Description

Rabies is an acute, progressive, fatal encephalomyelitis caused by neurotropic viruses in the family Rhabdoviridae, genus Lyssavirus (1,2). The disease is almost always transmitted by an animal bite that inoculates the virus into wounds. Very rarely, rabies has been transmitted by exposures other than bites that introduce the virus into open wounds or mucous membranes (3-5). All mammals are believed to be susceptible, but reservoirs are carnivores and bats. Although dogs are the main reservoir in developing countries, the epidemiology of the disease differs sufficiently from one region or country to another to warrant the medical evaluation of all mammal bites (6-8).

Occurrence

Rabies is found on all continents except Antarctica. In certain areas of the world, canine rabies remains highly endemic, including (but not limited to) parts of Africa, Asia, and Central and South America (8,9). Table 4-14 lists countries that have reported no cases of rabies during the most recent period for which information is available (formerly referred to as “rabies-free countries”).

Additional information can be obtained from the World Health Organization (http://www.who.int/rabies/rabnet/en/), the Pan American Health Organization (http://www.paho.org/english/ad/dpc/vp/rabia.htm), the Rabies Bulletin-Europe (http://www.rbe.fli.bund.de), the World Organization for Animal Health (http://www.oie.int/eng/en_index.htm), local health authorities of the country, the embassy, or the local consulate’s office in the United States. Lists are provided only as a guide, because up to date information may not be available, surveillance standards vary, and reporting status can change suddenly as a result of disease re-introduction or emergence (10,11).

Risk for Travelers

Rabies vaccination is not a requirement for entry into any country. However, travelers to rabies-endemic countries should be warned about the risk of acquiring rabies and educated in animal bite prevention strategies (12-16). Travelers with extensive unprotected outdoor exposure such as might be experienced while bicycling, camping, hiking, or engaging in certain occupational activities, might be at higher risk even if their trip is brief. Also, children are considered at higher risk because of their tendencies to play with animals and to not report bites. Casual exposure to cave air is not a concern, but cavers should be warned not to handle bats (3).

Clinical Presentation

After infection, the incubation period is highly variable, but lasts approximately 1-3 months. The disease progresses from a nonspecific prodromal phase to paresis or paralysis; spasms of swallowing muscles can be stimulated by the sight, sound, or perception of water (hydrophobia); delirium and convulsions can develop, followed rapidly by coma and death. No treatment is effective after the development of clinical signs, but the extremely rare case of recovery after extensive medical intervention offers hope that future experimental therapeutics may be developed (17-18).

Prevention

Pre-exposure vaccination with human diploid cell rabies vaccine (HDCV), or purified chick embryo cell (PCEC) vaccine, may be recommended for international travelers based on the local incidence of rabies in the country to be visited, the availability of appropriate antirabies biologicals, and the intended activity and duration of stay of the traveler (19). Different schedules, alternative routes of administration, and other rabies vaccines besides HDCV and PCEC may be found abroad (20,21). Pre-exposure vaccination may be recommended for veterinarians, animal handlers, field biologists, spelunkers, missionaries, and certain laboratory workers. Table 4-15 provides criteria for pre-exposure vaccination. Pre-exposure vaccination does not eliminate the need for additional medical attention after a rabies exposure but simplifies postexposure prophylaxis in populations at risk by eliminating the need for rabies immune globulin (RIG) and by decreasing the number of doses of vaccine required. Pre-exposure vaccination is of particular importance for travelers at risk of exposure to rabies in countries where biologicals are in short supply and locally available rabies vaccines might carry a higher risk of adverse reactions (20). Pre-exposure vaccination may also provide some degree of protection when there is an unapparent or unrecognized exposure to rabies and when postexposure prophylaxis might be delayed. Planning is needed to ensure compliance in completion of the three pre-exposure vaccine doses, prior to commencing travel (22).

Travelers should be advised that any animal bite or scratch should receive prompt local treatment by thorough cleansing of the wound with copious amounts of soap and water (and povidone iodine, if available). This local treatment will substantially reduce the risk of rabies. Travelers who might have been exposed to rabies should be advised to always contact local health authorities immediately for advice about postexposure prophylaxis and should also contact their personal physician or state health department as soon as possible thereafter.

Equine rabies immune globulin (ERIG), or purified fractions of ERIG, has been used effectively in some developing countries where human rabies immune globulin (RIG) might not be available (20). If necessary, such heterologous products are preferable to no RIG administration in human rabies postexposure prophylaxis. The incidence of adverse reactions after the use of these products has been low (0.8%-6.0%), and most of those reactions were minor. However, such products are neither evaluated by U.S. standards nor regulated by the U.S. Food and Drug Administration, and their use cannot be unequivocally recommended at this time (19). In addition, unpurified antirabies serum of equine origin might still be used in some countries where neither human RIG nor ERIG is available. The use of this antirabies serum is associated with higher rates of serious adverse reactions, including anaphylaxis.

Tables 4-16 and 4-17 provide information on pre-exposure and postexposure prophylaxis. Routine serologic testing is not necessary for travelers who receive the recommended pre-exposure or postexposure regimen with HDCV or PCEC vaccines. Exposed travelers previously vaccinated with vaccines other than those produced by cell culture should receive the complete postexposure regimen unless they have developed a laboratory-confirmed virus neutralizing antibody response to the primary vaccination. Serologic testing is still recommended for travelers whose immune response might be diminished by drug therapy or by diseases. Rabies pre-exposure prophylaxis may not be indicated for travelers to the countries in Table 4-14, and postexposure prophylaxis is rarely necessary after exposures to domestic animals in these countries. Practitioners are urged to follow established current guidelines for schedules and doses of vaccine used in rabies prophylaxis (23).

ADVERSE REACTIONS

Travelers should be advised that they may experience local reactions after vaccination, such as pain, erythema, swelling, or itching at the injection site, or mild systemic reactions, such as headache, nausea, abdominal pain, muscle aches, and dizziness (19,20). Approximately 6% of persons receiving booster vaccinations with HDCV may experience an immune complex-like reaction characterized by urticaria, pruritus, and malaise. Once initiated, rabies postexposure prophylaxis should not be interrupted or discontinued because of local or mild systemic reactions to rabies vaccine.

PRECAUTIONS AND CONTRAINDICATIONS

Pregnancy

Pregnancy is not a contraindication to postexposure prophylaxis (19,20).

Age

In infants and children, the dose of HDCV or PCEC for pre-exposure or postexposure prophylaxis is the same as that rec-ommended for adults (19,20). The dose of RIG for postexposure prophylaxis is based on body weight (Table 4-17).

References

1. Warrell MJ, Warrell DA. Rabies and other lyssavirus diseases. Lancet. 2004;363:959-69.
2. Nel L. Vaccines for lyssaviruses other than rabies. Expert Rev Vaccines. 2005;4:533-40.
3. Gibbons RV. Cryptogenic rabies, bats, and the question of aerosol transmission. Ann Emerg Med. 2002;39:528-36.
4. Srinivasan A, Burton EC, Kuehnert MJ, Rupprecht C, Sutker WL, Ksiazek TG, et al. Transmission of rabies virus from an organ donor to four transplant recipients. N Engl J Med. 2005;352:1103-11.
5. Hellenbrand W, Meyer C, Rasch G, Steffens I, Ammon A. Cases of rabies in Germany following organ transplantation. Euro Surveill. 2005;10:E050224.6.
6. Fooks AR, McElhinney LM, Pounder DJ, Finnegan CJ, Mansfield K, Johnson N, et al. Case report: isolation of a European bat lyssavirus type 2a from a fatal human case of rabies encephalitis. J Med Virol. 2003;71:281-9.
7. Taplitz RA. Managing bite wounds. Currently recommended antibiotics for treatment and prophylaxis. Postgrad Med. 2004;116:49-52, 55-6, 59.
8. Gupta RK. Recent outbreak of rabies infections in Brazil transmitted by vampire bats. Euro Surveill. 2005;10:E051110.3.
9. Knobel DL, Cleaveland S, Coleman PG, Fevre EM, Meltzer MI, Miranda ME et al. Re-evaluating the burden of rabies in Africa and Asia. Bull World Health Organ. 2005;83:360-8.
10. Hore C. Important unusual infections in Australia: a critical care perspective. Crit Care Resusc. 2001;3:262-72.11.
11. Kim CH, Lee CG, Yoon HC, Nam HM, Park CK, Lee JC, et al. Rabies, an emerging disease in Korea. J Vet Med B Infect Dis Vet Public Health. 2006;53:111-5.12.
12. Wilde H, Briggs DJ, Meslin FX, Hemachudha T, Sitprija V. Rabies update for travel medicine advisors. Clin Infect Dis. 2003;37:96-100.
13. Strauss R, Granz A, Wassermann-Neuhold M, Krause R, Bago Z, Revilla-Fernandez S, et al. A human case of travel-related rabies in Austria, September 2004. Euro Surveill. 2005;10:225-6.
14. Smith A, Petrovic M, Solomon T, Fooks A. Death from rabies in a UK traveler returning from India. Euro Surveill. 2005;10:E050728.5.
15. Rendi-Wagner P, Jeschko E, Kollaritsch H, osterreichische Expertengruppe fur Reisemedizin. Travel vaccination recommendations for Central and Eastern European countries based on country-specific risk profiles. Wien Klin Wochenschr. 2005;117 Suppl 4:11-9.
16. Richardson M. The management of animal and human bite wounds. Nurs Times. 2006;102:34-6.
17. Jackson AC, Warrell MJ, Rupprecht CE, Ertl HC, Dietzschold B, O’Reilly M, et al. Management of rabies in humans. Clin Infect Dis. 2003;36:60-3.
18. Willoughby RE Jr, Tieves KS, Hoffman GM, Ghanayem NS, Amlie-Lefond CM, Schwabe MJ, et al. Survival after treatment of rabies with induction of coma. N Engl J Med. 2005;352:2508-14.
19. CDC. Human rabies prevention — United States, 1999. Recommendations of the Advisory Committee on Immuniza-tion Practices (ACIP). MMWR Morbid Mortal Wkly Rep. 1999;48(RR-1):1-21.
20. World Health Organization Expert Consultation on Rabies. World Health Organ Tech Rep Ser. 2005;931:1-88.
21. Khawplod P, Wilde H, Sirikwin S, Benjawongkulchai M, Limusanno S, Jaijaroensab W, Chiraguna N, et al. Revision of the Thai Red Cross intradermal rabies post-exposure regimen by eliminating the 90-day booster injection. Vaccine. 2006;24:3084-6.
22. Heudorf U, Tiarks-Jungk P, Stark S. Travel medicine and vaccination as a task of infection prevention. Gesundheitswesen. 2006;68:316-22.
23. Rupprecht CE, Gibbons RV. Clinical practice. Prophylaxis against rabies. N Engl J Med. 2004;351:2626-35.

TABLE 4-14. Countries and political units reporting no indigenous cases of rabies during 2005¹

TABLE 4-15. Criteria for pre-exposure immunization for rabies

TABLE 4-16. Pre-exposure immunization for rabies¹

TABLE 4-17. Postexposure immunization for rabies¹