NationalLibraryOfScotland/medical-history-of-british-india huggingface dataset:
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opinion regarding the differentiation of the cell substance into nucleus, nucleolus,
etc., but the general results are incontestable.
Fevers characterised by the presence of crescentic bodies in the
blood.
The clinical varieties of malarial fever which belong to this group are
according to the whole school of Italian observers, whose opinion has now been
confirmed by workers in many parts of the world—
1. Quotidian fever, and irregular fevers of a quotidian type.
2. Summer-autumn or malignant tertian fever.
Either of these may take on a very irregular course owing to the presence
of many generations of parasite in the blood, and thus give rise to the various
forms of irregularly continuous and remittent fevers.
In this class, the difficulty of following the cycle of life and development
of the parasite within the blood is much greater than in quartan and tertian
fevers. This is partly due to the extreme frequency with which the pyrexia
assumes an irregular type, and partly to the fact that, as all authorities are
unanimous in holding, the sporing forms are very rarely met with in the peripheral
blood, especially in simple cases. According to Marchiafava and Celli, the
account of whose investigations into these fevers, as met with in Rome, constitutes
the classic on the subject, the parasites belong to two distinct species :—
(1) That of quotidian fever, with a period of development of 24
hours.
(2) That of summer-autumn tertian fever, similar in its morphological
characters to No. 1, but with a cycle of 48 hours.
Grassi and Felleti again sub-divide the 1st species into two : viz., ( a ), the
pigmented, and ( b) the unpigmented quotidian parasite. I have not as yet been
able to satisfy myself that more than one species of crescent-producing parasite
occurs in this part of India, namely, the pigmented quotidian form. I have never
yet come across a case of the typical summer-autumn tertian form described
by Marchiafava and Celli.A l l t h e c a s e s w h i c h h a v e c o m e u n d e r o b s e r v a t i o n
have been of a quotidian type or irregularly remittent, and every fever of a
tertian type, in which blood examination has been carried out, was found
to be produced by the simple tertian parasite already described. The parasitic
forms seen in severe irregular remittents, however, have in many cases agreed
more closely with the descriptions of the malignant tertian forms given by the
Italian pathologists, than with those of quotidian ; but the morphological charac-
ters are too similar to admit of specific distinction unless a difference in
the period of development can be clearly proved, and this I have been unable to
do. Again, the unpigmented quotidian described by Grassi and Felleti, and
Medical Officers of the Army of India.
43
upheld as a distinct species by Mannaberg, must be very rare in Upper India, if
it occur at all ; no case of it has been observed here.
Cases of severe malignant remittents are fortunately not common in Lahore.
We know that when they do occur in the Punjab, that they frequently
assume an epidemic character, and that severe outbreaks of fever of this
type are commonest in autumn. No such outbreak has occurred during the
past two years, and the cases observed have consequently not been numerous.
Further experience may decide that certain of these are produced by a para-
site with a tertian cycle : but at present I have no data to warrant the adoption
of two species. The cases from which the accompanying drawings were made
were :—
(1) Simple Quotidian Fever.—Núr Muhammad, a P a t h a n f r o m G h a z n i ,
aet. 35, admitted on the 12th December 1895. He gave a history of perfect
health up to the 3rd December, when he was attacked by fever of a remittent
type and sought admission in hospital. Under treatment by quinine the fever
subsided, he felt well, though weak, and left hospital after six days' residence.
Three days afterwards he was again admitted, and stated that fever had re-
turned the day before. On this second admission his temperature was normal ;
he was pale and markedly anæmic, the tongue was coated with a heavy dirty
brown fur, the bowels were constipated and the appetite poor, the gums were
swollen, painful and slightly retracted from the teeth ; the spleen was slightly
enlarged, and the urine contained traces of albumen. From the 12th to the
evening of the 14th no quinine was given. The temperature, normal in the
morning, rose each evening to about 100º, the rise commencing at midday.
Eighty grains of Quinine Sulphate was given every day from the 14th to the 18th ;
the temperature rose to 99° on the 14th, was normal on the 15th, but again
reached 101º on the early morning of the 16th, the paroxysm having apparently
been postponed by the quinine. It remained normal after that date till he left
hospital on January 5th. Treatment by small doses of quinine, with iron, and
nourishing food was carried on from the 18th, and the man left hospital
apparently completely recovered. Anæmia had almost entirely disappeared,
the gums were healthy and the spleen had become nearly normal in size.
Albumen disappeared from the urine at an early stage of the treatment.
2. Malignant comatose Remittent Fever. —Haidar, a Muhammadan, aged
about 40, a beggar from Meerut, admitted on the evening of 14th November
1894. He was dull and stupid at the time of admission, but could answer ques-
tions, and gave a history of good health up to 12 days before, when he was
attacked by fever. The onset was accompanied by rigor and he stated that an
increase in fever preceded by a marked cold stage had occurred every day.
He had received no treatment.
The temperature is said to have been normal at the time of admission. At
G 2
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8 A.M. on the 15th it rose to 98.6. At 1 P.M., when first seen by me, the man was
found to be in a comatose condition, he could with difficulty be roused to open
the eyes and move, he could not answer questions, reflexes were present but lazy,
the pupils were equal and fairly normal in size. The tongue was moist and coated,
the spleen was not palpable but its area of dulness reached nearly to the costal
arch ; the hepatic dulness was increased, reaching to 1 inch below the costal
arch in the right mammary line. The lower lobe of the left lung was slightly
dull and the breathing over it was harsh. The urine contained no albumen. The
pulse was fairly full, 100 per minute, and the heart sounds were weak. The
temperature was 101 8ºFh.
Examination of the blood at 2 P.M. showed it to be swarming with parasites
to be afterwards described. Quinine was given in large doses by the mouth and
hypodermically, but the temperature rose to 103ºFh. in the evening and the
g e n e r a l c o n d i t i o n b e c a m e w o r s e . A t 7 A . M . o n t h e 1 6 t h t h e t e m p e r a t u r e w a s
9 9 . 2 , a t 8 1 0 2 . 4 , a t 1 P . M . 1 0 2 . 8 . T h e p a r a s i t e s w e r e a s n u m e r o u s a s e v e r i n
the blood, and melaniferous leucocytes abounded. At 6 P.M. the temperature
continued 102°, and no remission occurred during the night ; at 5 A.M. on the
1 7 t h i t w a s 1 0 2 . 5 , a n d d e a t h o c c u r r e d i n d e e p c o m a a t 6 1 5 A . M .
This case affords a good example of malignant comatose remittent
fever. The temperature was never very high, the severe symptoms were purely
cerebral, and the only clinical guide to a diagnosis of malaria was the man's
statement that the fever, though in his opinion it had not left him for
12 days, had been characterised by a daily exacerbation. Examination of the
blood at once settled the diagnosis, though the patient's condition was too grave
for improvement to follow treatment.
FORMS OF PARASITE.-(1) In Simple Quotidian Fever. —( a) During
a febrile paroxysm and for some hours afterwards :—The parasites then
seen were very small, with an irregular, badly defined outline, active amœboid
movement and only slightly lighter in colour than the hæmocyte on or in which
they lay. When at rest they became more or less ring-shaped, with or without
a projection extending from the ring ( Plate II., A, 1 to 3 ). After a few hours
small particles of pigment were found to appear, either irregularly scattered
through the cytoplasm or confined chiefly to the edges. The pigment in the
younger forms was sometimes of a reddish brown colour.
( b) Towards the commencement of a fresh paroxysm :—The bodies were
seen to be larger than before, to have assumed a circular shape, and to occupy
about ¼ to ⅓rd of a red-blood-cell ( Plate II, figs. A, 4 and 5 ). The cytoplasm had
become much more distinct, and the pigment had collected into a dark coarsely
granular mass in its centre, amœboid movement had ceased. Very rarely
sporing forms were seen ( fie. 5 ), in which division into a number of small spores
had occurred. In many cases the infected blood cell had become altered, but
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along with, in the younger or smaller forms, the chromophil granule ( 7 ). A
clear unstained area, corresponding in its appearances to the non-staining
" nucleus " of Mannaberg is occasionally to be seen (8, 9, 10), but its late
appearance and irregularity render it more probably of the nature of a
vacuole, or space due to irregular fixation. The cytoplasm of the largest
forms stains of a uniform azure colour ( 11 to 15 ), it is seen to contain the
melanin towards its centre, or grouped at one side. Two or three may
still be found in one hæmocyte. The final sporing stage, though rare as a
rule in the peripheral blood, was frequently seen in that of Haidar, and when
stained shows the characters drawn in fig. 47. Recalling in most ways the
appearances of the sporing body of tertian and quartan fevers, it differs in being
smaller and more irregular. The spores are, however, quite as distinct, and the
chromophil body in each stains deeply.
The bodies of the crescentic series. — T h e s e d i f f e r e n t i r e l y f r o m t h e
sporing bodies in their staining reaction. In place of a bright sky-blue colour
they assume, with acid hæmatoxylin (neutralized, after staining, with lithium
carbonate solution), a pale mauve tint which is very characteristic. This charac-
teristic difference in colour is well seen in the drawings in Plate 11., B,o f w h i c h
a l l , f r o m 1 t o 3 0 , w e r e m a d e f r o m o n e s l i d e o f t h e p e r i p h e r a l b l o o d f r o m t h e c a s e
of Haidar. As far as my experience goes, the crescentic bodies take
on an absolutely uniform stain in nearly all, if not quite all, instances. I have
not been able to substantiate the statement of Celli and Guarnieri, confirmed
by Mannaberg, that the equatorial region stains lightly and the polar deep-
ly. Each slide prepared from the case of Haidar must contain hundreds of
crescents and in no case have I been able to distinguish any variation in depth
of stain. With a solution of Ehrlich-Biondi's methyl-green-rubin—orange
stain, strong enough to colour a melaniferous leucocyte as in fig. 31, the cres-
cents do not take up the nuclear stain at all, but are uniformly stained pale red ;
with methyl blue they assume a pale blue colour ; and with acid hæmatoxylin
the uniform mauve shown in the drawings. This matter is of considerable im-
portance since the assumed existence of polar staining forms one of Mannaberg's
chief arguments in favour of the development of the crescents by a process of
syzygies.
In such stained preparations the process of growth of the crescent within
the red cell is well seen ( figs, 18 to 24 ). The hæmocyte stains less deeply and
finally contracts ; as long as any hæmoglobin remains it stains pink with eosin,
when the blood-colouring matter has entirely disappeared, the remains of the cell
from the " velum " first described and figured by Laveran, which assumes
the same violet stain as the crescent itself.
In the younger forms, the melanin is fairly equally distributed through the
cell contents ( Figs 18 to 20 ). It tends, as the parasite grows, to draw in towards
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for believing that the crescents themselves may also act the part of resistant
resting spores.
Very careful examination of, many film preparations, and, in the case of
Haidar, of preparations from the spleen and bone marrow, have afforded no data
confirmatory of Mannaberg's syzygies or conjugation theory ; though I was at
first strongly prejudiced in its favour and confidently hoped to recognise the
appearances depicted by him. Multiple parasites, in or on one hæmocyte, are
very common indeed, but though they frequently lie in actual contact, I have
seen nothing at all resembling a fusion of their protoplasmic contents. On the
other hand, fully developed multiple organisms with pigment concentrated, and
just on the point of sporing, are as common as multiple young forms.
One point of great interest is the fact, that young forms of the crescen-
tic series are extremely common in the red marrow, in which they are relatively
much more abundant than either in the spleen or peripheral blood. Many of
them seem to become free early, forming small spherical bodies with the typical
mauve staining reaction ( Pl. II., Fig. D., 4). Whether the crescents develop
chiefly or not in this position seems worthy of further investigation : it is difficult
otherwise to account for their abundance in the marrow. I have never seen
segmentation occur in a mature crescent, nor any evidence of its having occur-
red in any stained preparation.
The results of my observations therefore have been :—
(1) That the crescentic bodies have a uniformly staining cytoplasm.
(2) That they do not appear to be developed by a process of conju-
gation.
(3) That they are more common in the red bone marrow than elsewhere.
(4) That after a certain period they are readily distinguished from other
forms by their characteristic staining reaction.
(5) That they never show any differentiation into spores, and that they
do not divide by fission.
(6) That the process of flagellation which they undergo outside the body
has such uniform characters that it is difficult to believe that it is
not a vital process.
(7) That they agree in very many respects with the free spheres of ter-
tian and quartan fevers, with which they probably correspond
entirely in function.
Appearances met with post-mortem.
The only case of remittent fever in which I have been able to obtain a post-
mortem examination during the past two years was in that of Haidar above
described. This was, however, performed under very favourable circumstances,
the portions of tissue kept for microscopic examination were fixed at once, and
Medical Officers of the Army of India.
49
the preparations obtained were in good condition, and perhaps sufficiently in-
teresting to warrant a short description. At the autopsy the following macro-
scopic appearances were noted :-
The general nourishment was fairly good : the pupils were equally and
normally dilated.
The pericardium was normally moist, the heart weighed 10 ozs. after being
opened, the myocardium was of a dark brown colour, the aorta was atheromat-
ous and the aortic cusps were slightly thickened and puckered. The left lung
was partly adherent to the parietal pleura by old adhesions ; it weighed 1 lb.
2 ozs., and the lower lobe was the seat of marked hypostatic congestion : the
right lung was apparently normal.
The peritoneum was normally moist, the walls of the intestine had a dirty
brown colour from melanotic pigmentation but were otherwise normal. The
liver was enlarged, weighed 31b. 3 ozs., and was of a dirty sepia brown colour.
The cut surface was very dry and firm in consistence. The kidneys had
slightly adherent capsules, with slightly diminished cortices and congested
medullæ. Their colour was browner than normal. The suprarenal capsules
and pancreas were normal in characters. The spleen, 13 ozs. in weight, just
reached the costal arch. Its capsule was thickened, the external colour deep
iron-grey, on section the cut surface was firm and had a very deep purplish
sepia colour. The blood which exuded on pressure was of the same hue.
On opening the skull, the dura was fairly normal on its external surface,
the sub-dural and arachnoid fluids were much increased in amount. The pia
mater was dusky, as if sprinkled with soot. The brain weighed 21b. 12 ozs.
it was firm in consistence, and the grey matter throughout, both cortical and
nuclear, was much congested and of a dark sepia grey colour. No capillary
hæmorrhages were noted.
Microscopic examination showed the following to be the most important
changes :-
1.
The Brain.— T h e s m a l l a r t e r i e s a n d c a p i l l a r i e s t h r o u g h o u t t h e o r g a n , b u t
especially in the grey matter, were found to be loaded with red blood corpuscles,
almost every one of which contained a parasite on the point of sporing, with
central melanin pigment. So uniform and general was this condition that, with
a low power, the preparations presented the appearance of an injection of the
brain with a fine emulsion of charcoal. Such a vessel under a high power
( 1 / 1 2 i n c h o i l i m m e r s i o n ) , i s s h o w n i n P l . I I . , F i g . C .
I n s o m e p l a c e s e m b o l i o f
coarse granular pigment masses, free in the plasma, were also seen. In the
larger veins and arteries parasite-infected red cells were much less common
than in the capillaries, and in cross-sections of these vessels the diseased
cells could be seen to adhere to the vessel wall, forming a peripheral layer
similar to the arrangement assumed by leucocytes in inflammation. It appears
to be probable that a large part of this occlusion of the brain capillaries with H
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parasite-laden cells may be due to the parasites causing the affected hæmocytes
to become of lower specific gravity than the blood plasma, and thus to render
their circulation through narrow capillaries more difficult. They would thus get
filtered out of the blood and remain behind, while the healthy cells would be able
to pass on.
2. The Lungs.— T h e c a p i l l a r i e s o f t h e a l v e o l a r w a l l s w e r e i n a v e r y s i m i l a r
condition to those of the brain, being full of pigmented, parasite-bearing, red
cells, while the veins contained large phagocytic cells laden with coarse mela-
notic pigment.
3. The Liver.—Here the appearances met with were different. The hepa-
tic cells were in a state of cloudy swelling, with granular protoplasm and indis-
tinct nuclei ; the capillaries were distended at some parts, apparently contract-
ed at others, and all contained large numbers of macrophages and phagocytic
leucocytes deeply laden with thick, coarse pigment . The endothelial lining of
the capillaries was also deeply pigmented. No dark pigment existed in the
liver cells themselves, but most contained the golden brown pigment first de-
scribed by Kelsch and Kiener, in great abundance. This takes on a black
colour when treated with sulphide of ammonium and is apparently derived from
broken up red blood corpuscles and perhaps from hæmoglobin dissolved in the
blood plasma, which is excreted by the liver cells. The connective tissue stroma
throughout the organ showed marked proliferation of its cellular elements,
particularly in the neighbourhood of the branches of the portal veins.
4. The Spleen.—The capsule was thickened and the fibrous trabeculæ in-
creased in size, probably from old malarial infection. On the under surface
of the capsule and the margins of the sections of trabeculæ, proliferation of the
fibrous tissue cell-elements was marked. The pulp was full of parasites in all
stages of development ( Pl. II., fig. D. ), the spore-producing and young amœ-
boid forms being much commonest. In addition, the whole section was black
with large splenic cells ( fig. D. 7), and smaller leucocytes ( fig. D. 6 ), laden with
coarse accumulations of dark sepia pigment. A few nucleated red blood cells
were also seen ( fig. D. 5). The Malpighian bodies, and lymphocytes generally
wherever they occur, were found to contain no pigment.
5. The Kidneys —Contained fewer parasite-laden cells, but some, to-
gether with melaniferous phagocytes, were found in the intertubular capil-
laries, and those of the Malpighian tufts. The tubular epithelium throughout
was in a state of cloudy swelling. The capsule was thickened, and small areas
of excessive proliferation of interstitial fibrous tissue existed here and there in ir-
regular patches.
6. The Intestine.— T h e c a p i l l a r i e s w e r e a g a i n f o u n d t o b e f u l l o f p a r a s i t e
laden red cells, though much less so than those of the brain. No hæmorrhage
had taken place and the condition of the mucous membrane was healthy. In
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Scientific Memoirs by Medical Officers of the Army of India.
spore-forming and crescentic forms, the latter of which greatly preponderated.
Pigmented marrow cells ( fig. D. 8 ) large pigmented phagocytes and leuco-
cytes, nucleated red cells, ( fig. D. 8) and eosinophile leucocytes ( fig. D. 7),
not melaniferous, were also seen in abundance.
To sum up :—
S p o r e - f o r m i n g a n d a m œ b o i d b o d i e swere most abundant in the cere-
bral and pulmonary capillaries, less so in those of the liver, kid-
neys and intestine ; they were numerous in the splenic pulp and
red marrow.
Crescentic bodies were most numerous in the red marrow, they
also occurred in the spleen, but were more rarely seen elsewhere.
Melaniferous leucocytes and macrophages occurred everywhere through-
out the visceral vessels, but were most abundant in the hepatic
capillaries (which at many parts they almost completely blocked);
in the splenic pulp and in the bone marrow.
Lahore, August 1896.