Current and future approaches to the therapy of human rabies

Human rabies has traditionally been considered a uniformly fatal disease. However, recent decades have seen several instances in which individuals have developed clinical signs of rabies, but survived, usually with permanent neurologic sequelae. Most of these patients had received prophylactic rabies vaccine before the onset of illness. The best outcomes have been seen in patients infected with bat viruses, which appear to be less virulent for humans than strains associated with other rabies vectors. In 2003, an article by rabies experts suggested that survival might be improved through a combination of vaccine, anti-rabies immunoglobulin, antiviral drugs and the anesthetic ketamine, which had shown benefit in an animal model. One year later, a girl in Milwaukee who developed rabies after bat exposure was treated with some of these measures, plus a drug-induced (therapeutic) coma, and survived her illness with mild neurologic sequelae. Although the positive outcome in this case has been attributed to the treatment regimen, it more likely reflects the patient's own brisk immune response, as anti-rabies virus antibodies were detected at the time of hospital admission, even though she had not been vaccinated. This conclusion is supported by the failure of the "Milwaukee Protocol" to prevent death in numerous subsequent cases. Use of this protocol should therefore be discontinued. Future research should focus on the use of animal models to improve understanding of the pathogenesis of rabies and for the development of new therapeutic approaches.