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Rabies

Nature Reviews Disease Primers volume 3, Article number: 17091 (2017) Cite this article

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Abstract

Rabies is a life-threatening neglected tropical disease: tens of thousands of cases are reported annually in endemic countries (mainly in Africa and Asia), although the actual numbers are most likely underestimated. Rabies is a zoonotic disease that is caused by infection with viruses of the Lyssavirus genus, which are transmitted via the saliva of an infected animal. Dogs are the most important reservoir for rabies viruses, and dog bites account for >99% of human cases. The virus first infects peripheral motor neurons, and symptoms occur after the virus reaches the central nervous system. Once clinical disease develops, it is almost certainly fatal. Primary prevention involves dog vaccination campaigns to reduce the virus reservoir. If exposure occurs, timely post-exposure prophylaxis can prevent the progression to clinical disease and involves appropriate wound care, the administration of rabies immunoglobulin and vaccination. A multifaceted approach for human rabies eradication that involves government support, disease awareness, vaccination of at-risk human populations and, most importantly, dog rabies control is necessary to achieve the WHO goal of reducing the number of cases of dog-mediated human rabies to zero by 2030.

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Figure 1: Structure of the rabies virus.
Figure 2: The global distribution of dog-transmitted human rabies.
Figure 3: Spread of rabies virus within the nervous system.
Figure 4: Mechanisms of immune evasion of the rabies virus.
Figure 5: The spectrum of clinical rabies.
Figure 6: Algorithm for the evaluation of differential diagnoses.
Figure 7: Management of clinical rabies.

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Acknowledgements

A.R.F. and A.C.B. were financially supported by the UK Department for Environment, Food and Rural Affairs (Defra), the Scottish Government and the Welsh Government (grant number SV3500).

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Authors and Affiliations

  1. Animal and Plant Health Agency (APHA), Wildlife Zoonoses and Vector Borne Diseases Research Group, (WHO Collaborating Centre for the Characterisation of Rabies and Rabies-Related Viruses, World Organisation for Animal Health (OIE) Reference Laboratory for Rabies), Weybridge, New Haw, Addlestone, KT15 3NB, Surrey, UK

    Anthony R. Fooks & Ashley C. Banyard

  2. Institute of Infection & Global Health, University of Liverpool, Liverpool, UK

    Anthony R. Fooks

  3. Institute for Infection and Immunity, St. George's Hospital Medical School, University of London, London, UK

    Anthony R. Fooks

  4. French Agency for Food, Environmental and Occupational Health & Safety (ANSES)-Nancy Laboratory for Rabies and Wildlife (European Union Reference Laboratory for Rabies, WHO Collaborating Centre for Research and Management in Zoonoses Control, OIE Reference Laboratory for Rabies, European Union Reference Institute for Rabies Serology), Technopôle Agricole et Vétérinaire de Pixérécourt, Malzéville, France

    Florence Cliquet & Evelyne Picard-Meyer

  5. Institute of Molecular Virology and Cell Biology (WHO Collaborating Centre for Rabies Surveillance and Research, OIE Reference Laboratory for Rabies), Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Greifswald-Insel Riems, Germany

    Stefan Finke, Conrad Freuling & Thomas Müller

  6. Department of Medicine (Neurology) and (WHO Collaborating Centre for Research and Training on Viral Zoonoses), Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand

    Thiravat Hemachudha & Henry Wilde

  7. Thai Red Cross Emerging Infectious Disease-Health Science Centre, Thai Red Cross Society, Bangkok, Thailand

    Thiravat Hemachudha

  8. Department of Neurovirology (WHO Collaborating Centre for Reference and Research in Rabies), National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India

    Reeta S. Mani

  9. Ottawa Laboratory Fallowfield, Canadian Food Inspection Agency (WHO Collaborating Centre for Control, Pathogenesis and Epidemiology of Rabies in Carnivores), Ottawa, Ontario, Canada

    Susan Nadin-Davis

Authors
  1. Anthony R. Fooks
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  2. Florence Cliquet
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  11. Ashley C. Banyard
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Contributions

Introduction (A.R.F. and A.C.B.); Epidemiology (S.N.-D.); Mechanisms/pathophysiology (A.C.B., C.F., S.F., T.M. and T.H.); Diagnosis, screening and prevention (A.C.B., F.C. and E.P.-M.); Management (A.C.B., T.H., R.S.M. and H.W.); Quality of life (R.S.M.); Outlook (A.C.B. and A.R.F.); Overview of Primer (A.R.F.).

Corresponding author

Correspondence to Anthony R. Fooks.

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Competing interests

T.M., C.F. and S.F. have a research cooperation and project (2014–2019) with a German vaccine company on oral vaccination of wildlife (for example, mechanisms of oral vaccination and immunity and development of a novel oral rabies virus vaccine). All other authors declare no competing interests.

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Supplementary information S1 (video)

Rat dorsal root ganglion neurons were cultivated in compartmentalized chambers and infected with rabies virus expressing a green fluorescent protein (GFP)-tagged phosphoprotein (Bauer A. et al. Anterograde Glycoprotein-Dependent Transport of Newly Generated Rabies Virus in Dorsal Root Ganglion Neurons. J. Virol. 88, 14172-14183 (2014)). At two days post-infection, the axonal transport of labelled particles was analyzed by live confocal laser scanning microscopy. The time-lapse images show anterograde (from left to right) and retrograde (from right to left) transport of GFP-labelled particles. Scale bar: 3 μm. (AVI 3048 kb)

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Fooks, A., Cliquet, F., Finke, S. et al. Rabies. Nat Rev Dis Primers 3, 17091 (2017). https://doi.org/10.1038/nrdp.2017.91

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