as above shows what to all appearance were the Loeffler 
bacilli. They were not tested on animals. 
A week subsequent to the first visit these bacilli had disap- 
peared. 
Case 111 —Minnie 8., aged eleven years. A baby sister of 
patient had been ill two months previous with what, from the 
history, might have been diphtheria. The mother, who from 
this time inspected the throats of the children daily, found 
on the day of the visit to the writer slight redness in the 
throat. 
Status —Tonsils are swollen and red ; there is no membrane; 
the lacunas contain a soft yellow substance which can be le- 
moved in form of a plug (fibrinous). The whole picture one of 
lacunar amygdalitis. Temperature is slight, so that it was not 
taken. No glandular enlargements. Child in the best of 
spirits and condition. Examination of the plug, removed with 
sterilized scoop from the lacuna, showed diph'heria or Loeffler 
bacilli virulent in bouillon culture forty-eight hours old in dose 
of 0 5 c. c. to guinea-pigs. 
Two wmeks subsequently the angry appearance of the tonsils 
had disappeared. The one lacuna from which a yellow plug 
had been removed no longer showed reaccumulation of exudate. 
Child protests she is not ill and wants to return to school, 
which, of course, w7as not permitted. 
Two weeks after the first examination a plug was removed 
from the lacuna in the same tonsil in about the same situation 
as the first plug. The bacilli in this plug were no longer viru- 
lent. They will be discussed under the heading of the pseudo 
bacillus. 
In the above-cited cases we have a very mild form of 
onsillar lacunar diphtheria—mild from the outset, watched  ACUTE LACUNAR DIPHTHERIA OF THE TONSILS. 
all along- its course, absolutely no membrane anywhere, and 
the children at no time during their illness in bed. The 
sterilized scoop, entered into the same tonsils at the same 
situation, showed that, as in the first case, there were bacilli 
in the depths of the lacunae fully up to three weeks after 
the boy had shown no signs of lacunar plugs pouting from 
his tonsils. His case will be continued under the pseudo 
heading, and it will be shown that, as in Case 111, the viru- 
lent was finally replaced by a non-virulent bacillus. Roux 
and Yersin, in investigations upon membranous diphtheria 
of the tonsils, recorded cases in which bacilli of Loeffler 
had persisted for fully five weeks after the disappearance 
of membrane. The foregoing, I believe, are unique as 
showing the persistence of virulent bacilli in the depths of 
the tonsillar lacunm for weeks after complete convalescence. 
The non-virulent bacilli found in Cases I and 111 will be 
discussed in the second part of this paper. 
The second group of cases of lacunar diphtheria are 
those in which the symptoms, both local and constitutional, 
re somewhat more severe than in the first group of cases. 
The patients are quite ill; they suffer as do those patients 
who are affected with a severe follicular or lacunar amyg- 
dalitis of a simple infectious non-specific type (streptococ- 
cus). The fever is quite high, the prostration is more 
marked, and there are other symptoms of constitutional dis- 
turbance, such as pains in the limbs, furred tongue, and Joss 
of appetite. Locally the tonsils are seen to be enlarged, 
red, and there exudes from the lacunae a soft yellow fibrin- 
ous exudate. There is no membrane on the surface of the 
tonsil. There are glandular or lymph-node enlargements at 
the angle of the jaw. The following will illustrate : 
Case IV.—Annie C., aged four years, has been ill one day. 
She complains of sore throat; tonsils are quite large and red ; 
they present the typical appearance of a lacunar amygdalitis. ACUTE LACUNAR DIPHTHERIA OF THE TONSILS. 
7 
"When the patient gags, the tonsils protrude pink-red in color 
and from the lacunae there is expressed by the act of gagging a 
soft, yellow, consistent material. Temperature 101°, axillary. 
Child shows some prostration, but general condition is good 
Lymph nodes at the angle of the jaw on the left side can just he 
felt. 
Examination of the lacunar contents as exuded shows Loef- 
fler bacilli in almost pure culture, virulent. 
Case V.- -In this case the amygdalitis was complicated by 
symptoms of laryngeal involvement. These cases are impor- 
tant, showing as they do that, no matter how typical the lacunar 
amygdalitis, the larynx may be affected not by a simple but by a 
diphtheritic process, as are the tonsils themselves. These cases 
are especially apt to be judged as simple and non-specific. 
Case Yl.—Male, aged five years, has been coughing for 
three days. The tonsils are enlarged and have the typical fol- 
licular appearance. When the boy gagged it seemed as if the 
uvula, which curved upward, showed a minute yellow speck at 
its point. The voice is harsh and the cough croupy. No laryn- 
geal breathing. Prostration marked. Bacteriological examina- 
tion of the lacunar contents showed Loefiier bacilli. 
The third group of cases of lacunar diphtheria are those 
which from the outset show a malignant course. They do 
not remain of the pure lacunar type after the first few days. 
In the following case the change occurred on the third day. 
The nasal mucous membrane is drawn into the symptomatic 
picture of the disease. We thus have a case beginning 
in every way like a severe follicular amygdalitis of a non- 
specific type (streptococcus), ending in a fatal diphtheria 
with pronounced septic diphtheritic phenomena. 
Case Vll.—Baby, female, aged thirteen months. There had 
been a number of cases of “sore ” throat in the family (seven 
children), especially in that of a boy of eight years, whose 
throat, 1 regret to say, I did not examine bacteriologically. 
There was no membrane in this boy’s throat, and there was 
every appearance when I saw him of a simple non-specific an- 8 
ACUTE LACUNAR DIPHTHERIA OF THE TONSILS. 
gina. The mother also had suffered from a “sore” throat. 
The symptoms in all cases had been so mild as not to call for 
any outside advice. The baby had been ill for two days when 
first seen. The infant was very pale and quite prostrated ; rec- 
tal temperature, 102°. The lymph nodes on both sides of the 
neck, at the angle of the jaw, were much enlarged in packets. 
There was no skin eruption. The tonsils were enlarged, red, 
eroded, but had the appearance of a very severe lacunar amyg- 
dalitis; no nasal discharge. The following day the tonsils ap- 
peared less swollen and the amygdalitis an ordinary one. In 
view of the constitutional symptoms and a slight nasal dis- 
charge, I warned the mother to allow me to see the patient 
again if improvement was not rapid. Two days subsequent to 
this the tonsils had again swollen ; the discharge from the nose 
became much more pronounced. The tonsils were so much 
swollen as not to permit a view of the posterior pharynx. The 
discharge from between the tonsils now contained minute shreds 
of what proved to be membrane. 
Bacteriological examination of these shreds show Loeffler 
bacilli and large numbers of Roux’s cocci. The case ended 
fatally, with symptoms of septic diphtheria, including extensive 
glandular infection. 
The Diagnosis.—The constitutional symptoms give us 
very little clew to our diagnosis in the first group of cases, 
whereas in the third group the severe constitutional pros- 
tration from the outset leads us to suspect something more 
specific than simple amygdalitis. 
The range of febrile disturbance is also quite unreliable. 
Glandular swelling may be practically absent in the mild 
cases, though it will be seen that in some of these cases we 
had as an accompaniment of the diphtheria a swelling of 
the lymph nodes on one side only. On the other hand,, 
glandular swelling may be very marked in non-diphtheritic 
amygdalitis (streptococcus). The swelling of nodes on 
one side is peculiar to diphtheria, though I have very often ACUTE LACUNAR DIPHTHERIA OF THE TONSILS. 
seen it in non-diphtheritic cases. Albuminuria may he 
present or absent at first, when diagnosis is most important. 
It is apt to be present in simple streptococcus disease as 
well as in the diphtheritic cases. 
Henoch says, in a recent article upon the early clinical 
diagnosis of diphtheritic amygdalitis, that we must judge 
our cases from the consideration of a completed picture of 
the disease. It will also be seen that the diagnostic ele- 
ments presented by this great clinician—the fibrinous exu- 
date from the lacunae, the confluence of patches of fibrin 
on the surface of the tonsil, affection of both tonsils, the 
uvula and nasal mucous membrane, albuminuria, the occur- 
rence of several cases in one family—all apply either to the 
severe cases (third group), or appear late in the disease. 
To the writer it still seems that the only reliable test is the 
bacteriological one. There is now such a reaction as to en- 
courage the hope that soon this test will be applied by the 
general practitioner in daily practice. 
Part ll.—Bacteriological, 
. The methods pursued in the investigation of the cases 
in this paper included not only an examination of the secre- 
tions on the surface of the affected tonsils, but what seemed 
more interesting and, in fact, imperative was the examina- 
tion of the contents of the individual lacunae of the tonsils. 
The lacunae could only be studied in the older children, 
where they are of some size and in which it is possible to 
introduce a minute sterilized scoop or harpoon. In this 
way the plug or secretion in the depths of the lacunae was 
obtained for study, spread upon serum, and isolated finally 
upon agar-agar. The writer has been impressed by the 
fact that the tonsil may harbor for weeks in the depths of 
its lacunae, follicles, or crypts, as we may choose to call these 
structures, virulent diphtheria bacilli. In membranous 10 
ACUTE LACUNAR DIPHTHERIA OF THE TONSILS. 
diphtheria we are not surprised to find, after the membrane 
has cleared away, that the diphtheria bacilli persist in the 
numerous ulcerations or erosions left by the membrane on 
the surface. In lacunar diphtheria, as in Cases I and 111, 
where no membrane is formed in the whole course of the 
affection, we are surprised to find in the depths of the lacu- 
nae fibrinous plugs which persist for weeks and which con- 
tain myriads of virulent bacilli. Roux and Yersin found that 
in cases of membranous diphtheria the Bacillus diphtherice 
persisted in a virulent state as long as five weeks after all 
traces of membrane had disappeared from the fauces. I 
have had this condition of things repeated in lacunar diph- 
theria. The virulence of the Bacillus diphtherice can he 
preserved for an exceedingly long time outside of the body. 
It resists the drying process if shielded from the direct sun- 
light. A culture of the Bacillus diphtherice in the author’s 
possession, after having dried for months in an ordinary 
test-tube, so that the original agar was reduced to a dry crisp, 
showed after nine months a virulence in bouillon forty-eight 
hours old to the amount of half a cubic centimetre to old 
or young guinea-pigs. The scrapings of such a culture, 
though containing many involution forms such as have been 
pictured by the writer in his first article, grew most luxuri- 
antly in agar and bouillon. Old bouillon cultures, reduced 
by age from evaporation to a few drops from ten cubic 
centimetres, were found to abound in virulent living bacilli 
which grew upon agar. Roux and Yersin, in their last ar- 
ticle upon diphtheria, assume that the mild cases may yield 
bacilli which show a diminished virulence in animal ex- 
periment. The writer’s experience, at least in the class of 
cases examined, does not tend to confirm this view. Bacilli 
from the very mildest cases of lacunar diphtheria were 
found in pure culture virulent to guinea pigs in dosage of 
half a cubic centimetre of bouillon culture forty-eight hours ACUTE LACUNAR DIPHTHERIA OF THE TONSILS. 
old. This dose is now conceded by most writers to be 
small enough as a test of virulence. All animals injected 
with such an amount died within forty-eight hours with 
symptoms of virulent diphtheria (local haemorrhagic oedema, 
enlarged lymph nodes, pleuritic and peritoneal effusion). 
In Case I the Loeffler bacillus was isolated three weeks 
after all traces of tonsillar trouble had disappeared. These 
bacilli were preserved in separate cultures pure, and those 
isolated latest were found fully as virulent as the bacilli 
isolated at the outset of the disease. All these bacilli 
were cultivated from the lacunar plugs so often men- 
tioned in this paper. A dose of half a cubic centimetre 
of a bouillon culture invariably proved lethal to guinea- 
pigs of medium weight (three hundred and fifty to four 
hundred and fifty grammes) within forty-eight hours. 
In this way the bacilli obtained from the mild cases 
were compared with a very old culture which has been 
in the author’s possession over two years and which has 
been isolated by him from a virulent membranous diph- 
theria. Of this culture a tenth of a cubic centimetre will 
prove lethal to animals in varying time, but half a 
cubic centimetre will invariably prove lethal in forty-eight 
hours if bouillon cultures forty-eight hours old are used. 
In short, bacilli of a so-called diminished virulence—those 
which would require two or three cubic centimetres to 
prove lethal from bouillon cultures forty-eight hours old— 
were sought by the writer in the mild cases, not of mem- 
branous but lacunar diphtheria, and were not found. In 
the author’s experience, the mildest cases furnish as viru- 
lent bacilli as the most severe. In all this we assume that 
certain fixed laws in the preparation of all cultures are fol- 
lowed. The agar cultures are made from single colonies 
upon alkaline agar one per cent. These agar cultures are 
taken out of the thermostat after forty-eight hours. Bouil-  -ACUTE LACUNAR DIPHTHERIA OF THE TONSILS. 
lon cultures of simple pepton alkaline bouillon are prepared 
from these agar tubes. The bouillon is taken out of the 
thermostat after forty-eight hours. The animals used in 
testing virulence are always young animals, three hundred 
and fifty to four hundred and fifty grammes in weight. 
The bouillon cultures should be eight to ten cubic centi- 
metres in bulk and the supernatant fluid above the sedi- 
ment should not be poured otf, as has been done by many 
authors, and the thick residue used, but the whole culture 
is shaken up and half a cubic centimetre of this is used. 
Old animals even of medium weight show a certain amount 
of resistance to diphtheria and should not be used. The 
above are brought to the notice of the worker in diphtheria 
as a result of a long and tedious series of studies in this field. 
They will insure uniform results. 
The Pseudo Bacillus Diphtherice (Hofmann, Loetfler),— 
In the first paper of the writer four cases were recorded in 
which a bacillus was found which closely resembled the 
real bacillus, reacted much the same upon culture media, 
but lacked virulence completely. In the studies of this paper 
the writer has succeeded in isolating a bacillus from cases 
in which the virulent diphtheria bacilli had been found and 
which appeared in the same patient after a lapse of weeks. 
In ordinary stained preparations (Loeffler blue) an expert 
would have great difficulty in finding marked differences of 
form. They were lacking completely in virulence. 
The relationship of the real to the pseudo Bacillus 
diphtherice has lately been the subject of a critical review 
by Escherich. This critique was incited by the surprising 
discoveries of Fraenkel, who described a bacillus which in 
every way corresponded to the true Loeffler bacillus as to 
culture and stain, but which differed from it only in lack- 
ing virulence. Doses of two cubic centimetres seemed to 
be well borne by animals, whereas in five-cubic-centimetre ACUTE LACUNAR DIPHTHERIA OF THE TONSILS. 
13 
doses of a bouillon culture a lethal result followed. Fraen- 
kel isolated his bacillus from the human conjunctiva in 
cases in no way related to diphtheria. He concluded from 
his observations that he had before him the true Bacillus 
diphtherice, but reduced in virulence ; that the bacillus he 
had isolated and the Hofmann pseudo bacillus were identi- 
cal. In this way he championed the cause of Roux and 
Yersin, who maintain the same ground. Escherich does 
not agree with these observers. The writer of the present 
paper is inclined to look upon the whole question of rela- 
tionship of these two bacilli as an open question. But lit- 
tle has been proved on either side. The question is one of 
the widest range of importance. If the real Bacillus diph- 
therice can so completely lose its virulence as will be seen 
in the bacillus isolated in this study, certainly all known 
means have as yet failed to bring it back to its original 
state of virulence. Pasteur, in reducing the bacillus of 
charbon to a non virulent organism, did so by artificial 
means outside the animal economy, I therefore do not con- 
sider this fact brought forward by Roux and Yersin in 
support of their views as quite apt or all-satisfying. 
The following studies are certainly unique and are pub- 
lished at this time as peculiarly pertinent to this very im- 
portant question of the relationship of the real to the 
pseudo Bacillus diphtherice. 
Cases in which a bacillus, non-virulent, replaced the real 
Bacillus diphtherice after a lapse of time : 
Case I, lacunar diphtheria, virulent Bacilli diphtherice 
found up to three weeks after convalescence, then the non- 
virulent bacilli were found. 
If the reader will refer to Case 1 of the first group of 
cases of lacunar diphtheria it will be seen that up to the third 
week after the onset of the illness, and fully that time after 
the boy felt well and the tonsils had cleared, the tonsils and 14 
ACUTE LACUNAR DIPHTHERIA OP THE TONSILS. 
pharynx were in appearance normal, and were the seat of 
virulent bacilli. 
Three weeks, therefore, after the onset of the illness a 
sterilized silver scoop was introduced into the lacuna of the 
right tonsil and a fibrinous yellow plug was removed. 
This plug was found to contain almost exclusively a bacillus 
in every possible way as to shape and stain the exact coun- 
terpart of the real Bacillus diphtherias. It was non-motile, 
stained with Loeffier blue in broken areas, and was not de- 
colorized by Gram. There wrere clubbed shapes and involu- 
tion forms in abundance. A very close study of the viru- 
lent bacillus taken from the same case and tonsil earlier in 
the disease (fourteen days after the onset) and this present 
bacillus side by side showed a very slight difference in thick- 
ness of the two bacilli; the non-virulent seemed to stain 
a little thicker, but so slight was this difference that un- 
marked there is for practical diagnostic purposes but very 
little to fix upon, for at times the virulent bacilli are thicker 
than others, short and long. The length of both bacilli 
seemed and still appears identical. In growth there are 
distinct differences.* 
Bouillon is uniformly clouded after forty-eight hours 
and the deposit is much more abundant than that of the 
virulent bacillus. The reaction of the bouillon is distinctly 
alkaline after forty-eight hours. 
Agar-agar yields a growth in which we at once notice 
a luxuriance foreign to the virulent bacillus. The colonies 
upon agar-agar reach a fuller development in shorter time 
than the real bacillus. They seem whiter and more opaque. 
The above non-virulent bacilli were found up to the end 
* Measurements of the Loeffler virulent bacillus : Length, 2-2 fx to 
sjx ; width, (Hi jx to 08 /x. Some non-virulent bacilli (pseudo) of same 
case : Length, 2-6 fx to 4 p,; width, 0-6 fx to 0-178 fx. Involution forms, 
of course, vary widely from above. ACUTE LACUNAR DIPHTHERIA OF THE TONSILS. 
of the fifth week after the onset of the illness and were 
isolated in pure culture and are in the possession of the 
writer. The attempt to find them in the tonsil six weeks 
after the onset of the illness resulted only in their identifi- 
cation in smear preparations upon serum ; they were over- 
grown in twenty-four hours by staphylococci. 
Case 11, in which the virulent Bacillus diphtherice is re- 
placed in the same tonsil by a nan-virulent bacillus. 
This is Case 111 of the mild series of lacunar diphtheria 
cited in the first part of this paper (refer to history). The 
patient was seen four times, the second visit a day after 
the first. The tonsils had cleared, and the yellow streaks 
and lacunar appearances had disappeared; the tonsils were 
still red and enlarged. The Bacillus diphtherice, isolated 
from the right tonsil, had been found virulent. 
Third visit a week after the first one, and the tonsils 
apparently normal in size and appearance : no culture made. 
Fourth visit, fifteen days after the first: tonsils normal; 
child well; a sterilized scoop entered into the lacuna of 
the right tonsil, behind the anterior faucial pillar, as near 
as possible to the place where the virulent bacilli had been 
extracted. A large, yellow plug, which had been invisible, 
was removed from the depths of this lacuna. From this 
plug there was obtained a luxuriant growth upon blood 
serum of a bacillus the exact counterpart of the non-viru- 
lent bacillus isolated from Case I above. 
In the above two cases we have typical lacunar diph- 
theria in which no membrane was seen at any period of 
the disease, both of which cases were exceedingly mild in 
all their manifestations. In both cases the real bacillus— 
virulent—persisted for three weeks in one case and up to 
the second week in the other. The bacilli were all isolated 
from plugs of fibrinous exudate removed from the lacunae 
and sown upon blood serum. The various sets of bacilli 16 
ACUTE LACUNAR DIPHTHERIA OF THE TONSILS. 
were kept separated, and tested and found all to be of a 
like virulence, as stated in another part of this paper. At 
the beginning of the fourth week in one case after the 
first isolation of virulent bacilli, and the beginning of the 
third week in the other case, these virulent bacilli of diph- 
theria were replaced by a bacillus which was in every 
way, except in growth upon agar and in bouillon, the most 
accurate counterpart of the virulent original bacillus. It 
was, however, in both cases a harmless, non-virulent bacillus. 
Loeffler, in his second article upon diphtheria, asserts that 
in a case of an adult he had found the virulent and the 
non-virulent bacilli growing side by side upon the agar 
plate, and had isolated both. In this way he accounted for 
the famous pseudo Bacillus diphtherice of Hofmann, saying 
that the pseudo bacillus was an accompanying harmless 
bacillus of the real micro-organism. Roux and Yersin 
found the non-virulent or pseudo bacilli in cases of mem- 
branous diphtheria which early in the disease had yielded 
the virulent bacillus. The writer’s cases are the only ones 
in which the real and virulent bacillus was replaced in the 
same tonsil and, as near as could be judged, in the same 
locality, entirely by a rich growth of a non-virulent bacillus 
which the expert examination alone could only find the 
least remove thicker than the virulent bacillus, but of the 
same form and staining peculiarities. In order to be ex- 
plicit, we wish to repeat that this bacillus is non-motile, 
grows more luxuriantly upon agar than the virulent bacillus 
and the bouillon cultures (peptone bouillon) are not acid, as 
in the real bacillus, but alkaline after forty-eight hours in 
the thermostat. The bouillon deposits a more abundant 
sediment than the virulent and is more diffusely clouded. 
Roux, Yersin, and Escherich have called attention to the 
early acidity of the bouillon cultures of the virulent bacil- 
lus (forty-eight hours), and the author has had ample op- ACUTE LACUNAR DIPHTHERIA OF THE TONSILS. 
portunity to verify this important and invariable quality of 
the virulent bacillus. The non virulent bacillus stains ex- 
actly like the virulent micro-organism both in Loeffler blue 
and Gram stains. As stated, it seems, when closely studied 
side by side with the virulent bacillus, broader than the lat- 
ter. I doubt whether, in unmarked specimen?, the writer’s 
non-virulent bacilli could be distinguished by stain alone. 
We have the same clubbed and involuted forms shown by 
the virulent bacillus. I have noticed that it does not grow 
so luxuriantly in sugar bouillon as it does in the simple 
peptone bouillon. In the latter the shape of the non viru- 
lent bacillus is more complete as a bacillus form after forty- 
eight hours than that of the virulent bacillus, which is often 
seen in abortive forms at this time in bouillon culture. 
Animals do not react even to large doses (eight cubic 
centimetres of forty eight hours’ bouillon) of the non-viru- 
lent bacillus; a few guinea-pigs develop a slight oedema, 
which eventually disappears. After having received these 
large quantities of the non-virulent bacillus, four guinea- 
pigs were reinjected after the lapse of a week with half 
a cubic centimetre of the virulent bacillus with lethal 
effect in two cases within forty-eight hours; a third, in 
three days; and a fourth, an old, fully-developed pig, in 
four days. Thus the non-virulent bacillus was not a vac- 
cine against the virulent bacillus. These experiments, it 
will be recalled, were also performed with the non-virulent 
bacilli isolated in four cases of the first paper on this sub- 
ject by the writer with similar results. 
The literature of the non virulent or pseudo Bacillus 
diphtherioe is still in its infancy. Hofmann, Loeffler, 
Escherich, Fraenkel, Welch, Abbott, and the writer of 
this article have studied it. Its role and exact place in the 
morphology of diphtheria are still a mystery. The German 
school of bacteriologists all unanimously agree as to its 18 
ACUTE LACUNAR DIPHTHERIA OF THE TONSILS. 
place among the harmless saprophytes. Fraenkel is an ex- 
ception to this view and sides with Roux, who thinks that 
the non-virulent pseudo bacillus is a weakened form of the 
virulent bacillus and, under conditions not yet discovered, 
as stated was the case in charbon, may become a danger- 
ous, virulent micro-organism. 
In closing these studies upon diphtheria the writer 
wishes to emphasize the fact that the tonsil is an organ 
which possesses a circulatory activity hitherto not attrib- 
uted to it. It was formerly looked upon as an ana- 
tomical appendage whose purpose was problematic. Stohr 
has demonstrated the constant migration of leucocytes 
from the interior of the tonsil (follicles) to the surface, 
and therefore into the lumen of the lacunae. The writer 
is inclined to believe that future work may reveal that 
the tonsil in this functional activity exercises a destruc- 
tive influence upon pathogenic bacteria which may be on 
the surface of the tonsil or in the lumen of the lacunae. 
Blood lymph and serum possess inherent destructive powers 
upon the life of bacteria (Nuttall, Buchner, Prudden). 
Leucocytes also have the power of attracting within their 
substance bacteria. Both these conditions exist in the ton- 
sils. If we examine the lacunar plugs in lacunar diphtheria 
we find leucocytes which seem to contain within them 
cocci and bacilli. It may be that the prolonged retention 
of the Bacillus diphtherice for weeks in the depths of the 
lacunae under the intimate influence of the above-mentioned 
phenomena of lymph and leucocyte activity may not be 
without effect on one phase of the vitality of the Bacillus 
diphtherice—its virulence. Such a theory as the above is 
offered with the greatest of diffidence in view of our limited 
knowledge of the actual relation of these two bacilli. 
Note.—The experimental work of this paper was carried on in the 
Carnegie Laboratory. ACUTE LACUNAE DIPHTHERIA OF THE TONSILS, 
19 
Full List of Cases examined for Lacunar Diphtheria, and 
ivhich all presented the Typical Clinical Picture of an 
Case 
No. 
Sex. 
Age. 
Glandular en- 
largements at 
angle of jaw. 
Bacteriological 
results. 
Animal 
experiments. 
1 
Male. 
6 yrs. 
Right. 
Loeffler bacillus. 
Virulent. 
2 
Female. 
11 yrs. 
None. 
U U 
Not tested. 
3 
u 
11 yrs. 
u 
u u 
Virulent. 
4 
u 
4 yrs. 
Left. 
u u 
U 
5 
Male. 
5 yrs. 
Both. 
u u 
U 
6 
Female. 
4 yrs. 
None. 
Streptococcus. 
U 
1 
Male. 
3 yrs. 
“ 
8 
“ 
H 7r- 
Right. 
Loeffler bacillus 
Virulent. 
9 
“ 
13 mos. 
Streptococcus. 
10 
Female. 
4 yrs. 
Pseudo bacillus. 
Not virulent. 
11 
U 
20 mos. 
None. 
(( 
U U 
12 
a 
2 yrs. 
“ 
Streptococcus. 
13 
u 
1 yr. 
U 
Roux’s coccus. 
14 
Male. 
H yrs. 
U 
Pseudo bacillus. 
Not virulent. 
15 
U 
3 yrs. 
Both sides. 
Bacilli not pseu- 
do. 
U U 
16 
U 
4 yrs. 
Right. 
Loeffler bacillus. 
Virulent. 
11 
u 
H yrs. 
Both sides 
slight. 
Bacilli not pseu- 
do. 
Not virulent. 
18 
Female. 
22 mos. 
None. 
Bacilli not pseu- 
do, streptococ- 
ci. 
Streptococci, 
staphylococci, 
Roux’s coccus. 
a u 
19 
Male. 
8 yrs. 
Both. 
20 
Female. 
1 yr. 
a 
Streptococcus. 
Roux’s coccus. 
21 
Male. 
H yr- 
None. 
22 
U 
15 mos. 
a 
Loeffler bacillus. 
Virulent. 
23 
U 
11 mos. 
u 
Roux’s coccus. 
24 
a 
2 yrs. 
Right. 
Loeffler bacillus, 
Roux’s coccus. 
Virulent. 
25* 
Female. 
13 mos. 
Both. 
Loeffler bacillus. 
U U 
26 
15 mos. 
Left. 
Streptococcus, 
staphylococcus. 
21 
Male. 
5 yrs. 
Both. 
Streptococci, 
staphylococci. 
28 
Female. 
4 yrs. 
Both. 
Streptococci, 
Roux’s coccus. 
29 
Male. 
H yrs. 
Streptococcus. 
Acute Lacunar or Follicular Amygdalitis, 
* Marked Case V in paper, 20 
ACUTE LACUNAR DIPHTHERIA OE THE TONSILS. 
Case 
No, 
Sex. 
Age. 
Glandular en- 
largements at 
angle of jaw. 
Bacteriological 
results. 
Animal 
experiments. 
30 
Female. 
3 yrs. 
Streptococcus. 
81* 
U 
yrs. 
None. 
Loeffler bacillus. 
Lost; not tried 
on animals. 
32 
“ 
11 mos. 
U 
Streptococci. 
33 
“ 
3 yrs. 
Loeffler bacillus. 
Virulent. 
34 
Male. 
5 yrs. 
Streptococcus, 
Roux’s coccus. 
35 
Female. 
2£ yrs. 
Both. 
Streptococcus, 
Roux’s coccus. 
36 
Male. 
6 vrs. 
None. 
Streptococci. 
37 
U 
17 mos. 
U 
“ 
38 
U 
4£ yrs. 
U 
Staphylococci, 
streptococci. 
39 
U 
6 yrs. 
Left. 
Staphylococci, 
streptococci. 
* Sister to patient in Case I in paper. 
Abbott, A. 0. Johns Hopkins Bulletin, August, 1891. 
" Buchner, H. Abstracted in Baumgarten’s Jahreshericht, 
1888. 
Authorities referred to in the text. 
Escliericb, T. Berlin. Min. Wochen., Nos. 21 and 23, 1893 
Fraenkel, 0. Deutsche med. Wochen., 1893. 
Henoch. Deutsche med. Wochen., 1889, 897. 
Hofmann. Wiener med. Wochen., 1888, Nos. 3 and 4. 
Heubner. Jahrh.f. Kinderheilk., Bd. xxx, Heft 1 and 2. 
Loeffler. Deutsche med. Wochen., 1890; Gtrlbl. f. BaM., 
1887, vol. ii, p. 105. 
Nuttall. Zeitsch.f. Hygiene, Bd. iv, 1888. 
Pasteur. Comptes rend., Acad, sci., 1881. 
Prudden, T. M. Medical Record, 1890. 
Eoux and Yersin. Annal.de Vlnstil. Pasteur, Bd. iv, 1890, 
et seq. 
Stohr, Phillip. Virchow’s Archiv, vol. xcvii, p. 211.