AOYOMA’S REPORT UPON THE BUBONIC PLAGUE. 
[The substance of a report made to the Journal Club of the Johns Hopkins 
Hospital by Simon Flbxnek, M. D.] 
[From The Johns Hopkins Hospital Bulletin, Nos. 66-67, Septemher-Octoher, 1896.1 [From The Johns Hopkins Hospital Bulletin, Nos. 66-67, September-October, 1896. 
1 
AOYOMA’S REPORT UPON THE BUBONIC PLAGUE. 
[The substance of a report made to the Journal Club of the Johns Hopkins 
Hospital by Simon Elexner, M. I).] 
In October of 1894 an abstract of a report to the Journal 
Club of the Hospital, upon the subject of the bacillus of the 
plague, appeared in the Hospital Bulletin. The account 
there given of the micro-organism which had but a short time 
before been isolated from a number of cases of the black 
plague by Drs. Yersin and Katisato, and which was believed to 
be the cause of this devastating pest, was drawn from the reports 
of these investigators published at that time. The expedi- 
tion sent by the Japanese government, at the head of which 
was Dr. Katisato, contained Dr. Aoyoma, whose mission it was 
to study the clinical and pathological features of the disease. 
Dr. Aoyoma became himself infected with the disease a short 
time after the beginning of his studies at Hong-kong, and 
although he recovered, the report of his studies has only 
recently appeared,* As was to be expected, these relate more par- 
ticularly to the symptomatology and the pathological anatomy 
of the disease, although account is taken of the epidemiology 
and to a less* extent of the bacteriology and of the mode of in- 
fection. In order that the first report given in the Bulletin 
may be in a manner complete, it is considered desirable to 
append an abstract of Dr. Aoyoma’s recent report. 
In May of 1894 the Japanese consul in Hong-kong 
announced to the Japanese government that the plague had 
appeared in Canton. Immediately following, a quarantine 
first of nine days and later of seven was set upon incom- 
ing ships, and Dr. Katisato, with his assistant Ishigami, and 
Dr. Aoyoma with his-assistant Miyamoto and medical student 
Kinoshita, were sent to Hong-kong, where they arrived on the 
12th of June. Through the kindness of Dr. Lowson they 
* Mittheilungen aus den Mediciniscben Facultat der Kaiserlich- 
Japanischen Universitat, Band 111, No. 11, Tokio, 1895. 2 
were permitted to arrange for their work in one of the rooms 
of the Kennedy Town Hospital, where on the 14th they had 
established themselves ready for work. Unfortunately Aoyoma 
and Ishigami became ill with the pest on the 28th of June, 
owing to which the studies which are here to be given were 
limited to fifteen days of active service. In this time 19 
autopsies were held and 45 clinical cases studied, the latter 
more or less completely. In addition to these the opportunity 
of seeing a large number of cases in the Chinese hospitals had 
been embraced. 
Respecting the situation of Hong-kong and the condition of 
the soil, its inhabitants and houses, the following may be 
stated: Hong-kong is one of the widest of the islands situ- 
ated in the Gulf of Canton stream, and lies 142 km. south- 
east of the city of Canton, and 62 km. east of Macao, and is 
separated by a small body of water, which is used as a harbor, 
from the mainland. The island is mountainous, from two to 
five miles in length, and consists of granitic rock. Respect- 
ing the climate it may be stated that it is tropical, and the 
warmest months of the year are from March to November. 
The winter is also warm, and snow is not known in that 
locality. 
Victoria, which is the principal town, extends from east to 
west along the north coast, between the sea and the mountain- 
ous background, and follows the latter, as it is built in part 
upon the mountain side. In the most easterly part we meet 
the barracks, villas, factories and the European shops. The 
westerly and middle parts, which are lower, are the Chinese 
quarters. The portion of the town which was most affected 
is known as Taiping-chan, which lies in the middle of the 
city. As regards the streets themselves, excepting that they 
are narrow, they are the equals of the best European streets. The 
houses, which are usually two stories in height and built after 
the European fashion, number about 7900, of which 6600 
belong to the Chinese population. 
The number of inhabitants of Hong-kong is difficult to 
ascertain and probably reaches the neighborhood of 250,000. 
The report obtained from the water-supply bureau gave 163,- 
949, of whom 151,974 were Chinese. The overcrowding of the 
houses of the Chinese workmen has greatly increased during 3 
the past ten years. It is stated that in the ten years from 1881 
to 1891 the number of inhabitants of the city increased 41 per 
cent., while the houses increased only 13T9¥ per cent. The densest 
population is found in Taiping-chan, where.it would appear 
that in a house area of 0.173 acre 3740 Chinese live. The 
streets of this part are very narrow, the houses are two-storied, 
the windows small and few in number. The houses, which 
are long in form, are separated by partitions into two parts, 
each of which is further subdivided into a number of large 
rooms. In the earlier times one of these rooms housed a 
single family, but at the present, owing to overcrowding, these 
rooms have been divided by subpartitions into an upper and 
a lower compartment, and these compartments further by 
upright partitions, so that several rooms have been con- 
structed out of the original ones, in each of which a family 
now lives. The average size of the main room is 26x14 feet by 
10 feet high, and contains eight partitions averaging 7x6 feet by 
7 feet high, over which a sort of loft is often built to increase 
the accommodation, and in a room of this description from 
16 to 35 people live. 
The canalization is constructed so that one system of pipes 
receives the washings from the rains and the other the sewage 
from the kitchens, etc. The first works perfectly, whereas the 
other is for the most part in a very bad condition, so that 
stagnations frequently occur and the sewage is dammed back 
upon the houses. 
The city itself is provided with an excellent water supply, 
which at certain times is even subjected to filtration. The 
clothing of the Chinese is hygienically to be recommended. 
The only difficulty to be pointed out is, that although well 
conceived for the purpose, it is never under any circum- 
stances subjected to washing, which fact is equally true of 
their bedding. The personal habits of both the men and the 
women are almost beyond belief in their crudeness and neglect. 
Cleanliness on their part, or anything approaching it, is an 
absolutely unknown art. 
As regards the cause of the plague, it may be said that 
Katisato discovered bacilli in the blood and in the lymphatic 
glands which differed somewhat in their morphological char- 
acters but which agreed in their cultural properties. Accord- 4 
ing to Katisato, the bacillus which appears in the blood 
resembles the organism of chicken cholera, possesses a capsule, 
the middle portion staining very faintly; while the bacillus 
obtained from the lymphatic glands is somewhat longer, has 
rounded ends, and stains more uniformly than the other. The 
bacillus obtained by Yersin is stated to have rounded ends, to 
he easily stained with the aniline dyes, and to be decolorized 
with Gram’s method. The ends again stain more uniformly 
than the middle part. According to Katisato, the organism 
would at times stain by Gram’s method, and at others not. 
Aoyoma, however, observed that those contained within the 
lymph glands were decolorized, and those in the blood stained by 
this method. The number of organisms contained within the 
blood is usually not large, and may be so small that it is neces- 
sary to prepare a large number of cover-slip preparations in 
order to find sufficient for a diagnosis. On the other hand, 
they are found abundantly in the affected lymphatic glands. 
The study of the tissues has shown that in the lymph 
glands a variety of bacteria may be met with. As a constant 
and predominating species the lymph gland bacillus of Kati- 
sato is found, although in rare cases micrococci predominate. 
Careful observation, however, shows within these masses greater 
or less numbers of the pest bacilli, the streptococci occupying 
the blood-vessels rather than the gland substance. The pest 
bacilli in the tissues stained less intensely in alkaline methylene 
blue solution than the streptococci, and the staphylococci least 
of all. It is stated that while the streptococci retain the Gram 
stain, the bacilli and the staphylococci do not. It is sug- 
gested by Aoyoma that the forms described by Katisato as 
occurring in the blood and retaining the Gram stain may have 
been pairs of cocci and not bacilli at all. He regards the 
association of the bacilli and cocci as of great importance, 
inasmuch as in the greater number of instances the affected 
glands suppurate, while a very small fraction do not. Hence 
it is considered that the suppuration is caused not by the plague 
bacilli which are always present, but through the action of 
pus-producing bacteria which entered along with the former 
or later than these; and Aoyoma has further found that in 
suppurating glands the plague bacilli are either much dimin- 
ished in numbers or have entirely disappeared. 5 
It may be recalled that in the first reports of Katisato 
and of Yersin they stated that the bacilli might enter the 
body first through the respiratory tract, second the digestive 
tract and third, excoriations of the surface. Aoyoma, on the 
other hand, expresses the opinion that in the great majority 
of cases, if not in all, the entrance is through external wounds. 
He points out that physicians and nurses who are in attend- 
ance upon infected individuals and spend much time in the 
places in which the sick are kept, rarely become infected with 
the disease. In this epidemic, of all such persons who were in 
attendance upon the sick, only three Japanese physicians and 
one Chinese physician became infected, the nurses having 
entirely escaped. During the prevalence of the epidemic 300 
English soldiers volunteered to cleanse and disinfect the 
Chinese pest-houses. Of these only ten became affected with 
the disease. Thus it would appear as though an actual pest 
atmosphere did not exist and that the infection did not take 
place through the inspired air. Moreover, Aoyoma did not 
observe that the tracheal or bronchial glands were in a con- 
dition of intense inflammation, which he presumes would have 
been the case had the bacilli invaded through the air passages. 
Respecting the question whether the organisms are taken 
into the body through the drinking water or with the food, it 
may be said that the Chinese do not drink unboiled water, and 
never under any circumstances eat uncooked foods. That 
portion of the town (Taiping-chan) which was most infected, 
and in which the hygienic conditions were the worst, received 
its drinking water from the general supply. It is true that 
Katisato was able to cause infection in mice by introducing 
the bacilli into their stomachs through glass tubes, but it is 
stated by Aoyoma that Katisato does not any longer regard 
these experiments as being certain proof of infection through 
the alimentary tract. It is noteworthy that at autopsy the 
lymphatic apparatus of the stomach and intestines and the 
mesenteric lymph glands were never found greatly inflamed, 
and the last contained very small numbers of the bacilli only, 
or in certain cases none at all. Hence it is stated that all phy- 
sicians who observed this outbreak of the pest were forced to 
the idea that the bacilli entered chiefly through external 
wounds. 6 
In the great majority of cases the deep inguinal and the 
axillary glands, and in a small number of cases the superficial 
inguinal glands, of one side were first affected and afterwards 
other glands became involved. This fact is explicable only 
upon the assumption that the organism entered through small 
defects of the skin which were preseat either on the feet or 
the hands; and as the working class of Chinese usually go 
barefoot, such small defects can easily be imagined to exist. 
Further, as is known, the lymphatic vessels of the feet run to 
the deeper and lower inguinal glands, thus exposing these first 
in the great majority of cases. The superficial inguinal glands 
receive the lymphatics of the penis and the skin over the lower 
portion of the abdomen, and these are but seldom primarily 
affected. Of the nine Japanese whom Aoyoma observed, two 
women showed affection of the axillary glands, one of the sub- 
maxillary glands, whereas in the other no glandular affection 
could be detected, notwithstanding the fact that the bacilli 
were found in the blood. Of the Japanese men, four showed 
swelling of the axillary glands, and one only of the inguinal 
glands. This is interesting when it is considered that the 
Japanese do not go barefoot. It may also be mentioned that 
among the Chinese the women show affection of the axillary 
rather than of the inguinal glands. 
The wounds through which the infectious agent enters 
show, as a rule, no reaction. Notable exceptions to this state- 
ment are his own case, in which a lymphangitis was present, 
and that of his assistant, Nakahara, who succumbed to the 
disease and in whom lymphangitis was also observed, in both 
cases beginning in the hand and extending towards the axilla. 
Regarding the manner of diffusion of the bacilli, nothing new 
has been added in this report. The period of incubation of 
the disease is given at from two to seven days; and as regards 
the age and the sex of those affected, it may be said that the 
greater number of cases occur in young males. 
The following table gives the relative proportion of men, 
women and children affected: 
Men 
Women 
19.23 
Boys 
Girls 
9.45 7 
It is worth noting that Aoyoma himself did not observe a 
single case in newly-born children or sucklings, although an 
English physician, Dr. Lowson, claims to have seen five or six 
cases among the latter. 
The mortality in Hong-kong from the beginning of the 
disease until the 2nd of September is given as follows : 
Europeans 
11 
3 
Japanese 
10 
6 
Manilanese 
31 
1 
Erasinese 
3 
3 
Indians 
13 
10 
Portuguese 
18 
13 
Malayanese 
3 
3 
West Indians 
1 
1 
Chinese 
3619 
3447 
Number Affected. Number Died. 
Symptomatology. The symptoms of the disease during the 
last plague were not, as was stated by most authors, protean, but 
they were quite simple. The disease began for the most part 
without prodromata, with a chill, or even in the first instances 
with pain and swelling of the glands and with succeeding 
chill and fever. Prodromata when present were usually short 
and varied in duration from a few hours to two or three days, 
or perhaps somewhat longer. The symptoms in the prodromal 
stage are prostration, headache, nausea, vomiting, loss of 
appetite, vertigo, and only rarely pains in the lumbar region 
or in the back. In the cases of the affection of the more 
intelligent population, even before the outbreak of the fever, 
slight swelling and pain were noted in the glands; whereas 
in the more obtuse Chinese these slighter phenomena were not 
noticed. 
The temperature rises quickly to 39° or 40° C. or even 
higher, and remains high during the progress of the disease. 
Delirium sets in early, for the most part after the second day, 
aud continues day and night, although in the lighter cases it 
may be absent during the day. On the other hand, severe 
cases occur in which from the beginning until death super- 
venes the functions of the brain are intact. The pulse is 
usually of good volume, as a rule dicrotic and varies in fre- 8 
quency from 90 to 130 per minute. The spleen is palpable 
usually after the second or third day. It rarely can he felt 
more than a few cm. below the costal margins. The liver also 
is usually enlarged and palpable. 
The urine is in most instances of dark color, cloudy, con- 
tains albumen, and does not, as a rule, give the diazo reaction. 
A few casts, either hyaline or granular, and Avhite corpuscles 
are usually present. Very rarely the urine contains blood. 
After the first or second day the glandular affection becomes 
more marked, and those glands first involved may reach the 
size of an egg. The pain increases with the growth in size, 
although in some cases it may be absent excepting upon pres- 
sure. The glandular affection is characteristic, inasmuch as 
it begins in one group and then involves in succession others, 
as for example first the inguinal, then the axillary, then those 
of the neck, and finally the submaxillary glands. The glands 
of the neck, of the elbow and the knee are seldom primarily 
affected. Only very rarely do several sets of glands become 
enlarged at once. Very soon after the swelling of the glands 
the periglandular tissues become involved and then later the 
skin. In the milder cases, suppuration may not occur and the 
swelling gradually diminish and finally disappear. On the 
other hand, suppuration may occur even in glands but little 
enlarged. 
The temperature rises rapidly to 39 or 40 degrees, and in 
rare cases to 41 i degrees. In other instances the rise is more 
gradual. After remaining continuous for three or four days, 
there may be a critical fall, or the decrease may be gradual. 
In severe cases which recover the fever lasts from one to three 
weeks, and towards the end presents an irregular and remit- 
tent type. In not a few cases after the temperature has re- 
turned to the normal at the end of the first or the beginning 
of the second week there is a relapse, the fever now assuming 
a remittent character. The remittent fevers are suppurative; 
the fever is very rarely from the beginning remittent and 
irregular. 
Actual hemorrhages into the skin were observed but once 
by Aoyoma, although congested areas are not infrequent. 
These latter areas disappear upon pressure and are believed 
to be caused by the bites of mosquitoes. Respecting the ques- 9 
tion of the appearance of an exanthematous eruption, it is 
stated that a rapidly disappearing erythema may occur. 
Symptoms referable to the brain, with the exception of the 
delirium, were very rarely observed. Fibrillary twitchings 
occurred before death, and actual convulsions were seen in 
very rare instances. In only one case was opisthotonus 
observed. 
In the Foudroyante cases death may occur before any con- 
siderable glandular swelling can be made out; in the severest 
cases taking place on the second day. As a rule, death occurs 
from the second to the eighth day, and on an average on the 
fourth day. As suppuration of the glands rarely occurs before 
the tenth day it was not observed in these more rapid cases. 
When death takes place late in the course of the disease it 
may be due to a secondary pygemic infection. The suppura- 
tion of the glands may continue for months, so that the con- 
valescence of the patient is rendered very slow and tedious. 
When suppuration does not occur the glands gradually become 
smaller, although the enlargement may not entirely disappear 
for two or three months. 
Complications are stated to be quite frequent. Of these, 
nephritis occurs quite commonly in the severer cases. It 
develops as early as the third or fourth day of the disease, is 
accompanied with the appearance of a moderate amount of 
albumen in the dark red urine, and microscopically hyaline 
and granular casts, as well as white and red blood corpuscles, 
are found, (Edema was rarely seen, and when present, of light 
grade, and anuria was never observed. The blood which is 
present in the urine is not derived from parenchymatous 
hemorrhages, but from small extravasations into the mucous 
membrane of the pelvis of the kidney and the bladder, 
abscess formation in addition to the lymph glands was 
observed in the liver, lungs and other organs in the later 
stages of the disease. Icterus of a light grade, and presum- 
ably of catarrhal origin, was often present; in one case it 
reached a very high degree, and at the autopsy it was found 
that the common duct had been pressed upon by a group of en- 
larged lymphatic glands. Serous pleuritis occurred but seldom, 
and seemed when present to be associated with the enlarge- 
ment of the axillary glands. Pneumonia was seen in a single 10 
instance only, but bronchitis was much more common. Rarer 
complications are periostitis, lymphangitis, furunculosis of the 
skin, phlegmons which have their origin in the suppurating 
glands, carbuncle, singultus, and bloody stools. 
Respecting the question as to whether cases of the pest with- 
out glandular affection ever exist, it may be said that in three 
cases which came to autopsy and which were proven to have 
died of the plague, enlargement of the glands was not made 
out during life. 
The blood presented a dark red color, and the estimation of 
the corpuscles showed that the red corpuscles were only incon- 
siderably or not at all diminished, while the white were always 
increased. The number of white corpuscles per cubic mm. 
varied from 20,000 to 200,000; a control count of normal 
blood in a Chinese gave 10,000 white corpuscles to the cubic 
mm. The increase in white blood corpuscles is in the poly 
morpho-nuclear neutrophilic variety. Eosinophilic cells were 
very rarely seen. It is stated that the blood platelets were 
increased in number. 
During the short time that Aoyoma carried on his studies 
he made autopsies upon 19 cadavers. The following is in 
brief the result of his studies of these cases: There is not 
infrequently a post-mortem rise of temperature; in one case 
the temperature taken four hours after death in the rectum, 
with a thermometer which registered 43 degrees, could not be 
estimated because the mercury was driven to the top of the 
capillary tube. Post-mortem muscular contractions also 
occurred in a similar manner to those observed in cholera. The 
affection of the lymph glands in various regions of the body 
has already been referred to, and it remains to say that in no 
case did he find evidence of a primary affection of the pleural or 
peritoneal lymphatic glands. No matter in which part of the 
body the glands are primarily affected, the entire lymphatic 
apparatus of the body shows at least some swelling, and perhaps 
congestion as well. With the exception of minute ecchymoses 
nothing abnormal was observed in the heart. The lungs and 
the pleura were not the seat of inflammatory changes, although 
in the latter, in certain of the cases of primary axillary affec- 
tion, an increased amount of fluid existed in the pleural 
cavity. The spleen was enlarged, and sometimes considerably 11 
so. The kidneys showed the lesions of cloudy swelling, and 
often were congested. Small hemorrhages occurred in the 
mucous membrane of the pelvis. The liver was enlarged and 
hypersemic and the seat of parenchymatous degeneration. The 
stomach and intestines showed more or less injection of the 
mucous membrane and increase of the mucous section. The 
pia arachnoid was as a rule by per semi c and very oedematous. 
Purulent inflammations were never present in this situation. 
In few cases a moderate number of small hemorrhages were 
observed in these membranes. The fluid within the ventricles 
was moderately, never greatly increased. The substance of 
the brain showed a moderate oedema and numerous hemor- 
rhagic points. In one instance an extravasation of blood the 
size of a bean was found in the medulla oblongata, and in 
another one of the same size occurred in the pons. The pia 
arachnoid of the spinal cord was hyperaamic and oedematous. 
Lesions were not found in the cord itself. 
The increase in size of the lymphatic glands depends upon 
several factors, namely, hypersemia, exudation, hemorrhage, 
hyperplasia of the gland cells, and great development of bac- 
teria. The bacilli which are present are found in the earlier 
stages in the lymph spaces about the follicles, and later they 
are found within the follicles, the lymph sinuses and the 
medullary cords. The cells of the affected gland undergo 
various degenerative changes and may become necrotic. They 
lose their nuclei in the latter case, and a variable amount of 
nuclear detritus is present among the degenerated and necrotic 
cells. The hemorrhages are not limited to the gland itself, 
but may be found, as well as greater or less oedema, in the 
periglandular tissues. The usual fate of the enlarged glands 
is to suppurate, although in certain cases the swelling may 
disappear without suppuration and the glands return to 
normal; while in still others a fibroid induration may result. 
The suppuration is either of the nature of simple abscess for- 
mation, or preceding this there may be a necrosis of the gland 
substance; in certain cases the suppuration does not remain 
limited to the glands, but extends into the periglandular 
tissue. Sections of the lymph glands showed a variety of 
bacteria. It is stated that in the primary localization various 
bacteria may be associated. Among these can be distinguished 12 
the pest bacilli and cocci, and among the latter both strepto- 
coccus and staphylococcus forms may be discovered. Aoyoma 
considers the association of these organisms as very import- 
ant in determining the suppuration or non-suppuration of the 
affected glands. The spleen usually shows the presence of 
large numbers of bacilli, and among these more rarely micro- 
cocci, The pest bacilli were also, though not constantly, found 
in the interstitial substance of the kidneys and in the glome- 
rular capillaries. They were also present in the inter- and 
intra-acinous tissues of the liver. The mesenteric glands some- 
times contained the bacilli in small numbers; it is not stated 
whether or not they were found in the structures of the central 
nervous system.