Are We Getting Closer to the Treatment of Rabies?

Authors and Disclosures

Rodney E Willoughby Jr, MD

Rodney E Willoughby Pediatric Infectious Diseases, Medical College of Wisconsin, PO Box 1997, Milwaukee, WI 53201-1997, USA Tel.: +1 414 337 7070 Fax: +1 414 337 7093 rewillou@mcw.edu

Sidebar

Executive Summary

• Rabies is considered to be the world's most important zoonosis, but is a neglected disease.

• It is medically violent and 100% fatal, yet has no cytopathic effect and demonstrated minimal inflammation.

• Noncytopathic clearance is antibody mediated.

• Rabies vaccine and immune globulin may precipitate early death.

Treatment of rabies

• Anesthesiology-based strategy temporizes until natural immunity clears the infection.

• Rabies is associated with tetrahydrobiopterin deficiency and altered neurotransmission.

• Rabies patients develop generalized intracranial vasospasm.

• Ribavirin inhibits timely development of rabies-specific antibody.

Improved survival improves the science

• Immune responses can be characterized, and differ for bat and dog rabies.

• Metabolomics detects early elevations in quinolinic acid and later rises in lactic acid in human rabies.

New rabies vaccines & immunoglobulins will minimize the economic barriers to rabies prophylaxis

• Humanized monoclonal antibodies will replace human and equine immunoglobulins for prophylaxis.

• Human antibodies cloned from rabies survivors may prove to be therapeutic.

• Single-dose, live-attenuated rabies vaccines will permit simple veterinary outreach and routine childhood immunization in rabies-endemic regions.

Rabies is a model for altered neurotransmission in viral encephalitis

• Investigation of treatable disorders of neurotransmission can be applied to other encephalitides.

• Intracranial vasospasm can be sought noninvasively and treated in other encephalitides.

• Neuroprotectant drugs, used aggressively and in combination, may prove useful when intractable seizures or cerebral edema complicate infectious neurological disorders.