Rabies is a viral infection affecting the nervous system (peripheral and central), typically causing encephalitis and death. There are many deaths worldwide every year and prevention of the disease deserves more attention.
Rabies is caused by the rabies virus, genus Lyssavirus and family Rhabdoviridae. The genus Lyssavirus consists of over 80 viruses. There are about 10 viruses in the rabies serogroup, most of which only rarely cause disease in humans. The most common cause of rabies is the genotype 1 virus (classical rabies virus). It is an RNA virus, bullet-shaped with three component parts:
- Surface glycoprotein (G protein).
- Outer envelope (matrix protein).
It is transmitted in saliva by the bite of an infected mammal. The virus is fragile and inactivated by drying, ultraviolet rays and detergents. The rabies-related lyssaviruses - European bat lyssaviruses (EBLVs) and Australian bat lyssaviruses (ABLVs) - cause rabies much less often. The clinical presentation is indistinguishable from the classical rabies virus.
- Add notes to any clinical page and create a reflective diary
- Automatically track and log every page you have viewed
- Print and export a summary to use in your appraisal
- Any mammal can carry rabies but transmission occurs to humans most commonly worldwide from dogs. In some countries, bats, monkeys and cats can also transmit rabies.
- Not all individuals exposed to rabies virus develop the disease but, once symptoms occur, rabies is almost invariably fatal.
- The risk of developing rabies after a bite by a rabid animal varies with the site and severity of the wound.
After inoculation the following ensues:
- The exposure is usually a bite but can be from exposure of mucous membranes to infected body fluids or neural tissue (although much less likely). Infection does not occur through intact skin.
- Infection may occur from droplet (aerosol) spread. This is of concern when venturing into caves inhabited by bats.
- The virus enters the peripheral nerves. The virus is highly neurotropic and avoids immune defences by invading neural tissue.
- The virus then incubates for a period of time which reflects size of inoculum and distance to the central nervous system. The incubation period is usually between 3 and 12 weeks but can range from 4 days to 19 years. In 90% of cases incubation is less than 1 year.
- Shorter incubation periods are seen in those with multiple, severe wounds (particularly of the head, which is richly innervated), in children, and when post-exposure treatment fails.
- Amplification occurs until the single-stranded RNA nucleocapsid core spills into myoneural junctions, entering both motor and sensory axons. Prophylactic therapy at this point is futile and the disease advances with a uniformly fatal course.
- The virus spreads along axons (at about 1 to 2 cms per day) and enters spinal ganglions.
- Multiplication of the virus in the ganglions is marked by onset of pain or paraesthesia at the inoculation site. This is a hallmark symptom.
- Spread through the nervous system is now more rapid (at about 30 cms per day) and marked by a progressive encephalitis.
- Finally, the virus spreads peripherally, including to the salivary glands.
- Rabies occurs in all continents of the world except Antarctica, although some countries are rabies-free.
- Knowledge exists to eliminate the threat of canine rabies but lack of motivation by governments, cultural issues and lack of funding prevent progress.
- There are estimated to be around 50,000 deaths from rabies worldwide every year.
- The UK, like Australia, although rabies-free, both have rabies-related viruses in their bat populations. In the UK, rabies-related viruses have been detected in Daubenton's bats but not in the most common species of bats. Knowledge of prevalence and epidemiology in the bat population is limited, but the possibility of exposure is significant and has implications for preventive measures.
- Rabies is much more prevalent in developing countries, particularly India.
- A dramatic fall occurred in fox-adapted rabies in Western Europe at the end of the 20th century with vaccination of wild and domestic animals.
- In the UK, deaths from classical rabies continue to occur in people infected abroad. However, it is rare with only 24 deaths since 1902.
- Animals involved in human transmission include:
- Dogs (97% of cases worldwide).
- Racoons (significant in some USA eastern coastal states since the 1950s).
- Skunks (central USA and California).
- Other possible, but very rare, causes of transmission:
- Contact with open cuts, sores or wounds.
- Careless handling of dead animals.
- Contact with mucous membranes (mouth, nasal cavity, eyes).
- The illness has an insidious onset. Patients may not recall the exposure because the incubation period can be so long.
- Early symptoms include pain and paraesthesia around the wound or inoculation site, malaise, fever and headache.
- The disease can present with hydrophobia, hallucinations and behavioural disturbance (for example, mania).
- It then progresses to an ascending flaccid paralysis with sensory disturbances and coma.
- Death results from respiratory paralysis. Once clinical symptoms develop, no specific treatment will prevent death and supportive treatment only can be given.
- Five cases of survival of human rabies have been documented, all in people who had either been previously vaccinated or who had received post-exposure prophylaxis.
Stages of the disease
The stages of the disease in clinical context are:
- No symptoms.
- Virus transfers from periphery to CNS.
- Variable duration (usually between 3 and 12 weeks but up to 19 years).
- No antibody response detectable.
- Prodromal stage:
- Virus enters CNS.
- Duration 2 to 10 days.
- Nonspecific symptoms:
- Pain or paraesthesia at the inoculation site is pathognomonic.
- Anxiety and agitation.
- Acute neurological stage:
- Objective and developing CNS disease with symptom pattern (determined by whether the brain or spinal cord is mainly affected).
- Duration 2-7 days.
- Different forms:
- 'Furious rabies', the more common form, (80%) with:
- Hyperexcitability, spasms and hydrophobia.
- The onset marked by increasing insomnia, periods of extreme agitation, delirium and hyperactivity.
- Episodes which may be accompanied by frothing at the mouth, difficulty swallowing, vomiting, and intense spasms affecting the muscles of deglutition and the accessory muscles of respiration.
- Hydrophobia, which is precipitated by attempts to drink or by the sight, sound or mention of water or other fluids.
- Accompanying features, which may include nuchal rigidity, photophobia, fasciculations, cerebellar signs, cranial nerve palsies, dysphasia, hypertonia or hypotonia, extensor plantar responses and convulsions
- Deterioration, which is marked by evolution of flaccid paralysis, coma and irregular respiration.
- Untreated individuals surviving for 2-12 days once symptoms develop.
- 'Furious rabies', the more common form, (80%) with:
- Paralytic, 'dumb' or 'apathetic' rabies (20%):
- This features ascending paralysis.
- It is more likely to pose diagnostic difficulties because spasms and hydrophobia seldom appear.
- The paralysis begins in the bitten limb in around a half of cases, spreads rapidly and symmetrically, and may be misdiagnosed as Guillain-Barré syndrome.
- Involvement of the muscles of deglutition, articulation and respiration generally occurs terminally.
- The average survival in several series is 7-12 days.
Assessment of the suspect animal
It may be appropriate for suspect animals to be observed in quarantine for 15 days.The contact animal in some cases may be available to be examined. The brain tissue in such cases (often bats) or when the animal is symptomatic is examined. Bats may transmit rabies without an obvious history of biting.
Investigation in humans
Assessment of patients with suspected rabies may involve a number of investigations.
- Bloods and laboratory studies:
- Virus detection in saliva, throat swabs, tears or tracheal aspirates is often possible.
- Isolation of virus from saliva is more successful in antibody-negative patients than in antibody-positive patients.
- It may be several weeks before the diagnosis is confirmed.
- Polymerase chain reaction (PCR) analysis can establish the diagnosis rapidly when applied to saliva, CSF, tears, skin biopsy samples or urine.
- Serial testing is recommended, because of intermittent shedding of the virus.
- CSF examination:
- CSF typically shows normal opening pressure and mixed pleocytosis.
- CSF protein is modestly elevated in one quarter of patients during the first week of illness.
- 80% show monocytosis after seven days of illness.
- MRI scan may show non-enhancing, ill-defined, mild hyperintensity changes.
- CT is normal.
- Electroencephalograph (EEG) usually shows diffuse slow wave activity or an isoelectric recording.
- Skin biopsy may be performed.
- Histologically eosinophilic cytoplasmic inclusions (Negri's bodies) are seen in 70% of cases.
- Immunofluorescence testing of skin biopsies (normally taken with hair follicles from the neck to show viral antigen in sensory nerve endings) can establish the diagnosis.
Postmortem diagnosis can be achieved by virus isolation, immunofluorescence of viral antigen in the brain and elsewhere, PCR analysis and electron microscopy of the brain.
- Preventive therapy for rabies, including wound cleansing and active and passive immunisation after a recognised exposure, is highly efficacious. Post-exposure prophylaxis is nearly 100% effective at preventing rabies.
- Without prophylaxis before the onset of prodromal symptoms, death is almost certain.
- There have been several survivors from rabies and all but one received rabies vaccine prior to the onset of clinical illness.
- Wound care:
- Clean the wound, using soap or detergent, under running tap water for several minutes. Then treat with a suitable disinfectant (eg 40-70% alcohol, topical iodine).
- Information gathering: name and address of the animal's owner to allow follow-up. This may require enlistment of help from local officials.
- It is important to determine the vaccination status of the animal.
- Local medical advice should be sought. They are likely to know the level of risk locally and be able to advise on the need for vaccination.
- Primary suturing of the wound should be avoided or postponed.
- As the incubation period for rabies can be prolonged, treatment should still be considered even if the interval from exposure is lengthy.
- Remember anti-tetanus prophylaxis.
- Active and passive immunisation. (See separate Rabies vaccination article for more information).
- The schedule used depends on:
- Level of risk (low, medium or high) in the country.
- Type of exposure (history of the animal/stray, likelihood of infection, etc.).
- The individual's immunity (details of previous vaccinations, if any).
Level of risk in country
Unimmunised or not completely immunised*
|None||No immunisation||No further immunisation|
|Low||5 doses human diploid cell vaccine (HDCV) on days 0, 3, 7, 14 and 30||2 doses on days 0 and 3|
|High||5 doses rabies vaccine on days 0, 3, 7, 14 and 30
PLUS human rabies-specific immunoglobulin (HRIG) on day 0 only
|2 doses on days 0 and 3|
Management after development of symptoms:
- Symptomatic rabies is almost invariably fatal and the treatment aims to alleviate suffering and support vital functions.
- Patients are usually managed in the ITU setting as appropriate.
- At present, there is no specific treatment of rabies.
- New efficacious antiviral compounds and optimised treatment protocols need to be developed.
It is essential to administer post-exposure prophylaxis correctly. Death is almost certain if early treatment fails to prevent progression to infection and prodromal symptoms.
- The cost of the full range of effective preventive measures is too expensive for developing nations and is expensive even for developed nations.
- However, with the post-exposure preventive regimes, it has been estimated that rabies can be prevented in around 327,000 people annually.
- Eliminating rabies in the reservoir animal species is not possible without an intersectoral approach including collaboration between animal and human health experts. There is an urgent need to establish national risk assessment systems in regions where surveillance is limited to non-existent.
- See Rabies vaccination separate article.
- Reduction of risk:
- Avoid contact with potentially rabid animals.
- Control of rabies in the animal population:
- Vaccination of domestic dogs, cats and ferrets.
- Euthanasia of unvaccinated pets in contact with rabid animal (or six months' isolation, and vaccination one month prior to release).
- The Pet Travel Scheme has replaced quarantine in the UK. This is a vaccination-based programme.
- Vaccination and control of certain wild animals:
- Control and localised oral vaccination of foxes.
- Animal control and vaccination strategies have proved successful in preventing spread of rabies in a number of countries.
- Immunisation of at-risk groups:
- Laboratory workers handling the virus.
- Workers handling imported animals.
- All handlers of bat species.
- Workers in at-risk jobs, in at-risk areas (for example, zoo workers, veterinary staff, local authority animal inspectors).
- Health workers likely to have contact with infected patients.
- Travellers to enzoonotic areas where work involves handling animals.
- Travellers to enzoonotic areas, who may be more than 24 hours from modern medical treatment.
- Active vaccination:
- Currently cell-culture derived vaccines are used. There are two licensed for use in the UK - human diploid cell vaccine (HDCV), or Rabies Vaccine BP Pasteur Mérieux®.
- Post-exposure vaccination has been very effective since introduction in 1980.
- Other cell-culture derived vaccines are available in other countries but these are no longer recommended.
- Passive immunisation:
- Human rabies-specific immunoglobulin (HRIG) should be used at the start of all primary post-exposure courses of rabies vaccine.
- The dose is HRIG 20 IU/kg body weight. It is administered around the cleansed wound or intramuscularly (anterolateral thigh) if the wound has healed or is not visible.
- It can be given for up to seven days after starting the vaccination course (active immunisation).
- This fearful disease dates back as far as the association between man and dogs.
- There is a possible reference as long ago as the 23rd century B.C. in Babylon which describes the disease in dogs and the lethal effect in man if bitten.
- The term hydrophobia was first used in a Roman description from the 1st century A.D.
- In the 16th century, Spanish soldiers were described as showing signs of madness after bites from vampire bats.
Further reading & references
- No authors listed; Meeting of the Immunization Strategic Advisory Group of Experts, November 2007--conclusions and recommendations. Wkly Epidemiol Rec. 2008 Jan 4;83(1):1-15.
- Immunisation - The Green Book; Dept of Health
- Gompf SG et al, Rabies, Medscape, Dec 2011
- Franka R, Rupprecht CE; Treatment of rabies in the 21st century: curing the incurable? Future Microbiol. 2011 Oct;6(10):1135-40.
- Yousaf MZ, Qasim M, Zia S, et al; Rabies molecular virology, diagnosis, prevention and treatment. Virol J. 2012 Feb 21;9:50.
- Briggs DJ; The role of vaccination in rabies prevention. Curr Opin Virol. 2012 Apr 11.
|Original Author: Dr Richard Draper||Current Version: Dr Louise Newson||Peer Reviewer: Dr Adrian Bonsall|
|Last Checked: 19/07/2012||Document ID: 2693 Version: 27||© EMIS|
Disclaimer: This article is for information only and should not be used for the diagnosis or treatment of medical conditions. EMIS has used all reasonable care in compiling the information but make no warranty as to its accuracy. Consult a doctor or other health care professional for diagnosis and treatment of medical conditions. For details see our conditions.