Rhabdoviridae: Rabies Virus

INTRODUCTION This family Rhabdoviridae infect a wide variety of hosts, including vertebrates, invertebrates. All members of this family has a distinctive rod- or bullet-shaped morphology. Human pathogens of medical importance are found in the genera Lyssavirus & Vesiculovirus. Only rabies virus, medically the most significant member of the genus Lyssavirus. Structure: The rabies virus is a negative-sense, non-segmented, single-stranded RNA virus measuring ~ 60 nm x 180 nm. It is composed of an internal protein core or nucleocapsid, containing the nucleic acid, & an outer envelope, a lipid-containing bilayer covered with transmembrane glycoprotein spikes .

Pathogenesis : Rabies virus is most commonly transmitted through the bite of an infected mammal. The virus may enter the peripheral nervous system directly, or may replicate in muscle tissue after entering the host, remaining at or near the site of introduction for most of the incubation period. Virus may enter the peripheral nervous system via the neuromuscular junctions, & moves rapidly centripetally to the CNS for replication; symptoms may develop shortly thereafter. The virus then begins to pass centrifugally to many tissues & organs, such as the salivary glands. Gross examination of the brain shows mild congestion of the meningeal vessels; microscopic examination usually demonstrates acidophilic intracytoplasmic neuronal inclusions. Epidemiology Rabies is found in most countries, with the exception of Australian islands, or areas achieving secondary elimination, such as the UK. Human rabies is almost always attributable to a bite (any penetration of the skin by the teeth). Non-bite exposures (contamination of an open wound or a mucous membrane via scratches, licks, & inhalation of aerosol) rarely cause rabies in humans.

Clinical Manifestations: Five general stages of rabies are recognized in humans: 1-Incubation, 2-Prodrome, 3-Acute neurologic period, 4-Coma, & death (or, very rarely, recovery) . No specific antirabies agents are useful once clinical signs or symptoms develop. 1-Incubation period in rabies, usually 30 to 90 days but ranging from 5 days to longer than 2 years after initial exposure. Incubation periods may be somewhat shorter in children & in individuals bitten close to CNS (e.g., the head). 2-Prodromal period After the incubation period .prodromal symptoms started which are nonspecific (general malaise, fever, & fatigue) or suggest involvement of the respiratory system (sore throat, cough, & dyspnea), GIT system (anorexia, dysphagia, nausea, vomiting, abdominal pain, & diarrhea), or CNS (headache, vertigo, anxiety, apprehension, irritability, & nervousness). More remarkable abnormalities ( agitation, photophobia, priapism, increased libido, insomnia, nightmares, & depression) may also occur. Pain or paresthesia at the site of virus inoculation, combined with a history of recent animal bite, should suggest a consideration of rabies

3-Acute neurologic period Begins with objective signs of CNS dysfunction. The disease may be classified as furious rabies if hyperactivity (i.e., hydrophobia) predominates & as dumb rabies if paralysis dominates the clinical picture. Fever, paresthesia, nuchal rigidity, muscle fasciculations, focal & generalized convulsions, hyperventilation, & hypersalivation may occur in both forms of the disease. 4-Stage of coma & death: At the end of the acute neurologic phase, periods of rapid, irregular breathing begin; paralysis & coma soon follow. Respiratory arrest may occur thereafter, unless the patient is receiving ventilatory assistance, which may prolong survival for days, weeks, or longer, with death due to other complications. Although life support measures can prolong the clinical course of rabies, rarely will they affect the outcome of disease. The possibility of recovery, however, must be recognized, & when resources permit, every effort should be made to support the patient. At least seven cases of human "recovery" have been documented.

Laboratory Diagnosis :The detection of rabies antigen, antibody, viral RNA, or the isolation of virus establishes a diagnosis of rabies. 1-Serial serum specimens for detection of rabies antibodies. 2-Saliva specimens for culture of virus. 3-Skin biopsies for direct immunofluorescence testing for virus antigen. One of the most rapid methods to diagnose rabies in humans is to perform a direct immunofluorescence test on a skin biopsy from the nape of the neck for evidence of rabies antigen. The direct immunofluorescence test is the most sensitive & specific method of detecting rabies antigen in skin & other fresh tissue (e.g., brain biopsy).. The diagnosis can also be established if virus is isolated from saliva after inoculation of neuroblastoma cells or laboratory rodents; The presence of antibody in the CSF confirms the diagnosis, but it may appear 2 to 3 days later than serum antibody .

Control: Animal rabies is prevented by vaccinating susceptible species, particularly dogs & cats. Oral vaccination of wildlife with attenuated & recombinant rabies vaccines by the use of vaccine-containing bait offers hope of controlling the disease in susceptible wild free-ranging animal populations. Human rabies is best prevented by avoiding exposures to the disease. When an exposure is suspected, the patient's physician should determine whether an exposure actually occurred & whether a risk of rabies exists in the geographic area . If treatment (postexposure prophylaxis) is necessary, it should be initiated promptly. Postexposure prophylaxis consists of the combination of local wound cleansing, human rabies immune globulin (HRIG) & rabies vaccine. Postexposure treatment will abort the infection, but there is no cure for clinical disease.