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    Rabies – Diagnosis and Treatment

    Environmental Injuries / Exposures, Infections, Neurological

    Last Reviewed on Feb 13, 2023
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    Context

    • Rabies is an acute, rapidly progressive, viral encephalomyelitis that is uniformly fatal 7-10 days after clinical signs develop.1-4,6,8,9,10
    • Bats are the only rabies reservoir in BC (prevalence estimated < 1%.)1,7
    • Bats, racoons, skunks, and foxes are potential reservoirs in other parts of Canada.6
      • Rodents are rarely infected and do not cause rabies.7
    • The rabies virus (RABV) is transmitted via infected saliva into a wound (bite), or through direct contact with a mucosal surface.1-4,6,8
      • Non-bite transmission is rare.1,6
      • Transmission cannot occur through intact skin, blood, urine, or food. 4,6,8,10
      • Inhalation/airborne transmission are possible, but exceedingly rare.2,8,9,10
    • Exposure to bat through sleeping in same room as bat – call local public health as risk exists and bites hard to detect.
    • RABV is inactivated if it dries out, is exposed to sunlight, or cleaned with ethanol, iodine, or detergent. 7

    Incubation Period:

    • Variable – ranging from 3 to 12 weeks.1-3,5,6,8,10

    Pathogenesis

    RABV travels via peripheral nerves, and ascends the spinal cord to the brain.2,8,10 It then disseminates causing widespread neuronal dysfunction and death.10

    Diagnostic Process

    The BCCDC1 provides a decision-making algorithm for risk assessment and management, and recommendations for post exposure prophylaxis available HERE (on page 3.)

    The algorithm suggests consideration of rabies post exposure prophylaxis (RPEP) if:

    • The exposure to a potentially rabid animal occurred outside of BC, or
    • The exposure occurred in BC and was a bat, or a dog/cat/ferret that was in known contact with a bat, or a dog/cat/ferret that imported in the last six months, or if the contact was with any animal exhibiting rabid signs.

    Approach to Evaluation

    Rabies should be considered for any patient presenting with an unexplained encephalitis, myelitis, or acute neurologic syndrome, and has a history of high-risk exposure.1,2,8,10

    • History & Physical:
      • Exposure Risk Assessment should include consideration of:10
        • Exposure species
        • Exposure type
          • NO risk: Touching animals, or licks on intact skin.
          • LOW risk: Minor scratches or contact without bleeding.
          • HIGH risk: Bites, scratches, or direct contact of saliva with a mucous membrane.
        • Exposure location
          • Proximal exposures, and/or to the face or hands are the higher risk.1
      • Signs and Symptoms:1,3,6,8,10,11
        • The first clinical manifestation is a nonspecific prodrome of fever, chills, malaise, sore throat, vomiting, headaches, and usually paraesthesias, neuropathic pain, or pruritis at the wound site.
        • Hydrophobia and aerophobia are the most rabies-specific signs and present in the first days of clinical onset.
        • After 2-10 days rabies enters one of two different clinical forms:
          1. Encephalitic rabies – CNS irritation predominate, autonomic dysfunction, hydrophobia, and aerophobia.
          2. Paralytic rabies – Rapidly progressing ascending weakness without the early signs of CNS irritation
    • Differential Diagnosis3
      • Absence of exposure history or specific signs (hydrophobia, aerophobia) makes the diagnosis difficult. The differential may include:

    • Investigations and Diagnosis:
      • Primary diagnosis relies heavily on a history of a high-risk exposure.10
      • No single test can rule out rabies.3,4
      • No test can detect RABV prior to symptom onset.3,4
      • No single test can diagnose rabies antemortem.4 Simultaneous testing of saliva, CSF, skin, and serum is required. 3,4,8
        • PCR for viral RNA is most sensitive at the beginning of the clinical course3,4,8
        • Serology sensitivity increases 1-2 weeks into the clinical course.3,4
      • Suspected cases with inconclusive antemortem testing should be considered for post-mortem testing.
    • Imaging:
      • Head CT is not helpful in the diagnosis of a RABV infection but does have a role in the workup to exclude other causes.
      • MRI can be helpful to differentiate rabies from other viral encephalitides.8

    Recommended Treatment

    Approach to Management:

    Rabies is a reportable disease and if suspected, or a high-risk exposure has occurred, local public health experts, the medical health officer, and infectious disease specialists should be consulted immediately.

    • For symptomatic patients:
      • Place on contact and droplet isolation 3
      • Immunization and immunoglobulin are contraindicated 1-3,8,10
      • Treatment is either supportive or palliative,3,8
      • Effective antiviral treatment does not exist.3
      • Even if the patient survives, neurologic outcomes will be severe 1,3,8
    • For asymptomatic, exposed patients:
      • Follow appropriate reporting, wound management, and post-exposure guidelines.
        • Washing with soap and water for least 15 minutes significantly reduce rabies risk.1

    Rabies Post Exposure Prophylaxis (RPEP): 1,2,4,6,8,11

    • RPEP is recommended for any high-risk exposure, or direct contact with a bat, regardless of time since the event.6 Laboratory testing is not required to initiate treatment.1,3,6
    • RPEP should not be delayed more than 48hrs,6 does not have any contraindications, and is recommended for children and pregnant women.3
    • RPEP consists of the rabies vaccine and rabies immunoglobulin (RabIg)
      • Rabies Vaccine:
        • 4 IM Doses (Days 0,3,7,14) add 5th dose (Day 28) if immunocompromised.
        • If concerned about an insufficient immune response, serology can be drawn 7-14 days after the vaccination series.
    • Rabies Immunoglobulin (RabIg)
      • 20IU/kg given on initiation of therapy (Day 0).
      • If possible, the full dose of RabIg should be infiltrated into the wound with any remaining volume administered IM.
      • If the wound site is unknown, the entire dose should be administered IM.
      • If RabIg is not administered at the initiation of the rabies vaccine series, it can be administered up to day 7.
    • Without RPEP, the probability of developing rabies is:10
      • 55% following a bite to the head/neck.
      • 22% following a bite to an upper extremity.
      • 9% following a bite to the trunk.
      • 12% following a bite to a lower limb.

    Quality Of Evidence?

    Justification

    Rabies treatment guidelines and PEP efficacy area are well established.

    High

    Related Information

    Reference List

    1. BC Centre for Disease Control. Chapter I – Management of Specific Diseases – Rabies.

      Communicable Disease Control [Internet]. Vancouver (BC): BCCDC; 2018 [cited 2022 April 12]. Available from: http://www.bccdc.ca/resource-gallery/Documents/Guidelines%20and%20Forms/Guidelines%20and%20Manuals/Epid/CD%20Manual/Chapter%201%20-%20CDC/BCRabiesGuidelines.pdf


    2. DeMaria A, Brown CM.  Clinical manifestations and diagnosis of rabies. In: Mitty J, editor. UpToDate. [Internet]. Waltham, Mass.: UpToDate; 2020 [cited April 10, 2022]. Available from: https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-rabies?search=rabies&source=search_result&selectedTitle=2~80&usage_type=default&display_rank=2#H9913584


    3. Recuenco S, Willoughby R. BMJ Best Practice Rabies [Internet]. London: BMJ Publishing Group Ltd. [updated 2021 Oct; cited 2022 April 12]. Available from https://bestpractice-bmj-com.eu1.proxy.openathens.net/topics/en-gb/903/pdf/903/Rabies.pdf


    4. Miller MJ, Binnicker MJ, Campbell S, et al. A Guide to Utilization of the Microbiology Laboratory for Diagnosis of Infectious Diseases: 2018 Update by the Infectious Diseases Society of America and the American Society for Microbiology.  Clinical Infectious Diseases [Internet]. 2018 Jun [cited 2022 April 12]. 67(6). Available from: https://www.idsociety.org/practice-guideline/laboratory-diagnosis-of-infectious-diseases/#toc-16


    5. BC Centre for Disease Control. Rabies Exposure. British Columbia Annual Summary of Reportable Diseases 2018. Vancouver (BC): BCCDC; 2019. p.99-103,107 and [cited 2022 April 12]. Available from: http://www.bccdc.ca/resource-gallery/Documents/Statistics%20and%20Research/Statistics%20and%20Reports/Epid/Annual%20Reports/2018%20CD%20Annual%20Report.pdf


    6. National Advisory Committee on Immunization. Rabies Vaccine. Canadian Immunization guide. 2015. [cited 2022 April 12]. Available from: https://www.canada.ca/en/public-health/services/publications/healthy-living/canadian-immunization-guide-part-4-active-vaccines/page-18-rabies-vaccine.html


    7. BC Centre for Disease Control. BC Rabies Guidance for Veterinarians [Internet]. Vancouver (BC): BCCDC; 2021 [cited 2022 April 12]. Available from: http://www.bccdc.ca/Documents/BC%20Rabies%20Guidance%20for%20Veterinarians%20April%202021.pdf

       


    8. World Health Organization. WHO Expert Consultation on Rabies. Technical Report Series 1012. 2018. http://apps.who.int/iris/bitstream/handle/10665/272364/9789241210218-eng.pdf?sequence=1&isAllowed=y (Accessed on April 12, 2018).


    9. Davis AD, Rudd RJ, Bowen RA. Effects of aerosolized rabies virus exposure on bats and mice. J Infect Dis. 2007 Apr 15;195(8):1144-50. doi: 10.1086/512616. Epub 2007 Mar 5. PMID: 17357050.


    10. World Health Organization. Rabies vaccines: WHO position paper – April 2018. Weekly epidemiological record. 2018 Apr 20; 93: 201-20. Available from: http://apps.who.int/iris/bitstream/handle/10665/272371/WER9316.pdf?ua=1


    11. BC Centre for Disease Control. BC Immunization Manual, Part 4: Biologic Products, Rabies Vaccine for POST-EXPOSURE Prophylaxis [Internet]. Vancouver (B.C): BCCDC; 2020 [cited 2022 April 12]. Available from: http://www.bccdc.ca/resource-gallery/Documents/Guidelines%20and%20Forms/Guidelines%20and%20Manuals/Epid/CD%20Manual/Chapter%202%20-%20Imms/Part4/RabiesPost-Exposure.pdf


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