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Hyperactivity of the sympathetic nervous system causes increased sweating, salivation, and lacrimation. Periods of extreme anxiety and maniacal behavior alternate with periods of calm awareness of surroundings, tempered with an ever-present sense of foreboding. Painful spasm of the muscles of deglutition leads to active refusal to take liquids (hydrophobia). This spasm may be elicited even by fanning the patient’s face (aerophobia), a useful diagnostic sign. Periods of obtusion occur and progress into coma. Death ensues secondary to cardiac or respiratory failure, usually within a week of the onset of symptoms.

Presumptive diagnosis may be made by consideration of the history, presenting signs and symptoms, and clinical course. The diagnosis is confirmed by one of four methods: (1) observation of the typical inclusion bodies (Negri bodies) in nerve cells after appropriate staining of pathological specimens; (2) immunofluorescence staining of pathological specimens; (3) virus isolation through culturing in mice or other animals; and (4) direct and indirect immunoperoxidase staining of tissue (Shope, 1982, 1984).

Existing Vaccines and Limitations

A 1982 survey identified 74 manufacturers of rabies vaccine worldwide. Most produced vaccine on a small scale and used outdated and suspect technologies, such as adult animal brain cultures (World Health Organization, 1984). Vaccines produced in this way contain myelin, which can provoke a demyelinating immunological disease in the vaccinee.

Vaccines consisting of inactivated viruses grown in the brains of suckling animals are used in South America (Shope, 1984). Seven to fourteen injections are required. The virus is purified by centrifugation to reduce the vaccine’s myelin content. Neurological reactions still occur with a frequency of about 5:100,000 vaccinees (Acha, 1981). These vaccines are effective and relatively inexpensive.

Prior to 1980, the rabies vaccine most used in developed countries for pre- and post-exposure prophylaxis was the duck embryo vaccine (DEV). It is inexpensive and potent, but requires from 17 to 23 separate injections to provide adequate levels of protective antibody. It does not induce the anti-N antigen response (described below) as well as do newer nerve tissue or cell culture derived vaccines (Shope, 1982). Immunological and neurological complications occur at low frequencies; neurological complications, including postvaccinal encephalitis and transient neuroparalytic illness, occur in 1:25,000 vaccinees and lead to death in 1:225,000 (Rubin et al., 1969). The DEV remains the major rabies vaccine in many parts of the world.

The newest available vaccine treatment for rabies is the human diploid cell vaccine (HDCV), which is an adapted, inactivated Pasteur strain of rabies virus. It is grown in human cell culture, inactivated, and purified by centrifugation. HDCV is very effective and produces protective post-exposure immunity with as few as six doses when used in conjunction with rabies hyperimmune globulin (RIG). It is less aller-



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