Rabies

Rabies occurs in warm-blooded mammals and is transmitted to man, most often by a bite or scratch from an infected animal, usually a dog Rabies

 

Key Messages

Rabies is a viral disease transmitted to humans usually by a bite or scratch from an infected animal (usually a dog).
The disease is preventable if the correct post-exposure prophylaxis (PEP) is provided quickly.
Accessing correct PEP can be challenging in some countries.
Rabies cases are rare in travellers but animal bites and scratches are not, travellers should be aware of the risk and know what to do if they are bitten or scratched.
Rabies is almost always fatal once symptoms appear.
Pre-exposure rabies vaccines are recommended for some travellers.

Overview

Rabies virus is a member of the genus Lyssavirus, of the family Rhabdoviridae, or bullet-shaped viruses. The virus attacks the central nervous system causing, progressive inflammation of the brain and spinal cord [1]. Rabies in humans is either the ‘furious’ form or ‘paralytic’ form. Symptoms of furious rabies can include hyperactivity, fluctuating consciousness, hydrophobic spasms (a reflex contraction of respiratory muscles following attempts to drink water). After a few days, death occurs by cardio-respiratory arrest [1]. Paralytic rabies accounts for about 30 percent of human cases. With this form of rabies the muscles gradually become paralysed, starting at the site of the bite or scratch. A coma slowly develops, and eventually death occurs [1]. Once symptoms are present, rabies is almost always fatal [1].

Rabies occurs in warm-blooded mammals (both domestic and wild) and is transmitted to man, most often by a bite or scratch from an infected animal, usually a dog. Rabies can also be transmitted when body fluids from an infectious animal (usually saliva) come in to contact with mucous membranes (e.g. on the eyes, nose or mouth) or broken skin [2].

Rabies is preventable if the correct post-exposure prophylaxis (PEP) is provided quickly. Tragically, many people fail to access this treatment. Human rabies cases are often unreported so it is difficult to provide reliable figures on the incidence worldwide. However, rabies is estimated to cause 59,000 human deaths annually [3]. Children are at particular risk, with approximately 40 percent of all PEP regimens being given to children aged five to 14 years [1]. Owing to their size and stature, children are often bitten around the face or head [4]. Bites in this area are expected to have a shorter incubation period (the time between infected animal bite/scratch and rabies symptoms appearing) [2].

Rabies is not common in western travellers [5] but an estimated 0.4 percent will experience an animal bite requiring PEP per month of stay in a rabies endemic country [6]. It is important that travellers visiting rabies endemic areas are aware of the risk and know what to do if they are bitten or scratched. PEP can be expensive and difficult to obtain in some areas [7].

Risk areas

Rabies exists on all continents except Antarctica [1]. Information and vaccine recommendations for individual countries can be found on our Country Information pages.

The risk of human cases is highest in countries where the virus circulates in dogs; these animals being the source of 99 percent of human rabies cases [2].According to the World Health Organisation (WHO), more than 95 percent of human cases occur in Africa and Asia, mainly in rural communities where measures to prevent dog to human transmission have not been implemented [1]. The limited availability of PEP in some countries contributes to the high mortality rates [1].

In Latin America and the Caribbean, efforts to eliminate rabies in dogs have had substantial impact [5]. The virus still occurs in dogs in some countries [5] but bats are now the source of most human rabies deaths in the Americas [1].

In some countries, rabies has been eliminated in dogs, but the virus still exists in terrestrial wild animals (those that live predominantly on land) and rabies related lyssaviruses may occur in bats. In North America and Europe the disease is mainly confined to wild animals (particularly bats, and foxes in Europe, and coyote, skunks and racoons in North America). In North America human cases have usually followed exposure to an infected bat.

Some countries such as UK, Australia and parts of Western Europe are considered free of rabies in terrestrial animals, however, in these area bats may carry lyssavirus. Although rare, bat lyssaviruses (bat rabies) can be transmitted to humans or other animals following contact with the saliva of an infected bat most often by a bite [8]. Bat lyssaviruses can cause disease in humans that is indistinguishable from rabies [9].

Most of Western Europe is rabies-free in terrestrial animals due to the success of co-ordinated wildlife oral vaccination programmes, together with the availability of effective commercial vaccination for domestic animals [10]. However, in 2009 an outbreak of rabies in wild animals occurred in the Friuli-Venezia Giulia region of north-east Italy, the first outbreak of rabies in Italy since 1995 [11]. Between October 2012 and March 2014 a total of 45 rabid animals (37 foxes, 5 dogs, 2 cattle and 1 cat) were reported in northern Greece [12]. These were the first cases reported in Greece since 1987 [13, 14]. Incidents involving imported animals also occur. In France, a rabid dog was imported from North Africa in 2011 [15] another infected dog was imported in May 2015 [16]. A rabid puppy was also imported into the Netherlands from Morocco via Spain in 2012 [17].

Risk for travellers

Cases of rabies in travellers are rare, however bites and scratches from potentially rabid animals occur more frequently and it is often difficult to determine whether an animal is infected [7].

Approximately two deaths due to imported human rabies have been reported each year in Europe, North America and Japan [5]. One third of the imported cases in 1990- 2010 were exposed to the virus in South and South-East Asia (predominantly India and the Philippines). Another third of the cases were from Africa, almost 20 percent from Latin America and the Caribbean, and over 10 percent contracted the virus in Eastern Europe or Central Asia [5].

A survey of 2,697 travellers receiving PEP in GeoSentinal clinics following possible exposure to the rabies virus between 1997 and 2012 found that 70 percent had been exposed while in Asia, mostly in South­east Asia [7]. Dogs accounted for most exposures among travellers, but non-human primates (such as monkeys) were responsible for one quar­ter of the possible exposure incidents. The proportion of non- human primate exposures was even higher among tourists, female travellers, and travellers to Southeast Asia. Cats and bats were the next most common animal exposures reported [7].

Rabies in UK Travellers

In Great Britain, the last case of indigenous rabies in a terrestrial animal occurred in 1922. The last recorded cases of animal rabies outside quarantine occurred in 1969 and 1970 when two imported dogs died soon after completing six months quarantine. Since then, nearly all cases of rabies in the UK have occurred in quarantined animals or in people who were infected abroad. The exception was human rabies in a bat handler infected with European Bat Lyssavirus 2 (EBLV2) in Scotland in 2002 [18]. The last reported case of rabies in a bat in Great Britain was in 2014 [19].

There were 25 human deaths in the UK from imported rabies between 1902 and 2005 [20]. Where information was recorded, all but one of these resulted from a dog bite). 64 percent of deaths (16 of 25) were following a bite that occurred on the Indian Sub-Continent [20].

Since 2000 five imported cases have been reported:

  • an overseas visitor from Nigeria who sustained a dog bite on the lower leg five months prior to clinical symptoms [21]
  • a UK resident who was bitten by a dog whilst in the Philippines [22]
  • a British woman who sustained a dog bite during a two week holiday to Goa, India and died of rabies in the UK in 2005 [23]
  • a British woman who had worked in an animal sanctuary in South Africa and died of rabies in Northern Ireland in January 2009 [24]
  • a British woman bitten by a dog whilst visiting South Asia in 2012 [25]

None of these cases were known to have received pre-or post-exposure rabies prophylaxis.

During 2011, over 1,300 enquiries were made to the Health Protection Agency relating to potential rabies exposures for which rabies PEP was issued for 1100 people in England and Wales. Exposures requiring PEP are commonly related to dog, cat, monkey and bat bites. Most of the bat exposures occurred in the UK [26].

Transmission

Rabies virus is found in the saliva of an infected animal. The virus is transmitted to humans by a bite or scratch, or when saliva from an infected animal comes into contact with broken skin or mucous membranes (eyes, nose, or mouth). Rarely, rabies has been contracted following laboratory exposure or after transplantation of organs from an infected individual [27, 28]. Person to person spread outside of these situations has never been proven [29].

Following exposure, the virus travels to the central nervous system via the peripheral nerves. The virus replicates in the brain and disseminates to many different tissues [29].

Signs and symptoms

The incubation period of rabies is usually between three and 12 weeks; in rare cases it can be as short as four days or as long as 19 years [29-30]. In more than 90 percent of patients, the onset is within one year of exposure. According to the WHO, the incubation period depends upon factors such as the amount of virus inoculated, the amount of tissue at the site of the bite or scratch, and the proximity of the bite to the central nervous system [2]. Bites to highly innervated regions such as the head, neck and hands are expected to have shorter incubation periods [2].

The early symptoms are often non-specific with fever, headache, myalgia (muscle pain), and fatigue. Paraesthesia (abnormal sensation such as burning, tingling or pricking) can occur at the site of the bite. The disease progresses either to the more common furious rabies, or the less common paralytic or ‘dumb’ rabies.

Furious rabies is characterised by laryngeal spasms, which occur in response to attempts to drink water; these can be accompanied by a feeling of terror. Deterioration, coma and death ensue over the following days.

The paralytic form of rabies is often misdiagnosed. Paraesthesia and weakness often first occur around the bite site and begin to ascend the bitten limb. The paralysis results in respiratory failure and inability to swallow. Death usually occurs within one to three weeks.

Diagnosis and treatment

All travellers who have a possible exposure to the rabies virus, whether by bites, scratches, or other means, should seek medical advice without delay. Seeking medical care also applies to travellers in areas considered low risk for rabies as other infections may be transmitted by the bite, or the animal may have been imported or crossed the border from an endemic country. Medical advice should be sought without delay even if pre-exposure vaccine was received.

There are no tests to diagnose rabies infection in humans before the onset of symptoms [2]. However the correct use of modern rabies vaccines, wound management and administration of rabies immunoglobulin (RIG) soon after exposure, is effective in preventing symptoms of rabies appearing, even following high-risk exposures in nearly all cases [2].

Unfortunately once the symptoms of rabies have appeared, the disease is almost always fatal [2]. There are no known survivors of dog rabies virus infection [29]. A few patients who have developed rabies following bat bites in the Americas have survived rabies [29, 31]. Rabies viruses in American bats seem to be less pathogenic than other related rabies viruses [29].

Preventing rabies

Avoiding animal bites

Contact with wild or domestic animals (including bats) during travel should be avoided. Travellers should be advised:

  • not to approach animals
  • not to attempt to pick up an unusually tame animal or one that appears to be unwell
  • not to attract stray animals by offering food or by being careless with litter
  • to be aware that certain activities may attract dogs (e.g. running, cycling)

Pre-exposure vaccines

Pre-exposure vaccines are recommended for travellers at continuous, frequent or infrequent risk, according to UK guidance [30] (see below). A record of vaccination should be carried and shown to those administering emergency treatment in a post-exposure situation. Receiving rabies vaccine prior to travel does not eliminate the need for post-exposure medical evaluation and additional doses of rabies vaccine. However, it does simplify and shorten the PEP regimen and eliminates the need for rabies immunoglobulin which is in short supply in many countries [32].

Action following a possible rabies exposure:

All travellers should be advised to perform first aid treatment and to seek medical advice as soon as possible. Modern rabies vaccines are now available in major cities of most developing countries [32]. However, immunoglobulin is in short supply worldwide, and may not be available in many countries, even in the major cities [32].

The following advice can be given regarding first aid following a possible rabies exposure:

  • Urgent action is required; treatment should be commenced as soon as possible after the exposure.
  • Immediately wash the wound with detergent or soap and running water for several minutes.
  • Apply a disinfectant to the wound such an iodine solution (tincture or aqueous solution of povodone-iodine) or 40-70 percent alcohol.
  • Apply a simple dressing to the wound.
  • Seek immediate medical advice about the need for PEP and possible antibiotics to prevent a wound infection.
  • Tetanus vaccine may be necessary if the traveller is not up-to-date.
  • Suturing of the wound should be postponed until PEP has started [30].

Vaccine information

Rabies pre-exposure vaccine

All those who are at continuous or frequent risk of exposure should be offered pre-exposure vaccine. Groups in these risk categories include:

  • laboratory workers routinely handling rabies virus
  • bat handlers who regularly handle bats
  • those who regularly handle imported animals
  • animal workers who regularly travel to rabies enzootic areas
  • health workers in rabies enzootic areas who may have direct contact with rabies infected patients

Most international travellers to rabies affected areas are considered to be at ‘infrequent risk’, but pre-exposure vaccines are recommended for those whose activities put them at increased risk.

For countries with rabies in domestic and wild animals these travellers include:

  • those visiting areas where access to post-exposure treatment and medical care is limited
  • those planning higher risk activities such as cycling and running
  • long-stay travellers (more than one month).

In countries where rabies has only reported in wild animals or bats, pre-exposure vaccines are recommended for a smaller group of travellers. See our Country Information pages to see individual recommendations for each destination.

The rationale for receiving a full course of three pre-exposure vaccines is to prime the immune system. An efficient antibody response is then expected post exposure following administration of two booster doses [33]. According to the UK schedule, these are given on days 0 and 3-7 [34]. Rabies immune globulin (RIG) which can be difficult to obtain, will not be necessary [34]. There have been no rabies deaths reported in individuals who have had pre-exposure vaccines and booster doses after exposure [29]. Pre-exposure vaccines may also protect an individual who has an inapparent exposure.

Accessing safe and effective rabies vaccine products in low income countries may be difficult, and vaccine derived from animal brain tissue may be the only type available. In some areas modern tissue culture rabies vaccines may only be obtained privately or in rabies treatment centres. RIG is frequently difficult to locate [32]. According to the UK schedule, those who have not had pre-exposure vaccines are advised to have 5 doses of rabies vaccine on days 0, 3, 7, 14, 28-30 plus RIG following high risk injuries [34].

Availability of vaccine

There are two rabies vaccines licensed for use in the UK, both of which are inactivated. Unlicensed products are occasionally available when licensed products are in short supply (please refer to manufacturer/distributor for these products).

Details of licensed vaccines are found in Table 1.

Table 1: Vaccine schedules
Vaccine Route of administration Schedule Pre-exposure recommendations[30] Age Range
Rabies Vaccine BP
(Human diploid cell vaccine)
(HDCV)
Intra-muscular 3 doses. Day 0, 7 and 28* Infrequent risk:
Primary course
(3 doses of vaccine)
No serological testing
Booster dose can be considered at 10 years post primary course if travelling again to a high risk area

Frequent risk:
Primary course
(3 doses of vaccine)
Booster at 1 year
Booster doses every three to five years OR based on results of serology**

Continuous risk:
Primary course
(3 doses of vaccine)
Serological testing at 6 month intervalsSingle booster if titre falls below (0.5 lU/ml

No minimum age stated in SPC***
Rabipur
(Purifiedchick embryocell vaccine) (PCECV)
Intra-muscular  3 doses. Day 0, 7 and 21 or 28* Infrequent risk:
Primary course
(3 doses of vaccine)
No serological testing
Booster dose can be considered at 10 years post primary course if travelling again to a high risk area

Frequent risk:
Primary course
(3 doses of vaccine)
Booster at 1 year
Booster doses every three to five years OR based on results of serology**

Continuous risk:
Primary course
(3 doses of vaccine)
Serological testing at 6 month intervals
Single booster if titre falls below (0.5 lU/ml

Can be given from any age***
The SPC should be consulted prior to the administration of any vaccine.
*see interrupted/accelerated courses below.
**see Rabies. Chapter 27. Immunisation against infectious disease. Table 27.1
*** Although the vaccine can be given at any age, the risk of animal bites may be higher once the child is independently mobile. Children are often bitten around the face or head, a type of bite considered to be a higher risk due to the expected shorter incubation period. A risk assessment should always be undertaken when considering rabies immunisation.

 

The vaccines shown in the table can be used interchangeably [30].

Intradermal route of administration

The intramuscular route is the preferred route to administer rabies vaccines. Pre-exposure rabies vaccination using the intradermal (ID) route is approved by the WHO [2], however the route is not licensed in the UK for any rabies vaccine and it requires expert practised technique [30]. It should not be used for travellers taking chloroquine for malaria prophylaxis as this drug suppresses the antibody response if the vaccine is given by the intradermal route [30].

Clinicians who choose to administer rabies vaccine intradermally must assume responsibility for using this method. The use of one vial to vaccinate more than one individual carries a risk of contamination and is not recommended [30].

Interrupted or accelerated courses

Ideally, those at risk should receive pre-exposure vaccination with three doses of rabies vaccine before travel. The 0, 7 and 21 day schedule can be given using either product, where there is less than four weeks before departure [30].

If there are time constraints to the full pre-exposure course, even a single dose is likely to prime the immune system; travellers should consider completing the pre-exposure course of vaccine during their travels. A record of vaccination should be carried as this will be useful during post-bite evaluation.

If less than the recommended three doses of vaccine have been administered pre-exposure, in the event of a possible exposure, a full post-exposure course of five vaccines will be recommended. However, RIG will not be usually necessary [34].

Because of immunologic memory, intervals longer than those routinely recommended between vaccine doses do not generally impair the immunologic response [35]. Therefore, individuals who have previously received an interrupted or incomplete course of vaccine, can resume and complete, rather than restart a vaccine course. Travellers should carry their vaccine records to show the health care professional managing post-exposure care. For those with impaired immunity, expert advice should be obtained.

Contraindications

Pre-exposure vaccines
  • Acute febrile illness or acute disease [36-37]
  • Confirmed anaphylactic reaction to a previous dose of rabies vaccine or any component of the vaccine [30]
Post-exposure vaccines

There are no contraindications to vaccination when post-exposure prophylaxis is indicated [29,35-36]. However, subjects considered to be at risk of a severe hypersensitivity reaction should receive an alternative rabies vaccine if a suitable product is available [37].

Post-vaccination serology (blood test)

Post-vaccination serology, to determine the level of rabies neutralizing antibody is recommended for those at continuous risk. It can be considered for those at frequent risk to determine whether a booster at three to five years is required. It is used as a guide to determine whether a booster of rabies vaccine is required. Most travellers are at infrequent risk and do not require serological testing.

Adverse events

Adverse events to rabies vaccine tend to be mild and transient and include itching, pain, and erythema (redness) at the injection site. Less commonly fever, malaise, headaches, dizziness, and urticarial (raised itchy rash) occur. Delayed hypersensitivity (allergic) reactions and neurological problems such as Guillain Barre have been reported [36-37].

Post-exposure management

This includes treatment of the wound and detailed risk assessment to determine necessary post-exposure prophylaxis with rabies vaccine and in some circumstances human rabies immunoglobulin. Necessary details of the exposure incident to be considered are:

  • site and severity of the wound
  • circumstances of the bite
  • species, behaviour and appearance of the animal involved
  • health of the animal following the bite
  • vaccination status of the animal
  • country the exposure occurred and origin of the animal
  • vaccination status of the individual at risk

A guide to PEP following risk assessment is available here.

Specialist advice should be sought for all individuals requiring post-exposure rabies management including possible bat exposures in the UK.

Advice regarding PEP in England and Wales is from Public Health England’s (PHE) Virus Reference Division, Colindale on 0208 200 4400. If they are not available, the duty doctor at PHE Colindale should be consulted (0208 200 6868).

In Scotland, contact the local on-call infectious diseases consultant (20) and in Northern Ireland the Regional Virology Service on 02890240503 or Public Health Agency Duty Room on 02890 553 994 (7) (20).

First Published :   09 Jul 2015
Last Updated :   25 May 2016

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