Human Rabies Prevention
Recommendations of the Advisory Committee
on Immunization Practices United States, 2008
These recommendations of the Advisory Committee on Immunization Practices (ACIP) update the previous recommendations on human rabies prevention (CDC. Human rabies prevention---United States, 1999:
recommendations of the Advisory Committee on Immunization Practices.
MMWR 1999;48 [No. RR-1]) and reflect the status of rabies and antirabies biologics in the United States.
This statement
1) provides updated information on human and animal rabies epidemiology;
2) summarizes the evidence regarding the effectiveness/efficacy, immunogenicity, and safety of rabies biologics;
3) presents new information on the cost-effectiveness of rabies postexposure prophylaxis;
4) presents recommendations for rabies postexposure and pre-exposure prophylaxis; and
5) presents information regarding treatment considerations for human rabies patients.
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Summary
These recommendations of the Advisory Committee on Immunization Practices (ACIP) update the previous recommendations on human rabies prevention (CDC. Human rabies prevention---United States, 1999:
recommendations of the Advisory Committee on Immunization Practices.
MMWR 1999;48 [No. RR-1]) and reflect the status of rabies and antirabies biologics in the United States. This statement 1) provides updated information on human and animal rabies epidemiology; 2) summarizes the evidence regarding the effectiveness/efficacy, immunogenicity, and safety of rabies biologics; 3) presents new information on the cost-effectiveness of rabies postexposure prophylaxis; 4) presents recommendations for rabies postexposure and pre-exposure prophylaxis; and 5) presents information regarding treatment considerations for human rabies patients.
These recommendations involve no substantial changes to the recommended approach for rabies postexposure or pre-exposure prophylaxis. ACIP recommends that prophylaxis for the prevention of rabies in humans exposed to rabies virus should include prompt and thorough wound cleansing followed by passive rabies immunization with human rabies immune globulin (HRIG) and vaccination with a cell culture rabies vaccine. For persons who have never been vaccinated against rabies, postexposure antirabies vaccination should always include administration of both passive antibody (HRIG) and vaccine (human diploid cell vaccine [HDCV] or purified chick embryo cell vaccine [PCECV]). Persons who have ever previously received complete vaccination regimens (pre-exposure or postexposure) with a cell culture vaccine or persons who have been vaccinated with other types of vaccines and have previously had a documented rabies virus neutralizing antibody titer should receive only 2 doses of vaccine:
one on day 0 (as soon as the exposure is recognized and administration of vaccine can be arranged) and the second on day 3. HRIG is administered only once (i.e., at the beginning of antirabies
prophylaxis) to previously unvaccinated persons to provide immediate, passive, rabies virus neutralizing antibody coverage until the patient responds to HDCV or PCECV by actively producing antibodies. A regimen of 5 1-mL doses of HDCV or PCECV should be administered intramuscularly to previously unvaccinated persons. The first dose of the 5-dose course should be administered as soon as possible after exposure (day 0). Additional doses should then be administered on days 3, 7, 14, and 28 after the first vaccination. Rabies pre-exposure vaccination should include three 1.0-mL injections of HDCV or PCECV administered intramuscularly (one injection per day on days 0, 7, and
21 or 28).
Modifications were made to the language of the guidelines to clarify the recommendations and better specify the situations in which rabies
post- and pre-exposure prophylaxis should be administered. No new rabies biologics are presented, and no changes were made to the vaccination schedules. However, rabies vaccine adsorbed (RVA, Bioport
Corporation) is no longer available for rabies postexposure or pre-exposure prophylaxis, and intradermal pre-exposure prophylaxis is no longer recommended because it is not available in the United States.
Introduction
Rabies is a zoonotic disease caused by RNA viruses in the Family Rhabdoviridae, Genus Lyssavirus (1--4). Virus is typically present in the saliva of clinically ill mammals and is transmitted through a bite. After entering the central nervous system of the next host, the virus causes an acute, progressive encephalomyelitis that is almost always fatal. The incubation period in humans is usually several weeks to months, but ranges from days to years.
As a result of improved canine vaccination programs and stray animal control, a marked decrease in domestic animal rabies cases in the United States occurred after World War II. This decline led to a substantial decrease in indigenously acquired rabies among humans (5).
In 1946, a total of 8,384 indigenous rabies cases were reported among dogs and 33 cases in humans. In 2006, a total of 79 cases of rabies were reported in domestic dogs, none of which was attributed to enzootic dog-to-dog transmission, and three cases were reported in humans (6). The infectious sources of the 79 cases in dogs were wildlife reservoirs or dogs that were translocated from localities where canine rabies virus variants still circulate. None of the 2006 human rabies cases was acquired from indigenous domestic animals (6).
Thus, the likelihood of human exposure to a rabid domestic animal in the United States has decreased substantially. However, one of the three human rabies cases diagnosed in 2006 was associated with a dog bite that occurred in the Philippines, where canine rabies is enzootic. The risk for reintroduction from abroad remains (7).
International travelers to areas where canine rabies remains enzootic are at risk for exposure to rabies from domestic and feral dogs.
Unlike the situation in developing countries, wild animals are the most important potential source of infection for both humans and domestic animals in the United States. Most reported cases of rabies occur among carnivores, primarily raccoons, skunks, and foxes and various species of bats. Rabies among insectivorous bats occurs throughout the continental United States. Hawaii remains consistently rabies-free. For the past several decades, the majority of naturally acquired, indigenous human rabies cases in the United States have resulted from variants of rabies viruses associated with insectivorous bats (5). The lone human case reported in the United States during
2005 and two of the three human rabies cases in 2006 were attributed to bat exposures (6,8). During 2004, two of the eight human rabies cases resulted from bat exposures. One of these rabies patients recovered and remains the only rabies patient to have survived without the administration of rabies vaccination (9). Rabies was not immediately recognized as the cause of death in the other 2004 patient, and organs and a vascular graft from this patient were transplanted into four persons, resulting in clinical rabies and death in all of the recipients (10).
Approximately 16,000--39,000 persons come in contact with potentially rabid animals and receive rabies postexposure prophylaxis each year (11). To appropriately manage potential human exposures to rabies, the risk for infection must be accurately assessed. Administration of rabies postexposure prophylaxis is a medical urgency, not a medical emergency, but decisions must not be delayed. Prophylaxis is occasionally complicated by adverse reactions, but these reactions are rarely severe (12--16).
For these recommendations, data on the safety and efficacy of active and passive rabies vaccination were derived from both human and animal studies. Because controlled human trials cannot be performed, studies describing extensive field experience and immunogenicity studies from certain areas of the world were reviewed. These studies indicated that postexposure prophylaxis combining wound treatment, local infiltration of rabies immune globulin (RIG), and vaccination is uniformly effective when appropriately administered (17--22). However, rabies has occasionally developed among humans when key elements of the rabies postexposure prophylaxis regimens were omitted or incorrectly administered. Timely and appropriate human pre-exposure and postexposure prophylaxis will prevent human rabies; however, the number of persons receiving prophylaxis can be reduced if other basic public health and veterinary programs are working to prevent and control rabies. Practical and accurate health education about rabies, domestic animal vaccination and responsible pet care, modern stray animal control, and prompt diagnosis can minimize unnecessary animal exposures, alleviate inherent natural risks after exposure, and prevent many circumstances that result in the need for rabies prophylaxis.
