Rabies

Narrative

Background

Healthcare-associated transmission of rabies virus has been documented between patients, although occupational transmission to HCP has not been confirmed.¹ Person to person transmission of rabies is rare and has been reported almost exclusively via cornea, tissue, and organ transplantation.^2,3-7

Guidelines for rabies vaccination of certain high-risk groups (e.g., persons who perform rabies laboratory diagnostic testing, those who frequently enter high density bat environments, and persons who work with potentially rabid mammals) are maintained by the Advisory Committee on Immunization Practices (ACIP) and described in Human Rabies Prevention — United States, 2008 Recommendations of the Advisory Committee on Immunization Practices (cdc.gov) (https://www.cdc.gov/mmwr/preview/mmwrhtml/rr5703a1.htm), with updates posted on the ACIP Vaccine Recommendations and Schedules | CDC website (https://www.cdc.gov/vaccines/acip/recommendations.html).⁸ Additional information regarding preexposure rabies vaccination is available on the CDC Rabies Preexposure Vaccinations website (https://www.cdc.gov/rabies/specific_groups/travelers/pre-exposure_vaccinations.html).⁹

Prevention of transmission of rabies in healthcare settings involves:

1. using Standard Precautions, that may include a gown, gloves, eye protection and a facemask, for patients with suspected or confirmed clinical infection, to prevent contact with potentially infectious body fluids and secretions;
2. rapidly diagnosing patients with clinical infection;
3. appropriately administering postexposure prophylaxis (PEP) to persons exposed to rabies virus; and
4. excluding potentially infectious HCP from work.

Use of appropriate personal protective equipment is a critical part of Standard Precautions that prevents exposures among HCP and the need for 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.

Occupational Exposures

Rabies virus is transmitted through direct contact (e.g., through broken skin or mucous membranes in the eyes, nose, or mouth) with saliva, tears and lacrimal secretions, or brain/nervous system tissue from an infected animal or person.¹⁰ Bite and non-bite (e.g., cerebrospinal fluid, brain tissue) occupational exposures from an infected person could theoretically transmit rabies to HCP, but no such cases have been confirmed. Casual contact, such as touching a person with rabies or contact with non-infectious fluid or tissue (e.g., urine, blood, feces), is not associated with a risk for infection. Rabies virus is not transmitted through contaminated objects or materials such as clothes or bedding.¹¹

An exposure to rabies virus in a healthcare setting could include being bitten by a potentially infectious patient, or having a patient’s saliva come into contact with a person’s eyes, mouth, or an open cut on the skin. Contact with wildlife on a healthcare facility’s premises, or in the community, remains possible, and HCP may have exposures outside the United States (https://wwwnc.cdc.gov/travel/yellowbook/2020/travel-related-infectious-diseases/rabies)¹² that are addressed by occupational health services upon their return. Occupational Health Services typically contact state public health officials for assistance in determining the likelihood of a rabies exposure in a specific situation before initiating post-exposure prophylaxis.⁸

Laboratory safety, exposures to rabies, and prevention in laboratory settings are described in Biosafety in Microbiological and Biomedical Laboratories (BMBL), 6th Edition (https://www.cdc.gov/biosafety/publications/bmbl5/index.htm).¹³

Clinical Features

Rabies onset is characterized by a non-specific prodrome that could be mistaken for other diseases. The first symptoms of rabies may be very similar to those of an influenza-like illness, including general weakness or discomfort, fever, or headache. These symptoms may last for days. There may also be discomfort or a prickling or itching sensation at the site of an initial bite, progressing within days to symptoms of cerebral dysfunction, anxiety, confusion, autonomic instability, and agitation. As the disease progresses, the person may experience delirium, abnormal behavior, hallucinations, hydrophobia (fear of water), dysphagia, and insomnia. Occasionally, rabies may present as a paralytic syndrome.^14,15

The acute period of disease typically ends after 2 to 10 days. Once clinical signs of rabies appear, the disease is nearly always fatal, and treatment is typically supportive.¹⁴ Among those without a history of receiving pre- or postexposure prophylaxis, less than 10 documented cases of human survival from rabies have been reported; the majority have had significant lifelong neurological deficits.

The incubation period may vary based on the location of the exposure site (how far away it is from the brain), the type of rabies virus, and any existing immunity.¹⁴ In humans, the incubation period averages 1 to 3 months but ranges from days to years.^16,17

Testing and Diagnosis

Patient history is important to identify a possible exposure to rabies and other encephalitides; in the absence of a possible exposure to rabies, more common causes of encephalitis (e.g., Herpes Simplex Virus, Varicella-Zoster Virus) are typically ruled-out before rabies is considered. However, rabies, for example from an unrecognized bat bite, could be a consideration in the absence of definite exposure history when a work-up has not yielded an etiology.¹⁸

Several ante-mortem tests are necessary to diagnose rabies in humans; no single test is sufficient to rule out rabies in a living person. Antemortem tests are performed on samples of saliva, serum, spinal fluid, and nuchal skin biopsies that include hair follicles at the nape of the neck. Saliva can be tested by real-time reverse transcription polymerase chain reaction. Serum and spinal fluid are tested for neutralizing and non-neutralizing antibodies to rabies virus. Skin biopsy specimens are examined for rabies antigen in the cutaneous nerves at the base of hair follicles by antigenic and molecular testing methods.¹⁹ Interpretation of rabies virus serology can be confounded in persons with a history of rabies vaccination or those who have received human rabies immune globulin within the last 14 days; a positive serological test, alone, must be accompanied with a thorough medical history to rule out these confounders.

Additional information about testing for rabies may be found on the CDC Rabies website (https://www.cdc.gov/rabies/index.html).²⁰

Postexposure Prophylaxis

The purpose of PEP is to prevent the rabies virus from establishing infection in the neural tissue of the host, and decisions about administration are usually made on a case-by-case basis after discussion with public health authorities. Contact information for consulting with state public health authorities is located on the National Association of State Public Health Veterinarians website (http://www.nasphv.org/Documents/StatePublicHealthVeterinariansByState.pdf ).²¹

HCP who report an exposure to rabies may be offered PEP depending on the nature of the exposure.¹⁶ In addition to PEP, all affected wounds should be washed promptly to reduce the amount of virus that may remain present in the wound.^8,16 Prophylaxis, when indicated, should begin as soon as possible after exposure.

Routine delivery of healthcare to a patient with rabies, without an exposure that could result in transmission, is not an indication for PEP. Additional detail regarding PEP for rabies is provided on the CDC Rabies Vaccine website (https://www.cdc.gov/rabies/medical_care/vaccine.html).^22-25

References

1. Peterson D, Barbeau B, McCaffrey K, et al. Human Rabies — Utah, 2018. MMWR Morbidity and mortality weekly report. 2020;69:121-124. doi:http://dx.doi.org/10.15585/mmwr.mm6905a1
2. Srinivasan A, Burton EC, Kuehnert MJ, et al. Transmission of rabies virus from an organ donor to four transplant recipients. The New England journal of medicine. Mar 17 2005;352(11):1103-11. doi:10.1056/NEJMoa043018
3. Houff SA, Burton RC, Wilson RW, et al. Human-to-human transmission of rabies virus by corneal transplant. The New England journal of medicine. Mar 15 1979;300(11):603-4. doi:10.1056/nejm197903153001105
4. Kusne S, Smilack J. Transmission of rabies virus from an organ donor to four transplant recipients. Liver Transpl. Oct 2005;11(10):1295-7. doi:10.1002/lt.20580
5. Vora NM, Basavaraju SV, Feldman KA, et al. Raccoon rabies virus variant transmission through solid organ transplantation. Jama. Jul 24 2013;310(4):398-407. doi:10.1001/jama.2013.7986
6. Maier T, Schwarting A, Mauer D, et al. Management and outcomes after multiple corneal and solid organ transplantations from a donor infected with rabies virus. Clinical infectious diseases: an official publication of the Infectious Diseases Society of America. Apr 15 2010;50(8):1112-9. doi:10.1086/651267
7. Vetter JM, Frisch L, Drosten C, et al. Survival after transplantation of corneas from a rabies-infected donor. Cornea. Feb 2011;30(2):241-4. doi:10.1097/ICO.0b013e3181e4572a
8. Manning SE, Rupprecht CE, Fishbein D, et al. Human rabies prevention–United States, 2008: recommendations of the Advisory Committee on Immunization Practices. MMWR Recommendations and reports: Morbidity and mortality weekly report Recommendations and reports. May 23 2008;57(Rr-3):1-28
9. Centers for Disease Control and Prevention. Rabies: Pre-exposure Prophylaxis. Updated May 4, 2022. Accessed July 8, 2022, https://www.cdc.gov/rabies/prevention/pre-exposure_vaccinations.html?CDC_AA_refVal=https%3A%2F%2Fwww.cdc.gov%2Frabies%2Fspecific_groups%2Ftravelers%2Fpre-exposure_vaccinations.html
10. Centers for Disease Control and Prevention. How is rabies transmitted? Updated June 11, 2019. Accessed July 8, 2022, https://www.cdc.gov/rabies/transmission/index.html
11. Centers for Disease Control and Prevention. Rabies Exposure in Healthcare Settings. Updated January 14, 2021. Accessed July 8, 2022, https://www.cdc.gov/rabies/specific_groups/hcp/exposure.html
12. Wallace RM, Petersen BW, Shlim DR. CDC Yellow Book: Health Information for International Travel: Rabies. Accessed September 29, 2022. https://wwwnc.cdc.gov/travel/yellowbook/2020/travel-related-infectious-diseases/rabies
13. Centers for Disease Control and Prevention; National Institutes of Health. Biosafety in Microbiological and Biomedical Laboratories, 6th Edition. US Department of Health and Human Services; 2020.
14. Centers for Disease Control and Prevention. What are the signs and symptoms of rabies? Updated December 23, 2021. Accessed July 8, 2022, https://www.cdc.gov/rabies/symptoms/index.html
15. Centers for Disease Control and Prevention. Information for Healthcare Providers. Updated January 14, 2021. Accessed July 8, 2022, https://www.cdc.gov/rabies/specific_groups/hcp/index.html
16. American Academy of Pediatrics. Red Book: 2018 Report of the Committee on Infectious Diseases. Rabies. 2018.
17. Rupprecht CE, Briggs D, Brown CM, et al. Use of a reduced (4-dose) vaccine schedule for postexposure prophylaxis to prevent human rabies: recommendations of the advisory committee on immunization practices. MMWR Recommendations and reports: Morbidity and mortality weekly report Recommendations and reports. Mar 19 2010;59(Rr-2):1-9.
18. Centers for Disease Control and Prevention. Information for Healthcare Providers. Accessed January 14, 2021, https://www.cdc.gov/rabies/specific_groups/doctors/index.html
19. Centers for Disease Control and Prevention. Rabies: Diagnosis in animals and humans. Updated September 20, 2011. Accessed July 8, 2022, https://www.cdc.gov/rabies/diagnosis/animals-humans.html
20. Centers for Disease Control and Prevention. Rabies. Updated May 4, 2022. Accessed July 8, 2022, https://www.cdc.gov/rabies/
21. Centers for Disease Control and Prevention. State and Local Rabies Consultation Contacts. Updated December 17, 2021. Accessed July 8, 2022, https://www.cdc.gov/rabies/resources/contacts.html
22. Centers for Disease Control and Prevention. Rabies Vaccine. Updated September 24, 2014. Accessed July 8, 2022, https://www.cdc.gov/rabies/medical_care/vaccine.html
23. Whitehouse ER, Peterson D, McCaffrey K, et al. Evaluation of Online Risk Assessment To Identify Rabies Exposures Among Health Care Workers – Utah, 2019. MMWR Morbidity and mortality weekly report. Jul 24 2020;69(29):956-959. doi:10.15585/mmwr.mm6929a3
24. Vora NM, Orciari LA, Bertumen JB, et al. Potential Confounding of Diagnosis of Rabies in Patients with Recent Receipt of Intravenous Immune Globulin. MMWR Morbidity and mortality weekly report. Feb 9 2018;67(5):161-165. doi:10.15585/mmwr.mm6705a3
25. Harrist A, Styczynski A, Wynn D, et al. Human Rabies – Wyoming and Utah, 2015. MMWR Morbidity and mortality weekly report. Jun 3 2016;65(21):529-33. doi:10.15585/mmwr.mm6521a1