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OVERVIEW

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The dog was certainly rabid. Joseph Meister had been pulled out from under him covered with foam and blood.

—Louis Pasteur, describing the 9-year-old boy he successfully immunized against rabies in July, 1885

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Overview

Rabies is an acute fatal viral illness of the central nervous system (CNS) commonly resulting in encephalitis. Rabies virus is a bullet shaped, enveloped, helical nucleocapsid containing a negative-sense RNA genome of the rhabdoviridae family. The word rabies is derived from the Latin verb “to rage,” which suggests the appearance of the rabid patient. It can affect all mammals and is transmitted between them by infected secretions, most often by bite. It was first recognized more than 3000 years ago and has been the most feared of infectious diseases. It is said that Aristotle recognized that rabies could be spread by a rabid dog. Rabies involves the development of severe neurologic symptoms and signs in a patient who was previously bitten by an animal (a rabid dog or wild animals). The incubation period is 10 days to 1 year. The virus replicates at the site of bite followed by entry into the peripheral nervous system at the neuromuscular junctions and spreads to the CNS, where it replicates exclusively within the gray matter and then spreads centrifugally to the autonomic nervous system. The neurologic manifestations are very characteristic, with a relentlessly progressive excess of motor activity, agitation, hallucinations, and salivation. The patient appears to be foaming at the mouth and has severe throat contractions if swallowing is attempted. Involvement of the respiratory center produces respiratory paralysis, the major cause of death. Recovery is rare. The postexposure vaccination is considered treatment for rabies because the killed rabies vaccine is given to people after exposure at days 0, 3, 7, and 14. In addition, hyper immune globulin serum should be instilled in the wound to neutralize the virus.

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VIROLOGY

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The rabies virus is a rhabdovirus, which is a bullet-shaped, enveloped, RNA virus, 70 nm in diameter × 180 nm in length, of the Lyssavirus genus and Rhabdoviridae family (Figure 17–1). The helical nucleocapsid (N) is composed of a single-stranded, negative-sense RNA genome and an RNA-dependent RNA polymerase enclosed in a matrix (M) protein covered by a lipid bilayer envelope containing knob-like glycoprotein (G). The knob-like glycoprotein excrescences, which elicit neutralizing and hemagglutination-inhibiting antibodies, cover the surface of the virion. In the past, a single antigenically homogeneous virus was believed to be responsible for all rabies; however, differences in cell culture growth characteristics of isolates from different animal sources (bats, cats, dogs, foxes, and skunks), some differences in virulence for experimental animals, and antigenic differences in surface glycoproteins have indicated strain heterogeneity among rabies virus isolates. These studies may help to explain some of the biologic differences as well as the occasional case of “vaccine failure.” Other pathogens in the rhabdovirus group include vesicular stomatitis virus, which is an animal virus ...

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