New ACIP Recommendations for Human Rabies Postexposure Prophylaxis
On June 24, 2009 the Advisory Committee on Immunization Practices (ACIP) voted in favor of accepting a recommendation from the ACIP rabies work group to reduce the number of rabies vaccine doses for postexposure prophylaxis (PEP), from 5 doses as recommended in the 2008 ACIP document on Human Rabies Prevention, to 4 doses for most individuals. These recommendations will not become official until accepted by the CDC Director and published in the MMWR.
Questions and Answers
- What are the new recommendations for human rabies postexposure prophylaxis (PEP)?
- Why were new recommendations considered?
- What evidence supported acceptance of these new recommendations?
- When will formal recommendations be published?
- How does the new schedule affect people with certain primary or secondary immune deficiencies?
- Have other aspects of PEP been changed?
- When can I begin using these new recommendations for PEP?
- Will existing vaccine product inserts be changed to reflect new ACIP recommendations?
- Should a health care provider be concerned about off-label usage by following the new ACIP recommendations?
What are the new recommendations for human rabies postexposure prophylaxis (PEP)?
The new recommendations for PEP reduce the number of human rabies vaccine doses to 4 given on days 0, 3, 7, and 14 by eliminating the previously recommended 5th dose on day 28. Human rabies immune globulin (HRIG) continues to be recommended (20 IU/Kg) on day 0 for persons not considered previously immunized for rabies as defined in the 2008 ACIP recommendations.
Why were new recommendations considered?
During 2008, ongoing rabies vaccine supply limitations reinforced the need to emphasize basic human rabies prevention and prophylaxis recommendations. A national work group of experts, consisting of representatives from state and federal health agencies, academia, and relevant professional organizations, was convened to provide recommendations in response to a limited human rabies vaccine supply, as well as guidance in the event of a possible shortage of rabies biologics. One of the recommendations for responding to a shortage situation was to reduce the number of PEP vaccine doses from 5 to 4. Upon review, ACIP requested formation of an ACIP work group to gather and evaluate available evidence to consider the 4 dose PEP regimen as a permanent recommendation for rabies PEP in the United States.
What evidence supported acceptance of these new recommendations?
A panel of rabies experts conducted an extensive review of historical rabies studies and current literature concerning the pathogenesis of rabies virus, clinical vaccine trials, animal studies, epidemiologic surveillance, and health economics to determine the immunogenicity, effectiveness, and safety of a 4 dose PEP vaccination regimen. The panel found significant evidence to suggest that 4 doses of vaccine elicit an immunological response equivalent to the 5 dose series.
When will formal recommendations be published?
Provisional recommendations based on data presented to the ACIP at the June 24, 2009 meeting will be posted to the ACIP website within a few weeks. Formal updated recommendations on human rabies prevention reflecting the new 4 dose schedule will be published in the MMWR in several months.
How does the new schedule affect people with certain primary or secondary immune deficiencies?
The safety and effectiveness of vaccines in people with immune deficiencies are determined by the nature and degree of immunosuppression. Immunosuppressed persons (either due to illness, medication, or therapy for the illness or condition) should continue to receive rabies PEP according to the previously used 5 dose schedule. One or more serum samples should be tested for rabies virus neutralizing antibody by the rapid fluorescent focus inhibition test to ensure that an acceptable antibody response has developed after completing the series. A patient who fails to seroconvert with an acceptable antibody response after the fifth and last dose should be managed in consultation with their physician and appropriate public health officials.
Have other aspects of PEP been changed?
No, these recommendations pertain only to elimination of the 5th (day 28) dose of vaccine. Other PEP recommendations as defined in the 2008 ACIP recommendations on human rabies prevention (i.e. exposure assessment and HRIG administration.) remain unchanged.
When can I begin using these new recommendations for PEP?
State and local health departments as well as health care providers should begin to consider plans for implementation of these recommendations with the appearance of the provisional guidelines which will be available on the ACIP website shortly. Implementation of these new recommendations should begin following their publication in the MMWR.
Will existing vaccine product inserts be changed to reflect new ACIP recommendations?
Current vaccine product labels and inserts are not expected to be changed.
Should a health care provider be concerned about off-label usage by following the new ACIP recommendations?
While the new ACIP recommendations are based on evidence that support a 4 dose regimen, vaccine manufacturers likely will continue to support the product insert that was developed at the time the product was licensed by the FDA. Rabies PEP decisions are complex, determined in part after thorough discussion between a patient and health care provider and frequently with public health consultation. The CDC will follow the guidance provided by the ACIP recommendations, developed from an evidence-based approach, and recommend the 4 dose regimen for PEP.
Historically, ACIP recommendations have not always coincided with label claims and have, on occasion, made off-label recommendations based upon current scientific evidence presented to the committee. In the past, ACIP recommendations regarding intradermal administration of rabies vaccine in the United States preceded changes to vaccine labeling and licensing. The function of ACIP is to evaluate the available evidence and to make immunization recommendations based on the most recent data.
Additional Information
ACIP Website
CDC Rabies website
2008 ACIP Human Rabies Prevention recommendations
Page last reviewed: July 1, 2009
Content Source: National Center for Zoonotic, Vector-Borne, & Enteric Diseases (ZVED)
