NationalLibraryOfScotland/medical-history-of-british-india huggingface dataset:
296
' Lahore Canine Fever' and 'Tick Fever' of dogs
This sums up the efforts made to prove a bacterial etiology in this parti-
cular form of canine fever. The evidence is unconvincing. The writer has on
several occasions isolated Salmonella-like organisms from the faeces of dogs
affected with ' Lahore Canine Fever'. He has equally frequently isolated
similar types of organism from healthy dogs and has refused to consider their
potential pathogenicity, in that the serum of affected dogs failed to betray the
slightest trace of agglutination and their inoculation by various routes yielded
consistently negative results.
Finally, the study of the temperature charts of the affected dogs and their
clinical syndrome in comparison with the known syndrome and pyrexial phase
of Salmonella infections in the human subject, enhanced the uncertainty of
accepting a bacterial etiology for this affection of dogs. The writer is further
convinced of the insupportability of the claims to establish a bacterial etiology
as he had an opportunity of subjecting certain of the fever cases, from which
the Salmonella-like strains were isolated, to post mortem examination. The
findings were identical, both on the pathological and histological grounds, with
those present in ' Lahore Canine Fever.'
SYMPTOMATOLOGY
The disease is of sudden onset. Without any warning, a dog which had
appeared perfectly normal a few hours previously, is found dull and dejected.
The temperature is discovered to be higher than the physical condition would
seem to indicate and is within the range of 104°—106°F. The usual conco-
mitant features of fever are present. The degree of dejection which is present,
the ' tucked up ' appearance, the acute epigastrial pain evinced, the occasional
vomiting of a bile-stained fluid, are all typical. A peculiar symptom, and one
frequently present, is a thin serous discharge, occasionally blood-tinged, from
one or both nostrils. The nose may become partially occluded when this
exudate dries or becomes thicker and the increased difficulty of respiration,
the rapid breathing consequent on high fever, may lead the unwary observer
to a fallacious diagnosis of pneumonia, and when, as not infrequently happens,
an exanthematous eruption occurs in the inside aspect of the thighs, a mistaken
diagnosis of distemper may be made.
A second peculiar symptom which is worthy of notice, is a slight puffy
swelling in the mandibular space.
The fever, in spite of symptomatic treatment, undergoes little if any remis-
sion until the fifth to the seventh day, when it may suddenly drop to 102°F.,
within which range it may remain for several days. (It should be noted here
that the normal temperature of the healthy adult dog in India is 100°F. and
not 101—101.5°F. as commonly stated.)
The remission of fever is accompanied by a transient occasionally severe
diarrhoea, the faeces being orange in colour and acrid in odour. The urine,
which is darker than normal, contains traces of albumen. Haemoglobinura is
absent. The gums at their dental margins are angry, red and swollen and a
typical mouth foetor is present,
298
'Lahore Canine Fever' and 'Tick Fever' of dogs
(ii) Haemoglobin percentage estimation (Tallquist scale);
(iii) Variations in blood cytology.
The following data emerged from these simple routine observations :
(a) At the onset of fever, there is a marked leucocytosis, many of the
leucocytes being of an immature type resembling the promyelocyte ;
(b) Platelets are obviously more numerous;
(c) Erythrocytes are normal in size, although a peculiar vacuolation is
frequent (corps demi-lune).
(d) The haemoglobin percentage is normal;
(e) As the disease progresses, vacuolation of the erythrocytes increases
and large mononucleated cells make their appearance. These are
typical histiocytes and two forms, one large and possessed of a
kidney shaped nucleus and one smaller, with a rounded nucleus, are
observed. The cytoplasm of these cells is hyaline and agranular.
Gradually these cells increase in number until they are very evident.
(f) After the lapse of about two weeks, the haemoglobin percentage falls
to about sixty, and from this period to the last week or two of
the illness, it fluctuates around this figure.
(g) It is apparent that there is no destruction of erythrocytes or haemo¬
globinaemia in the circulating blood.
(h) The types and numbers of leucocytes present show a definite indi-
cation of a ' shift to the left'.
(i) The changes are progressive and towards the termination of the
disease there is a sudden and marked fall in the haemoglobin
percentage (20—30 per cent), while pathological changes in the
erythrocytes become apparent (normoblasts, polychromasia,
punctate basophilia, poikilocytosis, Howell-Jolly
bodies)—an
unfailing indication of rapidly approaching dissolution. The red
blood cell count falls to about two million per cmm.
In some few cases showing such a syndrome, cases in which repeated and
unavailing search has been made for protozoon parasites in the blood and in
which a negative diagnosis of ' tick fever ' has been made, the sudden appear-
ance of P. gibsoni in very scanty distribution is startling. It is this fact that
has led the writer to devote particular study to this disease. In such cases,
one may have to search a very large number of fields (50—100) before their
presence can be detected, and, when present, they usually occur singly or in
pairs. It is noteworthy that the occasional appearance of the parasite in the
blood seems to bear no relationship to the severity of the symptoms or the sharp
paroxysmal elevations of temperature. In fact it would appear that P. gibsoni
is certainly absent from the blood during these phases, only making its appear-
ance on alleviation of the fever.
J. F.
SHIRLAW
299
In the majority of cases, P. gibsoni has never been detected in the blood
throughout the course of the illness, even in the terminal stages when profound
anaemic changes are present.
The post mortem picture is typical and easily summarised : changes mainly
affect the spleen and liver. In acute cases of a short duration of illness, the
spleen is markedly enlarged, increased up to ten times the normal weight, dark
red in colour or even chocolate, the follicles enlarged and prominent. In one
case, the spleen was grossly enlarged, filling the abdominal cavity, intensely
haemorrhagic in appearance and several haemorrhagic infarcts were promi-
nent. The spleen in these cases is softer in texture and somewhat diffluent.
In more protracted cases it is firmer in texture, somewhat ' fibroid ' occasion-
ally, with less prominent follicles. The liver is similarly grossly enlarged : in
one case, 16.6 per cent of the body weight. (The percentage weight of the
liver to the body weight in health is 3 per cent. Sisson.). The organ appears
finely cirrhotic, darker or slaty in colour, the surface granular and studded
with petechiae and frequently bile-stained.
The blood is thin and watery.
The systemic lymph glands are swollen and haemorrhagic.
The heart muscle usually shows an acute interstitial myocarditis.
The mucous membrane of the gastro-intestinal tract is covered with a
sticky mucuous deposit. Petechiae are frequently prominent and occasionally
discrete areas of ulceration. The duodenum in its first part is deeply stained
with bile and occasionally the pylorus.
In acute cases, the red bone marrow is hyperaemic and increased in amount
at the expense of the fatty marrow. In more chronic cases, this change is not
so evident.
Histopathological changes have been centred on the spleen, liver and
bone marrow.
SPLEEN
The follicular lymphoidal cells are increased in number and mitosis is
evident, especially in peripheral cells where these seem to be undergoing a
transformation into larger cells (polyblast, transitional plasma cells, and
macrophages) with a clear cytoplasm and irregular nucleus—a type of cell
which is prominent in the red pulp. It is possible that these cells are in actua-
lity cells which have originated from the red pulp and are not derived from the
peripheral cells of the follicle, which they would then appear to infiltrate. The
inconspicuous and shrunken appearance of the follicles in chronic cases would
seem to support the idea and it appears probable that in an advancing infection
the red pulp of the spleen, actively mitotic as are its component cells, gradually
infiltrates and replaces the white pulp.
The most characteristic changes are in the red pulp. There is a very
definite hyperplasia of the cells of this tissue, with prominence of the cords of
Billroth. Coincident with the marked hyperplastic changes, degenerative
300
'Lahore Canine Fever' and 'Tick Fever' of dogs
changes are noted. While mitosis and marked proliferation of the cells is
present, karryorhexis is evident in similar cells, the cytoplasm of which stains
faintly and appears as a mere rim around the disintegrating nucleus.
The majority of the cells present have clear, round nuclei, in which the
chromatin particles radiate from a central mass of nuclear chromatin. These
cells present themselves as typical reticular cells and similar cells are found
lining the spleen sinusoids. The second type of cell of numerical importance
is smaller than the foregoing. The nucleus is compact, deeply basophilic with
no internal structure. These are transitional lymphocytes and haemocytoblasts
(polyblasts). Interspersed with these are nucleated red blood cells in consi-
derable numbers. The venous sinuses are distended and the lining (littoral)
cells of the reticulo-endothelium show distinct mitosis. Many of the hyper-
plastic (macrophage) cells of the pulp contain blood pigment. A more import-
ant observation is that peculiar granules, staining intensely with Heidenhain's
iron haematoxylin, are found inside the cytoplasm of the polyblasts and reti-
cular cells. These granules are regular in size and appear in small well-defined
clusters. The nucleus of the cells in which they appear is distinct and free
from any degeneration. Similar forms, in larger clumps, may be found in
extracellular situations, as well as within the cytoplasm of the cells mentioned.
These forms stain indeterminately by the Romanowsky stains and judging by
a comparison of Heidenhain's stain on sections of the same tissue, it appears
that only a few of the bodies can be stained by this method. Pappenheim's
stain gives negative results. The changes of importance in the spleen may,
therefore, be summed up under three heads, intense and extensive cellular
hyperplasia, with the development of polyblasts and macrophages, haemato¬
poiesis, and the appearance of peculiar, structureless inclusion bodies of small
size, both within and without the proliferating cells.
LIVER
The changes in the liver are associated with an intense congestion. The
predominant feature is a reaction of the reticulo-endothelial cells lining the
sinusoids and the presence of blood pigment in these cells (cells of Kupffer)
which appear larger than normal. Necrosis and fatty degeneration is patchy
throughout the lobules and the appearance of an intense cellular infiltration
throughout, in some cases, suggests profound toxic excitation of the sub-
stance of the organ.
THE BONE MARROW
The bone marrow shows changes similar to those described in the red
pulp of the spleen, with an erythropoiesis of an exaggerated degree. ' Inclu-
sion bodies ' are much more prominent than in the spleen and they are also
found in the haemocytoblasts.
302
'Lahore Canine Fever' and 'Tick Fever' of dogs
normal saline from puppy No. 6, an acute experimental case (Chart No. 1),
which had been subjected to experimental treatment with S. U. P. 36.
No reaction occurred to the second inoculation but on 11th August
1935, the picture of an early commencing secondary anaemia was obtained
in blood film examination. The puppy was then destroyed by electrocu-
tion. No parasites had been observed in its peripheral blood. The weight
of this puppy was 22.5 lb. and at post mortem the spleen weighed six ounces
(i.e., 1.66 per cent of the body weight). According to Sisson, the weight of
the spleen in a normal sized dog—it is presumed that this is about
20 lb.—is 1½ to 2 oz. Accepting the lower figure 1½ oz. the normal percentage
of the spleen to the body weight is, therefore, in the region of 0.47 per cent.
The spleen of puppy No. 13 (Chart No. 5) was, therefore, according to these
figures, increased in weight by three and a half times the normal.
The liver weighed 1 lb. 12 oz., i.e., 7. 6 per cent of the body weight. It is
stated that, in health, the liver of the dog weighs approximately 3 per cent of
the body weight.
It will be seen then that, in spite of the failure to react to the inoculation of
virulent blood, there was a terminal secondary anaemia, co-ordinated with a
decided splenic and hepatic enlargement. The important observation is
that, in microscopic examination, the cellular reaction of the spleen and
liver was similar to that encountered in ' Lahore Canine Fever ', although
not so pronounced in degree.
Puppy No. 15 (Chart 6) was a somewhat similar case. It was inocu-
lated on 30th July 1935 with 5 c. c. of spleen emulsion in normal saline
from Puppy No. 12 (Chart 4), and observations were continued over
seventy-one days. The temperature remained practically normal over
the first month and no parasites were observed in daily examination, nor were
there any pathological alterations in the blood. The temperature over the
second month ran only one to two degrees, higher than in the previous month,
and on the forty-fifth day was 103.6°F. On the forty-ninth day, decided
anaemic changes commenced to show in the blood and these were strongly
progressive. P. gibsoni, in very scanty numbers, averaging one to two per
field, made its appearance on the sixty-fifth day, and was present in equally
scanty numbers until the seventy-first day, when the puppy died.
The weight of this dog was 21½ lb. At post mortem, the spleen weighed
eleven ounces, i.e., the percentage weight of the spleen was 3.2 per cent of the
body weight, or more than seven times the normal. The liver weighed 1 lb.
4 oz. or 5.3 per cent of the body weight, i.e., nearly twice the normal weight.
The spleen in this case was livid in colour, the pulp was soft in consistence and
haemorrhagic infarcts were noted. The liver was fatty and distinct acute
interstitial myocarditis was present, with areas of patchy necrosis of the mus¬
cular fibres. Histopathological lesions similar to those of 'Lahore Canine
Fever ' were found in the spleen and bone marrow. The liver was not affected
to such a marked degree.
J. F.
SHIRLAW
305
appearance in the last few days of illness. This case corresponds very closely
with those cases just mentioned in which, after weeks of negative blood exami-
nation, a case is accepted as authentic ' Lahore Canine Fever '—a diagnosis
only to be confounded by the sudden appearance of the parasite a day or two
before death.
Sufficient has been said, therefore, to prove that from the clinical stand-
point, there is a very strong analogy between the two diseases.
It is on post mortem and histopathological examination that the suspicion
becomes evident. Both diseases possess the following features in common:
profound secondary anaemia, marked enlargement of the spleen and liver,
hyperaemia of the bone marrow and increase of the red at the expense of the
white marrow. The heart muscle lesions common to both diseases have been
commented upon. The histopathological features of the spleen, liver and bone
marrow have been described in some detail and the only differences between a
case of experimental P. gibsoni infection and a case of authentic 'Lahore
Canine Fever ' are differences of degree and not of kind.
The most important observation, however, is that in ' Lahore Canine
Fever ', no true ring forms of P. gibsoni can be seen in sections of the blood-
forming tissues, even in Giemsa and Leishman stained preparations. This
would appear to vitiate the analogy, but it can be definitely stated that, simi-
larly, no ring forms can be found in the section preparations of P. gibsoni
infected dogs.
This may be due to a fault in technique but was guarded against by simul-
taneous staining of sections of the spleen of a bovine which had died from acute
Babesia infection. The ring forms of this parasite were easily demonstrable
by Leishman and Giemsa methods of staining. If, therefore, P. gibsoni was
present in the tissues examined and was overlooked, the presumption is that it
must have been in extraordinarily scanty numbers. If such was the case, it is
a striking fact in view of the marked cellular hyperplasia and reticulo-endothe¬
lial response, eventuating finally in a reversion to embryonal erythropoiesis
of this tissue.
The presence of peculiar inclusion like bodies, both in the littoral cells
and the proliferating true reticular cells of the red pulp of the spleen as well as
in the cells of the red bone marrow, have been noted in ' Lahore Canine Fever',
and equally in artificially produced P. gibsoni infection. When the histo-
pathology of ' Lahore Canine Fever ' was first studied it was considered pro-
bable that these were the products of nuclear degeneration. More extensive
study showed that, although these bodies did occur in cells which showed some
evidence of degeneration, they were more frequent in perfectly healthy cells in
which the nucleus and its membrane were intact. And, furthermore, aggrega-
tions of these bodies could be found in extracellular spaces, in some cases in
greater numbers than within the cells. It was decided, therefore, to determine,
whether these bodies possessed any specificity for the two fevers under study.
J. F.
SHIRLAW
307
These two infections, though clinically somewhat comparable, run an
entirely different course in haemocytological observations, although patholo-
gically comparable in the end result. In a P. canis infection there is an early
invasion, anisocytosis and destruction of the erythrocytes. The serum is ting-
ed, sometimes deeply, with haemoglobin liberated from the breaking down of
erythrocytes and there is an increase of the corpuscular sedimentation rate.
In a P. gibsoni infection, there may be an early and transient invasion of
the erythrocytes. There is, however, no anisocytosis and destruction of the
erythrocytes in the circulating blood, and no evidence of liberated haemoglobin
in the serum. (These observations are enhanced by the fact that in a P.
canis infection, haemoglobinuria is a characteristic symptom, whereas, in a
P. gibsoni infection, this symptom is never noted.)
At the same time, there is an increased fragility of the erythrocytes in a
P. canis, which is absent in a P. gibsoni infection.
It has already been noted that in an experimentally produced P. gibsoni
infection, the histiocytes of spleen origin (reticulo-endothelial) early make
their appearance. In a true P. canis infection, there is no such evidence of an
early involvement of the reticulo-endothelial system. Anaemic changes occur
during the latter phase of the infection and are obviously prompted by the
stimulus provided by the erythrocyte destruction and loss. It is believed,
from these observations, that P. gibsoni is essentially a parasite of the reticulo-
endothelium, unlike P. canis which appears primarily as a parasite of the
erythrocytes.
On this basis, apart from the experimental pathological evidence which
has been produced, it is possible to explain the infrequency of P. gibsoni in
the circulating blood and even its total absence during the course of the disease.
And it is then possible to understand the reluctance to accept ' Lahore
Canine Fever' as a P. gibsoni infection.
In addition to this consideration, previous workers have been impressed
by the dysenteric symptoms, accompanied by rapid wasting, which, are not
infrequent. It is, apparently, these symptoms which have prompted several
workers to consider the disease ' Canine Enteric Fever'.
Osmand Bodman and Cooper (unpublished work) noted intestinal
ulceration as one of the prominent lesions in their investigations, and it was
from such cases that they obtain the Salmonella strains mentioned earlier in
this note. Symons [1926] and Clive Webb [1906] have drawn attention,
however, to the frequency with which dysentery and intestinal ulceration
complicate the syndrome of an authentic P. gibsoni infection. It is certain that
a few dogs normally harbour Salmonella strains and it is possible that under
the stress of debility induced by the primary protozoan infection, these orga-
nisms, potentially latent, assume a pathogenic role. Against this possibility,
however, must be mentioned the fact that such cases fail to give a positive
Widal test against the Salmonella strains isolated.
308
'Lahore Canine Fever' and 'Tick Fever' of dogs
Lastly, it is believed that much of the refusal to consider the possibility
of ' Lahore Canine Fever ' as being in reality a P. gibsoni infection, has origi-
nated in the widespread belief that Novarsenobillon and similar drugs have a
specific curative effect in P. gibsoni infections. While a very few cases of
' Lahore Canine Fever' have been successfully treated with Tryparsamide
and Novarsenobillon, the great majority of cases have failed to respond to
treatment. The writer conducted a series of experiments on the treatment of
experimentally produced P. gibsoni infection in dogs. The results will shortly
be published, but at this juncture it may be stated that no drug was found that
could be said to have any curative or specific effect in this infection.
In view of the experimental evidence, supported by these observations,
it is believed that' Lahore Canine Fever,' which finds its counterpart in' Canine
Enteric Fever ' and ' Canine Typhus Fever' is, in actuality, ' Tick Fever ',
associated with P. gibsoni infection.
SUMMARY AND CONCLUSIONS
1. ' Lahore Canine Fever ' is one of the most important causes of death of
dogs in Lahore and evidence is adduced to show that it is the same disease as
has been investigated by workers in other parts of India and designated various-
ly ' Canine Typhus Fever ' and ' Canine Enteric Fever '.
2. The disease occurs during the tick seasons, but has not been accepted
as ' tick fever ', through general inability to demonstrate the causal parasite in
the blood of infected dogs, combined with the general refractoriness to treat-
ment with arsenical preparations.
3. The latter aspect of the disease will be dealt with in a later article.
4. An account is given of the clinical features and pathology of ' Lahore
Canine Fever' with a comparison of experimentally produced disease of P.
gibsoni origin.
5. The proof that ' Lahore Canine Fever ' is ' tick fever ' is based on the
following observations:—
(a) P. gibsoni is occasionally, with difficulty, demonstrated in the blood
at some stage of the illness, frequently just before death.
(b) The clinical syndrome of an authentic experimentally-produced
P. gibsoni infection corresponds in every detail with that of
' Lahore Canine Fever '.
(c) In both diseases the cytological changes occurring in the blood
cells and the method of production of secondary anaemia are
parallel.
(d) The histo-pathological changes in the reticulo-endothelial system,
especially in the spleen, reveal important findings which estab-
lish the relationship of ' Lahore Canine Fever ' to ' tick fever '.
J. F.
SHIRLAW
309
ACKNOWLEDGMENT
The microphotographs and colour drawings illustrating this article have
been prepared by Ahmed Baksh, Assistant Artist of this Institute, to whom
thanks are due.
REFERENCES
Bridges, R. F. and Scott, W. M. (1931). J. Roy. Army M. Corps. 56, 241-249.
Clive Webb, E. (1906). J. Comp. Path. Ther. 19, 1.
Datta, S. C. A. and Munro, D. A. (1935). Proc. 22nd Ind. Sc. Cong. Calcutta, p. 408.
Manifold, J. A. (1928). J. Roy. Army. M. Corps. 51, 402.
Patton, W. S. (1910). Bull. Soc. Path. Exot. p. 274.
Symons, T. H. (1926-27). Ind. J. Med. Res. 14, 293.
310
'Lahore Canine Fever' and 'Tick Fever' of dogs
Puppy No. 6.
Days of Disease.
Chart No. 1.
Temperature in Fahrenheit.
J.
F.
SHIRLAW
311
Puppy No. 7.
Days of Disease.
Chart No. 2.
Temperature in Fahrenheit.
312
'Lahore Canine Fever' and 'Tick Fever' of dogs
Puppy No. 10.
Days of Disease
Chart No. 3.
Temperature in Fahrenheit.