NationalLibraryOfScotland/medical-history-of-british-india huggingface dataset:
Medical Officers of the Army of India
25
access of the specific toxin will be associated with access of a
certain number of the toxogenic organisms, which find a congenial
nidus in the contents of the intestinal tract, as modified by the
establishment of the choleraic condition.
5. The choleraic condition may be present in individuals whose intestinal
contents are devoid of any appreciable choleraic vibriones, either
actual or potential, because it does not necessarily follow that a
lethal dose of the toxin should invariably be accompanied by any
of its specific factors. Thus, alcoholic intoxication may certainly
be present quite apart from the coincident presence of any yeast
or other alcohologenic fungi within the digestive tract.
6. In cases of cholera, in connection with which unequivocal choleraic
vibriones occur within the digestive tract, the intensity of the
choleraic condition does not necessarily bear any direct ratio to the
numbers of vibriones which are present, because the intensity of the
condition is dependent on the dose of elaborated toxin and not on
that of the elaborating organisms.
7. Vibriones, presenting all the characteristic features of those ordinarily
associated with cholera, may be present in the water-supply or else-
where in the environment,without any coincident occurrence of cases
of cholera within the latter, because mere presence of choleraic
vibriones in a given medium or locality certainly does not neces-
sarily imply their capacity for manufacturing physiological products
of an invariable quality. It is a matter of common laboratory experi-
ence that the physiological properties of schizomycete organisms
may be very greatly modified by the nature of their environment, so
that the presence of organisms which are capable of manufacturing
toxins, under certain conditions, does not necessarily imply any such
coincident presence of their specific toxins, e.g., hemp, etc.
8 The artificial administration of perfectly distinct species of vibriones
may lead to the development of the choleraic condition, because
organisms of perfectly distinct nature may, under certain cir-
cumstances, give rise to the manufacture of one and the same toxic
material in their environment. Alcohol is produced not only by
various species of saccharomyces, but also by mucorinic fungi such
as Chlamydomucor racemosus, and the allied species which consti-
tutes the efficient factor in the so-called " Darjiling bread," the
ferment employed by the natives of the Eastern Himalayas. It
does not, therefore, necessarily follow that any one species of schizo-
mycete organism should be the essential elaborator of the choleraic
toxin. (The administration of yeast fungi or alcohologenic mucorinic E
26
Scientific Memoirs by
fungi, apart from the products which they are capable of giving
origin to in their environment, will not lead to .alcoholic intoxication.
The administration of the specific product will do so, but the
administration of the specific factors will not.)
9. Mere introduction of choleraic patients into a locality is, apparently, per
se, incapable of determining any general development of the disease
there, but may occasionally be the cause of cholera among those
who come into direct relation with the patients or their effects. The
introduction of choleraic cases into any given locality certainly nor-
mally implies coincident introduction of large numbers of the specific
factors of the choleraic toxin, and may occasionally imply the in-
troduction of a certain limited amount of the latter in elaborated
form. If the factors alone be introduced, the outcome will necessarily
depend on whether local conditions do, or do not, permit of their
continued existence and of their elaborating the specific toxin; if a
certain amount of the toxin be imported in elaborated form, it may
suffice to induce intoxication in a certain number of cases, but, apart
from coincident importation of the specific factors and the presence
of favourable local conditions, the number must remain strictly
limited.
1 0 . T h e r e c a n b e n o q u e s t i o n i n r e g a r d t o t h e p o s s i b i l i t y o f t h e o c c u r r e n c e
of variations in the physiological properties of schizomycetes and
other vegetable organisms when cultivated under different external
conditions. It has been already pointed out that we have a striking
example of such variation in phanerogamic plants in the case of
hemp, and all bacteriological experience agrees in indicating the
extent to which similar variations occur in connection with schizo-
mycete organisms.
11. The theory does not in any way exclude the possibility that com-
mensal conditions may exert an important influence, but merely
transfers the commensalism from the interior of the digestive tract
to the general environment. A striking example of the influence of
commensalism in determining the persistent vitality and multiplica-
tion of a choleraic vibrio has already been given in a previous paper,
and if commensalism can act in this way, there can assuredly be no
ground for denying that it may have the effect of influencing the
nature of the specific products elaborated in connection with growth.
Commensalism may, therefore, very possibly act in determining
local predisposition, not merely by favouring the continued existence
of choleraic schizomycetes, but by favouring the elaboration of
their specific toxins.
Medical Officers of the Army of India.
27
1 2 . O n t h e o t h e r h a n d , i t b y n o m e a n s n e c e s s a r i l y f o l l o w s t h a t , i n e v e r y
case, excessive dirt, and therefore an excessive schizomycete popu
-lation in a locality, should invariably render the latter specially sub-
ject to cholera. Certain schizomycetes certainly play a commensal
part in relation to choleraic ones; but, as certainly, others are
inimical to them, and, as Nägeli long ago pointed out, an excess of
putrefactive schizomycetes may possibly be unfavourable to the
continued vitality and multiplication of specific pathogenic ones.
Commas and Cholera.
Buchner and others believed in a mixed infection owing, not to infection by
commas alone, but by commas in association with some unknown micro-organism
locally developed in certain places under certain conditions.
Rumpf holds that, although commas are the specific cause of cholera, their
presence in the intestinal tract does not necessarily give rise to cholera or cho-
leraic diarrhœa, but only where some dyspeptic conditions are present;— that
is, individual predisposition is the primary cause. Vibrios, apparently harmless,
although closely resembling Koch's, have been found in rivers in Germany.
According to Metchnikoff, man under normal circumstances is not ordi-
narily affected by the microbe of cholera.
Metchnikoff on the ground of a single experiment out of those which he tried
on the human subject, and with the bacillus of Paris of 1884, and in which ap-
parently truly choleraic symptoms were developed, affirms that Koch's bacillus
must be regarded as the specific cause of cholera, and that epidemiological facts
must be made to fit in with this !
The evidence goes to show that administration of large quantities of Koch's
bacillus only occasionally is followed by the appearance of cholera, and that the
bacillus may be present in the evacuations apart from any choleraic symptoms.
Metchnikoff has observed that the presence of certain schizomycetes favour,
and of others, retard or destroy growth of commas on gelatine plates.
Metchnikoff regards the influence of accessory schizomycetes in the intes-
tinal tract as favouring the earlier stages of development of the commas there.
Metchnikoff believes the Versailles vibrios to be like Koch's choleraic ones
in the fact that with a favouring intestinal flora they can cause the disease.
There is abundant record of cases of cholera in which no appreciable
commas were ever present in the intestinal tract, and Klein long ago pointed out
that no correspondence exists between the severity of a case of cholera and the
number of commas in the evacuation, and hence the evidence of the choleraic
state being induced by intestinal manufacture of the toxin breaks down
entirely.
E 2
28
Scientific Memoirs by Medical Officers of the Army of India.
Facts :—1. Artificial administration of comma-bacilli very rarely serves to induce
cholera.
2. Commas may be present in the intestinal contents of those to whom
they have been administered without any evidence of the establish-
ment of the choleraic condition.
3. Cholera may be present apart from any evidence of commas in the
intestinal tract, and the numbers of vibrios and severity of the case
do not necessarily run- parallel.
4. The administration of different species of commas may be followed
by the development of the choleraic state.
5. The physiological properties of commas and other schizomycetes
may unequivocally vary very greatly under different circumstances,
and consequently the nature of the products to which they give rise
in the substratum must also vary greatly.
Notes on the Malarial Parasite as observed in the blood
during life, and in the tissues post-mortem, at Lahore,
Punjab.
BY
SURGEON CAPTAIN J. MURRAY, M.B.,
PROFESSOR OF PATHOLOGY, LAHORE MEDICAL COLLEGE.
So much valuable literature has appeared on the subject of the malarial
parasite within the past few years, and so much of an authoritative character
has been written by observers who have devoted a large part of their time and
energies entirely to this work, that some excuse is necessary for venturing
to publish a report on investigations that are necessarily comparatively meagre
and unimportant. My apology for doing so lies in the fact that, so far as I
know, no definite statements have as yet been made regarding the biological
characters of the parasite as met with in India, in the light of the compara-
tively recent work of Golgi, Marchiafáva, Bignámi, Mannaberg, and other
observers, chiefly of Italian experience.
From the time of the discovery by Laveran in November 1880, of the so-
called Plasmodium malariæ, up to 1885, it was generally held that the parasite
met with in all cases of malarial fever was the same, and that the various forms
described by Laveran were, in all probability, but protean varieties of one species,
the life history of which was not known. No morphological or biological
distinctions were noted between the forms associated with the various clinical
types of malarial fevers. In 1885, however, Golgi was able to detect the pre-
sence of a distinct type in ordinary tertian, and another in quartan fever.
He was also successful in tracing the development of the parasite from a very
minute to a large sporing body, and in proving that the sporulation of one
generation of the mature parasites coincided with the febrile paroxysm. Some
time later, Marchiafáva and Celli, Canalis and others, following the lines of
investigation origainted by Golgi, confirmed his results as regards simple tertian
and quartan fevers, and, in addition, succeeded in proving to their own satisfaction
and to that of most unbiased critics, that these parasites, in their turn, differed
from those of quotidian fevers, and of the grave forms of malarial intermittents
and remittents to which they gave the name of " Summer Autumn Fevers."
During this period of progress, Laveran, the discoverer of the parasite,
maintained his original position, holding that the organism did not differ suffi-
ciently in the various clinical types of fever to warrant its division into distinct
varieties or species. In his book " Du Paludisme, " published in 1891, he sums
up his observations on the point by the following remarks :—" Tous ces faits
30
Scientific Memoirs by
tendent à démontrer qu'il n'existe pas de rapport direct et constant entre les
formes sous lequelles les hématozoaires.se présentent dans le sang, et les mani-
festations cliniques du paludisme; ou peut dire seulement que certaines formes
parasitaires is observent plus souvent chez certains malades; les corpes en
croissant, par exemple, dans les formes de rechute et chez les cachectiques,
ainsi que je l'ai etabli depuis longtemps." Indian medical literature has, as far
a s I k n o w , p r o d u c e d n o r e p o r t o f a c c u r a t e i n v e s t i g a t i o n s o n t h i s p o i n t . D r .
Vandyke Carter, in his interesting and valuable article on the malarial parasite
(scientific Memoirs, 1887 ) agrees with Laveran as to the probability of the vari-
ous forms belonging to one species ; but it is noteworthy that, in the only pure
quartan case in his series he found no crescentic forms, while in all the others,
which were quotidian or irregular in type, he observed these forms. The
drawings (which accompany the article) of the parasites seen in the quartan
case, correspond also in their characters with the form of parasite described
by Golgi, etc., as characteristic of quartan fever. Since the date of this article
many observers have published short records of their work in various medical
papers, but, as far as the writer knows, no attempt has been made to confirm
or refute the results arrived at in Europe, as to the various species and the
relation they bear to the chief types of the disease.
During the past two years the writer has had opportunities of observing
many cases of malarial fevers, and, in all of a definite and well marked type, has
been able to distinguish the marked peculiarities and characteristic life history
which have been noticed in similar cases in Europe. Though an account of
these observations may add nothing to our knowledge of the biology of the
parasite and its relation to disease, it may perhaps possess some value as a
confirmation of work already done elsewhere, and as a further proof of the
constant characters which the parasite presents in all countries in which it has
been observed.
The investigations of observers in all parts of the world during the past
15 years, render it now unnecessary to enter into an argument as to whether the
bodies present in the blood in malarial fevers are of a parasitic nature or not.
The almost universal position of opinion on this point is very well expressed by a
recent remark of Dr. Patrick Manson that " if Laveran's body is not a para-
site, then it is a most wonderfully contrived device in Nature for deceiving the
pathologist. " I have therefore thought it better in this short note, not to give
a full list of the cases examined by me with notes on each ; but to take two or
three typical examples of each group in which there could be no doubt as
to the clinical type of the fever, and to record, in a systematic form, the results
of the examination of the blood, giving at the same time reproductions of
drawings made from these selected cases, outlined by the camera lucida
and coloured from nature. These I have endeavoured to make absolutely
Medical Officers of the Army of India.
31
faithful, as far as my indifferent powers of drawing permit, and can only
regret that the apparatus at my disposal during the past two years has not
been such as to enable satisfactory photo-micrographs to be made with the
high powers necessary. All the drawings of blood cells and parasites have
been made by the aid of a Natchet's or Abbe's camera lucida with a Zeiss 1/1:2"
objective (oil immersion), and the No. 4 eye-piece, so the magnification is con-
stant.
Quartan Fever.
Cases of simple quartan fever are comparatively seldom available for con-
tinued investigation. They do not often apply for indoor relief, partly, pro-
bably, owing to the fact that the general health may be fairly well preserved
throughout a long period, partly to the circumstance that a belief pervails
amongst certain of the people in this part of India that " chauthe din ke
bukhár " is not susceptible of cure by medicine. Several cases have been
examined amongst out-door patients, but the two following may be taken as
typical.
1 .
S i k a n d a r K h á n ,
P a t h a n , æ t . c i r c . 3 0 , a n a t i v e o f B a n n u . T h i s p a t i e n t
was admitted in March. 1895, suffering from anæmia with dyspnœa, irregu-
larity of the cardiac action and dyspepsia. He had a history of syphilis of
some years' standing, and of occasional attacks of intermittent fever ; in autumn
1894, he had suffered from what had apparently been an attack of quotidian
intermittent fever. On examination, the spleen was found to be enlarged, pro-
jecting about 3 inches below the left costal arch in the mammary line. On the
11th his blood was examined at 10 A.M. with the object of counting the cor-
puscles. Up to this time he had had no fever for some months. With the
Zeiss D. D. objective and No. 2 eye-piece, melanin-bearing bodies were seen ;
on examination by a higher power they were found to be fully developed
spherical parasitic bodies, many showing typical daisy-shaped sporulation as
described by Golgi. The patient was told that he would have fever within a
very short time, and instructions were given to take his temperature carefully
every few hours. It began to rise at about 11 A.M., and at 2 P.M. registered
102.8, at which it remained till 5 P.M., when it began to fall, and by 11 P.M.
was again normal. On the 12th and 13th he had no fever, on the 14th at 2-30
P.M., the temperature rose to 101·8 and again remained above normal till 11 P.M.
Quinine was now administered, in 15 grain doses of the sulphate, three times
a day, and the patient had no further febrile paroxysm, The blood was ex-
amined at regular intervals with the results given below. The patient was given
quinine, in 10 grain doses, thrice a day, regularly during the succeeding fortnight,
and had no return of the fever up to the date of his leaving hospital in
May. During this time he improved very much in general health, the spleen
32
Scientific Memoirs by
diminished in size, the oligocythæmia and aglobulia disappeared, and he left
perfectly recovered.
2. Faizi, sweeper-woman, æt. 50, a native of the Lahore district, May
1895. The former case was one of an attack of quartan fever observed from
the beginning, before the onset of pyrexia, this has been chosen as a contrast,
as the condition had lasted more than a year before the patient came
under observation. She was a comparatively feeble old woman who gave a
history of regular quartan fever during the previous 14 months. Her lips,
conjunctivæ and nails were very pale, the tongue, gums and lips showed a
deposit of melanin and the spleen was enlarged, reaching the umbilicus. She
was kept under observation during three cycles of the fever, each paroxysm
occurred at its regular time, and the pyrexial period lasted for nearly 12 hours ;
during the intervening 60 hours of each cycle the temperature was normal or
slightly sub-normal. After the third period of pyrexia 10 grains of quinine was
administered 4 times a day, with the result that no more fever occurred. Ten
days after the commencement of treatment she insisted that she had perfectly
recovered and went home.
In each of the above cases the blood was examined at frequent intervals ;
the disease was of a pure type, and the appearances were identical in both.
The description given below, together with the figures, have been taken from
the notes made on the observations of both cases indifferently.
FORMS OF PARASITE. (1) The fresh blood, drawn and prepared on the slide
in the usual way, about 12 hours after the height of the pyrexia, was found to
contain the following forms of parasite :—
1st.—Small amœboid bodies, lying on or in the red blood cells, which
var i ed i n si ze f r om 1/ 6t h t o 1/ 3r d t he di amet er of a hæmocyt e ( P l . I . A . . 1
. a n d 2 .
)
These bodies exhibited fairly active, though slow, amœboid movements, as
shown by figs. A. 2a, 2b, 2c, which represent the changes in shape of one para-
site at intervals of about 2 minutes, drawn by means of the camera lucida.
With illumination by an Abbe's condenser with medium diaphragms, the
parasites appeared to be in the same plane as the mass of the red cell and
therefore within it. On using the open condenser with oblique illumination how-
ever, as recommended by Mannaberg, I arrived at the conclusion, early in my
observations, that in many cases in this young stage, they were situated not
in, but on the surface of the red cell. In the example drawn in figs. A. and K.
I had withdrawn my eye from the microscope for a moment after outlining 2c,
and, on again looking, found that the red cell appeared to be normal, while the
parasite had become circular in outline and was lying below it and to one side, as
shown in fig. 2d. It remained spherical and free for some minutes, exhibiting
no movement beyond that of the enclosed pigment which slowly altered its
position (2e) till it was finally absorbed and digested by a macrophage as shown
Medical Officers of the Army of India.
33
in fig. K. 3,4,5. In this case the parasite was undoubtedly extracorpuscular, the
red cell, which it had left remained perfectly normal in all its appearances. The
rapidity of approach of the macrophage, the way in which the long process of
granular protoplasm flowed towards the parasite and the remarkable manner in
which it avoided intervening red cells in its course, presented a most remarkable
picture. It certainly seemed that the parasite in leaving the red blood cell had
exposed itself to attack, and the phenomenon suggested that the organism had
commenced to lose vitality at an early period after having separated from its
source of nourishment, and had thus increased the attraction exercised by it
on the phagocyte.
2nd.—In addition to the intracorpuscular forms, several free, more or less
globular parasites similar to A. 2d could be seen at this stage, and a few larger
globular bodies A. 3. These had no amœboid movement, had perfectly clear,
rather highly refractive, protoplasmic cell contents, and presented many small
pigment granules, frequently, but not always, arranged peripherally and in lively
motion. The larger forms were of the same diameter as a red blood cell, or
nearly so, and are to be met with in all stages of the fever though they are
frequently by no means numerous and are thus likely to escape observation.
(2) At 20 hours :
—
The parasites had increased considerably in size, they still retained their
powers of lively amœboid movement as shown in figs. B, 1a to 1d, and 2a to 2d,
the various stages in each of which were drawn at intervals ranging from
2 to 5 minutes. The pigment granules were larger and more numerous and had
active movements.
This active movement of the melanin pigment is observable at some
stage at least of the life of all forms of the malarial parasite. It appears
to be of two well marked kinds : (a) In certain forms a dancing bubbling motion
is seen, in which the granules rise up in the parasite, then spread out towards
its sides irregularly. This has been well compared by Laveran to the
movement of pigment particles in boiling water : ( b) A slower, but equally
marked, movement of the pigment granules, in which they seem to flow along
in the protoplasm from one part to another, frequently in lines or streams.
This is well seen in the intra corpuscular stages of the quartan and tertian forms
up to the time when the pigment becomes quiescent, as described below, pre
-vious to sporulation.
Towards this time (20 to 24 hours), the bodies appeared to have become
completely intracorpuscular, they did not present the appearances described
above, when examined by oblique open illumination, and were never seen to
leave the red cells.
(3) At 36 hours :
—
The parasite was found to be still larger, filling nearly 2/3rds of the red cell, F