Antiviral therapy for human rabies.

Human rabies is virtually always fatal despite numerous attempts at aggressive therapy. Most survivors received one or more doses of rabies vaccine prior to the onset of the disease. The Milwaukee Protocol has proved to be ineffective for rabies and should no longer be used. New approaches are needed and an improved understanding of basic mechanisms responsible for the clinical disease in rabies may prove to be useful for the development of novel therapeutic approaches. Antiviral therapy is thought to be an important component of combination therapy for the management of human rabies, and immunotherapy and neuroprotective therapy should also be strongly considered. There are many important issues for consideration regarding drug delivery to the central nervous system in rabies, which are in part related to the presence of the blood-brain barrier and also the blood-spinal cord barrier. Ribavirin and interferon-α have proved to be disappointing agents for the therapy of rabies. There is insufficient evidence to support the continued use of ketamine or amantadine for the therapy of rabies. Minocycline or corticosteroids should not be used because of concerns about aggravating the disease. A variety of new antiviral agents are under development and evaluation, including favipiravir, RNA interference (for example, small interfering [si]RNAs) and novel targeted approaches, including interference with viral capsid assembly and viral egress.