Human rabies: a disease of complex neuropathogenetic mechanisms and diagnostic challenges

Rabies is inevitably fatal and presents a horrifying clinical picture. Human rabies can manifest in either encephalitic (furious) or paralytic (dumb) forms. The brainstem is preferentially involved in both clinical forms, though there are no clinical signs of brainstem dysfunction. Differences in tropism at the inoculation site or the CNS, in the route of spread, or in the triggering of immune cascades in the brainstem may account for clinical variation. Rabies still poses diagnostic problems, particularly the paralytic form, which closely resembles Guillain-Barré syndrome, or when a patient is comatose and cardinal signs may be lacking. Molecular methods allow reliable detection of rabies-virus RNA in biological fluids or tissue before death. Deviations from the recommendations on prophylaxis of the World Health Organization lead to unnecessary loss of life. To date, attempts to treat human rabies have been unsuccessful.