Rabies: still a uniformly fatal disease? Historical occurrence, epidemiological trends, and paradigm shifts.

Rabies has the highest case fatality of any infectious disease. Pathobiological and clinical insights have questioned the assertion that death is inevitable after onset of acute encephalomyelitis. Relying upon national laboratory-based surveillance, we reviewed records of human rabies acquired in the United States during 1960-2009. Changes in the epidemiology of human rabies were notable, due to improved animal management, safer and more efficacious biologics, and revisions in prevention guidelines. Historically, domestic animals were the most important source of infection. Since the 1990s, more human cases were associated with rabid bats. Prior to 1980, postexposure prophylaxis failures were reported. After development of modern rabies immune globulin and vaccines, none occurred. Of 75 human cases identified, only four patients survived. Rabies remains an extremely high consequence zoonosis, but the disease is not uniformly fatal, per se. Rabies is essentially preventable when primary exposures are averted, or appropriate prophylaxis occurs before illness.