Rabies has been a feared disease since ancient times. The rabies virus affects the brain and causes death within days. Tremendous advances by the pharmaceutical industry means that prevention and treatment with vaccines and immunoglobulins are available and accessible to treat this viral disease.
Rabies is a preventable viral disease of mammals most often transmitted through the bite of a rabid animal, as the rabies virus is passed in the saliva. But other contact with the saliva or brain tissue of an infected mammal can also cause the disease. Rabies virus infects the central nervous system, causing infection of the brain and ultimately death. Since Antiquity, the appearance of rabies symptoms has been a death sentence. Rabies is not, in the natural sense, a disease of humans – human infection is incidental to the reservoir of disease in wild and domestic animals. The word goes back directly to the Latin noun “rabies” which means “madness” or “rage”.
The time between exposure to the virus and ﬁrst symptoms of the disease is usually three weeks to two months, but the incubation period can be from 10 days to a year. Early symptoms of rabies in humans are non speciﬁc, consisting of fever, headache, and general malaise. As the disease progresses, neurological symptoms appear and may include agitation, anxiety, confusion, excitation, hallucinations, insomnia, paralysis, abnormal secretion of saliva, difﬁculty swallowing, and fear of water. Death usually occurs within several days after the onset of symptoms.
Over the past century, rabies in Europe has changed dramatically. Nowadays, more than 95 per cent of all animal cases reported annually occur in wildlife; domestic animals such as dogs, cats and cattle account for fewer than ﬁve per cent of rabies cases. Before 1950, the majority were in domestic animals. The principal rabies hosts today are wild carnivores (mainly foxes) and bats.
The number of rabies-related human deaths in Europe today is fewer than ﬁve per year, due to strict control programmes to prevent transmission from animals to humans. Prophylaxis with modern day vaccines has proven nearly 100 per cent successful. Human fatalities associated with rabies occur in Europe only in cases who fail to seek medical assistance, usually because people were unaware of their exposure.
Human rabies is still common in developing countries in Asia, Africa, and Latin America, where stray dogs are the major transmitters of the disease. The other risk of contracting rabies is a contact with wild animals such as foxes, wild cats, mongooses, bats, monkeys, jackals, and wolves. The Asian continent has the highest number of human rabies cases, as it accounts for more than 95% of all cases worldwide and about 35,000 deaths per year. Hence, exposure to rabid dogs is still the cause of over 90 per cent of human exposures to rabies and of over 99 per cent of human deaths.
There is no treatment for rabies after symptoms appear. Therapeutic measures are undertaken just to ease general symptoms after outbreak, however, a patient with manifest disease will die within several days.
Decades ago, the idea of getting vaccinated against rabies was nearly as frightening as rabies’ deadly symptoms, because it required a series of very painful injections into the abdomen. Today, for individuals who may be at risk of rabies, pharmaceutical research has developed an effective rabies vaccine regimen that provides immunity to the disease when administered after an exposure or for protection before an exposure. Available vaccines are prepared from cell cultures. Various types are employed, including human diploid cell, a lineage of monkey kidney cells, chick embryo cells, or foetal cells of the rhesus monkey. Although rabies among humans has become very rare in Europe, every year an estimated 50,000 people receive rabies pre-exposure or post-exposure prophylaxis.
Pre-exposure vaccination consists of three doses of rabies vaccine given within three or four weeks and is recommended for people of high-risk groups, such as veterinarians, hunters, forest workers, animal handlers, and scientists who work with live rabies vaccine in research laboratories or vaccine production facilities. Other people whose activities bring them into frequent contact with potentially rabid animals should also be considered for pre-exposure prophylaxis. In addition, international travellers likely to stay in areas of urban dog rabies which lack immediate access to appropriate medical care should be considered candidates for pre-exposure vaccination.
Pre-exposure prophylaxis does not eliminate the need for additional medical attention after a rabies exposure. However, it simpliﬁes therapy by eliminating the need for human rabies immune globulin (HRIG) and by decreasing the number of vaccine doses needed. It is also thought to enhance immunity in persons whose post-exposure therapy might be delayed.
Post-exposure vaccination is indicated for persons possibly exposed to a rabid animal. Possible exposures include animal bites, or mucous membrane contamination with infectious tissue, such as saliva. If a person gets bitten by an animal suspected to have rabies, the wound should be washed thoroughly with soap and lots of water. Bite wounds to the face, head, neck or hands must be taken very seriously.
Post-exposure prophylaxis is the only effective treatment against rabies. The vaccine induces the body’s own immune response that neutralises the virus before it reaches the nervous system and the brain. Therefore, vaccination has to begin as soon as possible after exposure with a regimen of one dose of HRIG and ﬁve doses of rabies vaccine over a 28-day period. HRIG and the ﬁrst dose of vaccine are to be given right after exposure.
There are still many aspects of the disease that are unknown. For example, there is no conclusive explanation for the sometimes very short or extremely long incubation period. Despite these continuing problems, there has been tremendous progress. Oral vaccination of wildlife with recombinant rabies virus vaccines is beginning to reduce the incidence of rabies among foxes and other transmitters of the disease.
As resources of HRIG are limited, research focuses on protective human monoclonal antibody products. Two such novel antibodies are in the stage of preclinical testing. Scientists are also trying to develop lower-cost vaccines to be used widely in countries which cannot afford the vaccine preparations currently available. One approach is attempting to develop a DNA-based vaccine.
After the development of the ﬁrst rabies vaccine by Pasteur in 1885, it had been hoped to eliminate the disease. However, this goal has not been achieved, because the virus is maintained in many animal populations. It may sound strange, but rabies may again have become an emerging infectious disease. Largely eliminated from dogs by vaccination programmes, the virus has re-emerged in some European countries as awidespread problem among wild mammals, particularly foxes, ferrets and bats. Also, the area where the virus is prevalent has grown; originating from countries of Eastern and Central Europe and now extending into the western parts of France and the Benelux countries.
Human deaths from rabies occur in countries with inadequate public health resources, limited access to preventive treatment, few diagnostic facilities and almost no rabies control programmes. Despite evidence that control of canine rabies through programmes of animal vaccination and elimination of stray dogs can reduce the incidence of human rabies to very low numbers, for the time being, the cost of these programmes prohibits their full implementation in much of the developing world, as this necessitates revaccination of millions of animals each year.
Unless more resources are devoted to such programmes, rabies will continue to represent a major threat for public health in Asian, African and Latin American regions.