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).



REGION COUNTRIES
 
Africa Cape Verde, 
Libya, 
Mauritius, 
Reunion, 
Sao Tome and Principe, and Seychelles 
Americas North: Bermuda, St. Pierre and Miquelon
 

Caribbean: 
Antigua and Barbuda, Aruba, Bahamas, Barbados, Cayman Islands, Dominica, Guadeloupe, 
Jamaica, Martinique, Montserrat, Netherlands Antilles, Saint Kitts (Saint Christopher) 
and Nevis, Saint Lucia, Saint Martin, Saint Vincent and Grenadines, 
Turks and Caicos, and Virgin Islands (UK and US)

South: Uruguay
 
Asia Hong Kong, Japan, Kuwait, Lebanon, Malaysia (Sabah), Qatar, Singapore, United Arab Emirates 
Europe Austria, Belgium, Cyprus, Czech Republic2, Denmark2, Finland, France2, Gibraltar, 
Greece, Iceland, Ireland, Isle of Man, Italy, Luxemburg, Netherlands2, Norway, Portugal, 
Spain2 (except Ceuta/ Melilla), Sweden, Switzerland, and United Kingdom2 
Oceania Australia2, Northern Mariana Islands, Cook Islands, Fiji, French Polynesia, Guam, 
Hawaii, Kiribati, Micronesia, New Caledonia, New Zealand, Palau, Papua New Guinea, Samoa, and Vanuatu 
1Bat rabies may exist in some areas that are reportedly free of rabies in other animals.
2Bat lyssaviruses are known to exist in these areas that are reportedly free of rabies in other animals.
3Most of Pacific Oceania is reportedly rabies-free.

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.

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).

Specific exposures likely to go unrecognized

References

Warrell MJ, Warrell DA. Rabies and other lyssavirus diseases. Lancet. 2004;363:959-69.
Nel L. Vaccines for lyssaviruses other than rabies. Expert Rev Vaccines. 2005;4:533-40.
Gibbons RV. Cryptogenic rabies, bats, and the question of aerosol transmission. 
Ann Emerg Med. 2002;39:528-36.
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.
Hellenbrand W, Meyer C, Rasch G, Steffens I, Ammon A. Cases of rabies in Germany 
following organ transplantation. Euro Surveill. 2005;10:E050224.6.
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.
Taplitz RA. Managing bite wounds. Currently recommended antibiotics for treatment 
and prophylaxis. Postgrad Med. 2004;116:49-52, 55-6, 59.
Gupta RK. Recent outbreak of rabies infections in Brazil transmitted by vampire bats. 
Euro Surveill. 2005;10:E051110.3.
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.
Hore C. Important unusual infections in Australia: a critical care perspective. 
Crit Care Resusc. 2001;3:262-72.11.
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.
Wilde H, Briggs DJ, Meslin FX, Hemachudha T, Sitprija V. Rabies update for travel 
medicine advisors. Clin Infect Dis. 2003;37:96-100.
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.
Smith A, Petrovic M, Solomon T, Fooks A. Death from rabies in a UK traveler returning 
from India. Euro Surveill. 2005;10:E050728.5.
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.
Richardson M. The management of animal and human bite wounds. Nurs Times. 2006;102:34-6.
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.
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.
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.
World Health Organization Expert Consultation on Rabies. World Health Organ Tech Rep Ser. 2005;931:1-88.
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.
Heudorf U, Tiarks-Jungk P, Stark S. Travel medicine and vaccination as a task of 
infection prevention. Gesundheitswesen. 2006;68:316-22.
Rupprecht CE, Gibbons RV. Clinical practice. Prophylaxis against rabies. N Engl J Med. 2004;351:2626-35.

CHARLES E. RUPPRECHT