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Rabies

Epidemiology and transmission

Rabies is spread through contact with infected secretions. Most often, contact occurs via a bite wound from an infected animal. Infected saliva can spread disease into open cuts. In caves, disease may occur when bat guano is aerosolized and inhaled. Dogs, cats, skunks, raccoons, bats, cattle and foxes are among animals that can transmit rabies. Travelers at high risk include veterinarians, spelunkers, and those who will handle wild animals. Long-term travelers to highly endemic countries such as Mexico, El Salvador, Guatemala, Peru, Colombia, Ecuador, India, Nepal, Philippines, Sri Lanka, Thailand, and Viet Nam are also at high risk. Travelers to developing countries who will not have access to medical care for prolonged periods may also consider pre-exposure prophylaxis. In its annual Health Information for International Travel, the Centers for Disease Control and Prevention publishes a list of countries that have no reported cases of rabies.

Etiology

Rabies is caused by a virus from the Rhabdoviridae family. The virus climbs up peripheral nerves to reach the central nervous system and disseminate through the body.

Clinical presentation

The incubation period is usually several weeks to one year. Rarely, several years may elapse before symptoms. Symptoms include agitation, hydrophobia, paralysis, apnea, and hypotension. Once symptoms develop, survival is extremely unlikely.

Preparing the international traveler

All travelers should be warned to refrain from petting or playing with animals. Even domesticated animals that have been vaccinated may spread disease if the vaccine was outdated or ineffective.
Immediate cleansing of bite wounds with soap and water reduces the risk of rabies substantially. Medical attention should be sought immediately for any exposure.
The human diploid cell rabies vaccine (HDCV, Imovax, Merieux Institute) is an inactivated vaccine and is the most commonly used product. The Michigan Department of Public Health also produces an inactivated rabies vaccine (RVA). Travelers at high risk should receive the pre-exposure vaccine series. This consists of an intramuscular (IM) injection on days 0, 7, and 21 or 28.
The HDCV is available in a less expensive, intradermal form. Antibody response to the intradermal form is less vigorous than to the IM injection. Therefore, IM injection is preferred whenever the series cannot be completed at least 30 days before departure. Antimalarial agents may reduce the antibody response to HDCV. If antimalarials must be given concurrently, the IM route of vaccination is preferred. Pain at the site of injection occurs in up to 70% of recipients. Serological testing is recommended at 2-year intervals to ensure that immunity is maintained. Booster doses may cause a serum-sickness type of reaction with urticaria, fever, and arthralgias.
Pre-exposure prophylaxis does not eliminate the need for subsequent vaccination in the event of an exposure. Unfortunately, rabies vaccine products in developing countries may be outmoded or simply unavailable. The Centers for Disease Control and Prevention's Division of Viral and Rickettsial Diseases may be contacted for questions.

**Table 3-14. Criteria for preexposure immunization for rabies**
Risk Category	Nature of Risk	Typical Populations	Preexposure regimen
Continuous	Virus present continuously, often in high concentrations Specific exposures likely to go unrecognized Bite, nonbite, or aerosol exposure	Rabies research laboratory workers,* rabies biologics production workers	Primary course: Serologic testing every 6 months; booster vaccination if antibody titer is below acceptable level†
Frequent	Exposure usually episodic with source recognized, but exposure might also be unrecognized Bite, nonbite, or aerosol exposure possible	Rabies diagnostic laboratory workers*, spelunkers, veterinarians and staff, and animal control and wildlife workers in rabies-epizootic areas	Primary course: Serologic testing every 2 years; booster vaccination if antibody titer is below acceptable level†
Infrequent (greater than general population)	Exposure nearly always episodic with source recognized Bite or nonbite exposure	Veterinarians, animal control and wildlife workers in areas with low rabies rates; veterinary students; and travelers visiting areas where rabies is enzootic and immediate access to appropriate medical care, including biologics, is limited.	Primary course: No serologic testing or booster vaccination
Rare (general population)	Exposure always episodic, with source recognized Bite or nonbite exposure	U.S. population at large, including individuals in rabies-epizootic areas	No preexposure immunization necessary.
* Judgment of relative risk and extra monitoring of vaccination status of laboratory workers is the responsibility of the laboratory supervisor (see U.S. Department of Health and Human Service's Biosafety in Microbiological and Biomedical Laboratories, 1999). † Preexposure booster immunization consists of one dose of human diploid cell [rabies] vaccine (HDCV), purified chick embryo cell (PCEC) vaccine, or rabies vaccine adsorbed (RVA), 1.0 mL dose, intramuscular (IM) (deltoid area). Minimum acceptable antibody level is complete virus neutralization at a 1:5 serum dilution by the rapid fluorescent focus inhibition test. A booster dose should be administered if titer falls below this level.

**Table 3-15. Preexposure immunization for rabies**
Vaccine	Dose (mL)	No. of Doses	Schedule (days)	Route
HDCV†	1.0	3	0, 7, 21 or 28	Intramuscular
PCEC	1.0	3	0, 7, 21 or 28	Intramuscular
RVA	1.0	3	0, 7, 21 or 28	Intramuscular
* Patients who are immunosuppressed by disease or medications should postpone preexposure vaccinations and consider avoiding activities for which rabies preexposure prophylaxis is indicated. When this course is not possible, immunosuppressed persons who are at risk for rabies should have their antibody titers checked after vaccination.Thus, preexposure immunization of immunosuppressed travelers is not recommended. † HDCV, human diploid cell vaccine; PCEC, purified chick embryo cell; RVA, rabies vaccine adsorbed.

**Table 3-16. Postexposure immunization for rabies**
Immunization Status	Vaccine/ Product	Dose	No. of doses	Schedule (days)	Route
Not previously immunized	RIG†	20 IU/kg body weight	1	0	Infiltrated at bite site (if possible); remainder intramuscular.
Not previously immunized	HDCV PCEC RVA	1.0 mL	5	0, 3, 7, 14, 28	Intramuscular
Previously immunized‡	HDCV PCEC RVA§	1.0 mL	2	0, 3	Intramuscular
* All postexposure treatment should begin with immediate thorough cleansing of all wounds with soap and water. † RIG, rabies immune globulin; HDCV, human diploid cell (rabies) vaccine; PCEC, purified chick embryo cell; RVA, rabies vaccine adsorbed. ‡ Preexposure immunization with HDCV, PCEC, or RVA; prior postexposure prophylaxis with HDCV, PCEC, or RVA; or persons previously immunized with any other type of rabies vaccine and a documented history of positive antibody response to the prior vaccination. § RIG should not be administered.

Adverse Reactions

Travelers should be advised that they can experience local reactions such as pain, erythema, and swelling or itching at the injection site, or mild systemic reactions, such as headache, nausea, abdominal pain, muscle aches, and dizziness. Approximately 6% of persons receiving booster vaccinations with HDCV can 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.

Age. In infants and children, the dose of HDCV, PCEC, or RVA for preexposure or postexposure prophylaxis is the same as that recommended for adults. The dose of RIG for postexposure prophylaxis is based on body weight (Table 3-16).