Treatment of rabies
- Alan C Jackson, MD, FRCPC
Alan C Jackson, MD, FRCPC
- Professor of Internal Medicine
- Head of the Section of Neurology
- University of Manitoba
- Section Editors
- Martin S Hirsch, MD
Martin S Hirsch, MD
- Editor-in-Chief — Infectious Diseases
- Section Editor — Viral Infections
- Professor of Medicine
- Harvard Medical School
- Morven S Edwards, MD
Morven S Edwards, MD
- Section Editor — Pediatric Infectious Diseases
- Professor of Pediatrics
- Baylor College of Medicine
Rabies remains an important disease because there are at least 60,000 human deaths every year worldwide, particularly in Asia and Africa where dog rabies is endemic . In geographic locations where human rabies is rare, the diagnosis may not be considered until relatively late in the clinical course. There is no known effective treatment for rabies.
Although rabies is usually preventable after recognized exposures with post-exposure rabies prophylaxis (eg, wound cleansing and administration of rabies vaccine and rabies immune globulin), the need for prophylaxis is not always recognized and may not be readily available in some areas. In addition, human rabies may present without a history of an animal exposure, usually because a bat bite was not recognized.
This topic will address the approach to managing patients with suspected or confirmed rabies. The epidemiology, clinical manifestations, diagnosis, and prevention of rabies are discussed elsewhere. (See "Clinical manifestations and diagnosis of rabies" and "Rabies immune globulin and vaccine" and "When to use rabies prophylaxis".)
CHOOSING A TREATMENT APPROACH
In patients with confirmed or suspected rabies, management options include a palliative or aggressive approach. As of June 2017, there have been 15 well-documented rabies survivors as described in the table (table 1) [2-19]. These cases do not include patients who had atypical features of rabies without the development of rabies virus neutralizing antibodies (since they were likely not cases of rabies) [20,21] or reports that did not have sufficient documentation [22,23].
Many factors influence the therapeutic approach in patients with rabies, including prognostic factors (table 2) and the risks of treatment (see 'Combination therapies' below). Although the relative importance of each of these factors is uncertain, in general:
- Hampson K, Coudeville L, Lembo T, et al. Estimating the global burden of endemic canine rabies. PLoS Negl Trop Dis 2015; 9:e0003709.
- Hattwick MA, Weis TT, Stechschulte CJ, et al. Recovery from rabies. A case report. Ann Intern Med 1972; 76:931.
- Porras C, Barboza JJ, Fuenzalida E, et al. Recovery from rabies in man. Ann Intern Med 1976; 85:44.
- CDC. Rabies in a laboratory worker--New York. MMWR Morb Mortal Wkly Rep 1977; 26:183.
- Tillotson JR, Axelrod D, Lyman DO. Follow-up on rabies - New York. MMWR 1977; 26:249.
- Galvez S, Basque M, Contreras L, et al. Survivor of rabies encephalitis in Chile. Platform presentation at the XXIVth International Meeting on Research Advances and Rabies Control in the Americas in Toronto, Ontario, Canada on October 27, 2013.
- Madhusudana SN, Nagaraj D, Uday M, et al. Partial recovery from rabies in a six-year-old girl. Int J Infect Dis 2002; 6:85.
- M N, V U, Rs M, et al. Unique clinical and imaging findings in a first ever documented PCR positive rabies survival patient: A case report. J Clin Virol 2015; 70:83.
- Weyer J, Msimang-Dermaux V, Paweska JT, et al. A case of human survival of rabies, South Africa. South African Journal of Infectious Diseases 2016; 31:66.
- de Souza A, Madhusudana SN. Survival from rabies encephalitis. J Neurol Sci 2014; 339:8.
- Karahocagil MK, Akdeniz H, Aylan O, et al. Complete recovery from clinical rabies: case report. Turkiye Klinikleri J Med Sci 2013; 33:547.
- Alvarez L, Fajardo R, Lopez E, et al. Partial recovery from rabies in a nine-year-old boy. Pediatr Infect Dis J 1994; 13:1154.
- Thakur BS. 2nd rabies survivor in country at P'kula hospital. Hindustan Times 2014.
- Hu WT, Willoughby RE Jr, Dhonau H, Mack KJ. Long-term follow-up after treatment of rabies by induction of coma. N Engl J Med 2007; 357:945.
- Ministerio da Saude in Brazil. Rabies, human survival, bat - Brazil: (Pernambuco). ProMED-mail 2008; 20081114.3599.
- Karande S, Muranjan M, Mani RS, et al. Atypical rabies encephalitis in a six-year-old boy: clinical, radiological, and laboratory findings. Int J Infect Dis 2015; 36:1.
- Kumar KV, Ahmad FM, Dutta V. Pituitary cachexia after rabies encephalitis. Neurol India 2015; 63:255.
- Manoj S, Mukherjee A, Johri S, Kumar KV. Recovery from rabies, a universally fatal disease. Mil Med Res 2016; 3:21.
- Willoughby RE Jr, Tieves KS, Hoffman GM, et al. Survival after treatment of rabies with induction of coma. N Engl J Med 2005; 352:2508.
- Centers for Disease Control and Prevention (CDC). Presumptive abortive human rabies - Texas, 2009. MMWR Morb Mortal Wkly Rep 2010; 59:185.
- Wiedeman J, Plant J, Glaser C, et al. Recovery of a patient from clinical rabies - California, 2011. MMWR 2012; 61:61.
- Rawat AK, Rao SK. Survival of a rabies patient. Indian Pediatr 2011; 48:574.
- Apanga PA, Awoonor-Williams JK, Acheampong M, Adam MA. A Presumptive Case of Human Rabies: A Rare Survived Case in Rural Ghana. Front Public Health 2016; 4:256.
- Marsden SC, Cabanban CR. Rabies: A significant palliative care issue. Prog Palliat Care 2006; 14:62.
- Thomas T, Barclay S. Continuous subcutaneous infusion in palliative care: a review of current practice. Int J Palliat Nurs 2015; 21:60, 62.
- Tarantola A, Crabol Y, Mahendra BJ, et al. Caring for patients with rabies in developing countries - the neglected importance of palliative care. Trop Med Int Health 2016; 21:564.
- Jackson AC, Warrell MJ, Rupprecht CE, et al. Management of rabies in humans. Clin Infect Dis 2003; 36:60.
- Hattwick MA. Human rabies. Public Health Rev 1974; 3:229.
- Jackson AC. Human disease. In: Rabies: Scientific Basis of the Disease and its Management, 3, Jackson AC (Ed), Elsevier Academic Press, Oxford 2013. p.269.
- Jackson AC. Therapy of human rabies. In: Rabies: Scientific Basis of the Disease and its Management, 3, Jackson AC (Ed), Elsevier Academic Press, Oxford 2013. p.573.
- Lafon M. Immunology. In: Rabies: Scientific Basis of the Disease and its Management, 3, Jackson AC (Ed), Elsevier Academic Press, Oxford 2013. p.387.
- Roy A, Phares TW, Koprowski H, Hooper DC. Failure to open the blood-brain barrier and deliver immune effectors to central nervous system tissues leads to the lethal outcome of silver-haired bat rabies virus infection. J Virol 2007; 81:1110.
- Appolinario CM, Jackson AC. Antiviral therapy for human rabies. Antivir Ther 2015; 20:1.
- Patel MM, Patel BM. Crossing the Blood-Brain Barrier: Recent Advances in Drug Delivery to the Brain. CNS Drugs 2017; 31:109.
- Merigan TC, Baer GM, Winkler WG, et al. Human leukocyte interferon administration to patients with symptomatic and suspected rabies. Ann Neurol 1984; 16:82.
- Warrell MJ, White NJ, Looareesuwan S, et al. Failure of interferon alfa and tribavirin in rabies encephalitis. BMJ 1989; 299:830.
- Bussereau F, Picard M, Blancou J, Sureau P. Treatment of rabies in mice and foxes with antiviral compounds. Acta Virol 1988; 32:33.
- Appolinario CM, Prehaud C, Allendorf SD, et al. Ribavirin has an in vitro antiviral effect in rabies virus infected neuronal cells but fails to provide benefit in experimental rabies in mice. J Virol Antivir Res 2013; 2.
- Centers for Disease Control (CDC). Human rabies--Texas. MMWR Morb Mortal Wkly Rep 1984; 33:469.
- Kureishi A, Xu LZ, Wu H, Stiver HG. Rabies in China: recommendations for control. Bull World Health Organ 1992; 70:443.
- Powers CN, Peavy DL, Knight V. Selective inhibition of functional lymphocyte subpopulations by ribavirin. Antimicrob Agents Chemother 1982; 22:108.
- Bussereau F, Chermann JC, De Clercq E, Hannoun C. Search for compounds which have an inhibitory effect on rhabdovirus multiplication in vitro. Ann Inst Pasteur Virol 1983; 134E:127.
- Superti F, Seganti L, Panà A, Orsi N. Effect of amantadine on rhabdovirus infection. Drugs Exp Clin Res 1985; 11:69.
- Zeiler FA, Jackson AC. Critical Appraisal of the Milwaukee Protocol for Rabies: This Failed Approach Should Be Abandoned. Can J Neurol Sci 2016; 43:44.
- Furuta Y, Takahashi K, Shiraki K, et al. T-705 (favipiravir) and related compounds: Novel broad-spectrum inhibitors of RNA viral infections. Antiviral Res 2009; 82:95.
- Yamada K, Noguchi K, Komeno T, et al. Efficacy of Favipiravir (T-705) in Rabies Postexposure Prophylaxis. J Infect Dis 2016; 213:1253.
- Shoulson I. Experimental therapeutics of neurodegenerative disorders: unmet needs. Science 1998; 282:1072.
- Hypothermia after Cardiac Arrest Study Group. Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med 2002; 346:549.
- Bernard SA, Gray TW, Buist MD, et al. Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med 2002; 346:557.
- Little NE, Feldman EL. Therapeutic hypothermia after cardiac arrest without return of consciousness: skating on thin ice. JAMA Neurol 2014; 71:823.
- Lockhart BP, Tsiang H, Ceccaldi PE, Guillemer S. Ketamine-mediated inhibition of rabies virus infection in vitro and in rat brain. Antivir Chem Chemother 1991; 2:9.
- Weli SC, Scott CA, Ward CA, Jackson AC. Rabies virus infection of primary neuronal cultures and adult mice: failure to demonstrate evidence of excitotoxicity. J Virol 2006; 80:10270.
- Sutherland BA, Minnerup J, Balami JS, et al. Neuroprotection for ischaemic stroke: translation from the bench to the bedside. Int J Stroke 2012; 7:407.
- Ikonomidou C, Turski L. Why did NMDA receptor antagonists fail clinical trials for stroke and traumatic brain injury? Lancet Neurol 2002; 1:383.
- Jackson AC. Current and future approaches to the therapy of human rabies. Antiviral Res 2013; 99:61.
- Jackson AC, Fu ZF. Pathogenesis. In: Rabies: Scientific Basis of the Disease and its Management, 3, Jackson AC (Ed), Elsevier Academic Press, Oxford 2013. p.299.
- Enright JB, Franti CE, Frye FL, Behymer DE. The effects of corticosteroids on rabies in mice. Can J Microbiol 1970; 16:667.
- Jackson AC, Scott CA, Owen J, et al. Therapy with minocycline aggravates experimental rabies in mice. J Virol 2007; 81:6248.
- Jackson AC. Is minocycline useful for therapy of acute viral encephalitis? Antiviral Res 2012; 95:242.
- Willoughby RE, Roy-Burman A, Martin KW, et al. Generalised cranial artery spasm in human rabies. In: Towards the Elimination of Rabies in Eurasia, Dodet B, Fooks AR, Müller T, Tordo N (Eds), Basel, Kager 2008. p.367.
- Rossiter JP, Jackson AC. Pathology. In: Rabies: Scientific Basis of the Disease and its Management, 3, Jackson AC (Ed), Elsevier Academic Press, Oxford 2013. p.351.
- Diringer MN, Bleck TP, Claude Hemphill J 3rd, et al. Critical care management of patients following aneurysmal subarachnoid hemorrhage: recommendations from the Neurocritical Care Society's Multidisciplinary Consensus Conference. Neurocrit Care 2011; 15:211.
- Bartanusz V, Jezova D, Alajajian B, Digicaylioglu M. The blood-spinal cord barrier: morphology and clinical implications. Ann Neurol 2011; 70:194.
- Bentivoglio M, Kristensson K. Tryps and trips: cell trafficking across the 100-year-old blood-brain barrier. Trends Neurosci 2014; 37:325.
- Solomon T, Marston D, Mallewa M, et al. Paralytic rabies after a two week holiday in India. BMJ 2005; 331:501.
- Weber DJ, Rutala WA. Risks and prevention of nosocomial transmission of rare zoonotic diseases. Clin Infect Dis 2001; 32:446.
- Gongal G, Mudhusudana SM, Sudarshan MK, et al.. What is the risk of rabies transmission from patients. Asian Biomedicine 2012; 6:937.
- World Health Organization expert consultation on rabies.2013 http://apps.who.int/iris/bitstream/10665/85346/1/9789240690943_eng.pdf (Accessed on June 14, 2017).
- Centers for Disease Control and Prevention. 2007 guideline for isolation precautions: preventing transmission of infectious agents in healthcare settings. https://www.cdc.gov/infectioncontrol/pdf/guidelines/isolation-guidelines.pdf (Accessed on June 14, 2017).
- CHOOSING A TREATMENT APPROACH
- PALLIATIVE APPROACH
- AGGRESSIVE APPROACH
- Supportive care in a critical care unit
- Combination therapies
- - Immunotherapies
- - Antiviral therapy
- - Neuroprotective therapies
- - Therapies to avoid
- Therapeutic coma
- Prophylaxis of cerebral vasospasm
- Drug delivery into the central nervous system
- INFECTION PREVENTION
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS