1. Should the patient have been in isolation? What was done for exposed contacts?

The patient should have been in strict isolation to prevent transmission of rabies virus in her secretions (especially saliva) from infecting health care workers. All health care workers that came into contact with this patient were given post-exposure prophylaxis. (See answer to question #4).

2. What is the incubation period for rabies?

The incubation period ranges from 10 days to a year, depending on the amount of virus introduced, the amount of tissue involved, the host immune mechanisms, and the distance the virus must travel from the site of inoculation of the central nervous system. Thus, the incubation period is generally shorter with face wounds than with leg wounds. Immunization early in the incubation period frequently aborts the infection.

3. Why is it difficult to diagnose this infection? What clinical symptom did this patient have which is classic for rabies (but is not always present)?

Refusal of liquids with apparent fear of water (agoraphobia) is a classically described symptom of rabies.

Laboratory diagnosis of rabies in animals or deceased patients is accomplished by indirect or direct demonstration of virus in brain tissue or scalp biopsy. Viral antigen can be demonstrated rapidly by immunofluorescence procedures. Intracerebral inoculation of infected brain tissue or secretions into suckling mice results in death in 3 to 10 days. Histologic examination of their brain tissue shows Negri bodies; both Negri bodies and rhabdovirus particles may be demonstrated by electron microscopy. Specific antibodies to rabies virus can be detected in serum, but generally only late in the disease.

In many areas of the world, the dog is the most important vector of the rabies virus to humans. Other important sources of disease are the wolf in eastern Europe, the mongoose in Africa, the fox in western Europe, and the bat in Latin America and the United States.

4. If the family had reported finding the bat in the patient=s room immediately to the physician or health department, what treatment would the patient have received?

The patient would have received rabies prophylaxis. Once symptoms appear, vaccine and immune globulin are ineffective. Postexposure prophylaxis requires careful evaluation and judgment. Every year more than one million Americans are bitten by animals, and in each instance a decision must be made whether to initiate postexposure rabies prophylaxis. In this decision the physician must consider (1) whether the individual came into physical contact with saliva or another substance likely to contain rabies virus; (2) whether there was significant wounding or abrasion; (3) whether rabies is known or suspected in the animal species and area associated with the exposure; (4) whether the bite was provoked or unprovoked (i.e., the circumstances surrounding the exposure); and (5) whether the animal is available for laboratory examination. Any wild animal or ill, unvaccinated, or stray domestic animal involved in a possible rabies exposure, such as an unprovoked bite, should be captured and killed. The head should be sent immediately to an appropriate laboratory, usually at the state health department, for search for rabies antigen by immunofluorescence. If examination of the brain by this technique is negative for rabies virus, it can be assumed that the saliva contains no virus and that the exposed person requires no treatment. If the test is positive, the patient should be given postexposure prophylaxis. It should be noted that rodents and rabbits are not important vectors of rabies virus.

The incubation period of rabies in dogs is short. Therefore, the animal can be observed and if it remains healthy for 10 days, it can be considered non-rabid.

Postexposure prophylaxis is based on immediate, thorough washing of the wound with soap and water; passive immunization with hyperimmune globulin, of which at least half the dose should be instilled around the wound site; and active immunization with antirabies vaccine. With human diploid vaccine, five doses given on days 1,3, 7, 14 and 28 are recommended.

Physicians should always seek the advice of the local health department when the question of rabies prophylaxis arises.

5. Who should routinely receive rabies virus vaccine?

Currently, the prevention of rabies is divided into preexposure and postexposure prophylaxis. Preexposure prophylaxis is recommended for individuals at high risk of contact with rabies virus, such as veterinarians, spelunkers, laboratory workers, and animal handlers. The vaccine currently used in the United States for preexposure prophylaxis employs an attenuated rabies virus grown in human diploid cell culture and inactivated with β-propiolactone. Preexposure prophylaxis consists of two subcutaneous injections of vaccine given 1 month apart, followed by a booster dose several months later.

Prevention is the mainstay of controlling human rabies. Intensive supportive care has resulted in two or three long-term survivals; despite the best modern medical care, however, the mortality still exceeds 90%. In addition, because of the infrequency of the disease, many cases die without definitive diagnosis. Human hyperimmune antirabies globulin, interferon and vaccine do not alter the diseases once symptoms have developed.