Last reviewed: 2 Jun 2022
Last updated: 27 May 2022
27 May 2022

ACIP updates rabies pre-exposure prophylaxis guidelines

The US Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP) have updated their rabies pre-exposure prophylaxis (PrEP) guidelines. PrEP is recommended in certain people who are at high risk for rabies exposure.

Fewer doses are now required in the primary vaccination schedule. ACIP recommends a two-dose intramuscular rabies vaccination series to replace the previously recommended three-dose schedule. Doses should be administered on days 0 and 7. As a consequence of this update, more people who are recommended to receive rabies PrEP might now be vaccinated because the two-dose series is associated with a lower cost and takes less time to complete.

The minimum acceptable rabies antibody titer, used to determine whether rabies vaccination booster doses are required, has been increased to 0.5 IU/mL. Historically, the minimum antibody titer recommended was 0.1 to 0.3 IU/mL. Therefore, when titers are checked, more people may require a booster dose than with the previous titer cut-off.

Recommendations for PrEP depend on the level of a person’s risk for being exposed to rabies. These risk categories have been redefined into 5 risk groups. Many people for whom serial titers were previously recommended every 2 years now require only a one-time titer (and booster if the titer is below a certain level), or a one-time booster. This means less frequent or no antibody titer checks for some risk groups.

Worldwide, approximately 59,000 human rabies deaths occur each year. In the US, 52 cases of human rabies were diagnosed between 2000 to 2020, 28 of which were indigenously acquired.

See Management: prevention

Original source of update



History and exam

Key diagnostic factors

  • history of recent scratch or bite from known vector
  • hydrophobia
  • aerophobia
  • limb numbness, pain, and paresthesia
  • pruritus
  • dysphagia
  • fever
  • change in behavior
  • agitation and confusion
  • hallucination
  • signs of autonomic instability
  • rapid progression of symptoms
  • weakness and paralysis
More key diagnostic factors

Other diagnostic factors

  • urinary or fecal incontinence
  • coma
  • abdominal pain
  • insomnia
  • seizures
  • slurred or stuttered speech
  • ataxia
Other diagnostic factors

Risk factors

  • recent scratch or bite from known vector
  • travel to/living in rabies-endemic country
  • occupational or recreational exposure
  • age <15 years
More risk factors

Diagnostic investigations

1st investigations to order

  • saliva PCR and viral culture
  • skin biopsy (neck) with direct fluorescent antibody (DFA) and PCR
  • CSF cytology
  • CSF biochemistry
  • CSF rabies neutralizing antibody
  • serum rabies IgM or IgG
  • CSF herpes simplex PCR
  • CSF enterovirus PCR
  • CSF West Nile virus IgM
  • serum N-methyl-D-aspartate (NMDA) glutamate receptor antibodies
More 1st investigations to order

Investigations to consider

  • serum arbovirus antibodies
  • serum Bartonella antibodies
  • serum Rickettsia antibodies
  • head MRI
More investigations to consider

Treatment algorithm


asymptomatic with recent vector exposure


symptomatic rabies



Sergio Recuenco, MD, MPH, DrPH

Associate Professor

Faculty of Medicine Sa Fernando

National University of San Marcos




SR declares that he has no competing interests.

Rodney Willoughby, MD



Medical College of Wisconsin




RW is an author of a number of references cited in this topic.


Dr Sergio Recuenco and Dr Rodney Willoughby would like to gratefully acknowledge Dr Kis Robertson, a previous contributor to this topic.


KR declares that she has no competing interests.

Peer reviewers

Peter Leggat, MD


School of Public Health

Tropical Medicine and Rehabilitation Sciences

Faculty of Medicine

Health and Molecular Sciences

James Cook University





PL is a member of the Australian Travel Health Advisory Group that is supported by a grant from GlaxoSmithKline. PL has received travel grants from GlaxoSmithKline to attend travel medical conferences in the last 5 years.

Allan Grill, MD, CCFP, MPH

Assistant Professor

Department of Family and Community Medicine

Dalla Lana School of Public Health

University of Toronto





AG declares that he has no competing interests.

  • Rabies images
  • Differentials

    • Herpes simplex virus infection
    • Enterovirus meningoencephalitis
    • West Nile virus encephalitis
    More Differentials
  • Guidelines

    • Use of a modified preexposure prophylaxis vaccination schedule to prevent human rabies
    • CDC health information for international travel (The Yellow Book). Chapter 4: infectious diseases related to travel - rabies
    More Guidelines
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