NationalLibraryOfScotland/medical-history-of-british-india huggingface dataset:
76
Scientific Memoirs by Medical Officers of the Army of India.
On Great Coco Island, which lies northward of the Andamans and is about
six miles long and about a mile and a half in greatest breadth, and is covered for
the most part with dense jungle, I, on two occasions and in different spots, saw a
crow-pheasant that appeared to be incapable of flight, as it made its escape by
running ; and it occurred to me that these birds might belong to a flightless
island race, in accordance with the explanation given by Darwin.
I still adhere to this opinion, and hope that some "Investigator" Natural-
ist will follow up these observations, It has been said that on the neighbouring
islet known as Table Island, the crow-pheasants have a particularly strong flight.
If this is so, it affords a sort of "control" experiment ; for Table Island, which
has an area of less than half a square mile, has been largely cleared of jungle for
the sake of the light-house, and on a very small island, deficient in cover, one
would expect the birds to be strong rather than weak flyers.
On Pitti Bank, which is a little uninhabited sand-cay of one of the most
submerged of the Laccadive atolls, we found, at the end of November 1891,
vast swarms of a large spescies of sea-tern breeding. There were nestlings in
every stage, but no eggs. Both old and young birds were quite free from fear,
the old birds, almost alighting on our shoulders as we landed, and the young
birds even those with their first plumage complete, submitting to capture without
any resistance. Dreadful havoc had been wrought among the young birds, chiefly
by large Cœnobite hermit-crabs, with which the islet swarmed, but also to some
extent by Ocypoda ceratophthalma. The young broods were simply huddled
together on the ground, without any sort of nest, so that in the absence of the
parents they were at the mercy of the crabs. Judging from the bones and
sprouting quills that covered the ground, hundreds of young birds must have
perished, and in several cases we saw recently killed bodies lying under a living
mound of voracious crabs.
On the Ganjam coast I once was witness to a remarkable exhibition of
sympathy on the part of some Brahminy Ducks. One out of a flock had been
shot, and fell, with only a wing broken, into a sheet of water, whereupon the
whole flock stopped and hovered, and one individual flew down and settled by
its wounded mate. Hume and Marshall, as Mr. Finn informs me, have recorded
similar instances of noble behaviour on the part of the Mute Swan, the Gray Lag
Goose, the Bar-headed Goose and the common Teal.
Some observations on Spirillum Fever, as seen in the Monkey.
Macacus Radiatus.
GEORGE LAMB, M.B., (GLASG.).
CAPTAIN, I. M. S.
(From the Research Laboratory, Bombay )
.
It has long been known that monkeys are susceptible to infection with the
spirillum of Obermeier, and that an injection of fresh material containing this
spirillum, whether taken from man or monkey, produces in this latter animal an
attack of fever fairly analogous to that which occurs naturally in the human su
b j e c t .
These facts were first demonstrated by Carter1 working in Bombay in 1877
and have since been confirmed by Koch and other observers. Moreover, since
the date of Carter's original publication spirillum fever as seen in the monkey,
artificially infected, has been carefully studied by many investigators with a view
to throwing more light on its pathology and especially with a view of building up
a theory as to the cause of the crisis and of the relapses, both of which phenomena
are such distinctive features of this disease in man. I shall have occasion to
refer to these observations later on.
Carter's observations 2 on spirillum fever in artificially infected monkeys are
briefly summarised as follows :—
(1) Out of 33 attempts to infect monkeys with fresh blood containing
spirilla he had 9 failures, i.e. , 73 per cent. of successes. Of these
9 failures, 6 injections out of a total of 22 were made with human
material, while 3 out of II inoculations were made with monkey's
blood.
(2) The mean duration of the incubation period he puts down to be from
3 ½ to 4 days, its range from 1 ½ to 5 days.
He also shows that there is a period immediately prior to the onset of
fever, during which spirilla in small numbers can be found in the
blood stream.
(3) The duration of the specific pyrexia he found to range between ½ and
3 ½ d a y s , t h e m e a n b e i n g2 d a y s . P y r e x i a w a s a l w a y s t e r m i n a t e d
by crisis.
7 8
Scientific Memoirs by
(4) A relapse was rare. He observed this to occur only in two animals
out of a total of 24 cases observed throughout.
(5) He states that no immunity seemed to follow an attack of this fever, as
monkeys inoculated with fresh spirillum material two or three
weeks after the crisis, went through a second specific attack in no
way different from the primary attack.
I have been able for the most part to confirm these observations and to
further extend them in several directions. That they require, however, some
modifications will be apparent from the results of the experiments which I have
now to put on record.
I have notes of 29 primary inoculations of spirillum material in the monkey.
Eight of these inoculations were made with human blood and 21 with blood taken
from other monkeys. The blood injected was collected at different times during
the course of the specific fever and always contained actively motile spirilla.
The quantity used in each case varied from 0.25 to 4 c.c. When human
blood was the material employed, it was taken, by means of a sterile syringe,
from the median basilic vein and injected into the monkey immediately after
withdrawal. When the material was got from a monkey, the blood was collected
by means of a canula inserted into the brachial, carotid or femoral artery : it
was received into a test tube containing a solution of citrate of soda 3 so as to
prevent clotting : it was injected always within 15 minutes after its withdrawal.
In two instances intra-peritoneal injection was employed : in all other cases
the material was inoculated subcutaneously in the pectoral region.
Out of 29 inoculations there were 5 failures, thus giving 83 per cent. of
successful infections. Three failures out of 8 attempts followed injection of
human material, i.e., 63 per cent. of successes, while there were 2 failures out
of 21 inoculations with monkey's blood, i.e., 91 per cent. of successes.
No explanation can be offered to account for all the failures that occurred.
That they were not due to a permanent natural resistance possessed by the
monkeys under experiment, is shown by the fact that all these animals were
attacked with the characteristic fever as a result of a second inoculation of
spirillum blood, at intervals ranging from 8 to 15 days after the unsuccessful
injection. In the case of one of the failures when monkey's blood was employed
as inoculation material, a diminution in the virulence of the spirilla as a result of
" passage " through a series of these animals can be brought forward, as we
shall see later, as an adequate explanation. But neither this explanation nor
that of an insufficient dose can account for the other unsuccessful attempts. For
in the second abortive case, when monkey's blood was used, the same amount of
material injected from the same syringe gave rise to a typical attack of spirillum
Medical Officers of the Army of India.
79
fever in a fresh monkey. Further, in the failures when human blood was employ
ed, the blood was taken in all instances from patients who were in the same
stage of the disease as those who had furnished the material for the successful
inoculations. Moreover, the blood in all cases contained actively motile spirilla.
Incubation period.— When the material was inoculated subcutaneously,
the incubation period was found, with one exception, to range between 2 and
4 days ; on this exceptional occasion, however, it was as long as 8 days. In 27
observations the mean time was found to be about 2½ days. There seemed to be
no relation between the amount of blood injected and the duration of the incuba-
tion period. Intra-peritoneal injection shortened the period of incubation con-
siderably. On the two occasions on which this method of inoculation was prac-
tised, spirilla were found in the blood within 18 hours and fever occurred within
36 hours after the injection.
I was also able to confirm Carter's observation that there is a period prior to
the onset of fever during which the blood contains spirilla in small amount and that
this period varies considerably in length. Further, the duration of the incubation
period appeared to bear no relation to the duration nor to the severity of the
pyrexial attack which followed.
Pyrexial period.—Twenty-six attacks were observed carefully throughout.
In all these the duration of the illness was found to be briefer than the primary
attack in man, never exceeding 5 days, while the mean was 3 days.
On two occasions only was the duration of the pyrexial period observed to
b e l e s s t h a n 1 d a y . Th e s h o r t n e s s o f b o t h t h e s e a t t a c k s c a n b e e x p l a i n e d a s
resulting from the diminution in virulence which this spirillum undergoes by a
series of " passages " through monkeys.
Spirilla were found to be present in the blood during the whole time that
the fever lasted. At the beginning of the attack they were few in number ; they
increased in amount as the attack progressed until on the last day of the fever
they were as a rule present in enormous quantity. Just before the crisis on
many occasions, large clumps of spirilla were observed both in the hanging drop
preparations of blood and in the fixed and stained films made from the blood.
Pyrexia was always terminated by crisis, the temperature in some cases
falling quickly much below normal.
Relapse.— Relapses were carefully watched for in all instances, but a recrudes-
cence of the fever after a definite period of apyrexia was observed to occur only
in one case. This relapse followed an unusually severe attack of 5 days'
duration after an interval of 7 days of apyrexia. It lasted for one day.
V
80
Scientific Memoirs by
Accompanying the fever during the relapse spirilla were found in abundance
in the blood.
Mortality.—The mortality among monkeys is evidently low, as there was
only one death among 26 attacks which were observed throughout. This death
occurred in a weakly female monkey on the second day after the crisis.
Postmortem—no spirilla could be found in the blood, while sections of the
spleen showed them in abundance, both lying free and inside polynuclear white
blood cells.
Relative proportion of the polynuclear cells to the other varieties of white blood
corpuscles.
In most acute bacterial infections, a considerable alteration in the relative
proportion which the polynuclear cells normally bear to the other varieties of
white blood corpuscles has been noticed. A similar alteration would, therefore,
be expected to occur in spirillum fever. With a view of investigating this ques-
tion, an estimation of the different kinds of white cells relatively to each other
was made from day to day in the case of seventeen monkeys. The method
employed was the usual one of counting a total of from two to three hundred
white cells in a film of blood doubly stained with eosin and methylene blue, and
at the same time placing each cell under its particular category. In this way
approximately, if not absolutely, accurate results can be obtained.
The blood of the normal monkey contains polynuclear cells in a rela-
tive proportion of from 55 to 60 per cent. of the total number of white blood
corpuscles.
On the day before the onset of an attack of spirillum fever the proportion
of polynuclear cells is found to be considerably increased, in some cases to as
high as 85 per cent. of the total number of white cells.
On the first day of pyrexia in most cases this high percentage of polynu-
clear cells has already begun to decrease, although in a few instances it is still
maintained.
This diminution continues throughout the course of the fever until on the
last day of pyrexia the proportion of polynuclear cells to the large mononuclear
cells and lymphocytes has regained the normal.
Immediately after the crisis, enumeration shows that the polynuclear cells
have still further diminished in number, their relative proportion being at this
time often as low as 20 per cent. of the total number of white blood corpus-
cles.
Medical Officers of the Army of
India.
8 1
The average of the counts made in the 17 cases, in which the relative pro-
portion of the polynuclear cells to the other white cells was estimated from
day to day during the period of infection, may be tabulated as follows :—
Normal
monkey.
Day before on-
set of fever.
1st day of
fever.
Last day of
fever.
Shortly after
c r i s i s .
Polynuclear cells
...
...
... 55 to 6o%
78%
69%
58%
4 3 %
Large Mononuclear cells and Lymphocytes
...
... 40 to 45%
22%
31%
42%
57%
No relative increase in the number of the large grained eosinophilous cells
was at any time observed.
Diminution in virulence by " passage." —It has been incidentally mentioned
above that the spirillum of relapsing fever becomes diminished in virulence by a
series of " passages " from monkey to monkey.
The observations which I have made in connexion with this question are
detailed as follows :—
Experiment I.
(1) Monkey S-2 —Received 1 c. c. of blood taken from a patient on the
fourth day of fever. This blood contained abundant spirilla. The
animal suffered from an attack of spirillum fever of 5 days' duration,
which attack was followed after an interval of 7 days by a relapse
which lasted for 1 day.
(2) Monkey S-4— R e c e i v e d 1 c . c . o f b l o o d t a k e n f r o m m o n k e y S . 2 o n t h e
day of relapse. It suffered from a typical attack of spirillum fever
of 3 days' duration.
(3) Monkey S-7 —Received l c. c. of blood taken from monkey S-4 during
the height of the fever. It also had an attack of spirillum fever
of 3 days' duration and died 2 days after the crisis. This animal
was a weakly female monkey, previously referred to.
(4) Monkey S-9 —Received 1 c. c. of blood taken from monkey S-7 on
the second day of fever. An attack of spirillum fever of 3 days'
duration resulted.
(5) Monkey S-10—Received 1 c. c. of blood taken from monkey S-9 on
the second day of fever. As a result an attack of spirillum fever
of only 2 days' duration ensued.
82
Scientific Memoirs by
(6) Monkey S-11—Recei ved 1 c. c. of bl ood t aken f r om monkey S- 10 on
the second day of fever. A short attack of spirillum fever of less
t h a n 1 d a y ' s d u r a t i o n r e s u l t e d . T h e s p i r i l l a w e r e p r e s e n t i n t h e
blood only in small quantity during the pyrexial period.
Experiment 2.
(1) Monkey S-14—Received 2 c. c. of blood taken from a patient on
the second day of the first relapse. It suffered from a typical attack
of spirillum fever of 2 days' duration.
(2) Monkey S-8 —Received 2 c. c. of blood taken from monkey S-14 on
the first day of fever. A severe attack of spirillum fever of 4
days' duration resulted from this inoculation.
(3) Monkey S-17—Received 2 c. c. of blood taken from monkey S-8 on
the fourth day of fever. It also suffered from an attack of spiril-
lum fever of 4 days' duration.
(4) Monkey S-19—Received 2 c. c. of blood taken from monkey S-17 on
the fourth day of fever. The attack of spirillum fever in this case
lasted for three days.
(5) Monkey S-20—Received 2 c. c. of blood taken from monkey S-19 on
the first day of fever, at which time there were abundant spirilla
in the blood. The duration of the attack of spirillum fever result-
ing from this inoculation was 2 days, and at no time were
spirilla abundantly present in the blood.
(6) Monkey S-21—Received 1.5 c. c. of blood taken from monkey S -20 on
the second day of fever. As a result this monkey did not suffer
from any fever nor were spirilla found in the blood at any time.
Ten days afterwards it was inoculated with spirillum material taken
from another monkey. As a result of this inoculation it went
through a typical attack of fever, associated with abundant spirilla
in the blood.
Experiment 3.
(1) Monkey S-23—Received 2 c. c. of blood taken from a patient on the
fourth day of the disease. It suffered as a result from fever of
4 days' duration. Spirilla were found abundantly present in the
blood during the pyrexial stage.
(2) Monkey S-21—Received 4 c. c. of blood taken from monkey S-23 on
the second day of pyrexia. Spirilla were plentiful in the blood at
this time. An attack of spirillum fever of only 2 days' duration
resulted.
Medical Officers of the Army of India.
83
(3) Monkey S-22—Received 4 c. c. of blood taken from monkey S-21 on
the second day of fever. Only slight fever of less than 1 day's
duration ensued. During the pyrexial period only a very few
spirilla were found in the blood.
It may be added that in all my experiments, monkey S-22 and monkey
S-11, cited above in experiment 2, were the only two cases in which the attack
was limited in duration to 1 day.
From the data collated above there can, therefore, be no doubt that this
spirillum is quickly diminished in virulence by a series of " passages " from mon-
key to monkey. From lack of opportunity, no experiments were made with a
view of ascertaining whether the virulence for man was also diminished by such a
series of " passages " through the monkey.
Immunity following one attack of spirillum fever.—Attention has been al-
ready drawn to the fact that Carter considered that no immunity was conferred
on monkeys by one attack of spirillum fever.
The data bearing on this subject, which I have now to present, clearly shows
that this opinion will have to be modified.
Fourteen monkeys were re-inoculated with spirillum blood at varying inter-
vals of time after recovery from a primary attack of fever.
In nine instances this interval varied from 3 days to 3 weeks. Of these nine
monkeys only one suffered from a second attack. In this case the first attack
had been a very mild one. The interval between the crisis and the second inocu-
lation was only 3 days . On the other hand, re-inoculation with spirillum blood
in another monkey at the same interval of time after the crisis, i.e., 3 days, was
unsuccessful.
It may further be added that in all cases fresh control monkeys were inocu-
lated with the same material and at the same time as these animals. These
controls received a much smaller quantity of blood than the others, viz., never
more than half, and sometimes as little as one-fifth, of the amount. They all
suffered as a result from a typical attack of spirillum fever.
In the case of the remaining five monkeys an interval of from 1 t o 3
months was allowed to elapse between the crisis of the primary attack and the
second inoculation. The quantity of material which these animals received was
a large one, ranging from 3 c.c. to 10 c.c. of blood. It was taken in two instances
from man and in the other cases from the monkey. As a result of this re-inocu-
lation four out of these five monkeys went through a second attack of fever.
These attacks were all mild and of short duration, viz., 2 days.
W
84
Scientific Memoirs by
From these experiments it is seen, therefore, that injection of spirillum
material within a period of 3 weeks after the crisis of the primary attack was
followed by a typical attack of spirillum fever in only 11 per cent. of cases, and
af t er a per i od of 1 mont h i n 80 per cent . of t he cases. Thi s l at t er number , i t
will be remembered, is practically the same percentage of successful injections
obtained as a result of inoculation of spirillum blood in fresh monkeys. It is
evident, therefore, that an attack of spirillum fever in a monkey confers protection
from a second inoculation, but that this immunity is lost after the lapse of a
short period of time, viz., about 4 weeks.
Further, by repeated injections of spirillum blood in increasing amounts at
short intervals of time, the duration of this period of immunity can be markedly
lengthened.
I have immunized several monkeys in this way. One example will serve to
illustrate the method employed and the results obtained :—
Monkey S-4.
7th December 1899. —Received 1 c. c. of spirillum blood taken from
another monkey.
10th December 1899. —
Suffered from an attack of fever accompanied
by spirilla in the blood.
11th December 1899. —
12th December 1899. —
19th December 1899. —Received 2 c . c. of spirillum blood taken from
monkey ; no resul t : 1 c. c. of t he same mat eri al caused a t ypi cal
attack of spirillum fever in a fresh monkey.
7t h January 1900.— R e c e i v e d 3 c . c . o f s p i r i l l u m b l o o d t a k e n f r o m
monkey : no result : 2 c. c. of same material caused a typical
attack of spirillum fever in a fresh monkey.
19th January 1900. —Received 6 c. c. of spirillum blood taken from
monkey ; no result : 2 c. c. of same material caused a typical
attack of spirillum fever in a fresh monkey.
1 0 t h F e b r u a r y 1 9 0 0 .
— R e c e i v e d 4
c . c . o f s p i r i l l u m b l o o d t a k e n f r o m
monkey, no result : 2.5 c. c. of same material caused a typical
attack of spirillum fever in a fresh monkey.
I7th February 1900.—Received 7 c. c. of spirillum blood taken from
monkey ; no result : 2 c. c. of same material caused a typical
attack of spirillum fever in a fresh monkey.
25th April 1900.—Received 4 c. c. of spirillum blood from a patient in
Arthur Road Hospital. This patient was in the middle of the
Medi cal Offi cers of the Army of Indi a. 8 5
primary attack, and his blood contained plentiful spirilla; no
result : 3 c. c. of the same material gave rise to an attack of
spirillum fever in a monkey, which 2½ months previously had
suffered from an attack of this fever, but which had not received
any inoculations of spirillum material in the interval.
Several monkeys have been treated in this way and with the same result.
The longest period in any instance which was allowed to elapse between the last
two inoculations was 2½ months. Further experiments may show that an
immunity of much longer duration than this could be conferred on monkeys
similarly treated.
Anti-bacterial properties of the serum and lymph of immune animals. —
We may now pass on to the consideration of the anti-bacterial substances
which are present in the serum and lymph of these immune animals, both in the
case of monkeys highly immunized by repeated injections of spirillum material,
and in the case of those which have recently recovered from a primary attack
of the specific fever.
The fact that such anti-bacterial substances make their appearance in the
blood as the result of spirillum infection in man and monkey was first demon-
strated by Gabritchewsky 4 . To his observations as well as to those of Bardach, 5
I shall have occasion to refer later on.
The presence of these substances can be readily demonstrated in vivo,
by employing a technique similar to that which Pfeiffer used to demonstrate the
same phenomena in the case of the cholera vibrio and the typhoid bacillus. The
method I used was as follows :
The blood, in which spirilla were present in very large numbers, was taken
by means of a canula from the femoral artery of a monkey on the second day of
attack, when the temperature was 105.6º F. It was received into a solution of
citrate of soda so as to prevent any clotting 6. One c. c. of this citrated blood
was then introduced in the usual way by means of a pipette, into the peritoneal
cavity of each of the monkeys under experiment. A small quantity of blood was
withdrawn at short intervals of time and examined ( a ) in a hanging drop prepar-
ation and ( b ) by fixing on a slide, removing the hæmoghlobin with acetic acid
and then staining with aniline gentian violet.
Using this method I made the following observations:—
(1) Injection into peritoneal cavity of monkey S-2. —This was a highly im-
munized animal which had received the last inoculation of spirillum material 8
days previous to the experiment now recorded. This inoculation consisted of 10
c. c. of blood taken from a patient on the third day of the first relapse.