Rabies

Rabies


Key facts
Rabies is widely distributed and present on all continents of the world. More than 55 000 people die of rabies each year. More than 95% of human rabies deaths occur in Asia and Africa.
Most human deaths follow a bite from an infected dog. Between 30% to 60% of the victims of dog bites are children under the age of 15.
Wound cleansing and immunizations, done as soon as possible after suspect contact with an animal and following WHO recommendations, can prevent the onset of rabies in virtually 100% of exposures.
Once the signs and symptoms of rabies start to appear, there is no treatment and the disease is almost always fatal.
The most cost-effective strategy for preventing rabies in people is by eliminating rabies in dogs through animal vaccinations.


Rabies is a zoonotic viral disease which infects domestic and wild animals. It is transmitted to other animals and humans through close contact with saliva from infected animals (i.e. bites, scratches, licks on broken skin and mucous membranes). Once symptoms of the disease develop, rabies is fatal to both animals and humans.

The first symptoms of rabies are usually non-specific and suggest involvement of the respiratory, gastrointestinal and/or central nervous systems. In the acute stage, signs of hyperactivity (furious rabies) or paralysis (dumb rabies) predominate. In both furious and dumb rabies, paralysis eventually progresses to complete paralysis followed by coma and death in all cases, usually due to respiratory failure. Without intensive care, death occurs during the first seven days of illness.

Incidence
Reliable data on rabies is scarce in many areas of the globe, making it difficult to assess its full impact on human and animal health. WHO commissioned a re-assessment of the burden of rabies in 2004. According to this study the annual number of deaths worldwide caused by rabies is estimated to be 55 000, mostly in rural areas of Africa and Asia. An estimated 10 million people receive post-exposure treatments each year after being exposed to rabies-suspect animals.

The assessment shows that Asia carries a larger part of the public health burden of rabies (with an estimated 31 000 deaths), although the estimate for Africa (24 000 deaths) is much greater than initially believed. Asia also carries 96.5% of the economic burden of rabies in the developing world with US$ 560 million spent each year mostly on post-exposure prophylaxis.

In the late 1990s and early 2000, rabies in wildlife was eliminated in the western European countries which conducted oral vaccination campaigns (i.e. Switzerland 1999; France 2000; Belgium and Luxembourg 2001 and the Czech Republic 2004). This technique could help to totally eliminate rabies from its terrestrial reservoirs in western Europe. Oral vaccination programmes for dogs are being evaluated in a few developing countries where canine rabies is endemic (e.g. India, the Republic of South Africa and Sri Lanka). Dramatic decreases in human cases of rabies have also been reported during recent years in South America and in some Asian countries, following implementation of programmes for improved post-exposure treatment of humans and the vaccination of dogs.

Transmission
In developed countries, rabies is present mainly in wild animal hosts, from which the disease spills over to domestic animals and humans. Recently, bat rabies has emerged as an important epidemiologic reservoir in some parts of the world (i.e. the Americas and Australia). In North America, most documented human rabies deaths occurred as a result of infection from the silver haired bat rabies virus variant and in Australia at least two human deaths have occurred from exposure to a previously unrecognized rabies virus. In South America, wildlife rabies, especially bat rabies is increasing. For the first time in 2003, more people died from rabies following bites from wildlife than from dogs in South America. However, dogs continue to be the main hosts in Africa and Asia and are responsible for most of the human rabies deaths that occur worldwide.

The most frequent way that humans become infected with rabies is through the bite of infected dogs and cats, wild carnivorous species like foxes, raccoons, skunks, jackals and wolves, and insectivorous and vampire bats. Cattle, horses, deer and other herbivores can become infected with rabies and although they could potentially transmit the virus to other animals and to people, this rarely occurs.

Post-exposure treatment
The most effective mechanism of protection against rabies is to wash and flush a wound or point of contact with soap and water, detergent or plain water, followed by the application of ethanol, tincture or aqueous solution of iodine. Anti-rabies vaccine should be given for Category II and III1 exposures as soon as possible according to WHO recognized regimens. Anti-rabies immunoglobulin (antibody) should be applied for all Category III exposures and for Category II exposures in immunosuppressed patients. Suturing (closing the wound) should be postponed, but if it is necessary immunoglobulin must first be applied. Where indicated, anti-tetanus treatment, antimicrobials and drugs should be administered to control infections other than rabies.

The use of purified horse immunoglobulins can provide at least a partial solution to the current problems of insufficient quantities and high cost of human immunoglobulin. Further details on pre- and post-exposure can be found in the WHO guidelines on rabies post-exposure treatment2.

In case of human exposure to animals that are suspected of having rabies, immediate attempts should be made to identify, capture or kill the animal involved. In case of a Category III exposure, post-exposure treatment should start immediately and can be stopped if the animal is a dog or cat and remains healthy after 10 days. Tissue samples should be taken from dead animals and sent to competent laboratories for diagnosis. The responsible veterinary services should be notified and information obtained on the epidemiological situation in the area.

Vaccines and immunization
Neural tissue rabies vaccines, still used in some developing countries should not be produced anymore. Highly purified and potent modern cell culture and embryonated egg vaccines should be used. Reduced vaccination schedules and routes for vaccine administration (particularly the intradermal route) have been successfully used in developing countries where the cost of the five dose intramuscular schedule is prohibitively expensive. In addition to the five-dose Essen regimen given on days 0, 3, 7, 14 and 28 in the deltoid muscles, two additional reduced intradermal treatment regimens also fulfill WHO requirements:

These are the Red Cross 2-site ("2-2-2-0-1-1") and the "8-0-4-0-1-1" intradermal schedules which have been evaluated and used extensively in some developing countries to replace nerve tissue vaccines where expensive intramuscular vaccination regimes are not an alternative. Intradermal injections should be administered by staff well trained in this technique.

Rabies immunoglobulin
Rabies immunoglobulins are expensive and may be in short supply or non-existent in most developing countries where canine rabies is endemic. However, rabies immunoglobulins should be administered in all Category III exposures and in Category II exposures that occur in immunosuppressed persons. Both purified equine rabies immunoglobulin and human immunoglobulin are used in developing countries. The full dose of rabies immunoglobulin, or as much as is anatomically feasible, should be administered into and around the wound site. Any remainder should be injected intramuscularly at a site distant from the vaccine administrative site.

If the dose of rabies immunoglobulin is too small to infiltrate all wounds, (as might be the case in a severely bitten child) the correct dosage of rabies immunoglobulin can be diluted in physiological buffered saline to insure more wound coverage.

Vaccination in immunosuppressed persons
Severely immunosuppressed patients may not develop an immunologic response after rabies vaccination. Therefore, prompt and appropriate wound care after an exposure is an essential step in preventing death. In addition, rabies immunoglobulin should be administered in all immunosuppressed patients experiencing Category II and Category III wounds.

Rabies in children
Where data is available, there is consistent evidence that between 30 - 60% of the victims of dog bites in canine rabies endemic areas are children under 15 years of age. The majority of these children may not be treated because their exposures go unreported to parents or health officials. In order to reduce the mortality rate in children, the following activities should be strengthened or initiated in countries where successful canine rabies vaccination or control programmes have not been put in place:

Promote proper and immediate care of dog bite wounds;
Increase access to modern cell culture vaccines in vulnerable populations including pre-exposure vaccination in children living in regions where canine rabies is highly endemic;
Promote proper application of effective and economical rabies post-exposure treatment;
Prevent dog rabies through dog vaccination and promotion of responsible dog ownership.
Conclusions
Prevention of human rabies must be a community effort involving both veterinary and public health officials. Rabies elimination programmes focused mainly on mass vaccination of dogs are largely justified by the future savings of discontinuing prevention programmes. However, until canine rabies is eliminated or at least well controlled, safer and more economical post-exposure treatments for humans are a desirable alternative to the use of nerve tissue vaccines. Pre-exposure vaccination has been widely and successfully used to prevent rabies in at-risk populations in industrialized countries and should be promoted in children living in regions where canine rabies is highly endemic. If rabies is not eliminated, expenses related to prevention of the disease in both humans and animals are likely to increase in developing countries.