Human Rabies Encephalitis Prevention and Treatment: Progress Since Pasteurs Discovery

Abstract

Rabies remains one of the most ancient and deadly of human infectious diseases. This viral zoonosis is transmitted principally by the saliva of infected dogs, inducing a form of encephalomyelitis that is almost invariably fatal. Since the first implementation, by Louis Pasteur in 1885, of an efficient preventive post-exposure treatment, more effective protocols and safer products have been developed, providing almost 100% protection if administered early enough. However, this disease still represents a major, but neglected public health problem, with an estimated 55,000 human deaths due to rabies reported each year, mostly in Africa and Asia. Once the first clinical signs appear, there is no effective treatment. A ray of hope emerged in 2004, with the report of a patient recovering from rabies after aggressive, innovative treatment. However, this case was not clearly reproduced and the identification of targets for antiviral treatment in cases of rabies infection remains a major challenge. In this context, this review presents the state-of-the art in the prevention and curative treatment of human rabies. We begin by describing the viral etiological agent and the disease it causes, to provide an essential background to rabies. An overview of the post-exposure prophylaxis of rabies in humans is then given, from its initial implementation to possible future developments. Finally, an analysis of the various antiviral compounds tested in rabies in vitro, in animal models or in humans is presented, focusing in particular on potential new strategies.

Neutralizing Antibody Response in Dogs and Cats Inoculated with Commercial Inactivated Rabies Vaccines

“…The fatality rate is nearly 100% in infected humans with symptoms. Developing countries in Asia and Africa have the highest prevalence of rabies, and more than 50,000 people die of rabies per annum worldwide [4]. Because the rabies virus can infect many animal species, eradication of the virus is thought to be impractical.…”

Status of antiviral therapeutics against rabies virus and related emerging lyssaviruses

“…Small-molecule antivirals in general have the advantages of cost-effective manufacture -addressing supply concerns -as well as high shelf-stability, enabling developing countries to stock-pile life-saving supplies [42]. Currently, there are no small-molecule inhibitors licensed for therapeutic use, despite several attempts at discovery [41,[54][55][56][57][58][59][60][61][62]. Based on previous antiviral activity of phenolic compounds against viruses such as HIV, herpes simplex virus and influenza virus, 24 representatives of this class were tested against RABV.…”

La rage

“…Différentes molécules ont été testées in vitro, et in vivo chez l'animal, voire chez l'homme : ribavirine, vidarabine, cytosine arabinosine, minocycline, kétamine, interféron , vaccination intradermique multi-sites, Ig antirabiques, anticorps antithymocytes, hautes doses de fragments d'Ig antirabiques, inosine pranobex, etc [28]. Mais une fois la maladie déclarée, aucun traitement n'a permis d'éviter l'issue fatale.…”

“…Les corticoïdes ont réduit la période d'incubation et accéléré la mort dans des modèles animaux, et ils sont donc à éviter. Quelques cas de survie prolongée ont été rapportés chez des patients ayant développé une symptomatologie de rage [24,28], mais ces patients avaient reçu un début de prophylaxie postexposition avant le début de la phase clinique. Un premier cas de survie en l'absence de vaccination antirabique anté-rieure a été décrit en 2004.…”