S.K.
James and A.J. Shearer
Department
of Anaesthesia and Intensive Care Unit, Ninewells Hospital and Medical School,
Dundee DD1 9SY
E-mail:
SJames251@aol.com
E-mail:
a.shearer@nhs.net
Rabies
had been eradicated from the indigenous animal population in the British Isles
by 1922 and the last reported death in a human infected from being bitten by a
rabid animal within our shores was in 1902.1 With strict quarantine
rules on animals being brought into the country, no rabies was detected in the
wild life until 1996 when the first case of a bat in Britain with European bat
lyssavirus was reported2 and this was followed in 2002 by the first
death of a human from a bite sustained in this country for 100 years.3,4
The unfortunate victim was a volunteer bat handler, who was bitten by a rabid
bat and he died in Dundee, Scotland. World-wide, almost all of the deaths that
occur are in Asian and African countries where canine rabies is endemic and
where it is estimated that 55,000 people die every year from rabies.5,6
There have been reports of overseas travellers from the UK being bitten by rabid
dogs abroad and ultimately dying of this feared disease back home after their
return. The latest victim was a lady from England who was bitten by a rabid dog
while on holiday in Goa, India.7,8
Although
serum is reportedly non-infective, all other bodily fluids, especially saliva,
are highly infectious. Direct human to human transmission has occurred only in
rare cases. There have been eight reported deaths probably caused by rabies in
recipients of corneal transplants from infected donors.9 Recently
four transplant recipients died from rabies after receiving organs from an
infected organ donor.10 The unfortunate donor had been previously
healthy but died following a subarachnoid haemorrhage. His kidneys, liver and an
arterial segment were donated and transplanted to these four recipients who all
developed encephalitis within 30 days after their transplants. There was rapid
deterioration, with agitation, delirium, seizures and respiratory failure,
progressing to coma and finally death an average of 13 days after the onset.
Post-mortem examination of CNS tissues from all these four patients and the
donor confirmed rabies. It was interesting to note that the donor had told
others of being bitten by a bat.
Until
recently, there had been only five documented cases of survival from possible
clinical rabies, and only one of those with a satisfactory neurological outcome.11
All five had received rabies vaccine before the onset of symptoms.
When the disease develops, multiple complications and multi-system
failure is common and for non-vaccinated patients the mortality was 100%, even
in those who had access to intensive care for organ support.12
Despite research, the fundamental cause of neuronal dysfunction rather than
neuronal death in rabid animals is not clear.13 In 2003 an expert
group of physicians and researchers reached a consensus on the management of
human rabies.11 They recommended an aggressive approach in selected
cases using a combination of rabies vaccine, human rabies immunoglobulin,
ribavirin, interferon alpha and ketamine.
Pre
or post exposure prophylaxis is successful but, until very recently, the
mortality from clinical rabies in those not given prophylaxis was believed to be
100%. In 2005, however, there was an interesting case report from the United
States of survival from confirmed rabies in a young girl who had not received
vaccine before the onset of symptoms.14,15 She had been bitten by a
bat that she had picked up from the floor in church and carried outside. Rabies
was not considered and post exposure prophylaxis was not sought. Symptoms and
signs suggestive of rabies developed approximately 30 days after the bite and
were subtle to begin with. There was progression of symptoms, and with a history
of bat bite, she was admitted to a tertiary care centre. Rabies specific
antibody was confirmed in her cerebral spinal fluid and serum. Attempts to
demonstrate rabies virus, detect viral antigen and amplify viral nucleic acid
from saliva and skin biopsies were unsuccessful. Her physicians discussed the
above mentioned aggressive management with her parents. They were willing for
their daughter to undergo this novel intensive care management with the
combination of deep coma, antiviral and anti-rabies medication. The girl
survived, albeit with fine motor difficulties and inco-ordination, and this was
reported as the first case of survival in someone who had not had
immunoprophylaxis before the onset of symptoms. Rabies is a killer disease if
appropriate pre and post exposure prophylaxis is not administered. The single
survival from rabies following onset of symptoms gives some hope but we know
little about the irreversible element of the disease progression. Survival may
be associated with neurological impairment.
Here
in Scotland, we have hundreds of travellers going abroad to exotic locations in
Asia and Africa where canine rabies is endemic. The recently reported death of a
traveller to India who was bitten by a rabid dog and who later succumbed to this
disease also highlights the issue of seeking immediate medical help and post
exposure prophylaxis. Travellers going abroad to endemic areas obviously need to
be aware of this.16 Cross-channel transport and perhaps altered
climate conditions may all have brought a pool of infected bats to this
"safe" rabies-proof haven. Although there is rabies surveillance in
all wild animals, the death in Dundee of the bat handler highlights the
importance of rabies immunisation in all game handlers and post exposure
prophylaxis when bitten by any wild animal, especially a bat.17 Three
of the cases mentioned above were bitten by bats!
Healthcare
workers need to be aware of this rare but lethal disease:- to administer
prophylaxis appropriately; to avoid delay in diagnosis when the disease
presents; to consider aggressive treatment early when it is more likely to
succeed; and to protect staff from contamination. The risk to staff is small but
measures must be taken to avoid contamination of mucous membranes and broken
skin with body fluids and prophylaxis reserved for when such contamination with
potentially infectious material occurs.5,18 There are no reported
cases amongst healthcare workers but there is a theoretical risk. Apart from
transplantation causing human to human spread, there are reported cases of
possible transmission by biting and by kissing.9 Airborne
transmission can occur and there have been reports of four deaths, two from bat
caves and two in laboratories.9,19
So
Beware and Be Aware!
REFERENCES
1.
UK Department of Health. Memorandum on rabies prevention and control. 5-10. 2000. London, DOH
2.
Whitby JE, Johnstone P, Parsons G, King AA, Hutson AM. Ten-year survey of
British bats for the existence of rabies. Vet Rec 1996; 139(20): 491-493
3.
Nathwani D, McIntyre PG, White K et al. Fatal human rabies caused by European
bat Lyssavirus type 2a infection in Scotland. Clin Infect Dis 2003; 37(4):
598-601
4.
Fooks AR, McElhinney LM, Pounder DJ et al. Case report: isolation of a European
bat lyssavirus type 2a from a fatal human case of rabies encephalitis. J Med
Virol 2003; 71(2): 281-289
5.
World Health Organization. WHO Expert Consultation on Rabies. WHO Technical
Report Series - No 931. 2004. Geneva, WHO
6.
Knobel DL, Cleaveland S, Coleman PG et al. Re-evaluating the burden of rabies in
Africa and Asia. Bull World Health Organ 2005; 83(5): 360-368
7.
Mudur G. Foreign visitors to India are unaware of rabies risk. BMJ 2005;
331(7511): 255
8.
Solomon T, Marston D, Mallewa M et al. Paralytic rabies after a two week holiday
in India. BMJ 2005; 331(7515): 501-503
9.
Centers for Disease Control and Prevention. Human Rabies Prevention - United
States, 1999: recommendations of Advisory Committee on Immunization Practices (ACIP).
48(No. RR-1), 8-9. 1999. MMWR
10.
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
11.
Jackson AC, Warrell MJ, Rupprecht CE et al. Management of rabies in humans. Clin
Infect Dis 2003; 36(1): 60-63
12.
Jackson AC. Update on rabies. Curr Opin Neurol 2002; 15(3): 327-331
13.
Jackson AC. Rabies pathogenesis. J Neurovirol 2002; 8(4): 267-269
14.
Centers for Disease Control and Prevention. Recovery of a patient from clinical
rabies--Wisconsin, 2004. MMWR Morb Mortal Wkly Rep 2004; 53(50): 1171-1173
15.
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
16.
Pounder D. Avoiding rabies. BMJ 2005; 331(7515): 469-470
17.
Pounder D. Bat rabies. BMJ 2003; 326(7392): 726
18.
UK Department of Health. Memorandum on rabies prevention and control. 18-23. 2000. London, DOH
19. Winkler WG, Fashinell TR, Leffingwell L, Howard P, Conomy P. Airborne rabies transmission in a laboratory worker. JAMA 1973; 226(10): 1219-1221