Rabies

Human Rabies, Human Exposure to Rabid or Potential Rabid Animal 

NOTE: This chapter discusses the prevention and management of rabies in humans and not animals

*The incubation period is related to the site of exposure; e.g., the incubation period is usually shorter if the virus is inoculated closer to the central nervous system and the exposure is more severe (more virus exposure results in a shorter incubation period).(3)

Managing Cases

Infection Prevention and Control

Use of appropriate personal protective equipment (PPE) is a critical part of Standard Precautions that prevents rabies exposures among healthcare personnel and the need for Post Exposure Prophylaxis (PEP). Adherence to standard precautions includes wearing gowns, gloves, a facemask, and eye protection when contact with patient secretions is possible, such as during intubation, suctioning of airways, and other common patient care activities.(4) These precautions should be used during the duration of the patient's care. Learn more about infection prevention and control precautions at Infection Prevention and Control Precautions | Health & Human Services.

Articles soiled with saliva should be disinfected.(1) The virus can be inactivated by a number of disinfectants including sodium hypochlorite, 70% isopropyl alcohol, ethanol, iodides, quaternary ammonium compounds, formaldehyde, phenol, and other agents. It is also inactivated by low (< 3) or high (> 11) pH and UV irradiation.(5)

Treatment

Clinicians faced with treating clinical rabies patients can either offer supportive therapy or an aggressive treatment plan. There is no single effective treatment for rabies once clinical signs are evident.(3)

If a patient who has rabies (or is suspected of having rabies) exposes another person to saliva (through a bite or via infectious material contacting an open wound or mucous membrane), rabies PEP of the contact should be started. Other people from the patient’s home, social, and work environment should be contacted to review their potential exposure.

Testing

In the U.S. antemortem and postmortem testing for humans is only available at the National Rabies Reference Laboratory at the Centers for Disease Control and Prevention (CDC). When determining to pursue human rabies testing contact CADE (800-362-2736 during business hours or 515-323-4360 after hours) to facilitate testing through CDC.

Prevention and Education

The most effective preventative step for human rabies is eliminating exposures to rabid animals, followed by providing exposed persons prompt PEP.(6) See ‘Managing Contacts’ for PEP recommendations and protocols. 

Managing Contacts

Protection of Humans Exposed to Animals

Under Iowa Code Chapter 351.39, Local Boards of Health are responsible for collecting human exposure reports and enforcing animal confinement. 

The need for post-exposure rabies prophylaxis (PEP) should be evaluated in the form of three questions:

1. Is the animal species known to carry rabies?
2. Did an actual exposure occur? and
3. Can the animal be confined or tested?

Step 1.  Is the exposing animal species known to carry rabies?

Only mammals can get and transmit rabies. Human exposure to non-mammals (birds, reptile, etc.) is never a risk for rabies transmission.(2) 

Wild Animals:

In wild animals the rabies risk varies by species:

• High-risk animals are those that commonly carry rabies. In Iowa, these include skunks, bats, raccoons, foxes, and coyotes.
• Medium-risk animals have very rarely been found to carry rabies in the U.S. and include large rodents such as beavers, muskrats, groundhogs, and woodchucks.
• Low-risk animals that almost never carry rabies in Iowa include small rodents, opossum, and lagomorphs. This includes mice, squirrels, chipmunks, and rabbits.

Dogs, Cats, Ferrets, Horses, and Livestock:

These animals can be infected with rabies virus. Exposures to dogs, cats, horses, and livestock need to be carefully evaluated, since a potential exists for these animals to harbor the virus. 

Other Species:

CADE is available for consultation calls 800-362-2736 during business hours or 515-323-4360 after hours. 

Once it has been determined that the exposing animal involved is a potential carrier of rabies, the clinician should move to the second step. 

Step 2.  Did an exposure actually occur?

Rabies is transmitted by introducing the virus into open cuts or wounds in skin or via mucous membranes. The virus will not cross intact skin.(1,2,7) Since the virus is present in saliva, actual exposures to the virus require bites, saliva contact to mucous membranes, or contamination of fresh, open cuts, wounds, or abrasions with saliva.(2) Whether or not an exposing animal has been vaccinated is immaterial because, though vaccination decreases the risk of the animal being rabid, it is not an absolute guarantee.(6)

Nonsalivary exposures to rabies virus rarely occur and include exposure to large amounts of aerosolized rabies virus (e.g. explorers of caves colonized by rabid bats); infected organs (e.g., corneas) transplanted from patients who died of unrecognized rabies; and exposure of open wounds or mucous membranes to other potentially infectious material (nervous tissue) from a rabid animal.  If the material containing the virus is dry, the virus can be considered noninfectious. Other contact, such as petting a rabid animal or contact with the blood, urine, skunk spray, or feces, does not constitute an exposure and is not an indication for prophylaxis.(7,8)

Bats pose a unique problem. The bite of a bat can be so small that it may be undetectable. People found in rooms with bats, who are unable to state, “I know the bat did not touch me,” should be considered potentially exposed. For example, persons that awaken to find a bat in the room or children alone with a bat in a room should be considered exposed to rabies.(7)

Once it has been determined that a potential exposure occurred, the clinician should move to the third step. (Can the animal be tested?).

Step 3. Can rabies be ruled out in the animal?

Bats:

If available, the bat should be tested for rabies.  If the bat is unavailable for testing, PEP should be administered.(7)

Wild Animals:

High-risk animals should be euthanized and submitted for rabies testing. Since viral shedding periods are not known for these animals, confinement is not appropriate. In cases in which the high-risk animal is unavailable for testing, it should be assumed rabid.(7)

Medium-risk animals have rarely been found to carry rabies in the U.S. and have very rarely, if ever, been found to be rabid in Iowa. If the medium-risk animal is available, it should be submitted for testing.  If the medium-risk animal is not available, the exposed person should consult with a trusted healthcare provider to determine whether prophylaxis is warranted.(7)

Low-risk animal exposures almost never require human rabies PEP, unless the circumstances surrounding the exposure were unusual (such as an unprovoked bite by a low-risk animal acting strangely).(9) If in doubt that a low-risk animal (such as a squirrel or a rabbit) was provoked or acting normally, CADE is available for consultation at 800-362-2736 during business hours or 515-323-4360 after hours.

Dogs, Cats or Ferrets:

Dogs, cats and ferrets that have bitten or otherwise exposed a human and appear healthy may be confined for 10 days instead of euthanasia and testing.(6, 7)

Dogs, cats and ferrets that are incubating rabies will begin to exhibit signs of the disease very soon after they begin shedding virus in saliva. If a dog, cat, or ferret remains alive the entire 10-day confinement, it could not have been shedding rabies virus in its saliva at the time of the bite or exposure.(2) This does not guarantee that the dog, cat, or ferret is not incubating rabies; only that it was not infectious at the time in which the human was exposed. If at any time during the confinement period a dog, cat, or ferret shows signs of rabies it should be immediately euthanized and tested.(6, 7) 

A dog, cat, or ferret that is not available for observation or testing should be considered potentially rabid and post-exposure prophylaxis should be initiated for the exposed person(s). If capture of the dog, cat, or ferret is likely in the near future, prophylaxis may be delayed up to 72 hours. If the exposing dog, cat, or ferret is not located within 72 hours PEP should be considered. However, if at anytime the exposing dog, cat, or ferret is found and either tests negative for rabies virus OR successfully completes the remainder of the 10-day confinement period, PEP could be discontinued.

Livestock:

Recommendations for livestock that expose humans are determined on a case-by-case basis. Contact CADE at 800-362-2736 during business hours or 515-323-4360 after hours for consultation.

Other Animal Species:

For exposure to other animal species, recommendations are made on a case-by-case basis. Contact CADE at 800-362-2736 during business hours or 515-323-4360 after hours for consultation. 

Laboratory Submission of Animal Specimens:

There are two laboratories in Iowa that provide animal rabies testing services and testing requires examination of the animal’s brain, so the animal should be euthanized without damaging the head. There are no antemortem tests available for animals.

Complete submission guidelines are available on each laboratory’s respective webpage.

• State Hygienic Laboratory at the University of Iowa
  • If a person had direct contact with a suspected or known rabid animal, the animal can be tested at no cost. If a pet had contact with the animal, the animal can be tested at the submitter’s expense.
• Iowa State University Veterinary Diagnostic Laboratory
  • If a person or domestic animal had direct contact with a suspected or known rabid animal, the animal can be tested at the submitter’s expense. Animals not known to have exposed anyone can also be tested for diagnostic purposes.

Quarantine

No quarantine is recommended for persons exposed to rabies.

Prophylaxis

Severe Bites above the Shoulder

If a patient is bitten by a high-risk animal above the shoulder, Iowa HHS recommends the healthcare provider consider starting post exposure prophylaxis (PEP) immediately. The closer the point of exposure is to the brain, the shorter the distance in which the virus must travel, therefore potentially resulting in a shorter disease incubation period.

If the animal subsequently tests negative for rabies, or if the animal is confined and is healthy at the end of 10 days (confinements can only be conducted for dogs, cats, and ferrets) PEP can be discontinued at that time.  If PEP is discontinued before the series is completed and the patient is exposed again in the future, the entire PEP series should be administered. If the PEP series is completed and the patient is exposed again in the future, only two doses of rabies vaccine on days 0 and 3 should be administered.

Human Post Exposure Prophylaxis (PEP)

Advisory Committee on Immunization Practices (ACIP) Rabies Post Exposure Prophylaxis Guidelines (7, 9)

*  These regimens are applicable for all age groups, including children. 

† If a tetanus toxoid–containing vaccine is indicated for persons aged ≥11 years, Tdap is preferred for persons who have not previously received Tdap or whose Tdap history is unknown. If a tetanus toxoid–containing vaccine is indicated for a pregnant woman, Tdap should be used. For nonpregnant women with documentation of previous Tdap vaccination, either Td or Tdap may be used if a tetanus toxoid–containing vaccine is indicated.(10)

§ Any person with a history of a complete pre-exposure or postexposure vaccination regimen with HDCV, PCECV, or rabies vaccine adsorbed, or previous vaccination with any other type of rabies vaccine and a documented history of antibody response to the prior vaccination.

¶ The deltoid area is the only acceptable site of vaccination for adults and older children. For younger children, the outer aspect of the thigh can be used. Vaccine should NEVER be administered in the gluteal area.

** Day 0 is the day the first dose of vaccine is administered.

NOTE: In not previously vaccinated persons, if HRIG was not administered when vaccination was begun, it can be administered up to seven days after the administration of the first dose of vaccine. Beyond the seventh day, HRIG is not recommended since an antibody response to the vaccine is presumed to have occurred.(7)

Immunocompromised patients(9):

• In addition to the regimen described in the table above, rabies PEP should be administered using an additional fifth 1-mL vaccine doses of HDCV or PCECV (i.e., 1 dose of vaccine on days 0, 3, 7, 14, AND 28), with the understanding that the immune response still might be inadequate.
  • The decision of whether individuals are immunocompromised should be determined by a physician. However, to assist with this determination, persons with the below conditions may need to receive five doses of rabies vaccine(11):
    • Congenital immunodeficiency
    • Leukemia
    • Lymphoma
    • Generalized malignancy
    • Therapy with alkylating agents, antimetabolites, radiation, or large amounts of corticosteroids
    • Antimalarial medications
    • Persons with HIV infection
    • Renal failure
    • Diabetes (uncontrolled)
    • Alcoholic cirrhosis
    • Asplenia
• When rabies pre- or postexposure prophylaxis is administered to an immunosuppressed person, one or more serum samples should be tested for rabies virus-neutralizing antibody by the RFFIT test to ensure that an acceptable antibody response (≥0.5 IU/mL (~1:50)) has developed after completing the series.
  • If no acceptable antibody response (≥0.5 IU/mL (~1:50)) is detected after the final dose in the pre- or postexposure prophylaxis series, the patient should be managed in consultation with Iowa HHS.(9)

Special Situations

Precautions and Contraindications to Rabies Prophylaxis

Pregnancy. Because of the potential consequences of inadequately treated rabies exposure, pregnancy is not considered a contraindication to post-exposure prophylaxis (PEP). Several studies have shown no indication of increased incidence of abortion, premature births or fetal abnormalities associated with rabies vaccination.  Rabies exposure or diagnosis of rabies in the mother is not an indication for pregnancy termination.(7)

Allergies. 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. When a patient with a history suggesting hypersensitivity to any rabies vaccine component must be given the vaccine, antihistamines can be administered. Epinephrine should be readily available to counteract anaphylactic reactions, and the person should be observed carefully in a medical setting during vaccination.(12)

Human Preexposure Prophylaxis (PrEP)

Recommendations for preexposure prophylaxis against rabies depend on the level of a person’s risk for being exposed to rabies.

Advisory Committee on Immunization Practices (ACIP) Rabies Preexposure Prophylaxis Guidelines (13)

*  These regimens are applicable for all age groups, including children. 

† The deltoid area is the only acceptable site of vaccination for adults and older children. For younger children, the outer aspect of the thigh can be used. Vaccine should NEVER be administered in the gluteal area.

§ Day 0 is the day the first dose of vaccine is administered.

¶ A booster dose should be administered if titers are <0.5 IU/mL (~1:50) by RFFIT at the time of the titer check.

NOTE: Preexposure vaccination (PrEP) does NOT eliminate the need for prompt post-exposure prophylaxis (PEP) if persons who have completed the pre-exposure vaccination series are subsequently exposed to rabies.(7)

Among persons with primary or secondary immunodeficiencies, the immune response to vaccines, including rabies vaccines, can be suboptimal. ACIP recommends that, when possible, preexposure prophylaxis (PrEP) be delayed until a temporary immunocompromising condition has resolved or immunosuppressive medications can be withheld. If an immunocompromising condition cannot be temporarily reversed, rabies vaccines can be administered, but antibody titer should be checked no sooner than 1 week (preferably 2–4 weeks) after completion of the 2-dose preexposure prophylaxis series and all booster doses (including those administered within 3 years of the primary series and in response to a low titer during the serial titer checks recommended for risk categories 1 and 2). If the titer is <0.5 IU/mL (~1:50) by RFFIT, a booster dose should be administered, followed by a subsequent titer check. If two such booster doses fail to elicit an acceptable antibody titer, Iowa HHS should be consulted for case-specific guidance. Participation in high-risk activities by persons confirmed or suspected to be immunocompromised should be avoided until the laboratory-confirmed minimum acceptable antibody titer is achieved or until public health authorities provide alternative guidance.(13) 

Management of deviations from the recommendations

Human Post Exposure Prophylaxis (PEP)

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 clinically inconsequential, but the effect of longer lapses of 2 weeks or more is unknown. For most minor deviations from the schedule, vaccination can be resumed as though the patient were on schedule. When substantial deviations from the schedule occur, Iowa HHS should be consulted for guidance and immune status should be assessed by performing serologic testing 7–14 days after administration of the final dose in the series.(7)

Human Preexposure Prophylaxis (PrEP)

Unavoidable delays of a few days from the recommended date of the second dose of the 2-dose primary series are clinically inconsequential. The effect of longer lapses of 2 weeks or more is unknown. When substantial delays occur, Iowa HHS should be consulted for guidance. The second dose of the primary series should not be administered before the recommended interval between doses has elapsed; if it is inadvertently administered earlier, Iowa HHS should be consulted for guidance.(13)

Additional Information

Rabies biologics currently available in the U.S.

Human Rabies Vaccine(12)

Human Rabies Immunoglobulin (HRIG)(12)

* Note HyperRab® immunoglobulin product has a different concentration compared to all other rabies immunoglobulins (including the very similarly named HyperRab™S/D)—requiring lower volumes to administer the recommended dose of 20 IU/kg; care should be taken to ensure the correct dose of immunoglobulin is administered to ensure adequate immune response.

Where to request rabies virus serology using the Rapid Fluorescent Focus Inhibition Test (RFFIT)

Three commercial laboratories perform the RFFIT for rabies virus antibody testing.(12)

Atlanta Health Associates*
309 Pirckle Ferry Road, Suite D300
Cumming, GA 30040
Phone: 770-205-9091 or 800-717-5612
Fax: 770-204-9021
www.atlantahealth.net

Kansas State University*
1800 Denison Avenue
Manhattan, KS 66506-5600
Phone: 785-532-4483
www.ksvdl.org/rabies-laboratory

Testing at KSU may also be requested through Quest Labs as Rabies Vaccine Response End Point Titer (order # 5789).

University of Missouri One Health–Rabies Laboratory*
Veterinary Medical Diagnostic Laboratory
University of Missouri
901 E. Campus Loop
Columbia, MO 65211
Phone: 573-882-3646 or 800-862-8635
Fax: 573-882-7120
Email: muvmdlrabies@missouri.edu
vmdl.missouri.edu/one-health-rabies

*Use of trade names, commercial sources, or private organizations is for identification only and does not imply endorsement by Iowa HHS.

References

1. Heymann, D. L. (2022). Control of Communicable Diseases Manual (21st ed.). Washington, DC: American Public Health Association.
2. Fooks, A. R., & Jackson, A. C. (Eds.). (2020). Rabies: scientific basis of the disease and its management. Academic Press.
3. CDC. (2024). Clinical Overview of Rabies. https://www.cdc.gov/rabies/hcp/clinical-overview/index.html
4. Kuhar, D., Babcock, H., Brown, V.A. et. al. (2024). Infection Control in Healthcare Personnel: Epidemiology and Control of Selected Infections Transmitted Among Healthcare Personnel and Patients. https://www.cdc.gov/infection-control/hcp/healthcare-personnel-epidemiology-control/rabies.html
5. Spickler, A.R. (2021). Technical Factsheet - Rabies and Rabies-Related Lyssaviruses. https://www.cfsph.iastate.edu/diseaseinfo/disease/?disease=rabies&lang=en
6. Brown, C. M., Slavinski, S., Ettestad, P., Sidwa, T. J., & Sorhage, F. E. (2016). Compendium of animal rabies prevention and control, 2016. Journal of the American Veterinary Medical Association, 248(5), 505-517.
7. Manning, S. E., Rupprecht, C. E., Fishbein, D., Hanlon, C. A., Lumlertdacha, B., Guerra, M., ... & Hull, H. F. (2008). Human rabies prevention—United States, 2008: recommendations of the advisory committee on immunization practices. MMWR Recomm Rep, 57(RR-3), 1-28.
8. WHO. (2018). Animal bites. https://www.who.int/news-room/fact-sheets/detail/animal-bites
9. Rupprecht, C. E., Briggs, D., Brown, C. M., Franka, R., Katz, S. L., Kerr, H. D., ... & Centers for Disease Control and Prevention (CDC). (2010). Use of a reduced (4-dose) vaccine schedule for postexposure prophylaxis to prevent human rabies: recommendations of the advisory committee on immunization practices. MMWR Recomm Rep, 59(RR-2), 1-9.
10. Havers, F. P., Moro, P. L., Hunter, P., Hariri, S., & Bernstein, H. (2020). Use of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccines: updated recommendations of the Advisory Committee on Immunization Practices—United States, 2019. Morbidity and Mortality Weekly Report, 69(3), 77.
11. CDC. (2023). Altered Immunocompetence - General Best Practice Guidelines for Immunization. https://www.cdc.gov/vaccines/hcp/imz-best-practices/altered-immunocompetence.html
12. CDC (2024). Rabies Biologics. https://www.cdc.gov/rabies/hcp/clinical-overview/rabies-biologics.html
13. Rao, A. K., Briggs, D., Moore, S. M., Whitehill, F., Campos-Outcalt, D., Morgan, R. L., ... & Blanton, J. D. (2022). Use of a modified preexposure prophylaxis vaccination schedule to prevent human rabies: recommendations of the advisory committee on immunization practices—United States, 2022. Morbidity and Mortality Weekly Report, 71(18), 619.