Street Virus Research Articles

Use of hyperimmune antirabies serum concentrates in experimental rabies

Hyperimmune antirabies serum concentrates have been prepared in rabbits and sheep. One injection of antiserum exerted a definite protective effect in hamsters and in guinea pigs which had been infected twenty-four hours previously with street virus. In contrast, a course of fourteen injections of phenolized rabies vaccine instituted twenty-four hours after exposure failed in all instances to protect the exposed animals from rabies. A combined antiserum plus vaccine treatment of exposed hamsters seemed neither to enhance nor to decrease the protective power of antiserum administered alone. An effective protective dose of antiserum has been calculated for guinea pigs and hamsters, and a tentative dose of 0.5 ml. per kg. of body weight has been suggested for use in humans after moderate exposure (twenty-four hours after exposure). Several cases of antiserum treatment of humans exposed to rabies have been described and discussed. In a general discussion of the problem the conclusion was reached that antiserum seems to have definite value and should be applied in every case of exposure to rabies, in conjunction with a short course of vaccine treatment.

In Vitro Cultivation of the Street Virus of Rabies

In Vitro Cultivation of the Street Virus of Rabies

The Potencies of Commercial Antirabic Vaccines

Summary Studies are made of the potencies of a large number of commercial phenolized and chloroform-killed anti-rabic vaccines using homologous and heterologous strains of challenge virus. Vaccinated mice have responded nearly equally to the two strains of fixed virus used; with one exception the vaccines developing the best protection against street virus were those most potent against these fixed viruses. All evidence points to the fact that a mouse test of vaccine potency made with fixed virus is a practical way of eliminating impotent commercial vaccines. It is shown that closely related strains of mice may differ in the immunity they develop following vaccination.

INFLUENCE OF AGE FACTORS ON SUSCEPTIBILITY OF MICE TO RABIES VIRUS

1. 7 to 9 day old mice are more susceptible than older mice to injections of fixed or street virus by any route. 2. 20 day old mice are more susceptible than 60 day old mice to peripheral but not intracerebral injection of fixed virus. 3. 20 day and 60 day old mice are equally susceptible to street virus.

On the evolution of fixed strains of rabies virus

We know, since the time of Pasteur, that repeated passage of rabies street virus from rabbit to rabbit after intracerebral inoculation, leads to a modification of its effect and the appearance of mutative characters. This takes place at a variable period of time depending upon the strain employed. The irreversibility and the permanence of these characters has led to the name of “fixed virus” once the street virus has become adapted for the rabbit.

Experimental Street Virus Rabies in White Mice. Studies on Passive Immunization. II.

Experimental Street Virus Rabies in White Mice. Studies on Passive Immunization. II.

Experimental Street-Virus Rabies in White Mice. Studies on Passive Immunization. I.

In a recent publication1 from our department it was reported that white mice could be afforded a certain degree of passive protection against intracerebral inoculations of rabies street virus if large amounts of antirabic serum were injected intraabdominally before the administration of virus. One experiment indicated that rabbit antirabic serum gave better protection than had previously been demonstrated for goat antiserum. The present report covers further evidence of the value of rabbit antirabic serum.Rabbits were immunized by weekly intramuscular injections of 5 cc. of a 5% fixed virus suspension in saline solution. Phenolized virus (1/2% phenol) was used for the first few injections; fresh virus was employed thereafter and immunization continued for at least 10 weeks. The serums of several rabbits were pooled, filtered and inactivated before use.Table I shows the protective value of rabbit antirabic serum when injected before intracerebral inoculations of street virus; three experiments are summariz...

Experimental Virus Infections in Chinese Hamster. I. Susceptibility to Fixed Rabies Virus

The characteristics of most viruses are best demonstrable by their effects on hosts. It is therefore desirable to determine the pathogenicity of a given virus for as many species of animals as possible. It seems to us of both practical and academic interest to find out the effect of various viruses upon the Chinese hamster, a species of rodent readily obtainable. In the present communication, the susceptibility of the Chinese hamster to fixed rabies virus is recorded. A strain of fixed rabies virus after 137 rabbit passages from a local street virus, was used. The brain virus preserved in 50% glycerin was thoroughly ground in a sterile mortar and suspended in saline solution. Normal Chinese hamsters weighing 20–30 gm. were divided into several groups and each group was separately inoculated with various dilutions of the rabbit brain virus through different routes. In intracerebral inoculation, the hamsters were anesthetized and 0.05 cc. of the ground virus suspension was injected through an opening in the skull posterior to the eye and lateral to the mid-dorsal line. In intraperitoneal, intratesticular, intramuscular and subcutaneous injections, 0.5 cc. of virus suspension was introduced each time. The latter 2 routes of injection were always made over the right thigh. Animals, after injection, were kept separately in cages and observed for over one month. After intracerebral inoculations, the infected animals began to show general weakness and tremor of different parts of the body in 5 to 8 days. This was followed by progressive unsteadiness of gait accompanied by weakness of the hind-legs, leading in 24 hours to definite paralysis. The upper limbs were found to be involved later. At the terminal stage all limbs became paralyzed, respiratory movements feeble and the skeletal muscles flabby.

Further Studies in Anti-Rabies Immunisation. Rabies Virus—Exalted and Classical Strains Compared

1. The occurrence of an exalted strain of rabies virus has been recorded and a definition given of virus de rue renforcé.2. The characteristics of exalted virus have been examined in respect of incubation time, fixation rate and absence of Negri bodies.3. An adequate classification of street virus strains has been suggested.4. Cross-immunity experiments have been carried out and, as a result of cross-protection tests and of crossed serum reactions, identity of exalted virus with the classical strain has been established.5. The employment of autogenous and polyvalent vaccines has been shown to be unnecessary in anti-rabies immunisation.

STUDIES ON THE INTRAPLANTAR INOCULATION OF RABIC VIRUS

The intraplantar inoculation of guinea-pigs was tried by the author with virus fixe, as done by a number of investigators with viruses of herpes and foot-and-mouth disease. The results obtained are summarized as follows:1. Inoculated into the planta with virus fixe, the guinea-pig would die from the symptom and course specific to rabies and contain the virus in its brain. The virus fixe thus can be passed through guinea-pigs by intraplantar inoculation.2. The virus after 5 plantar passages could not be apparently distinguished from the original virus fixe in the neurotropism. The decided opinion regarding this problem, however, must be established from the result of subsequent experiments.3. Animals resisting the intraplantar inoculation of virus fixe remain always resistant to similar treatments. This may be due to the development of local immunity following the first inoculation.4. By repeated intraplantar inoculations, the guinea-pig would become immune to the subdural injection of the original virus fixe. Out of 9 animals subjected to 3 treatments, only 1 case was found susceptible to the subsequent subdural inoculation. Such a well developed immunity of central nervous system against virus fixe seems never to have been observed in any of the hitherto known antirabic treatments.5. In guinea-pigs repeatedly treated, if they succumbed to the subdural inoculation of virus fixe, the interval between dates of inoculation and death tends to be prolonged. This may also prove the limited development of antirabic immunity in the central nervous system.6. Such immunity of central nervous system seems to disappear in a half year. The conclusion regarding its duration must be, however, positively determined by the further experiments.7. Virulicidal principles are detected in the serum of guinea-pigs thus immunized against virus fixe.8. The guinea-pig is also susceptible to the intraplantar inoculation of street virus.9. The author failed to detect the living virus in the brain of 1 guinea-pig, which succumbed to the subdural injection of virus fixe carried out 13 days after 3 intraplantar inoculations. It may probably be one example of neuro-infection auto-sterilisable (Levaditi).

Studies in Anti-rabies Immunisation

1. Statistical evidence and animal experiment have alike proved carbolised killed anti-rabies vaccine to be of undoubted efficacy in both pre-infectional and post-infectional treatment. Statistical evidence is furnished by the results of treatment of 90,000 patients, while experimental proof rests partly on the resistance shown by immunised animals to artificial infections with street virus, and partly on an estimation of degree and duration of rabicidal properties in their sera.2. The Bordet-Gengou reaction is of no value as a qualitative or quantitative test for the estimation of anti-rabies immunity.3. The efficacy of killed carbolised vaccine and probably of other antirabies vaccines is largely dependent on the concentration of the dosage and the period within which it is administered. Better results follow the giving of small doses over a number of days than the giving of larger doses over a shorter period.4. It is impossible to reduce below a certain limit the time over which the total quantity of vaccine ordinarily sufficient for complete immunisation can be usefully administered.5. The effect on rabbits of the subcutaneous injection of fresh-fixed virus is dependent on the quantity of virus introduced and on the duration of its period of administration. Few inoculations are more likely to cause death than several; repeated inoculations ordinarily confer immunity. Immunity thus acquired must have been produced within 11 or 12 days.

Negro bodies in the salivary glands and other organs in rabies

It has long been recognized that the bite of a rabid animal is the ordinary means of transmitting rabies. Quite naturally, therefore, the saliva was suspected of harboring the infectious agent and early investigators easily proved this to be the case. According to Hogyes 1 and others, Zinke 2 is credited with having been the first to produce rabies by introducing saliva from a rabid dog into wounds of another dog, a rabbit and a cock. Following at intervals Gruner,3 Magendie,4 Hertwig,5 Rey 6 and others have simply multiplied evidence of the virulence of the saliva of rabid animals, both carniverous and herbivorous. Excellent reviews of the literature on this subject are given by G. Hogyes, M. Casper,7 and J. Koch 8 so that any detailed references to it here seem unnecessary. A consideration of the work on this phase of the subject would seem to indicate that the saliva is more likely to be virulent in the case of animals infected with street virus than with

The Quinin Treatment of Rabies

three cases of hydrophobia in the human subject. As there were insufficient laboratory experiments on the quinin treatment for hydrophobia, and as this treatment was an almost universal failure when tried on human subjects, the following experiments are reported. It was found that the dose of quinin tolerated by a full-grown rabbit was approximately 1 grain. Larger doses repeated daily were usually fatal, and even the 1-grain dose daily was fatal in several cases. For guinea-pigs the daily dose was 0.5 grain. The quinin treatment was tested against not only the fixed virus, but also against street virus. The former was a six-day virus, while the latter killed rabbits in about ten days, and guinea-pigs in eight days. The virus was given intracranially; the bisulphate of quinin was used in all experiments, the injections being intraperitoneal.