NationalLibraryOfScotland/medical-history-of-british-india huggingface dataset:
0012
unconsciously, have operated in the direction of including within the serum
group the milder, to the exclusion of the severer, cases of plague." They
therefore believe that these statistics "do not afford any conclusive evidence of
the efficacy of Lustig's serum."
The Bombay Municipal Corporation having resolved to start the manufac-
ture of Lustig's serum on the spot, work was begun with five horses on the
1st of November 1898. Drs. Galeotti and Polverini were in charge of the labo-
ratory and Professor Lustig himself came to Bombay in January 1899 to see
its working and found it "completely satisfactory in every regard." Later in
the year Dr. Galeotti had to return to Italy, when Dr. Polverini, his assistant,
assumed charge and with the assistance of Dr. A. Mayr was responsible for
the production of the serum till the close of the Municipal Laboratory in June
1902. Dr. A. Mayr has kindly written out a clear statement of the methods
used by them in the immunisation of the horses ( vide Appendix A), which is
most valuable as giving the results of the experience accumulated in this matter.
The first trial of Lustig's serum as locally manufactured in Bombay was
made in the period from February to April 1899, and relates to 403 serum-
treated patients admitted to the Arthur Road Hospital under the care of Dr.
Choksy.
"In this series of observations only patients admitted in the acute stages
of the disease and in a non-moribund condition were treated with the serum.
The residuum of patients admitted to the hospital during the corresponding
period was, as in the series of observations that have just been considered, taken
as control." 24 The result was as follows :—
Cases.
Deaths.
Case-mortality,
per cent.
Control group
.
.
.
.
.
1,190
957
8 0 . 4 2
Serum
,,
.
.
.
.
.
403
249
6 1 . 7 3
It has been contended that the method of selection was a fair one, not tending
to the taking of a milder type of case for serum treatment; and that therefore
comparison with the control group is permissible. But on the other hand the
Indian Plague Commission point out that the exclusion of moribund patients
from the serum group is in fact substituting a set of patients with a case-mortality
of between 64 and 65 per cent. for one with a case-mortality of 100 per cent.,
and therefore to that extent lowering their death rate. Secondly, they remark
that it is not correct to compare the case-mortality of the Modikhana and
Maratha plague hospitals where serum was not used, with the control cases of
the Arthur Road Hospital, because, as only 25 per cent. of the total patients
13
admitted to the latter institution were chosen for serum treatment, an opportunity
was not afforded for an appreciable increase in case-mortality in the large number
of cases not so treated. They, therefore, conclude that this second series of
observations cannot be regarded as affording conclusive evidence of an advantage
accruing from serum treatment.
The third series of observations made at the Arthur Road Hospital is dealt
with at length by Mr. Haffkine in his report ( vide p. 28) and need not therefore
be referred to here.
In the other hospitals in Bombay, Lustig's serum was used as follows 25: –
MARATHA. HOSPITAL.
SERUM TREATMENT.
ORDINARY TREATMENT.
Difference
in lavour of
serum group,
per cent.
No. Deaths.
Case-
mortality,
per cent.
No. Deaths.
Case
mortality,
per cent.
1898, selection...
28
17
60.71
. . .
...
80 7
20.0
Nov. 1900 to Jan. 1901, selection 38
32
84.21
...
. . .
88.8
4.59
August to December 1901,
,,
44
31
70.45
203
161
79.31
8.86
April and May 1902, alternate
. 31
31
100.0
31
29
9 3 . 5 4
Nil.
In the first three sets of cases noted in the above table a process of selec-
tion was in force, which, however impartially applied, always precludes the
possibility of arriving at a perfectly definite conclusion. The fourth set of cases,
marked alternate, were under the supervision of Dr. A. Mayr, and formed a
series treated in serial succession with Lustig's and Roux's serum and ordinary
symptomatic treatment. With regard to these cases, Dr. Choksy remarks: 26
"The 31 cases under Lustig serum included 16 septicæmic cases, 2 were
received dead in their turn, and 3 non-septicæmic cases who were not injected
because they were moribund. Thus 21 cases became excluded as incurable
and there remained only 10 cases fit for treatment, all of whom died. Of the
31 Roux's serum cases 15 were septicæmic, I was received dead, and 2 non-
septicæmic cases were not injected because thy were moribund. Thus 18
cases were excluded, and of the 13 who remained, 2 recovered. There were
13 septicæmic cases among those under ordinary English treatment, and no
cases were received dead. Of the 18 thus remaining 2 recovered— one a semi-
convalescent case and another a mild case." He further notes that life was
prolonged noticeably in the serum treated cases.
In the Parel Old Government House Hospital in 1898 with Dr. Clemow in
charge, 13 cases "not selected in any way" were treated. "Every alternate
case of plague admitted to the wards, provided the diagnosis was certain and
14
the patient not absolutely moribund, was submitted to the injections."2 7
O f t h e s e
10 died, which is equivalent to a case-mortality of 77 per cent. These cases
were injected by Drs. Galeotti and Polverini with Florence-made serum.
In the Modikhana Hospital in 1900 a fairly extensive trial of Lustig serum
as made in Bombay was carried out by Dr. D. A. Turkhud, M.B. (Edin.), in
charge of that plague hospital. The method of selection was as follows :—
All acute cases of plague, about the diagnosis of which there could be no
doubt whatever, were taken for the trial, and each alternate case in the order of
admission into the ward, was taken for serum treatment. The following classes
of cases were not used either as controls or for serum treatment: ( a ) Convales-
cent plague cases; (b ) C a s e s a d m i t t e d i n t o t h e o b s e r v a t i o n w a r d a s b e i n g a t
that time not recognisable as certainly plague cases.
In these two categories 43 cases are included and it has been contended 2 8
that in excluding patients who on admission were "doubtful cases" of plague,
an unwarrantable interference with the alternate system was brought about.
But, as pointed out by Dr. Turkhud, had these cases been taken for serum
treatment when the diagnosis was arrived at after a day or so in hospital, it
might have been said that they were put under treatment too late, and anyhow
as the cases were left out of account altogether it does not appear why this
procedure should favour one side more than the other. The following shows
the result :—
MODIKHANA HOSPITAL.
Cases.
Deaths.
Case-mortality,
per cent.
26TH JANUARY TO 27TH FEBBUARY 1900.
Serum patients..
.
.
66
54
81.81
Control
„.
.
.
66
48
7 2 . 7 2
Observation ward patients.
. .
43
32
74.41
Excluding 30 cases dying within 30 hours of admission, the doses adminis-
tered varied from 20 c.c. (in one case) to 160 c.c. ; the average working out
at 49.4 c.c. for each case. Eleven cases received 100 c.c. or above.
In view of the unfavourable results obtained in this hospital, the following
criticism was made by Dr. Polverini,29
viz . :— (a ) That the alternate system
was not strictly observed. ( b ) That the serum was not given regularly or at
proper hours. ( c) That the doses were insufficient. ( d) That the total quantity
said to have been used was in excess of that supplied to the hospital. The first
heading has already been dealt with. As to ( b ) and ( c) Dr. Turkhud says, 30
" It is true that I was never, owing to other work, able to give the morning
15
injections before 8 o'clock," but otherwise the serum was administered regularly,
and in accordance with the instructions given by Dr. Polverini at the time as
regards dosage and method of injection. As to ( d) it appears some error must
have been made in the laboratory, for the amount used in the Modikhana Hospital
corresponds to the amount noted by Dr. Polverini in his own letters as having
been sent.
The only other cases treated with Lustig's serum in the Bombay hospitals
were eight in the Parsi fever hospital in 1899-1900, of which five died and three
recovered; and two selected cases treated in the Modikhana Hospital in 1901,
of which one died.
Yet one other attempt was made to treat patients with Lustig's serum on
the alternate plan. The operations were under the direct supervision of Major
W. E. Jennings, M.D. (Edin.), D.P.H., I.M.S., and carried out by Dr. C. T. Costello
at the Poona Plague Hospital. The experiment was begun on the 4th of
February 1902 and continued for a month, during which time 60 patients were
admitted to the hospital. Of these, five were not taken for the experiment for
the following reasons: three were "practically dead" (two of whom should have
been taken for serum treatment, and one for the ordinary treatment); one was a
patient almost quite recovered who was transferred from another plague hospital
on its closure; one was the son of a ward servant living on the premises about
whose illness there was some doubt and who, moreover, had suffered from plague
two years previously.
The exclusion of these cases in no way vitiated the test, as they were
regarded for this purpose as non-existent, and the next admission taken for
serum or ordinary treatment as the case might be. The fate of the remaining
55 patients is shown in the following table :—
Cases.
Deaths.
Case-mortality,
per cent.
Serum cases.
.
27
21
77.7
Control ,,
.
. .
28
20
71.4
The serum was given hypodermically and the amounts varied from 40 c.c.
to 1210 c.c.; the average administered being 348.5 c.c. Four patients received
less than l00 c.c.; nine received between 100 and 200 c.c.; two received between
200 and 300 c.c.; two received between 300 and 400 c.c. and 10 received 400
c.c. and above. The patients in the serum group received also the ordinary
symptomatic treatment.
16
A capsule of blood was taken from each patient on admission, and sent to
the Plague Research Laboratory, Bombay, where it was examined by culture and
injection into animals. The results are shown below :—
PLAGUE BACILL
Percentage of cases
in which found.
No examination
as the capsule was
broken when
received.
Found in
Not found in
Serum cases, 27 .
.
7
19
25.9
1
Control cases, 28
.
12
13
42.8
3
It will be noticed that the control patients showed a much larger number of
septicæmic cases on admission than the serum group of cases. It is certain
therefore that if there was any difference in the gravity of the cases in the two
groups of patients, the control group had the larger number likely to have a
fatal ending; for Captain E. D. W. Greig, M.B., B.Sc., I.M.S., proved,
about this time, from the examination of 132 plague cases in Bombay, that
the case-mortality of septicæmic cases is extremely high (97.6 per cent.) while
those in which bacilli are not present in the blood at an early period of the
disease, have a case-mortality less than half of this (44.1 per cent.). 31
The serum treatment appeared to have had no effect on the symptoms.
The average duration of illness was longer in the serum cases by 30 hours;
but this is largely accounted for by the chance that one serum case survived for
18 and another for 8 days. It is always difficult in small groups of cases to
apportion correctly cause and effect.
Cases in Private Practice.
In Dr. Choksy's papers on the "Treatment of Plague with Professor
Lustig's Serum," 32t h e r e i s p u b l i s h e d a n a c c o u n t o f 1 3 0 c a s e s o f p l a g u e t r e a t e d
by himself and other medical men in their private practice.
The following shows the results :—
Cases.
Deaths.
Case-mortality,
per cent.
Dr. Choksy's cases.
.
.
74
40
54.05
Cases in others' practice.
.
.
56
18
3 2 . 1 4
Total cases treated.
1 3 0
58
44.61
17
The difference in these two sets of figures may be accounted for on the
supposition that Dr. Choksy being rightly regarded as an expert in plague, was
called in consultation to see cases where the treatment of others had failed.
As regards the effects of early treatment on these private patients, Dr.
Choksy remarks :—" Of the 26 patients treated on the first day of illness,
4 succumbed and 22 recovered, whereas, of the 34 treated on the second day,
20 died and 14 recovered. The mortality rate in the former case being equiva-
lent to 15.38 per cent. only, as against 58.82 among the latter. And this clearly
indicates what a few hours delay would mean in the treatment of such a rapidly
fatal infection as that of plague."
The clinical effects noted by Dr. Choksy in these cases are much the same
as those already described by Mason, Simond and others ( vide supra ), viz. :
rising temperature was arrested in its upward course, and fell more rapidly than
usual ; buboes became hard and painless, and subsided without suppuration.
The general condition was improved, the mind became clearer, " hardly any
nervous prostration or enfeeblement of the circulation could be noticed ; sleep
became natural and the patient was generally cheerful, scarcely realising that he
was afflicted with such a grave infection as plague." These remarks, however,
apply only to cases treated on the first day of the illness, those injected on and
after the second day did not show the same amelioration of symptoms, " the
course of the disease was not always shortened and suppuration of the buboes
was the rule."
Terni's Serum.
Early in 1901 two small samples of this serum were received from the
Secretary of State for India, and from Messina direct. As only a small amount
of serum was received, Mr. Haffkine suggested that it should be tried on a
few " serious plague cases."
This was accordingly done at the Maratha hospital on 8th February 1901,
the patients being chosen by Mr. Haffkine and a Committee of three medical
men.
The first patient was a man aged 25, in the fourth day of the disease, with
temperature ranging from 102.8° to 103.2° F., pulse 108, feeble, respirations 24
per minute. Bubo in left groin, painful and œdematous. Plague bacilli were
present in the bubo, not in the blood. He got at once 61¾ c.c. of serum
hypodermically, but this had no effect on temperature, pulse and respiration.
In the afternoon of the same day he got 38 c.c. more of serum. Next day he
was quiet and collapsed, with slight cough due to commencing pneumonia. He
died on the 10th February, the serum having apparently had no effect whatever..
D
18
The second patient was a male, aged 35, admitted to hospital on the 11th
February 1901 in the second day of illness and treated on the 12th idem. The
patient was a strong man, quite sensible, and a markedly milder case than the
former one. Temperature ranged between 101.2° and 102.8º F., pulse 132
fairly strong, respiration 25 per minute. Bubo in left femoral region, painful
and œdematous. Plague bacilli were present in the blood as well as in the bubo.
He was given 59 c.c. of serum. Four hours afterwards he had a severe
rigor of short duration, during which the temperature fell to 97.8° F. The
temperature shortly after rose to 103° F. At 5 P.M. on the same day 60 c.c.
of serum was injected, but the man died 1½ hours after.
The history of the only other cases treated with this serum is given in
detail by Mr. Haffkine and Dr. Costello in the body of this report ( vide p. 37),
so it is necessary here to give information only as to its manufacture.
In a summary describing his methods forwarded with a letter, dated from the
Institutio d' Igiene, Messina, 27th October 1901, Dr. Terni says that having
found the benefit of using virulent cultures when preparing a vaccine for plague,
he "proposed to produce the vaccinating material directly in the bodies of
animals (guinea-pigs and monkeys) by injecting cultures in glycerinated bouillon
(3 per cent.) into the peritoneal cavity. In this manner an abundant exudation
is obtained, which is very rich in bacilli, and in toxic and anti-toxic substances
produced in the lymphatic cavity, similar to those obtained from a plague bubo.
The material is rubbed up with a sterile solution of 0.75 per cent. sodium chloride,
and 1 per cent. of sodium carbonate to prevent coagulation. It is then exposed
to fractional sterilization at 55 to 58° C. and then 0.5 per cent. of carbolic acid
is added. The exudation which is obtained is thready, almost gummy, very
different from the pus produced by pyogenic or other microbes of infection ;
and this characteristic suffices to indicate that no other germs have penetrated,
even before the bacteriological examination necessary to guarantee the purity of
the material."
With this material used as a vaccine Dr. Terni reports good results from
Rio-de-Janeiro, and he used it accordingly to immunise the animals destined to
furnish his curative serum. He says : "As to the serum, having proved that
horse serum is absolutely ineffective, because it does not destroy the toxines
and proteines of the plague bacillus, or only in very small proportions ; and that
injection produces in the blood scarcely any of those anti-bacterial and antitoxic
substances which are useful as curatives ; and after many attempts to produce a
more active serum with animals of different species, I have used by preference
mules and cattle. These were injected intravenously with the peritoneal exuda-
tion produced as for the preparation of the vaccine. The material is collected,
rubbed up with sodium chloride and sodium carbonate, filtered through a sterile
19
metal sieve with a mesh of 0.1 m.m., or through a piece of sterilised cloth.
It is inoculated intravenously in increasing quantities, beginning with 5 c.c., and
the animals then give a serum of exceptional curative value."
Brazil's Serum.
A trial consignment of this serum was received through the Secretary of
State for India towards the end of 1902. The consignment consisted of
36 sealed test tubes of serum, but unfortunately only 8 were found fit for
use on opening the boxes.
Under Mr. Haffkine's directions two cases were chosen " of a typically
severe type, in order to avoid such as might recover under treatment without
serum." One received hypodermically 66 c.c. of serum, the other t 10 c.c. Both
died, and no evidence was found either clinically or otherwise of benefit attri-
butable to the serum treatment. Both were treated in the Modikhana Hospital,
under the observation of Dr. Costello.
In August 1903 another consignment of 600 tubes was received with which the
trial reported on by Mr. Haffkine and Dr. West was made. ( Vide p.47.)
The mode of preparation of this serum is thus described by Dr. Vital
Brazil, Director of the State Serum Institute, San Paulo, Brazil33
:—
" The immunisation of the animals began in the middle of November 1899
soon after the appearance of the plague in the port of Santos. The animals were
prepared in the following way : — (1) by the injection of cultures killed by heating
to 60° C., the doses being gradually increased ; and (2) by the injection of living
cultures in doses gradually increasing in amount and virulence.
Experimentally the serum showed both preventative and curative action,
the animals experimented on being guinea-pigs, rats and rabbits. A dose of
0.5 of a cubic centimetre of serum was found sufficient to protect a guinea pig
weighing 500 grammes against an injection of virus which produced the death
of an unprotected guinea-pig in four days."
SUMMARY.
The trials of curative serum above described, and those more elaborately
dealt with in the subsequent part of this report relate to all the cases treated
in India up to May 1904, as far as they are known to the writer.
They may be conveniently divided into two categories :—
(a) Those in which the conditions of trial were reasonably accurate, and
where a series of control patients strictly comparable with those
treated with serum was available ; and
(b) Those in which though the records of the serum treated cases may
be accurate, yet the control patients, where such are reported,
D 2
20
were not in all respects strictly comparable for one reason or
another with those receiving the serum treatment.
The tables I and II below show at a glance the results obtained in each case.
TABLE I.—Conditions as in (a)
SERUM CASES.
CONTROL CASES.
No.
Deaths.
Re
-coveries.
Case-
mortality,
per cent.
No.
Deaths.
R e - c o v e r i e s .
Case-
mortality,
per cent.
Roux Yersin serum by Indian
Plague Commission (Banga-
lore).
49
3 1
18
63.26
54
29
25
5 3 . 7 *
Roux Yersin serum by Indian
Plague Commission (Bom-
bay).
28
23
5
82.14
2 8
24
4
85.7
Roux Yersin serum by Russian
Commission (Parel).
50
40
1 0
8 0 . 0
5 0
40
10
8 0 . 0
Roux Yersin serum by Dr.
Mayr (1902).
31
29
2
93.54
31
29
2
93.54
Roux Yersin serum by Dr.
West (Bombay).
68
45
23
66.17
68
41
27
60.29
TOTAL TREATED WITH ROUX
YERSIN SERUM.
226
168
58
74.33
231
163
68
70.56
Lustig's serum (Dr. Turkhud,
1900).
66
54
12
81.81
66
48
18
72.72
Lustig's serum(Dr. Mayr, 1902)
31
3 1
...
1 0 0 . 0 †
31
29
2
93.54
Lustig's serum (Poona, 1902).
27
21
6
77.7
28
20
8
71.42
Lustig's serum, 3rd series
(Bombay).
484
330
154
68.18
484
385
99
79.54
TOTAL TREATED WITH L
US-TIG'S SERUM.
608
436
172
71.71
609
482
127
79.14
TERNI'S SERUM
1 1 0
89
21
80.90
1 1 0
90
20
8 1 . 8 1
Brazil's serum (Maratha hos-
pital).
50
41
9
82.0
50
45
5
90.0
Brazil's serum (Modikhana
hospital).
20
17
3
85.0
20
15
5
7 5 . 0
TOTAL TREATEDWITH
BRAZIL'S SERUM.
70
58
12
82.85
70
60
10
85.71
* But vide p.7 supra, for details of comparison.
† Vide Dr. Choksy's remarks, p, 13, supra.
21
TABLE II.—Conditions as in (b).
SERUM CASES.
CONTRASTING CASES.
No.
D e a t h s .
Re-
cover i es.
Case-
mortality,
per cent.
No.
Deaths.
Re-
coveries.
Case-
mortality,
per cent.
Cases treated by Yersin in
private.
50
17
33
34.0
No contrasting cases.
Yersin's serum in Parel Hos-
pital.
23
14
9
60.86 General Hospital Mortality. 64.5
Yersin's serum in Charni Road
and Sahib's servants hosp
i-
tals.
8
5
3
62.5
86
62
24
72.1*
Roux Yersin serum by Ger-
man Commission.
26
13
13
50.0
No contrasting cases.
Roux Yersin serum by Cap-
tain Mason.
1 0 0
59
41
59.0
1 0 0 83
17
8 3 . 0 †
Roux Yersin serum by Dr.
Simond (Karad).
32
21
11
65.6
No contrasting cases.
Roux Yersin serum by Dr.
Simond (Karachi).
70
37
33
52.8
74
55
19
7 4 ‡
TOTAL TREATED WITH R
OUX YERSIN SERUM.
309
166
143
53.7
260
200
60
76.9
Cases treated by Professor
Lustig (Bombay and Poona).
30
6
24
20.0
No contrasting cases.
Lustig's serum, by Dr. Cle-
mow (1898).
13
10
3
77.0
No contrasting cases.
Lustig's serum, first series
(Bombay).
257
145
112
56.4
752
595
157
7 9 . 1 §
Lustig's serum, second series
(Bombay).
403
249
154
61.78
1,190
957
233
8 0 . 4 2 | |
Lustig's serum, Maratha hos-
pital, 1898 and 1900-01.
66
49
17
74.2¶General Hospital mortality 80.7 & 8 8 . 8
Lustig's serum, Maratha Hos-
pital, 1901.
44
31
13
70.45¶ 203
161
42
7 9 . 3 1
Lustig's serum in private prac-
tice.
130
58
72
44.61
No contrasting cases.
TOTAL TREATED WITH LUS-
TIG'S SERUM.
943
548
395
58.1
2,145
1,713
432
7 9 . 8
TERNI'S SERUM (1901)
2
2
. . .
1 0 0 . 0
No contrasting cases.
BRAZIL'S SERUM (1902)
2
2
...
1 0 0 . 0
No contrasting cases.
* Total mortality in this hospital.
† But vide p. 3 supra for details.
‡ But vide p. 5 supra for details.
§ But vide p. 11 supra for details.
|| But vide p. 12 supra for details.
¶ Selection method.
From a study of these tables it is evident that we have to deal with a
remedy much less effective than serum proves itself to be in the case of diph-
theria. This was recognised early in these trials, and it became necessary