SERUM TREATMENT IN TYPHOID FEVER. By Surgeon-Major G. M. Shewan.

The resistance to typhoid seen in the native? plains native at any rate?attracts at outset here, but the troop of explanations that would be required in even touching that subject, warns off. Moreover, " a certain dgards, one it semble que les progres de la science contemporaine ont fourni plus d'explications qu'ils n'ont apporte d'acquisitions nouvelles." A Charrin, Revue d'liygiene, No. 2, 1894, and this is a case in point.*

the

*

"

"

immunity, immunity acquired during: first insymbiose," exhausted terrain," altered intestinal

Inborn

fancy.

"

flora, &c.

"

" * * Davidson tells us * Among the theories that have been advanced to account for the comparative immunity of the adult native population, it has been suggested that this disease is extremely common among native children, and that the comparative freedom which adults appear to enjoy is due to an immunity conferred by a previous attack in early life. We well know that the children " of natives in India suffer much from " fever accompanied in many instances by diarrhoea ; but we hardly think it this of without to theory immunity accept very possible definite proofs which, at the present time, are not forth-

coming."

******

this, at the International Congress in London in 1891, Surgn.-Col. Hendley, referring to hygienic conditions in Native States, spoke of native mothers suckling their Before

long after they could run, and of ten thousand fat dogs scavenging in a town of fifteen thousand souls. It would be wrong, he said, for us to interfere with natural defences such as these, except in replacing them with a really good sanitary service. At the same Congress he went on to say that many Indian physicians believe we so rarely see typhoid in the native, because he is infected in infancy as a rule. At any rate, whatever we or our grandfathers thought, the resistance to typhoid seen in the adult native, can no longer be referred to anatomo-physiological race difference. children

We must consider now that in an environment fatal to our young soldier, the native is alone defended by inbred habit and peculiar conditions of life, and that, in fact, he has acquired a degree of immunity as we now define that word. Typhoid is known to be prevalent among Gurkhas. This to do with a native hill prevalence, it is said, has nothing " entourage, but is because, he feeds very much like

Europeans,

drinks alchoholic beverages

and

eats

meat." Well, if the little man does all that, so does the "plains native" in great part; yet we note no varying receptivity among "castes" and communities there. In first infancy?below 2 years?prognosis in typhoid The symptoms are those of a septicaemia, is very grave. or a subacute gastro-enteritis; temperature is subnormal ; prostration is profound. Then during second infancy,?from 2 to 5 years,?the disease only occurs in mildest form. Here they say, * *

16

INDIAN MEDICAL GAZETTE.

122

Nor need I trouble here with the difference " between vaccination and serum treatment; I necessarily have to refer to both under the one heading. Disease germs act by "toxines" they secrete, and much that before was vaguely referred to "infection," is now spoken of as In serum treatment applied, "intoxication." we consider two acts in the life history of a disease germ, multiplication of the germ and secretion by it of a poison to be taken as direct cause of the disease. Infection therefore we are to prevent, by opposing multiplication of the germ on the one hand, intoxication by its poison on the other. Pasteur's vaccination against rabies is our best example of the first; Behring's serum treatment of diphtheria illustrates the second. All animals tested as yet are naturally refractory to typhoid. Until 1892, Chantemesse and Widal had only been able to obtain by inoculation a tumefaction of Peyer's patches in one guinea-pig. Inoculation of animals therefore, with this small degree of resemblance in any lesions produced, was once invoked to disprove specific power in Eberth's bacillus. Then, however, Chantemesse and Widal on the one hand, and Sanarelli on the other, independently came to see, that by successive passage through guinea-pigs virulence in the germ could be greatly heightened. They went on and found that with the germ then, they could always arouse in other guinea-pigs a disease condition characterised by general congestion of all mucus membranes, of the intestinal mucus membrane in particular, and marked desquamation of epithelium and swelling of lymph follicles in this last. Instead of fever, however, there was always fall in temperature until death. Sanarelli explained that. "

Our knowledge of immunisation and serum treatment advanced more rapidly then. For " vaccine," Chantemesse and Widal, as far back as 1888, had used a bouillon culture sterilised filtration. Sanarelli's culture was also steriby lised by raising to 120?C. Breiger, Kitasato and Wasserman, however, only raised their culture to 80?C., and by concentrating and treating with alchohol then, obtained a vaccine which might hold the living germ, and which frequently caused accidents at the seat of injection. The soluble vaccines were found preferable, but speaking generall}', results disclosed that a lasting immunity was acquired by animals by the 3rd "

prognostic est des meilleurs ; ici se voient surtout, les f^bricules ou typhoidettes, qui sont souvent confondues * * * '' avec les embarras gastriques (LeGeudre? dela Fievre 1895.) Typltoide, Therapeutique Now in Indian general practice, putting chest disease aside, we are seldom very sure of the cause of death in native children under 2, I think. Many may say, they have been more fortunate ; but how often have even these been able to exclude a septicaemia or a subacute gastroenteritis I would ask, and how often have they had to do " in the older native child ? with " les embarras gastriques le

.

[April

1896.

and that immunisation was more with the amount of injection survived. As the animals were found very sensitive to the poison, injections had to be most carefully watched, and here again the guinea-pig was the animal of choice, the rabbit being far too sensitive. or

4bh

day,

complete

Arrived at immunisation

then,

we

find it was first went power in and they

Breigev, Kifcasato, and Wasserman that on to prove a preventive and curative

tlie serum of animals vaccinated, received support at once from experiments by others. Bitter and also Bruschettini at the time, working with rabbits, threw much doubt on serum's curative power at least, and here first Stern came in, with experiments showing the wonderful protecting power in human serum, and which we notice at the end. Before all, however, we must allow that it was again the simultaneously published accounts of experiments by Chantemesse and Widal and by Sanarelli, that alone can be accepted as giving solid footing to these powers in the serum. Their researches first substantially proved that, by injecting the serum before or at the moment of injecting the virus, development of typhoid becomes impossible; that where b cc. of serum injected at the same time and at the same point as the virus would suffice, 2 cc. would be required if the injections be made at different points, or the serum be injected before the virus. The extremely rapid course of experimental typhoid in even the guinea-pig might have led us to believe a serum powerless in such " marche foudroyante," but these experimenters saw they could "trick" the malady half an hour Sanarelli even sucor one hour after infection. ceeded in saving a guinea-pig by injecting the peritoneum with 6 cc. of the curative serum 5 hours after injecting the virus. In their control experiments the serum of animals not vaccinated proved useless. To have done with experimental typhoid then, these and other authors applied results to man; but with the space remaining, and because of the important bearing it seems to have on a serum treatment here, as shortly as possible, I only notice the work done by Stern. (a.) Into the peritoneum of the guinea-pig or the mouse, Stern first injected the serum of convalescents taken during the 26 days following disappearance of fever. His results were for the most

part positive.

In using instead a serum collected during the ten years following a fever attack, he had positive results three times out of five. (c.) He found that by far the most powerfully acting serum ivas that taken from subjects who had died of the fever. (d.) He obtained positive results with larger doses of serum taken from subjects who had never had the fever.

(6.)

.

April

1896.]

CROMBIE: A RETROSPECT.

I need not go further than this. With Stern's and until we put them to test we are even wrong to think that we cannot obtain our protecting serum from a healthy " young immunised native in the dirtiest plains village" at hand. In this, the land of cholera it seems we are taking on trust, that a serum treatment against cholera can have no more lasting result than it is known to have in diphtheria, and I believe we are awaiting Haffkine's return with "Professor Pfeiffer of Berlin" to further establish this. Typhoid we have always with us, we cannot compare typhoid with cholera,?as some of us appear to think,?we have no excuse for delay. With our rapidly advancing knowledge of serum treatment in other disease?with our young soldier here and with the experiments of Chantemesse and Widal, of Sanarelli, and above all of Stern, in this disease with the native's acquired immunity, and I might say with the cause of that immunity staring us in the face; we are waiting, as we did in "snake-bite," expecting some Frenchman or other to come in and give us a hand.

experiments alone,

123

Serum Treatment in Typhoid Fever.

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