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Part 1, Chapter 12: Manual Appendix VII

Rabies and Rabies Vaccine



Although rabies rarely affects humans in the United States, thousands of persons receive rabies vaccine every year, principally for postexposure prophylaxis.  The likelihood of human exposure to rabies from domestic' animals has decreased greatly in recent years.  In every year since 1976, more than 85 percent of all reported cases of animal rabies have been among wild animals, the most important source of possible infection for humans in the United States.  However, for persons traveling overseas to developing countries with endemic rabies, the dog remains the animal most likely-to transmit rabies.


Both whole-virion and subvirion human diploid cell rabies vaccines (HDCV) are available.  For preexposure rabies prophylaxis, a three-dose series of HDCV of either type given as one milliliter (m1 ) doses intramuscular (IM) on days 0, 7 and 28 provides adequate antibody levels in virtually all recipients.  The CDC currently accepts a titer of five by the rapid fluorescent-focus inhibition test as adequate.

The whole virion HDCV produced but the Merieux Institute has been used for preexposure immunization in a regimen of three 0.1 ml dose on each of days 0, 7 and 28.  Experience gained with over 2,000 persons vaccinated in the United States by the intradermal (ID) route has shown that antibody is produced in all recipients, although the mean response is somewhat lower and may be of shorter duration than with comparable IM immunization.  Except for persons suspected of being immunosuppressed, postvaccination serology is not necessary following IM or ID immunization in the United States.  Antibody response in some groups vaccinated ID outside the United States has been found to be inadequate for reasons not yet determined.  Preliminary data suggest that concurrent administration of malaria chemoprophylyaxis may be a factor in the lowered immunologic response of persons vaccinated overseas.  It should be noted that Merieux Institute, the manufacturer, has not yet met the packaging and labeling requirements necessary to obtain approval by the Food and Drug Administration (FDA) for the ID route of administration.  The one ml vial presently available is intended for IM use and contains no preservatives.  To minimize the risk of contamination and loss of vaccine potency, the reconstituted vaccine must be used immediately.  Data on ID immunization are not available for Wyeth Laboratories vaccine.  Proper postexposure rabies prophylaxis is determined by whether or not the persons have had previous preexposure or postexposure prophylaxis.  Persons with:

  • had previously received postexposure prophylaxis with HDCV,
  • have received a three-dose IM preexposure regimen of HDCV,
  • have received a three-dose ID preexposure regimen HDCV in the United States, or
  • have a previously documented adequate rabies titer should receive two doses of HDCV, one dose on each of days zero and three.

The human rabies immune globulin (HRIG) is not recommended in these circumstances.  Persons not meeting the above criteria should be treated with a single of each days 0, 3, 7, 14, and 28.  The HRIG should be administered at the beginning of HDCV postexposure prophylaxis but can be given up to the 8th day after the first dose of HDCV was given.  The HRIG dose should be divided; up to half should be infiltrated into the area of the wound if possible, and the rest administered IM, but not in the same site as HDCV.  Only IM administration of HDCV is indicated for postexposure prophylaxis.


Preexposure immunizations should be considered for high-risk groups:  animal handlers, certain laboratory workers and field personnel, and persons planning to be in countries or areas of countries for more than one month where rabies is a constant threat.  Persons whose vacations or avocations bring them into contact with potentially rabid animals should also be considered for preexposure immunization.  Persons with continuing risk of exposure should receive a booster dose every 2 years and, if the titer is inadequate, be given a booster dose.  If there is substantial risk of exposure to rabies, preexposure rabies prophylaxis may be indicated during pregnancy.

The decision to provide specific postexposure antirabies treatment should include the following consideration:

  1. Type of exposure-rabies is transmitted primarily by the bite of infected animals.  It may be also transmitted by introducing the virus into open cuts or wounds in skin or via mucus membranes by saliva or other potentially infectious material from a rabid animal and, rarely, by aerosol exposure.
  2. Species of biting animal - carnivorous wild animals (especially skunks, raccoons, and foxes) and bats are most commonly infected with rabies in the United States.  Elsewhere in the world, dogs, cats, carnivorous wildlife, and bats are major vector.  The likelihood that domestic cats or dogs in the United States will be infected varies from region to region.  Rodents are rarely infected.  Consultations with the State or local health department may be helpful.
  3. In biting incidents, an unprovoked attack is more indictive of a rabid animal than a provoked attack.


Following postexposure prophylaxis, local reactions such as pain, erythema, and swelling or itching at the injection site are very common, and mild systematic reactions such as headache, nausea, abdominal pain, muscle aches, and dizziness are reported by about 20 percent of recipients.  Systematic allergic reactions ranging from hives to anaphylaxis occur in an estimated 11 per 10,000 vaccines.  Four cases of transient neuroparalytic illness have been temporarily associated with HDCV administration; two following administration of whole virion vaccine and two following subvirion vaccine.  No permanent sequelae or deaths have been associated with administration of HDCV.


Corticosteroids and other immunosuppressive agents can interfere with development of active immunity.  Vaccine should not be administered to persons known or suspected of being immunosuppressed, or to those who are receiving steroids or immunosuppressive therapy.  It is especially important that serum be tested to ensure an adequate rabies antibody response.