Rabies: CDC Updates and Simplifies Preexposure Prophylaxis Vaccination Recommendations

Judy Stone, MD

May 19, 2022

Each year, there are about 59,000 deaths from rabies globally. Most of these occur outside the United States and are the result of dog bites. Since infection with rabies is almost always fatal, there has been considerable attention given to vaccinating people at high risk before likely exposure and responding immediately to those bitten by a rabid animal.

The Centers for Disease Control and Prevention (CDC) recently revised its preexposure prophylaxis (PrEP) recommendations for rabies. Under the previous 2008 guidelines, PrEP injections were given on days 0, 7, and 21 and cost more than $1100. In trying to simplify recommendations and make immunization less expensive, the agency designated five risk levels with different advice based on the level of risk.

The first two groups are those with very high risk of occupational exposures — either working with rabies virus in the laboratory or working with or having contact with bats or performing animal necropsies. They are now advised to get two doses of rabies vaccine on days 0 and 7. The lab workers should have titers checked every 6 months to ensure that they remain adequately protected. And a booster should be given if the titer drops to <0.5 IU/mL. The second group, with bat exposures, should have titers checked every 2 years.

Risk category 3 is those with long-term (>3 years) exposure to mammals other than bats that might be rabid. This group would include veterinarians, wildlife biologists, animal control officers, and spelunkers (cavers). Category 3 also includes travelers who may encounter rabid dogs, which is not a risk in the US. They would get the same initial two doses. The new recommendations for a third dose are based either on a titer drawn 1-3 years later being <0.5 IU/mL or choosing to give a booster between 3 weeks and 3 years after the second dose.

The same groups are covered in Risk Group 4, but these are expected to have less than 3 years of potential exposure after PrEP. They would receive two doses on days 0 and 7.

Finally, Group 5, at the lowest risk, includes most of the US population. They do not require any PrEP.

Dr Agam Rao

Agam Rao, MD, CAPT, US Public Health Service, CDC, told Medscape Medical News that the CDC's Advisory Committee on Immunization Practices (ACIP) has been working on updating the 2008 rabies PrEP recommendations for several years. The committee wanted the new guideline to be "as easily followable as possible but also based on the evidence itself."

There were two significant problems the committee tried to address. "One was that travelers who book their travel on kind of short notice don't have enough time to get that third dose, which at the earliest can be given on day 21," Rao said.

The second problem is that "a three-dose series [is] just really expensive. And what we found from data that had been published since the last ACIP recommendations is that fewer people than we recommend get vaccinated were getting vaccinated. So hopefully, the two-dose series helps with that."

The ACIP used an adapted Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to determine the certainty of the evidence for immunogenicity. The ACIP also used an evidence to recommendations (EtR) framework. "This incorporates a lot of other factors like the acceptability, usability, equity, all of these other variables that are important to the evidence being translated into recommendations," Rao said. A table details their analysis.

Rabies expert Thiravat Hemachudha, MD, professor of neurology at WHO Collaborating Centre for Research and Training on Viral Zoonoses, Chulalongkorn University Hospital, Bangkok, Thailand, told Medscape Medical News via email that "the ACIP relies mostly on serology, whereas the rest of the world cannot afford the test or testing may not be available."

He added: "The issue of 'long-term immunogenicity' after receiving [PrEP is] an anamnestic response. All standard tissue culture rabies vaccines with appropriate dosage and route of delivery, either IM or ID, are considered safe and effective. There are many studies in Asian countries confirming that with only one primary series of PrEP, ID or IM with reduced doses, can produce immunity for as long as 20 years. Therefore, serology check is not necessary in general populations in rabies endemic countries where most of rabies deaths occur. Investigation of all death cases was performed in Thailand and did not reveal any failure. Cases with PrEP in the past who died did not receive a booster after exposure."

Rao offered one additional suggestion to clinicians faced with an urgent need to get a rabies titer: "They really should reach out to the lab (with all the information) before they send the specimen for the titer check…so that the testing can be facilitated. All of these laboratories have the capacity to do stat and ASAP testing…Clinicians do not know that they can call laboratories directly and expedite this sort of testing." 

Rao emphasized that PrEP does not eliminate the need for postexposure prophylaxis (PEP). Still, it eliminates the need for rabies immunoglobulin and decreases the number of vaccine doses required for PEP. "I hope more people will take advantage of the titer checks and potentially save the patient some money," she concluded.

Rao and Hemachudha have disclosed no relevant financial relationships.

MMWR. Published May 6, 2022. Full text

Judy Stone, MD, is an infectious disease specialist and author of Resilience: One Family's Story of Hope and Triumph Over Evil and of Conducting Clinical Research , the essential guide to the topic. You can find her at drjudystone.com or on Twitter @drjudystone .


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