[Bovine tuberculosis in Madagascar].
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Biomedical subjects
Publications and source records attributed to J Blancou.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.
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Rabies, a viral disease affecting all warm-blooded animals, is prevalent in most parts of the world, where it propagates amongst wild animals, particularly the fox and dog. The public health and economic consequences of infection in man and livestock are well known. Attempts to control the disease by vaccinating wild carnivores with inactivated or attenuated rabies virus remain controversial, and we have instead evaluated here the potential of a recombinant vaccinia virus to protect foxes against the disease. We have found that the administration of vaccinia virus (VV) or a recombinant harbouring the rabies surface antigen gene (VVTGgRAB) is innocuous to foxes. The recombinant virus can elicit the production of titers of rabies-neutralizing antibodies equal or superior to those obtained with conventional vaccine, and 10(8) plaque-forming units (PFU) of VVTGgRAB administered subcutaneously, intradermally or orally confers complete protection to severe challenge infection with street rabies virus.
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Although fox rabies has been reported in every country that has foxes, current foci of fox rabies are limited to Europe and North America. The fox rabies virus has unique characteristics that seem to be the result of adaptation through successive passages, i.e., high pathogenicity for the fox, excretion in saliva of a high proportion of infected animals, and low frequency of postinfection immunity. The spread of fox rabies is greatly favored by the characteristics of the genus Vulpes--ubiquity, broad diet, prolific nature, and its particular ethology and ecology. Animals may be immunized by oral vaccination, but natural mechanisms that also can terminate outbreaks are discussed.
Rabies is prevalent in most parts of the world. An extensive reservoir of the disease is present in the population of wild animals. The fox in particular is a major vector of the disease in North America and Europe. Although attempts to control rabies by vaccination of wild carnivores with attenuated rabies virus have met with some success, this approach remains controversial. The potential of a recombinant vaccinia virus expressing the rabies glycoprotein for the protection of foxes against rabies was examined. Both the parental (wild-type) and recombinant viruses were found to be innocuous to foxes. Inoculation of live recombinant virus via the subcutaneous, intradermal, or oral routes uniformly elicited high titers of neutralizing antibodies, and animals that received 10(8) plaque-forming units of the recombinant virus in bait resisted severe challenge with live rabies virus.
Successful oral immunization of wildlife against rabies has strongly stimulated research in the past decade. New approaches have been developed for vaccine production (e.g.: use of recombinant vaccines) as well as for better potency or safety testing procedures. It appears that Man should also consider two important phenomena which already existed in nature before his research. The first one is an adaptation of the rabies virus, by serial passages, which favours the spreading of the disease among a sole animal species. Bites of this species vaccinate other species more often than they kill them, leading sometimes, to the mutual exclusion of potential vector. The next phenomenon is the self-control of the first one due to an over-adaptation of the virus to its vector species. It leads to unappropriate level, or delay, of reexcretion of the virus, therefore to the transformation of a rabies epizootics into rabies enzootics. Oral vaccination would thus appear as an useful tool to eradicate the disease after it reached this enzootic stage.
Campaigns of fox vaccination against rabies were carried out in Belgium, grand-duchy of Luxembourg and France in September 1986, June and September 1987. The SAD B19 attenuated strain of rabies virus, contained in baits (Tübingen baits) was used as vaccine. Baits were distributed at a range density of 11 to 15 baits per km2. First results are very encouraging. A recombinant vaccinia virus harbouring the rabies virus glycoprotein gene has been developed. This recombinant virus can be given to the fox by the oral route and protects it against rabies virus challenge; it is also innocuous for the fox and other non-target European species. A first trial of fox vaccination against rabies using this recombinant vaccinia-rabies virus has been carried out in Belgium, on a military domain, in October 1987.
When challenged by intramuscular route with the rabies strain CVS, mice treated with cyclophosphamide and then vaccinated died during the four days following vaccination in larger numbers and earlier than controls which had been treated but not vaccinated. This phenomenon can be transferred, via splenocytes of mice treated with cyclophosphamide and then vaccinated, into syngenic mice infected 24 h earlier by a large amount of virus (10.000 LD50 by intracerebral route). On the other hand, mice infected with a small amount of virus (1 LD50 by intracerebral route) can be protected by transferred splenocytes. These data suggest that an immunopathological phenomenon is involved in experimental rabies of mice, supported by direct or indirect action of T lymphocytes against infected target cells. Possible implications of this hypothesis in pre- or post-exposure vaccination are discussed.