Rabies

Description

Rabies is an acute, fatal encephalomyelitis caused by neurotropic viruses in the family Rhabdoviridae, genus Lyssavirus. It 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. 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.

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 Afghanistan, Bangladesh, Brazil, Bolivia, China, Colombia, Ecuador, El Salvador, Guatemala, Haiti, India, Indonesia, Mexico, Myanmar (Burma), Nepal, Pakistan, Peru, the Philippines, Sri Lanka, Thailand, Vietnam, and Yemen. The disease is also found in dogs in many of the other countries of Africa, Asia, and Central and South America, except as noted in Table 4-14, which 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, the Pan American Health Organization, 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 status can change suddenly as a result of disease re-introduction.

Table 4-14. Countries and political units reporting no indigenous cases of rabies during 20031

Region Countries
Africa Cape Verde, Libya, Mauritius, Réunion, São 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 Armenia, Cyprus, Hong Kong, Japan, Kuwait, Lebanon, Malaysia (Sabah), Qatar, and Singapore
Europe Belgium, Denmark2, Finland, France2, Gibraltar, Greece, Iceland, Ireland, Isle of Man, Italy, Luxemburg, Malta, Netherlands2, Norway (mainland), Portugal, Spain2 (except Ceuta/Melilla), Sweden, Switzerland, and United Kingdom2
Oceania3 Australia2, 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 Travellers

Travellers to rabies-endemic countries should be warned about the risk of acquiring rabies, although rabies vaccination is not a requirement for entry into any country. Travellers with extensive unprotected outdoor exposure in rural areas, such as might be experienced while bicycling, camping, hiking, or engaging in certain occupational activities, might be at high risk even if their trip is brief. Casual exposure to cave air is not a concern, but cavers should be warned not to handle bats.

Clinical Description

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 by coma and death.

Prevention

Preexposure vaccination with human diploid cell rabies vaccine (HDCV), purified chick embryo cell (PCEC) vaccine, or rabies vaccine adsorbed (RVA) may be recommended for international travellers 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 traveller. Preexposure vaccination may be recommended for veterinarians, animal handlers, field biologists, spelunkers, missionaries, and certain laboratory workers. Table 4-15 provides criteria for preexposure vaccination. Preexposure 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. Preexposure vaccination is of particular importance for travellers at risk of exposure to rabies in countries where biologicals are in short supply and locally available rabies vaccines might carry a high risk of adverse reactions. Preexposure vaccination may also provide some degree of protection when there is an unapparent or unrecognised exposure to rabies and when postexposure prophylaxis might be delayed.

Table 4-15. Criteria for preexposure immunisation for rabies

Risk Category Nature of Risk Typical Populations Preexposure regimen
Continuous Virus present continuously, often in high concentrations

Specific exposures likely to go unrecognised

Bite, nonbite, or aerosol exposure		 Rabies research laboratory workers1, rabies biologics production workers Primary course: Serologic testing every 6 months; booster vaccination if antibody titer is below acceptable level2
Frequent Exposure usually episodic with source recognised, but exposure might also be unrecognised

Bite, nonbite, or aerosol exposure possible		 Rabies diagnostic laboratory workers1, cavers, 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 level2
Infrequent (greater than general population) Exposure nearly always episodic with source recognised

Bite or nonbite exposure		 Veterinarians, animal control and wildlife workers in areas with low rabies rates; veterinary students; and travellers 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 recognised

Bite or nonbite exposure		 U.S. population at large, including individuals in rabies-epizootic areas No preexposure immunisation necessary.

1Judgment 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).
2Preexposure booster immunisation 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.

Purified equine rabies immune globulin (ERIG) has been used effectively in some developing countries where human rabies immune globulin (RIG) might not have been available. If necessary, such heterologous product is 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 that occurred 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. In addition, unpurified antirabies serum of equine origin might still be used in some countries where neither human RIG nor ERIG are available. The use of this antirabies serum is associated with higher rates of serious adverse reactions, including anaphylaxis.

Travellers 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 a povidone-iodine solution if available; this local treatment will susbstantially reduce the risk of rabies. Travellers 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.

Tables 4-16 and 4-17 provide information on preexposure and postexposure prophylaxis. Routine serologic testing is not necessary for travellers who receive the recommended preeexposure or postexposure regimen with HDCV, PCEC, or RVA vaccines. Exposed travellers previously vaccinated with vaccines other than those produced by cell culture should receive the complete postexposure regimen unless they have developed a laboratory-confirmed antibody response to the primary vaccination. Serologic testing is still recommended for travellers whose immune response might be diminished by drug therapy or by diseases. Rabies preexposure prophylaxis may not be indicated for travellers to the countries in Table 4-14, and postexposure prophylaxis is rarely necessary after exposures to terrestrial animals in these countries.

Table 4-16. Preexposure immunisation for rabies1

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

HDCV, human diploid cell vaccine; PCEC, purified chick embryo cell; RVA, rabies vaccine adsorbed.

1Patients 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 immunisation of immunosuppressed travellers is not recommended.

Table 4-17. Postexposure immunisation for rabies1

Immunisation Status Vaccine / Product Dose No. of doses Schedule (days) Route
Not previously immunised RIG

plus

HDCV or
PCEC or
RVA		 20 IU/kg body weight

1.0 mL		 1



5		 0



0, 3, 7, 14, 28		 Infiltrated at bite site (if possible); remainder intramuscular.

Intramuscular
Previously immunised2, 3 HDCV
PCEC
RVA3		 1.0 mL 2 0, 3 Intramuscular

RIG, rabies immune globulin; HDCV, human diploid cell (rabies) vaccine; PCEC, purified chick embryo cell; RVA, rabies vaccine adsorbed.

1All postexposure prophylaxis should begin with immediate thorough cleansing of all wounds with soap and water.
2Preexposure immunisation with HDCV, PCEC, or RVA; prior postexposure prophylaxis with HDCV, PCEC, or RVA; or persons previously immunised with any other type of rabies vaccine and a documented history of positive antibody response to the prior vaccination.
3RIG should not be administered.

Adverse Reactions

Travellers should be advised that they may 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 characterised 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 4-17).

Bibliography
  • Arguin PM, Krebs JW, Mandel E, et al. Survey of rabies preexposure and postexposure prophylaxis among missionary personnel stationed outside the United States. J Travel Med. 2000;7:10-4.
  • CDC. Human rabies prevention — United States, 1999. Recommendations of the Advisory Committee on Immunisation Practices (ACIP). MMWR Morbid Mortal Wkly Rep. 1999;48(RR-1):1-21.
  • Fooks AR, McElhinney LM, Pounder DJ, 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.
  • Gibbons RV. Cryptogenic rabies, bats, and the question of aerosol transmission. Ann Emerg Med. 2002;39:528-36.
  • Jerrard DA. The use of rabies immune globulin by emergency physicians. J Emerg Med. 2004 ;27:15-9.
  • Moran GJ, Talan DA, Mower W, et al. Appropriateness of rabies postexposure prophylaxis treatment for animal exposures. Emergency ID Net Study Group. JAMA. 2000;284:1001-7.
  • Rupprecht CE, Hanlon CA, Hemachudha T. Rabies re-examined. Lancet Infect Dis. 2002;2:327-43.
  • Taplitz RA. Managing bite wounds. Currently recommended antibiotics for treatment and prophylaxis. Postgrad Med. 2004;116:49-52, 55-6, 59.
  • Warrell MJ, Warrell DA. Rabies and other lyssavirus diseases. Lancet. 2004;363:959-69.
  • Wilde H, Briggs DJ, Meslin FX, et al. Rabies update for travel medicine advisors. Clin Infect Dis. 2003;37:96-100.

- Charles E. Rupprecht

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