NationalLibraryOfScotland/medical-history-of-british-india huggingface dataset:
GOAT TISSUE VACCINE FOR CONTROL OF OUTBREAKS OF RINDERPEST
79
occurred. Twenty animals were selected for this test, 16 cattle and 4 buffaloes.
The animal from which the virus was taken died of rinderpest.
All the animals immunised in this herd were allowed to mix freely with diseased
ones and no case of post-inoculation infection occurred.
The theoretical danger of animals contracting the disease during the negative
phase, appears to us to be negligible. In our experience cases of sickness after
injection have been genuine reactions to the inoculation or animals inoculated
during the incubation period of the disease. In our opinion the small quantity of
attenuated vaccine injected has not had any definite influence on the course of the
disease in these cases.
PREPARATION OF THE VACCINE FOR USE IN THE FIELD.
The ampoules sent out contain approximately 1 gram of spleen tissue in each.
This is prepared by removing the tissue and placing it in a glass mortar and emulsify-
ing with 0.75 saline solution. The saline is added gradually and decanted at intervals
until 100 c.c. have been used and the tissue thoroughly emulsified. This process
takes fully half an hour and at the end there should be only small particles of fibrous
tissue remaining in the mortar. We use an enamelled mug with a lid to contain the
emulsion to protect it from sunlight and dust. Small quantities are decanted into
a Petri dish for inoculation as required. The emulsion must be used on the day it is
prepared and be protected from excessive heat and sunlight.
In conclusion we wish to refer briefly to the work on goat virus done by Dr. J.
T. Edwards while at Muktesar. In the first instance the passage of bull virus
through goats was carried out with the object of removing piroplasms. After a
series of about 30 passages he discovered that it had acquired a very definite degree
of attenuation also. In view of this he hoped to work out a satisfactory vaccine
for use against rinderpest in place of serum alone and Serum Simultaneous methods
of inoculation. Mr Haddow continued the investigation work and evolved the
spleen tissue vaccine under report. From the results now published it seems that
this goat spleen vaccine fulfills the hopes of both investigators to a very great
extent. It is realised that the tissue vaccine has only been applied to plains animals
in Bengal and that it must be tentatively applied to other breeds in other provinces,
but from the known results of the work with goat blood virus in other provinces,
notably in the Central Provinces and Mysore, there is every reason to expect results
similar to those in Bengal. Should this be the case, the application of goat tissue
vaccine alone will revolutionise the methods of control of rinderpest in India.
G
80 THE INDIAN JOURNAL OF VETERINARY SCIENCE AND ANIMAL HUSBANDRY [ IV, I,
TABLE I.
Summary of goat virus (blood) alone inoculation in the scene of outbreak of rinderpest
in Bengal, 1933.
—
Cattle . . .
Buffaloes . .
Total
Number
Inoculated.
1,765
9
1,774
Reactors.
58=3.3 %
4=44 %
62=3.4 %
Death.
10=0.57 %
Nil
10=0.57 %
Remarks.
Details of reaction after inoculation.
2nd day .
.
.1 cow. .
3rd „ .
.
. 18 cows. .
7th day and upwards 39 cows 2.2%
Details of deaths.
† 5th day after inoculation 2 cows,
7th „ „
„
8 cows
0.45 %
N.B— *Out of 58 reactors 19 appear to have been vaccinated during the normal period of incuba¬
tion.
† Out of 10 deaths 2 died on 5th day after vaccination and were probably already infected
at the time of inoculation.
TABLE II.
Summary of rinderpest tissue vaccine (goat) inoculation in the scene of outbreak of
rinderpest in Bengal, 1933-34.
—
Cattle . . .
Buffaloes. . .
Total .
Number
inoculated.
10,119
645
10,764
Reactors.
167=1.6%
52=8.0 %
219=2.0 %
Deaths.
51=0.5 %
Nil.
51=0.47 %
Remarks.
Details of reaction after vaccination.
1st day 1 animal
2nd „ 5 animals
3rd „ 16 „
22 animals.*
Remainder 145 are the actual re
actors to vaccine=1.4 %
Details of deaths.
5th day . 4 died
6th „ . 2 „
7th. „ . 8 „
14.†
Remainder 37 apparently died as
result of vaccination=0.34.
N.B.—* Out of 167 reactors 22 appear from the records to have been vaccinated within the normal
incubation period.
† Out of 51 deaths 14 appear to have been within the normal incubation period when vaccina-
ted.
SELECTED ARTICLES
RABIES. A REVIEW OF RECENT ARTICLES, XIX..
BY
A. G. McKENDRICK.
[ Reprinted from Tropical. Discuses Bulletin, Vol. 30, No. 9, September 1933.]
1. VIRUS.
In a fully illustrated paper Levaditi, Schoen and Mezger 1 collect the researches
already summarized (this Bulletin, Vol. 30, p. 134), from communications to the
Bull. Acad. Med. and the C. R. Soc. Biol. They hold the opinion that the
" parasite of rabies " should be called Glugea Lyssae, and not as has been proposed
by Manouelian and Viala, Encephalitozoon rabiei. The morphological appearances
in no way resemble those of Encephalitozoon cuniculi. The spores of the latter have
a uniform appearance, and their volume in rabbits and mice is invariable. Their
structure is perfectly definite and so also are the cysts or pansporoblasts which
enclose them. The oxyphil corpuscles described by Levaditi and his co-workers in
rabies infections of mice, though they resemble in certain stages those described by
Manouelian and Viala in the rabbit and the dog, are in reality pansporoblasts con-
sisting of an infinity of sporules of dimensions which are almost ultramicroscopic.
The sporules do not posses definite characters at all comparable with the spores of
Encephalitozoon cuniculi.
A further study of the cystic stage of ' Glugea Lyssae' in the white mouse has
been made by Levaditi and Mezger 2 , using dark ground illumination with a
magnification of about 1,800 diameters. The cysts measure from 5 to 20 micro-
millimetres. They are covered by a refractile membrane, and are round or ovoid
These sacs contain the young cysts whose number is proportional to the size of the
envelope. The young cysts are also covered by a refractile membrane, they enclose
a dark substance, and are separated from each other by granular material.
. For the eighteenth of this series see Trop. Dis. Bull. Vol. 30, pages 133-143.
1 Levaditi (C.), Schoen (R.) and Mezger (J. G.). Etude morphologique du virus rabique. Arch.
Internat. Med. Experim. 1932. Dec. Vol. 7, No. 4, pages 655-692. With 21 figs. and 1 coloured plate.
(Refs. in foot-notes).
2
Lovaditi (C.) and Mezger (J. G.). Structure polykystique du parasiæ de la rage. C. R. Soc. Biol,
1933, Feb. 10, Vol. 112, No. 5, pp. 440-442. With 1 fig.
( 81 )
G 2
82 THE INDIAN JOURNAL OF VETERINARY SCIENCE AND ANIMAL HUSBANDRY [ IV, I.
That the ' noyau optique basal' of Nicolau and Kopciowska and what Thomas
and Jackson call the . nucleus oculomotorius' is a seat of election for Negri bodies
has been already referred to (Vol. 28, p. 744 and Vol. 29, p. 600). [There is no
doubt in the reviewer's mind that the seat of election described by the latter authors
in October 1930 is the same as that described by the French authors in May 1932].
The French authors, it will be remembered, found Negri bodies in this region in
fixed virus rabies of rabbits. They 3 confirm this observation in the case of two
strains of fixed virus, one a virus of Chien fou isolated by Mathis and Constanti¬
nesco (Vol. 29, p. 597), and the other a highly virulent strain of fixed virus isolated
by Jonnesco in Rumania (Vol. 30, p. 136). In the case of the Mathis strain the
inclusions are much more numerous and of larger dimensions in the seat of election
than in the horn of Ammon. In the case of the Rumanian strain they are so small
and rare as to be practically non-existent in the horn of Ammon, whereas in the
elective zone they are numerous, of large dimensions, and show the characteristic
internal structure.
A full account of the occurrence of rabies in the Union of South Africa is
given by Neitz and Marais 4 . The summary by Dutoit quoted in this Bulletin,
Vol. 28, pp. 742-743, brought the history up to 1928. It now appears that since
that date the existence of rabies has been proved in thirty instances, and presumed
on clinical evidence in six other instances. Of these, eight have occurred in the
human subject. As before genets and meerkats appear to be the most usual source
of infection. Photographs of these animals are given, and also maps showing the
distribution of the disease. The probable origin of the infection is discussed, and
methods of control, adopted and proposed, are considered.
It will be remembered that Vaucel, Boisseau and Saleun proved by cross
immunity experiments that a strain of street virus from Brazzaville (French
Equatorial Africa) was identical with the rabies virus of Europe. Vaucel and
Saleun 5 have now studied three other strains of virus from the same vicinity. In
each case they have experienced no difficulty in passaging the strain through many
generations, and in two, crossed immunity experiments have shown that the viruses
were identical with rabies. " In spite of the diversity and indefiniteness of the
3
Nicolau (S.) and Kopciowska (L.). Rage du lapin, à virus fixe, et corps de Negri; dénombrement
comparatif des inclusions dans la come d'Ammon et dans la zone elective (noyau optique basal),
C. R. Soc. Biol. 1933, Feb. 10, Vol. 112, No. 5, pp. 445-448. With 2 figs.
4
Neitz (W. O.) and Marais (I.P.) Rabies as it occurs in the Union of South Africa. Union of
South Africa 18th Report, Director Vet. Services and Animal Industry, Onderstepoort, Pretoria, 1932.
Aug. pp. 71-93. With 5 figs. and 6 maps, 32 refs.
5 Vaucel (M.) and Saleun (G.). Rage canine en Afrique Equatoriale Francaise. Bull. Soc. Path,
Exot, 1932, Dec, 14, Vol. 25, No. 10, pp. 1018-1021.
RABIES
83
symptoms observed in the animal, the three strains which have been studied have
behaved, from the histological point of view, like those of true rabies."
An exceptionally virulent strain of street virus is described by Palawandow
and Serebrennaja 6 . It was obtained at the Odessa Institute from the saliva of a
twelve-year-old girl, bitten by a dog on the leg. She had received no treatment and
developed rabies after an incubation period of two months. The first passage of
saliva intramuscularly into a guinea pig gave an incubation period of 12 days. In
eleven subdural subpassages in guineapigs the incubation varied from 1 to 4 days
and averaged about 2½ days. The manimal lethal dose was 0.2 cc. of a 1 in 75,000
dilution. The virus is now in its 40th passage. After the eleventh passage a
feature of extraordinary interest was noticed that the incubation periods gradually
lengthened. From the 10th to the 29th passages the incubation for guineapigs was
3-3½ days, and for rabbits 3-4 days. After the 29th the incubation period for
guineapigs was 4-6 days, and for rabbits 5-7 days ; in fact the virus had become
fixed virus. (It is impossible to reconcile these facts with the view which is usually
held that fixed virus is a virus which has become accommodated to the easier mode
of transmission from brain to brain, whereas street virus is accustomed to a much
more complicated transmission from saliva to nerve-endings and central nervous
system and vice versa at each passage. The authors assume that in the case of the
Sokolan strain (described above) the virus comes to equilibrium as a fixed virus
after the elimination of some accelerating influence.)
The strain of fixed virus employed at Budapest has been examined by Aujeszky
and Kerbler. 7 This virus was taken from a dog by Högyes in 1886 and is now in
(approximately) its 17,000th passage. The dose which will kill with certainty when
injected subdurally is 0.15 cc. of a dilution of 1 in 6,000, that is to say 0.025
milligrammes of brain substance. The incubation period has shortened—paralysis
on the 5th day—and the period of illness has also diminished.
In a previous communication (this Bulletin, Vol. 29, p. 189), Shope drew
attention to the close resemblance between the virus of the " mad itch " of cattle
in America, and the pseudorabies of Aujeszky. He has now 8 carried out cross
immunity experiments between a " mad itch " virus obtained from a cow in Iowa,
and a pseudorabies virus furnished by Aujeszky from Budapest. The various
6
Palawandow (Haidar) and Serebrennaja (A. I.). Ueber einig Eigentumlichkeiten der im Odessaer
Balderiologischen Institute isolierien Strassenvira. Ztschr. f. Immunitatsf, u. Experim. Therap. 1933.
Vol. 78, No. 3-4, pp. 230-233, 12 refs.
7
Aujeszky (A.) and Kerbler (F.). Ueber Veranderungen der biologischen Eigensehaften des Virus
fixe. Giorn. di Batteriol. e Immunol. 1933, Feb. Vol. 10, No. 2, pp. 257-266,10 refs. English summary.
8
Shope (Richard E.). Identity of the Virus causing 'Mad Itch' and Pseudorabies. Proc. Soc.
Experim. Biol. and Med. 1932, Dec. Vol. 30, No. 3, pp. 308-309.
84 THE INDIAN JOURNAL OF VETERINARY SCIENCE AND ANIMAL HUSBANDRY f IV, I.
mixtures of serum and virus were stored in the refrigerator over night. The results
were as follows:—
Virus.
Pseudorabies
....
„ . . . .
„
.
.
.
.
Mad itch
.
.
„ . . . .
„ . . . .
Serum.
Normal .
.
.
.
.
.
Pseudorabies convalescent . .
Mad itch convalescent . . .
Normal
.
.
.
.
.
.
Pseudorabies convalescent . .
Mad itch convalescent . . .
No. of
Guineapigs.
5
6
4
5
6
4
No. died.
5
0
0
5
0
0
1 cc. of a 10 per cent. suspension of virus was mixed with 0.5 cc. serum from
a pig: 1.5 cc. of the mixture was inoculated subcutaneously. " In recognition of
the identity . . . the mad itch virus will in future be designated as Pseu-
dorabies Virus (Iowa strain)."
In a second communication 9 Shope continues his study of this strain.
The virus was passaged separately through the brains of 9 guineapigs and 12
rabbits. From titration experiments it appeared that following fatal cerebral
infection the virus is ten times more prevalent in rabbit brain than in guineapig
brain, and that the guineapig is about 100 times more resistant to subcutaneous
dosage than is the rabbit. " Over and above the working of these two factors,
guineapig passage appears to achieve some actual attenuation of virus when tested
by subcutaneous inoculation into guineapigs."
According to Remlinger and Bailly 10 the virus of the pseudorabies of
Aujeszky when injected into the tissues of a receptive animal does not suffer any
" eclipse " (Tropical Diseases Bulletin, Vol. 27, p. 252). It multiplies in situ until it
passes into the blood and from thence into the central nervous system. Here it multi¬
9 Shope (Richard E.). Modification of the Pathogenicity of Pseudeabies Vims by Animal
Passage. Jl. Experim Med. 1933. June 1, Vol. 57. No. 6, pp. 925-931.
10 Remlinger (P.) and Bailly (J.) Le siege du virus dans la maladie d'Aujeszky experimentale.
C. R. Sec. Biol. 1933, Vol. 113, No. 18, pp. 125-126.
98 THE INDIAN JOURNAL OF VETERINARY SCIENCE AND ANIMAL HUSBANDRY [ IV, I.
mouth disease from Southern Rhodesia. Reports from his District Veterinary
Officers are included which show that the original directions were in some
cases slightly modified but that the general principles laid down were adhered
to, one or other of the methods being adopted. Generally speaking, the idea was to
" burn the disease out " instead of allowing it to smoulder indefinitely, and to
establish, belts of immune cattle between infected and clean areas. The Chief
Veterinary Surgeon states, " It was indicated in my report for 1931 that two of the
methods recommended by the Director of Veterinary Research, Mr. LI. E. W. Bevan,
for the rapid spread of infection in areas likely to become infected were adopted.
The direct contact method, that is, the introduction of diseased animals was carried
out on a large scale in the Victoria area with very satisfactory results. In all other
areas the intra-nasal method of inoculation was practised. The total number of
cattle inoculated during the year was 185,388. The results were extraordinarily
satisfactory, the reactions being invariably well marked, practically 100 per cent.,
excluding calves, and all signs of active infection had generally disappeared in less
than four weeks from the date of inoculation. In two instances only was there
any variation from the normal reactions ; in these, fresh cases of disease continued
to appear up to thirty days from the date of inoculation. Inoculation, of course,
cannot be successful unless a cattle-free belt is established between the area in which
it is being carried out and the surrounding clean country. The method usually
adopted was to concentrate the cattle for inoculation and, where feasible, move
cattle not in immediate contact with infection outwards, thus creating a cattle-free
belt, both sides of which were strongly guarded." Since the elimination of the
disease from Rhodesia it has appeared in the Bechuanaland Protectorate, where it
is being dealt with by the intra nasal method of inoculation slightly modified to
local conditions. According to the latest reports some 85,000 cattle have been
treated.
In the course of this unique experiment on an enormous scale, several interesting
observations were made by officers in the field. With regard to the duration of
immunity resulting from infection with the Rhodesian virus the Chief Veterinary
Surgeon states, "There is no doubt that it gives a complete immunity for a consider-
able period. This is demonstrated by the inoculation with proved virulent blood
of 266 head of transport oxen at the Nuanetsi Ranch which had been infected about
fourteen months previously. Not a single beast showed the slightest sign of a
reaction to the inoculation."
One officer presents evidence which indicates that calves born of cows shortly
after recovery from natural infection are immune. Concerning methods of dis-
semination of the disease in Rhodesia, experience has gone to prove the accuracy of
the earlier theories. The Chief Veterinary Surgeon writes :—" It can be stated with
86 THE INDIAN JOURNAL OF VETERINARY SCIENCE AND ANIMAL HUSBANDRY [ IV, I.
inoculated by this route. That the viruses were potent was proved by control
experiments using various routes.
II. SYMPTOMATOLOGY.
A case of rabies with an incubation period of 14 months is described by
Hajare. 13
The clinical features of two cases of rabies are reported from Philadelphia,
U. S. A., by Reisman, Fox, Alpers and Cooper 14 . In one of the cases an
autopsy was parformed, and the microscopic appearances in the brain and cord are
described in detail. Neither case presented any unusual features.
III. DIAGNOSIS.
Serebrennaja and Pugatsch 15 recount their experiences in the diagnosis of
rabies. During six years they have examined 1,096 brains of suspected animals.
Of the three methods of staining employed, those of Stutzer, Muromzew and
Turewitsch, they have found the last to be the most exact. The composition of
this stain given as haematoxylin, acid fuchsin and picric acid, without further
details. From their results they conclude that Negri bodies are living growing
bodies with a definite life cycle.
IV. PATHOLOGY.
It will be remembered that Marie 16 obtained contradictory results when rabies
virus was inoculated intramuscularly, intravenously or subscutaneously, after the
reticulo-endothelial system had been blocked with Indian ink. He has now
repeated these experiments with the difference that the infecting dose was intro-
duced into the peritoneal cavity. The experimental details will be published
later; the conclusions are stated to be as follows : (1) That even large doses of
fixed virus do not infect when introduced into the peritoneal cavity is well known
(2) If, however, Indian ink emulsion is previously injected, infection occurs in
13 Hajare (S.S.). A Case of Rabies with an unusually long Incubation Period.—Indian Med. Gaz.
1933. Apr. Vol. 68. No. 4. p. 212.
14 Riesman (David), Fox (W. W.), Alpers (B. J.) and Cooper (David A.) Hydrophobia. Report
of Two Fatal Cases with Pathologic Studies in One.—Arch. Intern.. Med. 1933. May, Vol. 51, No. 5.
pp. 643-655. With 8 figs.
15 Serebrennaja (A.) and Pugatsch (E.) Ueber die Rolle der Negrikorper bei der Diagnose-
stellung and Aetiologie der Tollwut.—Zent. f. Bakt. I. Abt. Orig. 1933. Feb. 23. Vol. 127, No. 7-8,
pp. 417-426.
16 Marie (A. C.) De L'infection rabique par la voie peritoneale.—C. R. Soc. Biol. 1932, Dec. 16,
Vol. III, No. 39, pp. 869-870.
RABIES
87
guineapigs with an incubation period of from 9-20 days. In two sets of six
animals, only one of the first set and two of the second failed to contract the
disease. (3) A suspension of 'Deinse' (2 cc. phosphate disodique 5 per cent.,
with 0.5 cc. chloride of calcium 5 per cent.) gave a similar result. (4) Guineapigs
which survived after intraperitoneal injection of fixed virus (without previous
treatment by Indian ink) were found to be not immune to intraocular inoculation.
Havens and Mayfield 17 continue their study of the antigenic properties of
rabies virus (Vol, 29, p. 601). In the earlier communication it was found that
fixed virus immune serum failed to cause flocculation of 1 out of 16 strains of
street virus. The authors have now found three other strains which were not
agglutinable. The antigenic composition of these inagglutinable strains are
investigated in the present communication, using fixed virus as a basis for com-
parison. Nine strains (including the 4 non-agglutinable strains and one of
fixed virus) and nine homologous immune sera, were set up against each other.
The fixed virus was agglutinated by all the sera in approximately the
similar degree, suggesting that all the strains possessed a common factor. ' That
they possessed additional factors in their antigenic composition was shown by the
failure of all but one to agglutinate to the titre of the fixed virus'. No two of
the strains appeared to be identical. Cross absorption tests were then carried
out. That the absorption was specific was indicated by the fact that normal
brain suspensions had no absorptive power. Marked dissimilarities between parti-
cular strains were observed, but again there was evidence of the existence of some
common factor. Viricidal tests were then carried out and these again disclosed
the existence of ' apparently fundamental differences between the strains. They
also indicated, however, that it is the common factor that is most essential in the
production of immunity . The differences observed seem to be due to the pre-
sence or absence in whole or in part, of additional antigenic factors.
Greval 18,1 9 describes in detail a method based upon the Wassermann tech-
nique, for estimating the degree of complement fixation. He proposes to use
this method both for comparisons of sera, and for comparisons of antirabic vac¬
cines as antigens. From experiments, which are not given in detail, it appeared
that the antigenic capacity of vaccines improved with keeping, and that rabbit
17 Havens (Leon C.) and Mayfield (Catherine R.). Antigenic Properties of the Virus of Rabies. II.
Multiplicity of Strains as shown by Agglutinin Absorption and Neutralization.—JL Infect. Dis. 1932.
Nov.—Dec. Vol. 51, No. 3, pp. 511-518.
18 Greval (S. D. S.). On Rabies. Complement Fixation in Rabies; the Technique, its Purpose and
Associated Considerations.—Indian Jl. Med. Res. 1933. Jan. Vol. 20. No; 3. pp. 913-920. [13
refs.]
19 Greval (S.D.S.). The Role of Serology in Rabies.—Indian Med. Gaz. 1932. Dec. Vol. 67,
No. 12. pp. 676-678. [13 refs.]