Antivirals for human use against rabies and prospects for their future application

Rabies is probably the deadliest and most severe encephalitis known to humankind. Caused by any lyssavirus, it is recognised as a disease of the poor, the less fortunate and the young. No other known infectious disease can cause 100% mortality, and rabies and the clinical manifestations which precede a death from the disease are often described as excruciating. Animals are not spared this deadly illness either, essentially every mammal can be infected with the virus, resulting in the development of lethal encephalitis. However, rabies is also one of the few infectious diseases that can be prevented through vaccination. Yet, its mortality figures are on the increase. Only a small number of patients have been reported to have survived rabies once infection has been established; a survival based on pre-/post-exposure prophylaxis, natural induction following infection or experimentation and the intuition of attending physicians, while available antivirals have previously been used without success. Therefore, the need for novel and innovative interventions is urgent. In this paper, the authors summarise past failures in treating the disease and highlight future hopes in the field of rabies treatment.