Clinical Pathways
Clinical Pathways
Results available expeditiously
Results available expeditiously

Results available expeditiously

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Action

Decision

Tests positive by dFAT?

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Yes → Administer PEP (Class II)
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No → Do not administer PEP (Class II)

Background

The diagnosis of rabies in animals requires brain tissue and is performed post mortem. Historically, the presence of intracellular accumulations of viral particles, called Negri bodies, were considered pathognomonic for rabies, but histology studies have been replaced by more sensitive and specific methods. The dFAT is most widely used. A negative dFAT on a subject animal can reliably exclude rabies. The dFAT requires expensive equipment and, in response, the more cost-effective direct immunohistochemical test (dRIT) has been developed and validated, increasing the availability of testing in resource-limited regions. Enzyme-linked immunosorbent assay (ELISA) techniques are also available, but are less sensitive. Rabies diagnostic tests are available through the CDC Rabies Laboratory.

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References
  1. Pieracci EG, Pearson CM, Wallace RM, et al. Vital signs: trends in human rabies deaths and exposures - United States, 1938-2018. MMWR Morb Mortal Wkly Rep.2019;68(23):524-528. (Surveillance) DOI: 10.15585/mmwr.mm6823e1
  2. Hampson K, Coudeville L, Lembo T, et al. Estimating the global burden of endemic canine rabies. PLoS Negl Trop Dis. 2015;9(4):e0003709. (Retrospective)
  3. Fooks AR, Cliquet F, Finke S, et al. Rabies. Nat Rev Dis Primers. 2017;3(1):17091. (Review) DOI: 10.1038/nrdp.2017.91
  4. De Serres G, Dallaire F, Côte M, et al. Bat rabies in the United States and Canada from 1950 through 2007: human cases with and without bat contact. Clin Infect Dis. 2008;46(9):1329-1337. (Retrospective; 61 patients)
  5. Nigg AJ, Walker PL. Overview, prevention, and treatment of rabies. Pharmacotherapy. 2009;29(10):1182-1195. (Review) DOI: 10.1592/phco.29.10.1182
  6. Ma X, Monroe BP, Cleaton JM, et al. Public veterinary medicine: public health: rabies surveillance in the United States during 2018. J Am Vet Med Assoc. 2020;256(2):195-208. (Surveillance)
  7. Dato VM, Campagnolo ER, Long J, et al. A systematic review of human bat rabies virus variant cases: evaluating unprotected physical contact with claws and teeth in support of accurate risk assessments. PLoS One. 2016;11(7):e0159443. (Systematic review)
  8. US Centers for Disease Control and Prevention. “Domestic Animals.“ 2018. Accessed March 10, 2021. (CDC website)
  9. Sikes RK, Cleary WF, Koprowski H, et al. Effective protection of monkeys against death from street virus by post-exposure administration of tissue-culture rabies vaccine. Bull World Health Organ. 1971;45(1):1-11. (Basic science)
  10. Hennenfent AK, Iyengar P, Davies-Cole J. Assessing rabies knowledge gaps in human and animal healthcare professionals practicing in Washington, DC-a one health approach. Zoonoses Public Health. 2018;65(8):947-956. (Survey; 1077 respondents)
  11. Fooks AR, Banyard AC, Horton DL, et al. Current status of rabies and prospects for elimination. Lancet. 2014;384(9951):1389-1399. (Review)
  12. Hemachudha T, Laothamatas J, Rupprecht CE. Human rabies: a disease of complex neuropathogenetic mechanisms and diagnostic challenges. Lancet Neurol. 2002;1(2):101-109. (Review) DOI: 10.1016/s1474-4422(02)00041-8
  13. Srinivasan A, Burton EC, Kuehnert MJ, et al. Transmission of rabies virus from an organ donor to four transplant recipients. N Engl J Med. 2005;352(11):1103-1111. (Case series; 4 patients)
  14. Lu XX, Zhu WY, Wu GZ. Rabies virus transmission via solid organs or tissue allotransplantation. Infect Dis Poverty. 2018;7(1):82. (Case series; 13 patients)
  15. Simani S, Fayaz A, Rahimi P, et al. Six fatal cases of classical rabies virus without biting incidents, Iran 1990-2010. J Clin Virol. 2012;54(3):251-254. (Case series; 6 patients)
  16. Johnson N, Phillpotts R, Fooks AR. Airborne transmission of lyssaviruses. J Med Microbiol. 2006;55(Pt 6):785-790. (Basic science)
  17. Messenger SL, Smith JS, Rupprecht CE. Emerging epidemiology of bat-associated cryptic cases of rabies in humans in the United States. Clin Infect Dis. 2002;35(6):738-747. (Retrospective; 57 patients)
  18. De Serres G, Skowronski DM, Mimault P, et al. Bats in the bedroom, bats in the belfry: reanalysis of the rationale for rabies postexposure prophylaxis. Clin Infect Dis. 2009;48(11):1493-1499. (Surveillance; 14,453 households)
  19. Hemachudha T, Ugolini G, Wacharapluesadee S, et al. Human rabies: neuropathogenesis, diagnosis, and management. Lancet Neurol. 2013;12(5):498-513. (Review)
  20. Begeman L, GeurtsvanKessel C, Finke S, et al. Comparative pathogenesis of rabies in bats and carnivores, and implications for spillover to humans. Lancet Infect Dis. 2018;18(4):e147-e159. (Review)
  21. Boland TA, McGuone D, Jindal J, et al. Phylogenetic and epidemiologic evidence of multiyear incubation in human rabies. Ann Neurol. 2014;75(1):155-160. (Case report)
  22. Warrell DA, Davidson NM, Pope HM, et al. Pathophysiologic studies in human rabies. Am J Med. 1976;60(2):180-190. (Case series; 6 patients)
  23. Pathak S, Horton DL, Lucas S, et al. Diagnosis, management and post-mortem findings of a human case of rabies imported into the United Kingdom from India: a case report. Virol J. 2014;11:63. (Case Report)
  24. Bernard KW, Mallonee J, Wright JC, et al. Preexposure immunization with intradermal human diploid cell rabies vaccine. Risks and benefits of primary and booster vaccination. JAMA. 1987;257(8):1059-1063. (Clinical trial; 124 patients)
  25. Manning SE, Rupprecht CE, Fishbein D, et al. Human rabies prevention--United States, 2008: recommendations of the Advisory Committee on Immunization Practices. MMWR Recomm Rep. 2008;57(RR-3):1-28. Accessed March 10, 2021. (CDC ACIP practice guidelines)
  26. Nicholson KG, Farrow PR, Bijok U, et al. Pre-exposure studies with purified chick embryo cell culture rabies vaccine and human diploid cell vaccine: serological and clinical responses in man. Vaccine. 1987;5(3):208-210. (Randomized controlled trial; 177 patients)
  27. O’Brien KL, Nolan T, Rabies SWo. The WHO position on rabies immunization - 2018 updates. Vaccine. 2019;37 Suppl 1:A85-A87. (WHO clinical practice guidelines)
  28. Hampson K, Abela-Ridder B, Bharti O, et al. Modelling to inform prophylaxis regimens to prevent human rabies. Vaccine. 2019;37 Suppl 1:A166-A173. (Retrospective)
  29. 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 Recomm Rep. 2010;59(Rr-2):1-9. Accessed March 10, 2021. (CDC ACIP clinical practice guidelines)
  30. Gautret P, Angelo KM, Asgeirsson H, et al. Rabies post-exposure prophylaxis started during or after travel: a GeoSentinel analysis. PLoS Negl Trop Dis. 2018;12(11):e0006951. (Retrospective; 920 patients)
  31. Dacheux L, Reynes JM, Buchy P, et al. A reliable diagnosis of human rabies based on analysis of skin biopsy specimens. Clin Infect Dis. 2008;47(11):1410-1417. (Comparative; 51 patients)
  32. Duong V, Tarantola A, Ong S, et al. Laboratory diagnostics in dog-mediated rabies: an overview of performance and a proposed strategy for various settings. Int J Infect Dis. 2016;46:107-114. (Review)
  33. Laothamatas J, Sungkarat W, Hemachudha T. Neuroimaging in rabies. Adv Virus Res. 2011;79:309-327. (Review)
  34. Bhaumik S, Kirubakaran R, Chaudhuri S. Primary closure versus delayed or no closure for traumatic wounds due to mammalian bite. Cochrane Database Syst Rev. 2019;12(12):CD011822. (Cochrane systematic review)
  35. Rupprecht CE, Briggs D, Brown CM, et al. Evidence for a 4-dose vaccine schedule for human rabies post-exposure prophylaxis in previously non-vaccinated individuals. Vaccine. 2009;27(51):7141-7148. (Review)
  36. Both L, Banyard AC, van Dolleweerd C, et al. Passive immunity in the prevention of rabies. Lancet Infect Dis. 2012;12(5):397-407. (Review)
  37. Langedijk AC, De Pijper CA, Spijker R, et al. Rabies antibody response after booster immunization: a systematic review and meta-analysis. Clin Infect Dis. 2018;67(12):1932-1947. (Systematic review and meta-analysis)
  38. Mattner F, Bitz F, Goedecke M, et al. Adverse effects of rabies pre- and postexposure prophylaxis in 290 health-care-workers exposed to a rabies infected organ donor or transplant recipients. Infection. 2007;35(4):219-224. (Retrospective; 290 patients)
  39. Wilde H. Failures of post-exposure rabies prophylaxis. Vaccine. 2007;25(44):7605-7609. (Case series; 7 patients)
  40. World Health Organization. Rabies vaccines: WHO position paper, April 2018 - recommendations. Vaccine. 2018;36(37):5500-5503. (WHO clinical practice guidelines)
  41. Appolinario CM, Jackson AC. Antiviral therapy for human rabies. Antivir Ther. 2015;20(1):1-10. (Review)
  42. Willoughby RE Jr, Tieves KS, Hoffman GM, et al. Survival after treatment of rabies with induction of coma. N Engl J Med. 2005;352(24):2508-2514. (Case report)
  43. Pappaioanou M, Fishbein DB, Dreesen DW, et al. Antibody response to preexposure human diploid-cell rabies vaccine given concurrently with chloroquine. N Engl J Med. 1986;314(5):280-284. (Randomized controlled trial; 51 patients)
  44. Tantawichien T, Jaijaroensup W, Khawplod P, et al. Failure of multiple-site intradermal postexposure rabies vaccination in patients with human immunodeficiency virus with low CD4+ T lymphocyte counts. Clin Infect Dis. 2001;33(10):E122-E124. (Observational; 10 patients)
  45. Nasser R, Rakedzon S, Dickstein Y, et al. Are all vaccines safe for the pregnant traveller? A systematic review and meta-analysis. J Travel Med. 2020;27(2). (Systematic review, meta-analysis)
  46. Kessels JA, Recuenco S, Navarro-Vela AM, et al. Pre-exposure rabies prophylaxis: a systematic review. Bull World Health Organ. 2017;95(3):210-219C. (Systematic review)
  47. Kessels J, Tarantola A, Salahuddin N, et al. Rabies post-exposure prophylaxis: a systematic review on abridged vaccination schedules and the effect of changing administration routes during a single course. Vaccine. 2019;37 Suppl 1:A107-A117. (Systematic review)
  48. Shantavasinkul P, Tantawichien T, Wilde H, et al. Postexposure rabies prophylaxis completed in 1 week: preliminary study. Clin Infect Dis. 2010;50(1):56-60. (Prospective; 131 patients)
  49. De Pijper CA, Boersma J, Terryn S, et al. Rabies antibody response after two intradermal pre-exposure prophylaxis immunizations: An observational cohort study. Travel Med Infect Dis. 2018;22:36-39. (Observational; 430 patients)
  50. Kerdpanich P, Chanthavanich P, De Los Reyes MR, et al. Shortening intradermal rabies post-exposure prophylaxis regimens to 1 week: results from a phase III clinical trial in children, adolescents and adults. PLoS Negl Trop Dis. 2018;12(6):e0006340. (Randomized controlled trial; 885 patients)
  51. Soentjens P, Andries P, Aerssens A, et al. Preexposure intradermal rabies vaccination: a noninferiority trial in healthy adults on shortening the vaccination schedule from 28 to 7 days. Clin Infect Dis. 2019;68(4):607-614. (Randomized controlled trial; 500 patients)
  52. Tarantola A, Ly S, Chan M, et al. Intradermal rabies post-exposure prophylaxis can be abridged with no measurable impact on clinical outcome in Cambodia, 2003-2014. Vaccine. 2019;37 Suppl 1:A118-A127. (Retrospective; 3318 patients)
  53. Cantaert T, Borand L, Kergoat L, et al. A 1-week intradermal dose-sparing regimen for rabies post-exposure prophylaxis (RESIST-2): an observational cohort study. Lancet Infect Dis. 2019;19(12):1355-1362. (Observational; 116 patients)
  54. Bharti OK, Madhusudana SN, Gaunta PL, et al. Local infiltration of rabies immunoglobulins without systemic intramuscular administration: an alternative cost effective approach for passive immunization against rabies. Hum Vaccin Immunother. 2016;12(3):837-842. (Observational; 269 patients)
  55. Bakker AB, Python C, Kissling CJ, et al. First administration to humans of a monoclonal antibody cocktail against rabies virus: safety, tolerability, and neutralizing activity. Vaccine. 2008;26(47):5922-5927. (Prospective, basic science; 57 patients)
  56. Gogtay NJ, Munshi R, Ashwath Narayana DH, et al. Comparison of a novel human rabies monoclonal antibody to human rabies immunoglobulin for postexposure prophylaxis: a phase 2/3, randomized, single-blind, noninferiority, controlled study. Clin Infect Dis. 2018;66(3):387-395. (Randomized controlled trial; 199 patients)
  57. De Benedictis P, Minola A, Rota Nodari E, et al. Development of broad-spectrum human monoclonal antibodies for rabies post-exposure prophylaxis. EMBO Mol Med. 2016;8(4):407-421. (Prospective, basic science)
  58. Alberer M, Gnad-Vogt U, Hong HS, et al. Safety and immunogenicity of a mRNA rabies vaccine in healthy adults: an open-label, non-randomised, prospective, first-in-human phase 1 clinical trial. Lancet. 2017;390(10101):1511-1520. (Prospective; 101 patients)

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