Rabies

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All except 6 people with Rabies have died. The Milwaukee Protocol seems promising.

LogoKeyPointsBox.pngRabies is a zoonotic disease caused by a neurotropic virus of the Lyssavirus genus.[1]
LogoKeyPointsBox.pngThe risk and benefits of treatment of rabies from an animal bite depend upon multiple factors which need to be carefully evaluated. Always provide informed advice as soon as possible as treatment within a day might be life saving
LogoKeyPointsBox.pngThe UK and Ireland are free of rabies, apart from in bats. This is sometimes referred to as being free of "terrestrial" rabies.[2]

Contents

Introduction

A rightly feared disease, it is a mammal zoonosis that can be transmitted essentially by any mammal. Although worldwide dogs are the most important vector, bats, mongooses, foxes, raccoons or even domestic cats might become the major vector after successful canine control measures. Bats are likely to have been the original vector, and tend to cause the disease where it has been controlled in dogs, and host multiple associated viruses that cause rabies. Human transplantation transmission has been reported repeatedly with major implications (one incident caused 4 deaths[3] and another required treatment of a large number of healthworkers[4]).

Aetiology

There are a number of related rabies viruses of the genus Lyssavirus, mostly found in bats. Bullet shaped RNA virus with the classic disease caused by the rabies virus. These viruses are clinically indistinguishable - they all cause classical rabies.

Flag of the United Kingdom.png

Bat rabies - carried by bats - has been a greater risk in the UK than other types of rabies - this is caused by European bat Lyssavirus (EBLV)

The virus tends to reproduce first in the salivary glands.

Clinical

Incubation varies between 4 days to 6 years with non specific symptoms such as fever and headache. Encephalitic type symptoms often evolve in days. The length of the incubation period relates to the distance the virus has to travel along nerve cells from the site of the inoculation to the brain. A bite to the ankle, for example, is likely to take much longer to produce symptoms than a bite to the thorax, head, or neck.

Clinical symptomatology, once believed to be unique, may be variable, which can cause missed diagnosis.

  • Classic - furious rabies
    • Excessive saliva production
    • Hydrophobia ("fear of water") develops late with difficulty swallowing, panic when presented with liquids to drink, and inability to quench thirst.
  • Paralytic rabies (20%)
    • Muscle weakness
    • Loss of sensation
    • Paralysis
    • Often without hydrophobia

Prodrome of severe paraesthesia possible.

Investigations

Diagnostic tests

The most reliable test is post-mortem on a sample of brain tissue, using immunofluorescence and/or electron microscopy. In humans multiple PCR diagnostic tests on saliva and serum may give a diagnosis before death.

Radiology

Treatment

Medical

Post-exposure prophylaxis as per the guidance in the Immunisation "Green Book" and at the HPA's rabies page. (Note that there is a shortage of rabies immunoglobulin, which is expected to last at least until October 2009: during this shortage amended guidance should be followed.[5])

  • Human Rabies Immune Globulin 20 U/kg IM once after exposure, preferably with first dose of rabies vaccine.
    • There is evidence for excellent outcome for vaccination within one day of exposure but it is hard to estimate risk as not all animal or even rabid animal bites progress to rabies. For example young children are known to be at higher risk due to the typical locations of bites.
    • The (relatively high) incidence of insignificant (in total context) adverse effects is well documented[6]
  • There is limited evidence for other treatments. Despite a widely publicized single report of good outcome from established rabies encephalitis involved induction of coma with ketamine and midazolam with viral treatment with ribavirin and amantadine (although ketamine may also have antiviral activity) until native immune response matured[7][8], this has failed to produce survivors in at least 4 other cases[9]. Conventional intense antiviral treatment good outcome is reported as 1 in 5 survivors with good outcome but most do not survive[10] so better evidence is awaited.

Surgical

Wound cleaning.

Prevention

Animal management is the keystone of any modern programme for the prevention and control of rabies. Oral vaccine is possible for some wild animal populations[11] and such approaches are much more effective than culling alone. Stray animal removal and mandatory parenteral vaccination (aim to vaccinate a minimum of 60 to 70%) can eliminate canine rabies. Reproductive control can help. Bat rabies control presently emphasises preventing contact with bats rather than ineffectual (and illegal) culling.

The risk of rabies is hard to assess. The likelihood of rabies may be very low; but the hazard - a near certain and very unpleasant eventual death if you develop rabies - is very severe. Given the severity of the rabies hazard, and the low risks associated with treatment, it may be appropriate to "err on the safe side": to have a low threshold for vaccination in advance of potential exposure, and for treatment (post-exposure vaccination +/- immunoglobulin) even when the likelihood of exposure or infection is low.

Vaccination

Vaccination - see Green Book for details.

Pasteur's original vaccine and most subsequent vaccines including ones commonly used in the areas where people are at highest risk are prepared in animal central nervous system tissue. More modern human diploid cell vaccines offer higher potency and lower risk of adverse reaction.

Dogs

  • Vaccinate dogs[12]
  • Remove rabid & stray dogs (and change social/cultural attitudes that prevent this)!
  • Try to prevent introduction from other vectors such as wild foxes

Bats

QuotationMarkLeft.png All bats, including those in the UK, may carry rabies related viruses and so careful assessment of potential exposure is required. Bats may carry rabies and related lyssaviruses without signs of disease. Therefore exposure to bats or their secretions may constitute an exposure to virus in countries which are declared rabies free in terrestrial animals. In the UK, bats are the only reservoir of rabies or related lyssavirus, but they are a protected species and cannot be destroyed to determine rabies status if caught. QuotationMarkRight.pngPHE rabies guidance

In 2002 a bat handler died as a result of handling a sick bat in Scotland. This was the first death from rabies contracted in the UK in 100 years. [13] [14] [15] [16]

Health and veterinary advice issued jointly by Defra, the Scottish Executive, and the Department of Health, states:

"People who find a sick or ailing bat should not approach or handle the bat but seek advice from the Bat Conservation Trust (0845 130 0228). Licensed bat handlers and anyone who regularly handles bats in the UK should ensure that they have an up-to-date vaccination against rabies and should always take other precautionary measures, including the wearing of protective gloves, when handling bats.
"Anyone bitten or scratched by a bat should also seek immediate medical attention.
"More details are available at the DEFRA website."

(A leaflet DEFRA Rabies Policy Unit. "I’ve found a bat – what do I do?" is available from DEFRA.[17])

Post exposure prophylaxis

Provided a bite is not very close to the brain and immunisation starts very soon after the bite, the immune system can be persuaded to generate immunity quicker than the virus produces disease. Passive immunity is added with human rabies immune globulin in addition to active immunisation.

See Green Book[18] and guidance from Public Health England[19] for details.

Notification

Rabies should be notified on suspicion.

ICD code

A82

External links

References

  1. Parize P, Dacheux L, Larrous F, Bourhy H, the French network of antirabies clinics. The shift in rabies epidemiology in France: time to adjust rabies post-exposure risk assessment. Euro Surv 2018;23(39):1700548, DOI: 10.2807/1560-7917.ES.2018.23.39.1700548 (https://www.eurosurveillance.org/content/10.2807/1560-7917.ES.2018.23.39.1700548).
  2. Singh AJ, Chipman RB, de Fijter S, Gary R, Haskell MG, Kirby J, et al. Translocation of a Stray Cat Infected with Rabies from North Carolina to a Terrestrial Rabies-Free County in Ohio, 2017. MMWR Morb Mortal Wkly Rep 2018;67(42):1174-1177 PMID: 30359345, DOI: 10.15585/mmwr.mm6742a2 (https://www.cdc.gov/mmwr/volumes/67/wr/mm6742a2.htm).
  3. Srinivasan A, Burton EC, Kuehnert MJ, Rupprecht C, Sutker WL, Ksiazek TG, Paddock CD, Guarner J, Shieh WJ, Goldsmith C, Hanlon CA, Zoretic J, Fischbach B, Niezgoda M, El-Feky WH, Orciari L, Sanchez EQ, Likos A, Klintmalm GB, Cardo D, LeDuc J, Chamberland ME, Jernigan DB, Zaki SR. Transmission of rabies virus from an organ donor to four transplant recipients. The New England journal of medicine. 2005 Mar 17; 352(11):1103-11.(Link to article – subscription may be required.)
  4. Mattner F, Bitz F, Goedecke M, Viertel A, Kuhn S, Gastmeier P, Mattner L, Biertz F, Heim A, Henke-Gendo C, Engelmann I, Martens A, Strüber M, Schulz TF. 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 Aug; 35(4):219-24.(Link to article – subscription may be required.)
  5. Health Protection Agency. HPA Briefing Note (2009/006). Issued 03/03/2009. Last viewed 4/3/09
  6. Mattner F, Bitz F, Goedecke M, Viertel A, Kuhn S, Gastmeier P, Mattner L, Biertz F, Heim A, Henke-Gendo C, Engelmann I, Martens A, Strüber M, Schulz TF. 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 Aug; 35(4):219-24.(Link to article – subscription may be required.)
  7. Willoughby RE, Tieves KS, Hoffman GM, Ghanayem NS, Amlie-Lefond CM, Schwabe MJ, Chusid MJ, Rupprecht CE. Survival after treatment of rabies with induction of coma. The New England journal of medicine. 2005 Jun 16; 352(24):2508-14.(Link to article – subscription may be required.)
  8. Hu WT, Willoughby RE, Dhonau H, Mack KJ. Long-Term Follow-up after Treatment of Rabies by Induction of Coma. The New England journal of medicine. 2007 Aug 30; 357(9):945-6.(Link to article – subscription may be required.)
  9. Hemachudha T, Sunsaneewitayakul B, Desudchit T, Suankratay C, Sittipunt C, Wacharapluesadee S, Khawplod P, Wilde H, Jackson AC. Failure of therapeutic coma and ketamine for therapy of human rabies. Journal of neurovirology. 2006 Oct; 12(5):407-9.(Link to article – subscription may be required.)
  10. Hu WT, Willoughby RE, Dhonau H, Mack KJ. Long-Term Follow-up after Treatment of Rabies by Induction of Coma. The New England journal of medicine. 2007 Aug 30; 357(9):945-6.(Link to article – subscription may be required.)
  11. Yakobson BA, King R, Amir S, Devers N, Sheichat N, Rutenberg D, Mildenberg Z, David D. Rabies vaccination programme for red foxes (Vulpes vulpes) and golden jackals (Canis aureus) in Israel (1999-2004). Developments in biologicals. 2006; 125:133-40.
  12. Cleaveland S, Kaare M, Tiringa P, Mlengeya T, Barrat J. A dog rabies vaccination campaign in rural Africa: impact on the incidence of dog rabies and human dog-bite injuries. Vaccine. 2003 May 16; 21(17-18):1965-73.
  13. BBC news item
  14. pubmed: 15746109 Smith A, Morris J, Crowcroft N. Bat rabies in the United Kingdom BMJ. 2005 Mar 5;330(7490):491-2 available free (30/04/2007)
  15. DEFRA (UK) on bats (nb - link may have been changed)
  16. HPA (UK) on rabies
  17. DEFRA Rabies Policy Unit. I’ve found a bat – what do I do?. July 2006. Or download via DEFRA website.
  18. Salisbury D, Ramsay M, Noakes K. Chapter 27: Rabies. Immunisation against infectious disease. v3.0, updated 28 November 2012 ed. London: HMSO, 2012:329-45
  19. Public Health England. Rabies post-exposure treatment: management guidelines. 2018; Updated 03 Jul 2018; Accessed: 2018 (05 Jul): (https://www.gov.uk/government/publications/rabies-post-exposure-prophylaxis-management-guidelines).