Globally, about 59,000 human rabies deaths occur each year, and 98% of these deaths are caused by the canine (dog) rabies virus variant. In the United States, the canine rabies virus variant has been eliminated, but wildlife variants (such as bat, raccoon, and skunk rabies virus variants) remain. Hawaii is the only U.S. state that is rabies-free. About 5,000 animal cases of rabies are reported each year in the United States. In the 21-year period between January 2000 and December 2020, 52 cases of human rabies were diagnosed in the United States, and 38 of these were caused by rabies acquired in the United States. No U.S. cases occurred in people who had previously received rabies vaccine as pre-exposure prophylaxis.
Ask the Experts: Rabies
Two rabies vaccines are available in the United States. Both vaccines contain inactivated rabies virus. HDCV vaccine (Imovax, Sanofi) is produced in human diploid cell culture. PCECV vaccine (RabAvert, Bavarian Nordic) is produced in chick embryo cell culture. Both types are considered equally safe and effective. The products are interchangeable: it is acceptable to administer a mixed-brand series, if needed.
Yes. The two rabies vaccines licensed for use in the United States are interchangeable.
In May 2022, CDC published new ACIP recommendations reducing the primary PrEP rabies vaccination series from 3 doses to 2 doses (administered intramuscularly on days 0 and 7) for all people at elevated risk for exposure to rabies. This was done based on strong evidence that the 2-dose schedule would provide the same protection as the previously recommended 3-dose primary series for up to three years. The less costly 2-dose schedule conserves rabies vaccine supplies, which have been subject to national shortages at times, and may increase adherence with PrEP recommendations.
Five categories of risk were created based upon variables including elevated risk of unusual, unrecognized, or recognized exposures and whether elevated risk is sustained over time, or not. For individuals in risk categories 1–3 (all with sustained elevated risk expected to last more than 3 years after the primary series), ACIP recommends periodic rabies vaccine antibody titer checks at different intervals, and/or booster vaccination. See the table on pages 622–623 of the MMWR published on May 6, 2022, (www.cdc.gov/mmwr/volumes/71/wr/pdfs/mm7118a2-H.pdf) for each risk category’s antibody titer and/or booster dose recommendations for sustained pre-exposure prophylaxis over time.
No. Doses of rabies vaccine given in the gluteus should not be counted as valid and should be repeated. If repeating the invalid dose results in an interval between doses more than 3 days longer than the recommended interval, then you should perform a rabies serology 7–14 days after administration of the final dose in the series to ensure an adequate immune response to the series. For more information about rabies serology, see www.cdc.gov/rabies/specific_groups/doctors/serology.html.
In May 2022, CDC published updated ACIP recommendations for rabies PrEP based on risk categories. All people in categories 1-4 should receive a 2-dose primary PrEP rabies vaccine series. People in categories 1-3 require additional long-term follow-up with periodic antibody titer checks and/or booster doses, depending on the category. See the table on pages 622-623 of the MMWR publication for details: www.cdc.gov/mmwr/volumes/71/wr/pdfs/mm7118a2-H.pdf.
In brief, the risk categories are as follows:
- Risk category 1: elevated risk of unrecognized or recognized exposures, including unusual or high-risk exposures (e.g., laboratory or rabies vaccine production settings)
- Risk category 2: elevated risk, exposures typically recognized but may be unrecognized (e.g., people who frequently interact with bats or collect suspected rabies samples)
- Risk category 3: elevated risk, exposure nearly always recognized (e.g., veterinary workers, people who handle wildlife reservoir species, spelunkers [because of bats], and certain travelers who have increased risk and may have trouble obtaining safe post-exposure prophylaxis)
- Risk category 4: same type of risk as category 3, but risk period is time-limited (no more than 3 years)
- Risk category 5: low risk, typical person living in the United States (PrEP not recommended)
The ACIP statement (“Human Rabies Prevention-United States, 2008, Recommendations of the Advisory Committee on Immunization Practices”) was published in MMWR on May 23, 2008. This document updated the status of rabies and anti-rabies biologics in the United States. To view this document, go to www.cdc.gov/mmwr/PDF/rr/rr5703.pdf.
In March 2010, ACIP eliminated the fifth dose of vaccine given post-exposure to previously unvaccinated persons with no immunosuppression. To view these recommendations, go to www.cdc.gov/mmwr/pdf/rr/rr5902.pdf.
In May 2022, ACIP eliminated the third dose of vaccine given in the primary series for pre-exposure prophylaxis and introduced updated risk categories with customized recommendations for long-term follow up after completion of the 2-dose primary series. To view this document, visit www.cdc.gov/mmwr/volumes/71/wr/pdfs/mm7118a2-H.pdf.
Treatment after an exposure (PEP) in a previously unvaccinated person requires receiving a dose of human rabies immune globulin (HRIG) and four (or five if the person’s immune system is suppressed) doses of vaccine. Pre-exposure prophylaxis (PrEP) requires only two doses of vaccine and no immune globulin. If a person who is up to date with the recommended PrEP schedule is exposed to rabies, the person’s PEP treatment is completed with two doses of vaccine (on day 0 and day 3).
Human rabies immune globulin (HRIG) is the IgG fraction of plasma from human donors who have received multiple doses of rabies vaccine and have high levels of anti-rabies antibody. HRIG is administered once to previously unvaccinated individuals exposed to a rabid animal to provide rabies virus neutralizing antibody coverage until the patient responds to vaccination by actively producing virus-neutralizing antibodies. HRIG is administered once on day 0 at the time postexposure prophylaxis (PEP) is initiated, in conjunction with human rabies vaccine. If HRIG was not administered when vaccination was begun on day 0, it can be administered up to and including day 7 of the PEP series. If anatomically feasible, the full dose of HRIG is infiltrated around and into any wounds. Any remaining volume is injected intramuscularly at a site distant from vaccine administration. HRIG should not be administered in the same syringe or at the same anatomic site as the first vaccine dose. However, subsequent doses (i.e., on days 3, 7, and 14) of vaccine in the 4-dose PEP vaccine series can be administered in the same anatomic location in which HRIG was administered.
Every attempt should be made to adhere to the recommended vaccination schedules. Once vaccination is initiated, delays of a few days for individual doses are unimportant, but the effect of longer lapses of weeks or more is unknown. Most interruptions in the vaccine schedule do not require reinitiation of the entire series. For most minor deviations from the schedule, vaccination can be resumed as though the patient were on schedule. For example, if a patient misses the dose scheduled for day 7 and presents for vaccination on day 10, the day 7 dose should be administered that day and the schedule resumed, maintaining the same interval between doses. In this scenario, the remaining doses would be administered on days 17 and 31. When substantial deviations from the schedule occur, immune status should be assessed by performing serologic testing 7–14 days after administration of the final dose in the series. Postexposure prophylaxis with rabies vaccine is described in detail at www.cdc.gov/mmwr/pdf/rr/rr5902.pdf.
Yes. A pregnant person should receive rabies vaccine if indicated. No fetal abnormalities have been reported with the rabies vaccine. A pregnant person can receive routine pre-exposure vaccination against rabies if the risk of exposure is high.
Most reactions to this vaccine are mild, such as soreness and redness at the injection site. Moderate problems, including hives, pain in the joints, and fever, are possible in a small percentage of patients (6%) given booster doses. Once initiated, rabies prophylaxis should not be interrupted or discontinued because of local or mild systemic adverse reactions to rabies vaccine. Usually, such reactions can be successfully managed with anti-inflammatory and antipyretic agents, such as ibuprofen or acetaminophen.
The rabies vaccine is not recommended for routine use in the general population. Anyone for whom the pre-exposure vaccine is recommended should not receive a dose when they are moderately or severely ill.
Unless rabies can be ruled out by diagnostic testing of the bat, rabies postexposure prophylaxis (PEP) is recommended. Because the details of these recommendations are fairly complex and depend on various factors, consultation with state and local health departments should be sought.
Your best source is to contact your local or state public health agency. You can find contact information by going to www.cdc.gov/rabies/resources/contacts.html.
In a situation where the person’s vaccination status is not aligned with current recommendations at the time of exposure, the person should receive the same postexposure prophylaxis (PEP) regimen as an unvaccinated person. This includes human rabies immune globulin (HRIG) and 4 doses of vaccine (days 0, 3, 7 and 14).
For details on this and other scenarios related to sustaining long term immunogenicity in recipients of the 2-dose rabies primary series, please refer to the figure on page 624 of the May 6, 2022, MMWR at www.cdc.gov/mmwr/volumes/71/wr/pdfs/mm7118a2-H.pdf.