NationalLibraryOfScotland/medical-history-of-british-india huggingface dataset:
3
It will be noticed that the case mortality in hospital is almost the same as
that recorded for the same class of patients in Dr. West's report on the trials
with Roux's serum last year (vide p. 60).
Further trial of serum made on this system was carried out about the same
time by the German Plague Commission on 26 patients in the Bombay Plague
Hospitals. Of these 13 died and 13 recovered 4 ; but as noted by the Indian
Plague Commission, these results are not compared with any parallel series of
controls, and are not therefore of much statistical value, though the case
mortality is below the average met with in plague.
The serum used for these cases is described by the German Commission as
belonging to " the older " sample supplied to them, and they record that " the
only certain inference which can be drawn is that the injections of serum have
had no perceptible immediate or remote harmful results."
The next trial with Roux-Yersin serum was made by Captain H. D. Mason,
M .
R . C . S . , R . A . M . C . ,
i n t h e S t a t e o f C u t c h , d u r i n g M a y a n d J u n e 1 8 9 7 .
The serum was obtained direct from the Pasteur Institute in Paris. " The serum
was administered to human plague patients in doses from 10 to 6o c.c. The
smaller closes were employed in the cases first treated, the larger doses being
resorted to as experience was gained. Quantities larger than 60 c.c. were not
administered, because it was found that with this last dose the patients began
to suffer from painful swelling of the joints.5"
The amount given varied from 10 c.c. (in one case) to 220 c.c. The
following table shows the numbers who received (a) less than 100 c c. of serum,
(b) those who received 100 c.c. and above, and (c) those who received 200 c.c.
or above, with the case mortality in each :—
Number.
Deaths.
Percentage m o r t a l i t y .
Patients receiving less than 100 c.c.
.
28
13
4 6 . 4
""100
c.c. and above
•
66
41
6 4 . 1
"
"
200 c.c. and above
.
6
5
8 3 . 3
TOTAL
.
1 0 0
59
59.0
Control cases
.
1 0 0
. 8 3
8 3 . 0
Unfortunately it is not possible to compare the case-mortality of these
serum-treated patients with a parallel set of control cases, for " The plague cases
that served as controls were admitted to the Brahmapuri Hospital at Cutch Mandvi
during the period of eight days (from the 25th of May to the 2nd of June 1897)
at the height of the epidemic, when the fatality of the disease was extreme as is
B 2
4
evidenced by the mortality of 83 per cent. in the hospital. The plague patients,
however, who were treated with serum, were, with the exception of the first 5
cases treated, admitted to hospital during a period of four months of a declining
epidemic, when we may presume the type of the disease to have been much
milder. Again, only 31 of the 100 serum cases were admitted into the Brahmapuri
Hospital, this apparently being in consequence of the decline of the epidemic in
Cutch Mandvi. The remaining 69 cases were admitted into hospital in smaller
places in the neighbourhood of Cutch Mandvi. The serum cases were thus
hardly comparable with the control cases. It is indeed recognised by Captain
Mason that the average severity of the disease in the control was greater than
that in the serum cases." A comparison of the serum cases treated in the
Brahmapuri Hospital from the 30th of May to the 9th of June 1897, i.e. , within
a week after the date of admission of the last control case shows the following
result :—
Number.
Deaths.
Percentage
mortality.
Serum-treated patients. ...
1 9
14
73.7
Control " ...
.
.
o o 1
83
83.0
As the Indian Plague Commissioners remark, " In view of the more favour-
able results arrived at by these last comparisons, it is obviously possible that the
diminished mortality of the serum cases which is exhibited by the first table may
be referable quite as much to the decline in the virulence of the epidemic as to
an effect exerted by the serum treatment."
The effect of the serum treatment on the clinical symptoms is said by
Captain Mason to be, a reduction of temperature, with a calming effect on the
patients and a general amelioration of their condition. In the graver cases,
however, this fall of temperature and general improvement is transitory, " the
symptoms again become serious and the disease appears to run its course as if
the serum had not been given.' "
The serum treatment did not prevent the appearance of secondary buboes,
nor had it any effect on cases of primary plague pneumonia.
The Indian Plague Commissioners 8 c o n c l u d e b y s a y i n g t h a t t h e s t a t i s t i c s
" are inconclusive as to the value of the serum employed by him. At the same
time, we are disposed to think that the favourable impression which was created
on the mind of Captain Mason by his observation of the clinical effects of the
serum treatment furnishes a presumption in favour of the utility of Yersin's
serum."
5
The next observations with this serum were those of Dr. Simond of the
Pasteur Institute, Paris, who came out to India and conducted the experiments
personally.
At Karad in the Satara District, 32 persons were treated by him between
the 5th and 24th September 1897, in the hospital there.9 The doses varied
from 10 c.c. (in one case) to 30 c.c.; and the largest total given to any one
patient was 90 c.c. in 4 doses. The following table shows the numbers who
received ( a ) less than 40 c.c. and ( b ) 40 c.c. and above :—
Patients receiving less than 40 c. c..
Number.
Deaths.
Percentage
mortality.
11
9
81.8
Patients receiving 40 c.c. and above. ...
.
20
1 1
55.0
P a t i e n t s r e c e i v i n g u n k n o w n q u a n t i t y . ..
1
1
...
TOTAL .
32
21
65.6
Among the patients who received 40 c.c. and above there were two non-
fatal cases marked doubtful plague by Dr. Simond. If these be eliminated, we
get a case-mortality of 61.1 instead of 55, which again closely approximates to
the results got with Roux's latest serum. Unfortunately there is no information
as to the case-mortality of a series of comparable control cases.
Dr. Simond's second trial was made by him at Karachi in May and June
1898. The records of 70 cases are available, 37 of which were fatal, a case-
mortality of 52.8 per cent. The Indian Plague Commissioners state : 10 " The
case-mortality of these patients is not compared by Dr. Simond with the case-
mortality of any series of controls. When the fact is taken into consideration
that a large number of pneumonic cases were included in the group, and that all
convalescent patients were excluded, it would seem reasonable to conclude
that the mortality was below the average of that usually met with in plague."
They also point out that the case-mortality in the Seth Vishandas Hospital,
where most of the patients were treated, was, in the period before 9th May
(when the serum treatment was begun) 70 per cent. among 288 cases; that in
the period from 9th May to 6th June (when the serum was being used) the case-
mortality among 74 non-serum-treated cases was 74 per cent. and among 47
serum-treated cases 47 per cent., giving a gross mortality in the hospital at this
time of 63 per cent. among 121 cases; and that in the period after the serum
treatment was stopped the case-mortality among 38 cases was 55 per cent.
6
From these figures they conclude that ( a) the type of case admitted to
hospital while the serum was being used, was gradually becoming less severe, as
indicated by the progressively lessening case-mortality returned from the
hospital ; this corresponding to the rapid decline of the epidemic in the latter
half of May and beginning of June 1898 in Karachi town ; and ( b) that possibly
the cases in the non-treated group "included a large number of moribund or
hopeless cases," for otherwise it is hard to explain the somewhat higher case-
mortality as compared with the rate in the pre-serum period, and the dispropor-
tionate height as contrasted with the immediately succeeding period. It is thus
impossible to form "a definite conclusion as to the effect exerted by the serum
on the case-mortality."
It is unfortunately impossible to found anything on the figures showing that
the serum was more effective when used in the first days of illness, for the
reason that the patients universally declared they were recently affected, from
fear of prosecution for concealment of cases.
As to the clinical effects of the serum, it appears that "in fatal cases the
treatment had not the slightest permanent effect on the temperature." 11 In
certain cases, however, the temperature fell two or three degrees, especially after
the evening injection. In cases ending in recovery, the serum appeared to act
in much the same way, and the temperature did not reach normal any sooner
than under ordinary treatment. The pulse, however, often became less rapid,
and the tongue clean and moist after an injection of serum, and general
improvement in symptoms was seen in many cases, even when recovery did not
eventually ensue. The serum had no effect on septicæmic or pneumonic cases,
and hardly any on cases developing secondary pneumonia, nor did it prevent this
latter complication. Convalescence was likewise not affected by the treatment,
and four cases developed rheumatic articular pains.
The Indian Plague Commissioners made trial of samples of this serum,
kindly placed at their disposal by the authorities of the Pasteur Institute in
Paris. Patients were treated by Lieutenant Stewart Douglas, I.M.S., at Banga-
lore in December 1898 and January 1899. 12 The cases in the South Camp
Hospital were treated with serum, those in the North Camp Hospital were
observed as controls ; both hospitals admitting a similar class of patients.
In all, 49 plague patients were treated, these being all the cases of undoubted
plague admitted, save those manifestly convalescent or in articulo mortis. Of
these, 31 died giving a case-mortality of 61.2 per cent. The serum was adminis-
tered once a day, the quantity given to the first 28 cases varied from 10 c.c. to
20 c.c., and to the remaining 21 cases 40 c.c. on the first day, and generally
20 c.c. on each subsequent day. Seventeen patients received less than 40 c.c.
of serum, and of these 10 died, a percentage case-mortality of 58.8 ; while 32
7
patients received 40 c.c. of serum or more and had 21 deaths, a percentage case-
mortality of 65.6. With the exception of eight all were well marked bubonic
cases.
For the purpose of comparison the Indian Plague Commissioners give the
following table which shows the admission of plague patients to the North and
South Camp hospitals during the period covered by the administration of
serum :—
North Camp Hospital—no serum used .. . •
Number,
Deaths.
Case-mortality
per cent.
54
29
53.7
South Camp Hospital, where most of the cases
were treated with serum... .
73
35
47.9
It will be seen that there is a difference of 5.8 per cent. in favour of the
hospital where serum was largely used, but it is pointed out that no conclusion
can be drawn from this as the figures are small, and the previous history of the
two hospitals showed that the patients in the North Camp Hospital always had the
highest case-mortality. Thus, before the serum treatment was begun, 365 cases
in the North Camp Hospital showed a case-mortality of 75 per cent., while 686
in the South Camp Hospital had a case-mortality of 58 per cent., a much
greater difference than the above. " It was not observed that any of the symptoms
were markedly alleviated by the serum treatment, or that the life of the patients
was prolonged. The serum treatment did not give any better results in the cases
where it was inaugurated early than in the cases where it was inaugurated in the
later stages of the disease." 1 3
The plague epidemic in Bangalore having died out, the rest of the serum
was used in the Modikhana Hospital, Bombay, where Dr. Turkhud, who was in
charge, kindly arranged that every second patient should be placed at the disposal
of the Plague Commission for serum treatment. The actual treatment and
recording of results was undertaken by Captain Walton, M.B.,
F . R . C . S . , I . M . S . , a n d L i e u t e n a n t S t e w a r t D o u g l a s , I . M . S . , w h i l e D r s . W r i g h t a n d R u f f e r ,
members of the Plague Commission, watched the results.
The amount of serum injected was usually 40 c.c. on admission, often
followed by a second dose of 20 c.c. later in the day; and on subsequent days
two doses of 20 C.C. each.
As regards the total amount of serum administered we find 13 patients
received less than 100 c.c. and that all these died; 13 received 100 c.c. or more,
of whom 9 died, a percentage case-mortality of 69.2; and two received more
than 200 c.c., of whom one died and one recovered.
8
The following shows the general result :—
Number.
Deaths.
Case mortality,
per cent.
Control group ... . . . . . .
28
24
85.71
Serum group ... . . . . . .
28
23
82.14
The control and serum groups were strictly comparable. All were bubonic
cases, all were males between 10 and 60 years of age, and the patients admitted
to hospital and treated in the early and late stage of the disease were represented
in nearly equal proportions in both groups. " The serum cases admitted and
treated early with serum do not show any diminished case-mortality as compared
with the untreated cases admitted in the same stage," nor do those treated early
compare favourably with those treated later in the course of the disease. 1 4
As regards the effect of serum treatment on the clinical features of the
disease as illustrated by these cases at Bangalore and Bombay, the Plague
Commissioners observe 1 5
t h a t t h e t e m p e r a t u r e f r e q u e n t l y f a l l s w i t h i n t h r e e o r
four hours after injection of the serum, but that this fall is only of temporary
duration; and that occasionally a rise of temperature follows its administration.
No characteristic difference in the temperature curve can be discovered when a
series of charts of treated and non-treated cases are compared.
The pulse is often also affected in a temporary manner, becoming stronger,
fuller and slower. Occasionally the pulse was not affected in cases where a
favourable effect was produced on the temperature.
The respiration rate follows the pulse rate very closely, a distinct temporary
improvement often following the administration of serum.
" The serum appears to exert no effect whatever on the buboes," and
" little or no influence on the supervention or course of the lung complications
which are so commonly met with in plague."
The effect of the serum injection on delirium and other nervous symptoms
was favourable in many cases, but by no means constant. Apparently con-
valescence in those who recovered was not affected in any way, nor was life
appreciably prolonged in the fatal cases by the treatment.
The only other trial in India of serum made on this plan, besides the cases
reported on by Dr. West, was one conducted by the Russian Plague Commission
with serum prepared in the Imperial Institute of Preventive Medicine,
St. Petersburg.
The patients treated were those admitted to the Parel Hospital, Bombay,
during March and April 1897. Every alternate patient was treated with the
serum, the treatment being withheld only when the diagnosis of plague was
9
uncertain or when the patient was actually on the point of death. The serum was
given hypodermically: at first 20 c.c. daily in one dose; later, an additional 10 c.c.
was given in the evening, and later still the morning dose was increased to 30 c.c.
These doses were finally increased to 40 c.c. in the morning and 20 c.c.
at night. " More than half the cases were treated with the later doses."16
The following table shows the result :—
Patients receiving serum
.
.
. .
Number.
Deaths.
Percentage
mortality.
50
40
8 0
,, not receiving serum . . .
50
40
8 0
There is nothing to show that the serum was more effective when given early
in the course of the disease.
Dr. Clemow, who was in charge of the hospital, could not satisfy himself that
the serum had any effect on the temperature, or on the ordinary complications of
the disease.1 7
" It is impossible, in view of the above," say the Indian Plague Commission, 16
" to arrive at any other conclusion with regard to the effect of the serum
employed than that which was arrived at by Dr. Jassenski, of the Russian Plague
Commission, who conducted the test of the serum, and which was concurred in
by Captain Jennings and Dr. Clemow, namely, that the serum was an absolutely
indifferent substance with no influence either for good or evil, on the course of
acute plague."
Haffkine's Anti=plague Serum.
Shortly after plague was recognised in Bombay, Mr. Haffkine was deputed
by the Government of India to investigate plague from the bacteriological point
of view, and to devise, if possible, a prophylactic for that disease. In November
1896, that is some six weeks after his arrival in Bombay, he began the inoculation
of some 20 horses with plague microbes with the object of obtaining an anti-
plague serum from them. The material employed for immunising the animals
was a culture of plague germs in broth, such as is used in the manufacture of the
plague prophylactic.
The initial dose was 5 c.c. of such a culture some two weeks or so old.
" These animals in the course of several months or a year, could be brought to
such a state that they could be safely inoculated with a litre or a litre and a half
instead of 5 c.c." 1 8
The injections were in all cases hypodermic, and besides a large number of
horses, cattle, sheep and goats were used. The goats all succumbed to a c
10
chronic disease induced by the injections, associated with wasting and swelling
of the joints, and their serum therefore was not used. Serum from the
horses, cattle and sheep was used in a large number of cases at Poona in
the autumn of 1897. Preliminary experiments on animals had proved its
efficacy in small doses to protect against lethal injections of living plague
germs. 19 It was first used on human beings in the Byculla Jail and Arthur
Road hospital, Bombay, in the early part of the same year. On account of the
small amount of serum then available no clear indication as to its usefulness, or
otherwise, could at that time be obtained. The serum procured from the animals
was therefore stored in hermetically sealed test tubes till a sufficient amount had
accumulated for the purposes of a crucial test. In the autumn of 1897, when
plague was on the increase in Poona, an opportunity presented itself of making a
series of systematic observations on the plague patients admitted to the special
hospital there.
Mr. Haffkine, accompanied by the present writer, accordingly visited the
plague hospital every morning, and by the kindness of Captain J. L. T. Jones,
M.B., I.M.S., in charge of the hospital, was enabled to treat with this serum every
alternate patient admitted to the hospital during the three hours or so we
remained there daily.
As most of the cases were admitted in the morning as the result of house-
to-house visitation by the authorities, and as some 20 or 30 patients were
admitted daily, it was possible to obtain in a fortnight a decided opinion on the
usefulness of the serum. No selection was made except when two patients
arrived simultaneously. In such a case that patient was chosen for injection
who seemed to us to be in the more serious condition. In this way close on
200 cases of plague passed through our hands, half of which were treated with
varying amounts of serum, often in very large amounts. No evidence from
clinical observation was obtained of any effect attributable to the serum, and the
case-mortality was, probably on account of the method of selection noted above,
some 14 per cent. higher in those treated with serum than in the controls.
A hint of beneficial action was obtained in the case of patients treated with the
sheep serum ; but none in the case of those injected with the cattle or horse
serum prepared in this way.
No further experiments were therefore performed with this serum.
Lustig's Serum.
Professor Lustig of Florence, having by experiment on small animals arrived
at the conclusion that a curative serum for plague could be prepared by the
injection of horses with nucleo-albumen derived from masses of plague germs
treated with certain chemicals, was sent to Bombay by the British Government
11
in June 1897 for the purpose of trying his serum on human beings. By this
time the plague epidemic of the first year had run its course and only a few
sporadic cases were available for this purpose. Dr. Choksy, the Medical Officer
in charge of the Arthur Road Hospital, where it was first tried, reported that it
was "the only serum which gave anything like satisfactory results as out of
7 cases treated with this serum 6 recovered, and at Lanowli 16 cases were treated
and 12 recovered."20 Professor Lustig reports 21 that in Bombay and Poona he
treated 30 patients with 24 recoveries.
On the strength of these favourable results and the report of further
experiments on animals in Florence, the Municipal Corporation of Bombay
asked Professor Lustig to prepare serum for them in Florence and agreed to
engage the services of Dr. (now Professor) G. Galeotti, Professor Lustig's
Assistant, and to arrange for the manufacture of serum on the spot. Dr.
Galeotti and his Assistant Dr. Polverini arrived in Bombay on the 11th of
March 1898 bringing a supply of serum which had been made in Florence by
Professor Lustig.
The cases treated with this Florence-made serum numbered 257, all under
the care of Dr. Choksy at the Arthur Road Municipal Hospital, and admitted
in the period from March to October 1898. The serum was given hypodermi-
cally in doses of from 10 to 30 c.c. night and morning. "The patients to
whom the serum was therapeutically administered were to some extent selected,
all moribund patients being excluded, except in March and part of April. The
case-mortality of the selected patients who were submitted to the serum treat-
ment was compared with the case-mortality in the remainder of the hospital
patients, including, as this did, the moribund patients who were excluded
from the serum group. The results as set forth by Dr. Choksy were as
follows" 22: -
Cases.
Deaths.
Case-mortality,
per cent.
Ordinary treatment.
.
752
595
79.1
Serum
.
.
.
257
145
56.4
The Indian Plague Commission then proceed to discuss whether these two
groups of cases are strictly comparable as regards severity and the distribution
of moribund and convalescent patients, and arrive at the conclusion 23 "that
when the desire to test the serum only on cases that seemed capable of benefit-
ing from the treatment, and in particular upon patients who seemed likely to
live more than 24 hours after admission, came to be a factor in the selection of
cases for serum treatment, an influence was introduced, which must, no doubt