MUKTESAR, FOR THE YEAR ENDING THE 31ST MARCH, 1925
27
in greater detail, and the most important studies envisaged are, (i) factors in the production
of immunity, particularly in the development of a large yield of " antibodies," in the
circulating blood of animals, (ii) the possibility of fly transmission of the disease, and
(iii) the relationship between the disease and other complicating infections, notably coc-
cidiosis and piroplasmosis.
(1) Immunity researches. The conceptions entertained following upon an extensive
series of experimental observations regarding the nature of the reaction of a susceptible
animal to rinderpest have been stated in the preceding Report, and the practical or eco-
nomic issues in the section dealing with anti-serum manufacture in the present Report.
The pertinent conclusions are (i) that an animal susceptible to rinderpest elaborates free
antibodies, discoverable in its circulating blood in proportion to the degree of reaction
(as estimated by the pyrexia) it sets up to infection and from which it makes a good
recovery, (ii) that a solid, durable immunity, is nevertheless set up subsequent to infec-
tion which produces no outward clinical manifestation, or is even followed by a " symp-
tomless " affection, and (iii) that the methods hitherto practised of so-called " hyper¬
immunization " have no real merit, as would be assumed from the name, in driving up
the titre in circulating antibodies above that developed by the animal after the lapse of
a certain interval from the time when the pyrexia caused by the initial infection has
ceased. These conclusions would appear to apply at least most forcibly to the animal
used for a number of years as a serum producer for economic reasons in the laboratory,
namely, the plains buffalo of Northern India. They are not so strikingly evidenced with
the hill bull.
In the old routine process of " hyperimmunization," the animals destined to yield
the anti-serum were treated first by injecting them simultaneously with virulent blood
and a protective (but not definitely regulated) dose of serum. After an interval of three
weeks they were bled for serum, and then treated with a massive inoculation of virulent
blood; usually, no prolonged general disturbance followed this intervention, and the
animals were bled again for serum in eight and ten days. This process of massive viru-
lent injections followed after these intervals by bleedings was prosecuted indefinitely
although the experience of the laboratory over three years ago had indicated that it was
not profitable to repeat the treatment for a long time, partly on account of the develop-
ment of extensive abscesses at the sites of injection, and the animals were discontinued
from use after three months. A mixed serum obtained from these bleedings was usually
found on test to be of sufficient potency to render valuable service in the preventive
inoculation of susceptible animals in the field, but not infrequently" brews " were obtained
which fell below the desired potency. The first bleeding was found on test to be the
most valuable, but sometimes the second bleeding (after the first hyperimmunization)
furnished serum which transpired to be somewhat better; thenceforward the sera obtained
from successive bleedings diminished in potency. In some carefully executed tests it
was found that the potency was well sustained for twelve bleeding periods, and that the
potency curve showed a very occasional marked rise, due to an undiscoverable cause,
during its descent. On other occasions, as during extensive manufacture at Izatnagar in
1923-24, the potency was not maintained in a satisfactory state for more than two bleeding
periods; in this particular experience the staff employed had inadvertently " blocked
out" the initial reaction in the buffaloes by administering an excessive dose of anti-
serum simultaneously with the virus. In the series of tests upon the duration of potency
at successive bleedings in which this quality was well sustained the buffaloes had mani-
fested a " mild, but decided " reaction in the course of the preliminary immunization.
Evidence of this kind, the practice of the Philippine authorities recently published, and the
significant work of WEIL and BREINL upon the production of antibodies in guinea-pigs
and rabbits following upon infection with the virus of human typhus led to the institution
of experiments at Muktesar upon the relationship of the initial pyrexia to the amount
and duration of development of circulating antibodies. Preliminary trials indicated that
there was a close analogy between the phenomena exhibited in antibody development
in rinderpest and in typhus. The Indian buffalo corresponded with the guinea-pig in
behaviour towards these respective diseases, by the elaboration of antibodies quantita-
tively definitely correlated with the " amount" of pyrexia. The hill bull corresponded in
some measure again with the rabbit: this latter animal is stated by the authors not to have
responded by the development of circulating antibodies; the hill bull certanly responds
fairly well for a short time after the cessation of well defined pryexia, but in any event
the period during which the presence of antibodies in the circulating blood can be well
demonstrated is a fleeting one, not exceeding two or three weeks at most, even with the
application of routine " hyperimmunization."