NationalLibraryOfScotland/medical-history-of-british-india huggingface dataset:
64
it be, and whatever be its degree of susceptibility, offers a certain
amount of resistance to charbon and to othar microbes; it acts
against them through the medium of its cellular elements and its
fluids. Fodor has clearly shown the bactericidal rôle of the blood of
the rabbit in the case of the virus of charbon; he has observed that
these microbes, injected into the veins or sown in fresh blood taken from
the animal, are destroyed in large numbers. The susceptibility of the
rabbit to charbon after intravenous injection is explained by the localiza-
tion of the bacteria in the parenchymatous organs, where it can develop
free from the harmful influence which the blood exerts upon it, and
finally invade this medium. Nuttal has likewise observed the bacteri-
cidal action of the blood, either normal or defibrinated, of the rabbit,
mouse, pigeon, sheep, dog; of the aqueous humor, the pericardial fluid
of the dog and rabbits to the charbon virus. Buchner also has recog-
nized it in the blood of the rabbit and dog; and he attributes it to the
serum itself. Wurtz has besides observed that the bacillus anthracis,
either in the state of rods, filaments or spores, is destroyed after an
hour's sojourn in white of egg at 38º C. Behring, Nissen, Metchnikoff
and Roux, etc., have noted the bactericidal properties of the blood of
the rat. On account of this bactericidal property of the blood and
other fluids acting against the bacteria, we may explain why a small
dose of the virus may fail to produce the disease, whilst a large one
may do so.
The bactericidal action of the serum of the blood is aided in its anti-
microbian work by the intervention of the cells of the tissues, more
particularly that of the leucocytes which play the part of phagocytes.
The spleen, according to the observations of Bardoch, producing phago-
cytes, exercises a great influence; it plays an important part, protecting
the blood against the invasion of microbes. In 25 dogs deprived of
their spleens, 19 succumbed to charbon, whilst 5 only in 25 animals
with the spleen intact contracted the disease. Again, whilst normal
rabbits bore the anti-charbon vaccination by Chamberland and Roux's
method, which will later be described, rabbits, whose spleens had been
removed, died in the proportion of 26 to 35 from the first vaccine.
Leucocytes act not only against the adult bacilli, but also against
the spores.
Smirnof, Bitter, Lubarsch, and Fischer have observed that the bacilli
may preserve their virulence for several days in the animal tissues of
immune animals, such as sheep and frogs. From the experiments of
M. Trapeznikoff recently published, we may draw the following conclu-
sions; in refractory animals the amœboid cells, the leucocytes accu-
mulate at the seat of inoculation and devour the spores, or ingest
65
and transport them to the various organs which exercise a bacteri-
cidal or sporicidal influence such as, if not to actually destroy them,
renders their germination difficult; when the spores have had time to
germinate before being taken up by the cells, the bacilli to which they
give existence are seized and destroyed by leucocytes; the spores taken
up remain for a long time alive and virulent, and if the phagocytes
which have taken them up weaken and die, they germinate, become
transformed into filaments, which may in their turn be taken up and
destroyed; in animals not refractory, the spores are seized by the
leucocytes in the same manner, but they germinate and destroy them.
Manner in which the bacilli, etc., act upon the system.—The ba-
cillus, introduced into the system, develops and multiplies, determining
death in various ways. It lives and multiplies at the cost of organic
liquids; it lives and multiplies in the blood, after having first invaded
the lymphatic ganglia and system lying between the seat of its entry
or inoculation, and the confluence of the lymphatic with the circulatory
system; it often forms a felting, more or less compact, in the ganglia
and in the blood-vessels; it occasions vascular ruptures and more or less
numerous hæmorrhages, by reason of the emboli which it forms and
the diastatic matter which it secretes, which acts on the tissues, softens
the walls of the vessels, etc.
The bacilli being ærobic, requiring air, absorb oxygen and give out
carbonic acid in its place; they abstract oxygen from the red corpuscles,
which being also ærobic retards their development; they finally, by
abstracting oxygen, render the blood progressively asphyxic and unfit
for the proper nutrition of the tissues. The black colour which the
blood assumes is explained in this manner, and also the deep tint of the
tissues which has earned for the malady the name of charbon. This
asphyxiating action, however, does not suffice to explain death, taking
into consideration the fact that the bacilli are often found in very small
numbers in the blood, and that it has undergone other changes.
The bacilli becoming numerous in the vessels occasion real em-
barrassment to the circulation, if anything more when the blood becomes
viscous; they form emboli in the vessels, diminish the fluidity of the
blood, render the globules more sticky on account of a diastase which
they secrete, determine vascular obliterations and hæmorrhages (Tous-
saint). Similar lesions are produced in the various species of animals;
they are particularly remarkable in soliped animals; they are accom-
panied by voluminous œdemata in the neighbourhood of the ganglia, and
collection of fluid in the serous sacs, etc., In certain charbonous
animals the bacilli may take up their abode in the pia mater, become
very abundant in the vessels, and determine death by causing vascular
F
66
alteration in the nervous centres ; hence it is indicated that they should
be searched for in these organs when the animals have shown sign of
cerebral localization of the malady; this mode of action, as is the case
with the preceding one, does not always suffice to explain death.
It is more particularly by producing a veritable intoxication that the
bacteria determine death. The microbes of charbon in fact secrete toxic
matters. Charbonous blood previously filtered and then mixed with
normal blood, renders the globules of the latter more agglutinative
(Pasteur) ; this implies the presence of some diastase. Besides this,
according to Toussaint, we produce a local inflammation in animals which
are refractory to the disease with filtered blood, which proves the
presence of a soluble pathogenic substance. Hofa has found a very
active ptomaine in cultures of the virus made on meat. M. Chauveau,
by inoculating 100 grammes of the blood of a sheep dead of charbon, has
caused rapid death of the inoculated sheep which was previously vac-
cinated ; death was due to veritable poisoning, and there was no mul-
tiplication of the germs in the blood. M. Gamaleia, by treating the
spleen of a charbonous animal with strong alcohol, and afterwards
removing the coagulum with water, has obtained a liquid which caused
high fever in the rabbit.
To sum up, then, when an animal has become accidentally or experi-
mentally inoculated, the bacilli multiply at the seat of inoculation, and
secrete diastatic and toxic products. They set up irritation, inflamma-
tion, exudation, local infiltration and œdema which serves as a culture
medium for them, and extend towards and about the ganglia where the
lymphatics come off. Bacilli pass into the lymphatic vessels ; the
microbes soon arrive in the neighbouring ganglia, set up inflammation,
multiply, then pass into the efferent vessels and arrive at a second gang.
lion, and finally are conducted into the blood-stream ; arrived in the blood,
they multiply and go no further, excepting when vascular ruptures occur;
it is on this account that if we inject the virus into a vein, animals die
without presenting other lesions than those of the vessels; and also that
physiological secretion, such as bile, urine, milk, the products of glands,
do not contain the germs unless as the result of vascular ruptures;
in fact charbon appears as an intravascular blood disease. But vas-
cular lesions in the form of ruptures are common in charbon, more
especially in solipeds, and the ox and sheep, etc. The circulation is
impeded in the capillaries by the accumulation and felting of the
bacilli and by the viscosity of the blood ; the bacilli form agglomerated
masses which obstruct the circulation in the tortuous capillaries. In
the rabbit they pass through vessels, which easily rupture ; in the
sheep, ruptures are produced in the kidney and intestine, whilst in
solipeds ruptures are numerous and occur in various organs, the serous
67
membranes, in the connective tissues, etc. With these changes, the
asphyxiating supply of bacilli increases more and more, as does also
the sum of their diastatic and toxic secretions, and death occurs more
particularly as a consequence of poisoning by these.
Degrees of Receptivity— Predisposing causes—Immunity.—
Charbon may attack the various domesticated animals, and likewise
man ; but the receptivity varies with the species, individuals, the age,
mode of entry of the virus, and the quantity and quality of the virus
absorbed.
Herbivora—the sheep, goat, ox, horse, stag, and deer—are endowed
with a great receptivity to the virus of charbon. Viewed from the stand-
point of the occurrence of spontaneous charbon, sheep and goats come
first, then the large ruminants and solipeds. The small domesticated
animals, such as the rabbit and guinea-pig, are very susceptible, and
although they are not as a rule exposed to conditions which render the
spontaneous development of charbon likely, they contract it very readily
when inoculated. The sheep and the horse take inoculated charbon
readily: the ox shows a greater resistance.
Camels contract the disease, it is said. As regards the rabbit, guinea-
pig, and mouse, nothing is easier than to infect them experimentally by
subcutaneous inoculation ; in ten to fifteen hours a local œdema, accom-
panied by an elevation of temperature, appears ; the inoculated animals,
apart from these symptoms, seem to be in perfect health until a short
time before death, which occurs in 36 to 48 hours in the guinea-pig and
48 to 60 in the rabbit. Some moments before death the animals become
agitated, respire quickly, fall into a state of coma, and succumb after
some convulsions with notable lowering of the temperature. During
the last moments of life bacilli appear in the blood, and at the autopsy,
besides the ordinary signs of charbon already mentioned, we always
observe at the point of inoculation the presence of a gelatinous exudation,
transparent, sometimes faintly red-tinged, containing ordinary rods, in
fewer numbers, but longer than those met with in the blood.
The pig is generally endowed with a very slight receptivity ; he may
occasionally contract charbon experimentally or accidentally. The
carnivora—dogs and cats—are also less apt to contract charbon sponta-
neously ; cases of accidental contagion have nevertheless been recorded,
and the transmission of the disease by inoculation has been obtained.
As to birds, their receptivity is still less; it is not noted in them as
occurring by natural infection, and it is only by submitting them to
experimental inoculation, under special conditions, that we can produce
charbon in them. Lastly, man may be infected in different ways as has
already been shown.
F 2
68
If such is the influence of species, it is necessary to add that it may
be modified more or less by influences, which remain to be examined, by
race, individuality, age, mode of inoculation, by certain debilitating
influences, and by the quantity and quality of the virus.
Race may exert a considerable influence, rendering quasi-refractory
animals belonging to species the most predisposed. So it is in the ovine
species, the Algerian races offering a natural resistance to charbon.
Algerian sheep were introduced on this account to the shores of the
Mediterranean. This peculiarity of the Algerian sheep, well known to
breeders in the south-east of France, has been verified experimentally by
M. Chauveau. However, the resistance of Algerian sheep is not always
absolute; it may be overcome by the introduction of a strong dose of the
virus (Chauveau). From observations made it appears that certain of
these sheep contract spontaneous charbon, and also that the quasi-immu-
nity becomes much weaker, and finally lost in those animals which are
imported and reared in France. Also, according to M. Chauveau,
French sheep imported into Algeria do not appear to acquire a like im-
munity, and it is therefore beyond doubt that the immunity is due to
race. The Indian sheep is very susceptible to the disease. Horses,
which in Sardinia, Russia, Siberia, etc., are frequently attacked, are
more rarely so in France and Central Europe. Toussaint says the ass,
and Tayon more particularly the African ass, contracts charbon less
easily than does the horse.
Certain subjects belonging to species the most susceptible, may some-
times present an individual immunity not becoming, infected in danger-
ous centres, escaping experimental infection by ingestion, and sometimes
even resisting inoculation. This individual immunity may be due to
the great resistance of the organism to the disease, or, better, to a certain
degree of natural vaccination which the animals have undergone in the
media where they live.
The age of animals contributes greatly to modify their receptivity;
with a few exceptions it is more especially in youth that the contagium
is virulent; young animals belonging to quasi-refractory species may be
more easily infected than adults. In the same way young pigs ordina-
rily contract charbon after inoculation (Crookshank and Peuch) ; young
birds and puppies may be infected in large proportion by inoculation
(G. Colin, Œmler).
The mode of introduction of the virus may also exercise real influ-
ence upon the degree of receptivity of the animal. We may, for example,
give fatal charbon to animals not naturally susceptible, by inoculating
them subcutaneously with the virus; bovine animals appear to be less
sensible to contagion by inoculation than to natural contagion, whilst
horses, again, are more susceptible to inoculation than to naturally-
69
contracted charbon. Again, injection of the virus into the anterior
chamber of the eye is more fatal in the pigeon than is subcutaneous in-
oculation. Numerous influences may modify the receptivity of the ani-
mals ; these are for the most part influences which are of a debilitating
nature. So, as Pasteur has shown, we may render the fowl susceptible
by lowering its temperature; and Giber shows that, inversely, we may in-
oculate the frog successfully by raising the temperature. Sheep are, ac-
cording to Rodet, rendered susceptible by bleeding before inoculation,
Feser states that feeding on watery foods intensifies the action of the
virus. Bardach says that ablation of the spleen, and the intravenous in-
jection of inert powders, increase the receptivity in the dog. According
to Charrin and Roget, fatigue renders white rats, which are often refrac-
tory, more apt to contract charbon. Canalis and Morpurgo state that
inanition commenced some days before inoculation, or even afterwards,
renders the pigeon susceptible to charbon, and it is the same with the
fowl. Privation then may result, as I have observed, in many animals
in increase or even creation of susceptibility. So also, according to
Platania and Wagner, the introduction into the system of such sub-
stances as curare, alcohol, chloral, enables us to give charbon to the frog,
fowl, and pigeon. So may previous disease or bad hygienic conditions
increase the receptivity of animals.
The quantity and the quality or energy of the virus has a consider-
able effect on the susceptibility of individuals to charbon; the least
susceptible animals may be rendered more or less gravely ill by the
introduction of strong large doses of the virus, more particularly when
it is very active. Algerian sheep, for example, may become charbon-
ous after inoculation with very large doses of virus (Chauveau). To sum
up, the differences which have been observed regarding the receptivity
of animals relates to the species, race, individuals, age, state of health,
hygienic conditions, the mode of entry of the virus, and its quality
and quantity. This resistance is variable; it is more or less permanent
and complete: it rarely, however, enables animals to withstand experi-
mental inoculation. It is explained by the increase and diminution
of the power of the phagocytes and the bactericidal state of the
tissues; the influences which diminish it act by lessening these two
powers.
Natural immunity leads us to the consideration of acquired or con-
ferred immunity of vaccination, and the attenuation of the virus of
charbon.
Attenuation of the virus of charbon.—We were led to the idea
of vaccination and the enquiry into a mode of attenuation of the virus
of charbon, by the observation of the non receptivity of animals which
had previously suffered from an attack of the disease.
70
M. Pasteur, after having observed that fowls fed upon food soiled
with the material of fowl cholera, became vaccinated, endowed with
immunity, and rendered refractory, when they did not die, also noticed
that certain sheep which had ingested food soiled by the virus of char-
bon, escaped death after having been visibly ill, and that they after.
wards resisted inoculation with charbonous material. He asked himself
if it might not, under these circumstances, be possible to vaccinate sheep
against the disease by previously submitting them gradually to the
ingestion of food soiled by the spores of charbon (July 1880). After
this, M. Pasteur observed, in September 1880, that the cow might recover
spontaneously from charbon, and that once recovered she was vaccinated.
Pasteur then came to the conclusion that ovine and bovine animals
which had recovered from spontaneous charbon or from the inoculated
disease were immune. M. Chauveau also noted the immunity of Algerian
sheep and the immunity of lambs born of a mother inoculated with
the disease during gestation.
Attenuation by heat.—M. Pasteur having succeeded in attenu-
ating the virus of fowl cholera and transforming it into a vaccine,
Toussaint attenuated the virus of charbon, and invented the procedure
of attenuation by heat, and also that of attenuation by the use of an
antiseptic. Inspired by the discoveries of Pasteur, who vaccinated
the choleraic virus and found that the vaccinated fowl resisted cholera,
Toussaint sought and found the first means of vaccinating charbonous
blood by following a method different to that which had led Pasteur
to vaccinate the virus of cholera, and which had been kept a secret.
He defibrinated charbonous blood, passed it through linen, and then
filtered it, after having diluted it, through twelve folds of paper; he
inoculated the filtrate into a first series of animals, which it rendered
seriously ill, but which recovered, and were found to be vaccinated.
However, Toussaint, who essayed to vaccinate with a charbonous humor
deprived of microbes, recognized that it was a dangerous method, as the
filters of tenallowed bacilli to pas sthrough them, which destroyed the
animals instead of protecting them. Filtration is in fact a defective
mode of procedure. Generally, filtered blood gives, by inoculation, one
or other of the following results : it induces charbon and destroys the
animal; or it gives nothing, and does not confer immunity. We cannot
obtain a charbonous blood so surely vaccinal by diluting it, as by
filtration, which arrests the majority of the bacteria.
Toussaint, abandoning the procedure of attenuation by filtration, had
recourse to the employment of heat. He observed a fact of great
importance, which has served as a basis to the general method of attenu-
ation of virus; he recognized that, by the employment of heat, we
could diminish the power of charbonous virus to such an extent as to
71
be able to inoculate it without causing the death of the animal, and
that we could at the same time confer an immunity against the attacks
of a non-attenuated virus.
He obtained charbonous blood, suitable for inoculation, which did
not produce charbouous fever in a fatal degree, but only a very slight
attack, and which conferred immunity, by heating for ten minutes, at
55° C., charbonous blood which had been previously defibrinated. Scarce-
ly had this mode of procedure been published than it was attacked by
Pasteur, who was not, however, able to confute the fact that heat was
capable of attenuating the virus of charbon. Toussaint was for the
moment mistaken as to the explanation of the mode of action of heat
and believed that the heating destroyed the bacteria; he attributed
the immunity to the introduction into the organism of a material which
was antagonistic to the development of the bacteria. In reality he
was nearly, in so thinking, attributing the immunity which he had
obtained to the action of heat in attenuating the virus.
Pasteur denied this explanation; he remarked that the bacillus
could resist a temperature of 55° C. for ten minutes, and even for a
longer time ; he recognized that the bacilli were modified, and that it
was not the soluble product formed by it during its life which was the
cause of the vaccination in Toussaint's experiments; he observed that
when heat was sufficiently applied to kill the microbes, as could be
assured by culture, inoculation was not preventive. However, as we
shall see later, the soluble products are capable of conferring immunity.
Besides this, Trasbot had recognized that the blood of the fœtus of a
sheep dead of charbon, which did not contain any bacilli, did not pos-
sess any vaccinal properties.
Pasteur recognized, in short, that in the procedure of attenuating by
heat he might arrive at one of the three following results: frequently
the virus, the bacilli, are killed by the heating, and inoculation does
not give immunity; at other times the virus retains mortal virulence
and inoculation kills; at other times, again, the bacilli are attenuated
and inoculation may confer immunity, though the bacilli thus attenuated
are not of the nature of stock, but may regain their virulence in the
organism and in cultures.
Toussaint was then the first demonstrator of the possibility of pre-
serving from charbon by preventive inoculations ; he first succeeded in
attenuating the virus and rendering it vaccinal, and although his method
has not furnished altogether the practical solution of vaccination, it is
nons the less true that it has in the end done so after perfecting and
development by M. Chauveau. On the other hand, the method of
attenuation by heat offers immense advantages by permitting us to
attenuate virus, the agent of which has not been determined. It has