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Eleven questions about rabies in Africa This is an adaptation of a previous paper that was based on questions prepared following a survey made among school children, students and teachers in 1985. Its objective is to inform people about rabies with no or very few technical and scientific words. 1. What micro-organism causes Rabies? Rabies is caused by a virus, the Rabies virus, that can infect all mammals, including man. The virus has a great affinity for nervous system. The disease is due to the replication of the virus in the nervous tissue (as the virus replicates, the disease is said infectious). The disease is only transmitted by an infected individual to a receptive one (the disease is said contagious). Rabies virus, as every virus, cannot replicate by itself in the outside environment, such as organic matter, soil, water, etc ... (it is different from most bacteria). It must enter a living mammalian cell and then utilises this cell to be replicated. The Rabies virus, which cannot replicate without the use of a receptive cell, is called an obligate intracellular parasite. Rabies virus is fragile, it may be destroyed by light, dryness, heat and acidic or basic environments. Low temperatures preserve the virus. It resists pretty well also to putrefaction when it is protected by organic matter, this means that cadavers of rabid animals can sometimes remain infectious for days. However, due to the great fragility of the virus, indirect transmission of the virus from a dead animal through the transport by a bird, an insect or any tool has never been recorded. The only possible transmission is a direct one, i.e. from the rabid individual to the uninfected one. • The Rabies virus belongs to the genus Lyssavirus in the Rhabdoviridae family, all these lyssaviruses have a characteristic bullet-shape aspect. There are currently 12 recognised species within the Lyssavirus genus which include Rabies and the Rabies-related viruses. All of these viruses are cause a fatal encephalitis (inflammation of the brain) with similar clinical signs. • The rabies virus is excreted in the saliva of infected animals. The virus can also be found especially in the brain and in the salivary glands of infected individuals. The amount of virus excreted depends on the virus strain, on the stage of infection and on the species of animal infected. • Locally, the rabies virus may be very closely adapted to a specific animal species that will maintain the virus; this species is called reservoir and vector of the virus. This adaptation is characterised by a very high sensitivity of the reservoir/vector species to this variety of rabies virus and also by the fact that the virus is always present in the saliva of the rabid reservoir/vector species. This phenomenon concerns the dog for instance in Africa and in Asia, it may concern wildlife (red fox in Europe, raccoon, skunk in Northern America, ... For example, the comparison of infection of dog and red fox by a fox adapted virus (isolated in Europe) and a dog adapted virus (isolated in Africa) shows that in the homologous tests (fox virus in foxes and dog virus in dogs), the virus shedding in saliva is 100% while it is only 60-80% in the heterologous system (fox virus - dog, dog virus – fox). If we estimate the dose necessary to infect the reservoir species with its "own" virus, i.e. dog virus for dog and fox virus for fox to 1, we need between 100,000 and 1,000,000 times more virus in the heterologous system. 1/10 2. How do we recognise Rabies in man and animals? The rabies virus multiplies mainly in the cells of the nervous system. From its site of entry, most often a bite, it travels along large nerve cells, the neurons. In the neurons, it causes important disruptions to the cells' function, but it does not cause obvious alterations to their structure. These disruptions lead to clinical signs. These symptoms depend on the area of the brain where the virus multiplies. However, despite their variation, these symptoms are characterised by a certain number of common points, whatever the species affected. • Rabies is often suspected because of a number of behavioural or character changes. Nevertheless, although "any change in habits should lead to suspicion of rabies", we should remember that "anything is rabies and nothing is rabies" – in other words, one should always suspect rabies when exposed to susceptible animals, especially in rabies endemic areas such as Africa. The behavioural and character changes usually occur 3 to 4 weeks after exposure of the individual to the virus, however, even these times can vary greatly and clinical signs may also not be evident. • The actual symptoms of rabies and rabies-related viruses are a little more characteristic. They include those of infectious diseases in general such as: loss of appetite, refusal to eat or drink, fever, prostration, etc. Rabies symptoms also include changes due to the disturbances in nervous system, especially locomotor (movement) troubles, frequent and unusual vocal sounds, excessive salivation, swallowing impossibility, paralysis, paresis, etc. Aggressiveness may be associated with rabies, but is not always observed. It should also be noted that refusal to swallow and spasms of the throat when presented with liquid (hydrophobia) are specific to man and are not systematic. • Rabies can be, and frequently is, misdiagnosed clinically as other diseases or conditions such as: botulism, tetanus, food poisoning, cerebral malaria (especially in Africa) and Guillain-Barré syndrome can exhibit similar symptoms. As clinical signs of rabies are only evocative, the definitive diagnosis of rabies can only be made in laboratory with tests that detect the virus itself or some of its parts. Laboratory tests are usually only done on dead animals, although they can be done on sick animals, but with a reduced sensitivity. The best test for diagnosis uses a small piece of the deceased animal’s brain. This test that uses fluorescent antibodies specific of rabies virus is the Gold-standard test for rabies diagnosis. 3. Is Rabies always fatal? If so, how long does it take? Two situations must be distinguished: • What may happen after exposure to a rabies or a rabies-related virus? • What may happen when, after exposure, the first symptoms have manifested? The risks of contracting rabies after exposure These risks vary depending on the circumstances of the exposure, the individual infected and the origin of the virus. To be able to reach nervous tissue, rabies virus must be in contact with a mucosa (eye for instance) or be "injected" under the skin, most often trough a bite. This risk has been classified by the World Health Organization, it increases in the following order: 2/10 • Contact of the virus with perfectly healthy and unwounded skin: No risk • Contact with mucous membrane or abraded skin (for example, licking of lips or eyes, mild bite wound, scratching of paw soiled with saliva, etc.): Increased risk • Deep bite wounds near nerve centres or innervated areas (head, hands, neck, etc.): Maximum risk But even this maximum risk rarely reaches 100%, except when the virus is perfectly adapted to the species exposed (see question 1). Such a case, for example, may be when a local dog is bitten by another dog or jackal, whereas the risk is markedly lower in instances of infection between different species, for example, when a man is bitten by a rabid dog. However, no matter the degree of exposure, wounds should always be washed immediately and thoroughly with warm soapy water and a physician should be consulted and notified of the potential rabies exposure as soon as possible. The risk once symptoms have manifested Once symptoms have manifested, the risk of death is extremely high. It was long considered to be absolute ("rabies is always fatal"), however, several later observations have indicated that truly rabid animals could survive after the first symptoms of rabies have manifested – especially when the animal was exposed to a virus that was not adapted to that species. A few such cases have been reported in man, all of them with a specific treatment, but they constitute such exceptions that they cannot be taken into consideration for the prognosis of the disease. People must then continue to consider that, in the current absence of a specific antiviral therapeutic, an individual that exhibits the first symptoms of rabies will die of the disease. Death generally occurs a few days after the first signs of the disease. Longer periods, however, have been reported (e.g. 2-3 weeks), especially if supportive treatment for vital functions (respiration), analgesics (for pain) and to control nervous crises were administered. Sometimes, death can occur within a few hours. The rare individuals that have survived rabies generally exhibit irreversible nervous sequels. 4. How do man and animals risk rabies infection? Two conditions must be fulfilled for a successful infection to occur: • There must be transmission of an intact virus to the susceptible organism (see question 3-1). As noted above, the virus is practically only found in the nervous system, the salivary glands and the saliva. This infers that the host harbouring the virus is still alive, or that all or part of its body still contains virulent matter (See question 1). • The virus must reach the nerve endings to cause infection in the new individual. The virus must penetrate the skin and thus be brought into contact with the subcutaneous or muscular nerve endings, or be deposited on a permeable mucous membrane, which is always highly innervated (See question 3). In reality, because of all of these conditions, contact with the infectious virus is only made after a bite by a rabid animal or an animal incubating rabies (See remark), or when one is licked on a mucous membrane or abraded skin by such an animal. Another example may be if one comes into contact with the mouth (and saliva) of an infected animal without being bitten (e.g. herbivorous animals like cattle) with a wounded skin. 3/10 In order to avoid infection, the best strategy is to avoid unfamiliar animals – especially stray dogs and cats, as well as any wild animals showing unusual and familiar behaviour. Direct transmission between humans through saliva has not been identified so far. However, several cases of human to human transmission have been reported with grafts of cornea and more recently of other organs that had been taken from a person who died of rabies. Transmission by inhalation or aerosol is also highly unusual and can only happen in laboratories. Transmission through simple contact with an infected cadaver. Care should be taken by workers in slaughterhouses and hunters, especially when bushmeat is prepared. These people should take care when handling the cadavers, as they may risk exposure to other infectious diseases, including rabies. However, the virus still requires a point of entry like cuts or abrasions on the skin. Transmission through contact with contaminated objects is extremely unlikely. It is important to remember that rabies virus is very sensitive to many disinfectants and inactivating factors, which makes transmission from contaminated objects unlikely. Only deep wounds caused by instruments that have just been contaminated by the virus may be dangerous as it corresponds to an injection of infected tissue. Transmission by ingestion of meat from animals that have died of rabies is also highly improbable because rabies virus is mainly found in nervous tissue. This theoretical risk remains specific to carnivorous and omnivorous animals that eat the raw heads of infected dead animals. As soon as the meat and heads of the infected animal has been cooked, the virus becomes harmless. Important remark A very important point concerning rabies transmission is that infected animals may shed rabies virus in saliva before the onset of clinical signs, this period may reach 14 days for dogs and 29 for red foxes. Then a bite wound can be dangerous even if the animal that has bitten you does not show yet any symptoms of rabies. This is why a dog that has bitten an individual and is suspected of rabies, even if it appears healthy, is not put to death immediately. Rather, the dog is quarantined for 15 days by a veterinarian. If the animal is killed after the bite or during the quarantine period, the head must be immediately sent to the laboratory for diagnosis. If the animal does not show any signs of rabies at the end of this quarantine period, the conclusion is that when the bite occurred, there was no risk of rabies transmission. However, this does not exclude the fact that the animal can develop symptoms later and then die of the disease. If the animal dies during the quarantine period, its head must be sent to the laboratory for diagnosis. 5. How can we avoid contracting rabies? Rabies is due to the multiplication of rabies virus in brain. Once entered in the body, generally through a bite, the virus needs time to reach the brain and to induce the disease that kills. In order to avoid rabies, the following points are critical: • Avoid contact with the virus and risk of bite. In other words, avoid any suspected rabid or unfamiliar animals • Consult a health centre in case of bite or of contact with a suspect animal 4/10 • If the physician in the health centre decides to begin an anti-rabies treatment, never interrupt it on your own. • Be preventively vaccinated if you are at a high risk of exposure (veterinarian, laboratory worker, animal welfare worker, etc.) Avoid contact Except if you are trained to, never go toward a rabid animal and avoid contact with stray or wild animals. Rabid wild animals often approach humans and seem "tame". Never try to approach or handle a wild animal that does not go away from you when it has identified your presence. Attacks from domestic animals are usually more frequent – avoid any unfamiliar dogs and cats. Rabid dogs and cats often change their behaviour, try to hide and attack if you try to catch them, become more irritable or inversely more familiar and lose all instinct of preservation. In no case should they be handled, moved and most importantly, provoked. Herbivorous animals (cattle, goats, sheep, horses) often have difficulty in swallowing, or seem to have something lodged in their throat. Never try to remove the obstruction with bare hands. If contact could not be avoided Because of carelessness or deliberate attack from an animal, immediately and thoroughly wash the wound with soap and water for at least 10 minutes. Although washing the wound does reduce the risk, this first precaution is insufficient to prevent rabies infection. A physician should be seen immediately. Inform the physician that you suspect rabies infection. He will complete the local treatment and/or send the victim to an anti-rabies treatment centre for post-exposure vaccination. The wound should not be sutured as this helps the spread of the virus. Traditional healers do not carry vaccine, and may misdiagnose you, although more and more are being educated with regards to rabies. Many traditional healers may refer you to a clinic where you will be able to receive rabies vaccine and post-exposure treatment. In the case of an animal exposed to rabies, see a veterinarian immediately. The animal’s fate will depend on the circumstances of exposure and on the national regulation concerning rabies. Generally, the animal will be saved if it is vaccinated, identified and receives a booster vaccination within 5 days; otherwise, it will be euthanised. If the risk of contact is difficult to avoid. This is the case for domestic animals living in areas where rabies is common or when they cannot be watched all the time, such as hunting dogs, shepherd dogs, cats, cattle, sheep, goats etc. This is also the case for persons frequently exposed to the virus during their work (e.g. veterinarians, laboratory workers, etc). In this case pre-exposure vaccination should be sought after. This will also aid in the prevention of the disease if exposed (see question 6). The last interest of preventive vaccination is that it prevents domestic animals from transmitting rabies to people who care them. 6. Humans are usually vaccinated after exposure and animals before exposure. What is the reason for this difference? Rabies vaccination consists of the administration of a rabies virus which has been made harmless by either a chemical or a physical agent or by mutation. 5/10 The number of doses administered in a full course treatment depends on the postexposure protocol that is followed. Case 1: Immunisation of an animal or a human before contact with the rabies virus. A dose of vaccine is injected, then 1 or 2 booster dose(s) are injected within 2-3 weeks. 15-30 days later, the individual is immunised, one year later another booster must be injected. After this, for humans, booster may be administered every 3 to 5 years or only after a control of the immunity. This protection is essentially due to the elaboration and release in the bloodstream of antiviral substances specific to rabies virus (antibodies) that can neutralise the virus. It is a good idea to check this immunisation by measuring antibody levels, because, in some exceptional cases, the organism does not respond sufficiently to the vaccination. However, the testing of antibody levels can be expensive and can only be done in certain laboratories. Case 2: There has been an exposure to the rabies virus. In view of the fact that the rabies virus takes several weeks to reach the nerve centres, there is still time to vaccinate the exposed individual. It is recommended that the exposed person receives Post-exposure prophylaxis (PEP) within the first 48 hours after exposure. This will increase the chances of a full protection. The longer one waits for PEP, the greater the risk of becoming infected and dying. The patient will receive one vaccination immediately and then several more vaccinations for the next 3-6 weeks, depending on the vaccination schedule being used. Generally, humans are not given pre-exposure vaccination unless they are at a larger risk of infection than usual. This is the case for persons who are regularly exposed to the virus, because of working in an infected environment, being in close proximity to persons or animals that are or may be rabid, working in a laboratory, etc. In the other cases, in view of the conditions required for infection (see question 4), vaccination is unnecessary and expensive. An animal that is not vaccinated is never treated after exposure for the following reasons: • The efficacy of the treatment in animals is unknown. The rare attempts to treat animals have always been inconclusive • Even if the efficacy of such a treatment were demonstrated experimentally, species by species, in a small number of subjects, it would never be totally guaranteed. In terms of probability, vaccinating an animal after exposure would thus considerably increase the risk of rabies for the humans who live near it in false security. Exposed animals that have not been vaccinated are euthanised. When animals’ owners avoid declaring exposure in order to save their animal, they are taking an unacceptable risk for themselves, anybody near them and other animals in the area. This should encourage people to vaccinate all of their domestic animals when they are young, and receive booster vaccinations every year. Although this may seem costly, it will be cheaper than having to lose that animal to rabies infection. If the vaccinated animal is exposed, it simply requires a single booster vaccine immediately after exposure to ensure that it will survive. 7. Is vaccination efficacious and safe? No vaccination, whatever the type, can be guaranteed to be 100% efficacious and safe. However, the recommended anti-rabies vaccines (cell culture vaccine with killed virus) are 6/10 considered to be among the most efficacious and safe vaccines available. Some countries do still produce local anti-rabies vaccines that use animal brain tissue; these can be variable in effectiveness and can cause vaccine-induced secondary illness. World Health Organisation recommends to discontinue the production of such vaccines and to replace them by vaccines produced on cell culture using an inactivated (killed) virus. Efficacious? An anti-rabies vaccine used for preventive vaccination should titrate at least 1IU (International Unit) per dose and the one used for post-exposure prophylaxis 2.5IU per dose. These vaccines should induce a sufficient level of neutralising antibodies (over 0,5 international units/ml) in man or animals. All animal species (dogs, cats, cattle, goats, etc) can be immunised equally well against rabies, but each species may have some specific requirements, e.g. vaccine type, number of injections, etc. The veterinarian will be responsible for this. When a potent vaccine is used to protect a mammal (including man) the immunity is installed within 2 – 3 weeks after the first vaccination and 7 – 10 days after a booster. However due to variation in the ability of individuals to respond to vaccination, nearly 1% of the population will not respond or respond very poorly to vaccination because of a failure in the immune system and not because of a failure of the vaccine. Therefore, the efficacy of any vaccine can never be totally guaranteed, that is why when an animal is exposed to rabies, even though vaccinated and boosted, its movements are often controlled for 6 to 9 months and any death has to be reported to veterinary services. (see question 4). Safe? The recommended cell culture anti-rabies vaccines that are injected do not contain any living virus. Then, there is absolutely no risk to induce rabies with these vaccines. Some rare secondary reactions may be observed, mainly at the point of injection. Sometimes allergic reactions, in particular after repeated injections, can also be observed. However, these adverse reactions remain highly unusual and they can be predicted, prevented and treated. Nevertheless, anti-rabies vaccines are among the safest of vaccines when they are prepared and controlled according to modern methods. The only vaccines that may be less effective, or may produce side effects, are those which are produced under incorrect conditions or those that have not been stored properly. Live virus vaccines have caused some problems in animals; however, according to international recommendations these vaccines should not be used. • Note 1: Vaccinating an animal incubating the disease after an unknown contamination has never been demonstrated to prolong incubation of the disease. Vaccination can even sometimes accelerate the onset of symptoms. • Note 2: Vaccinated animals that appear healthy but still carry rabies have also never been observed. 8. What species transmit the virus? We must distinguish between the species that are able to be infected with rabies and those that are able to maintain the disease in a given place. All mammals, including man, can be affected with rabies if they are exposed to a sufficient quantity of virus. Only spe- 7/10 cific mammals allow the transmission and the persistence of a specific form of rabies – these animals are called vectors or reservoirs. Rabies has traditionally been associated with dogs, as they are the main vectors throughout Africa and parts of Latin America and Asia. More than 90% of human rabies cases are due to bites from rabid dogs. In addition to dogs, other species can maintain dog adapted rabies virus such as some wildlife species. For instance, in Africa, jackals and bat-eared foxes are also important wildlife vectors. In southern Africa, mongooses are also vectors of a specific rabies virus adapted to them. Some bats are also known to be vectors of the disease, especially vampire bats in Latin America, where this specific rabies frequently infects cattle. Other bat species can transmit rabies, but the majority of the rabid bats will appear sick or will also exhibit uncharacteristic behaviour (such as flying during the day, etc). It is important to remember that if all mammals are susceptible to rabies, only a few of them are reservoir - vectors for rabies. This means that people should be very careful when looking at eradication measures for rabies, as a wrong population may be targeted. A good, large scale surveillance based on laboratory diagnosis is essential to identify species important in the cycle of rabies because they constitute the majority of rabies cases, the other cases are contaminated by this reservoir? As soon as rabies is controlled in the reservoir, these spillovers will disappear. For instance, it means that it is useless to try to kill every jackal in an area infected by dog rabies to control dog rabies. This strategy has no effect on the rabies problem or may even make it worse. The best effort in rabies control is through effective and well-planned vaccination programmes of animals throughout the country. The vaccination of the reservoir will cut the rabies cycle that maintains the disease. The vaccination of domestic animals will eliminate the risk that domestic animals infected by the reservoir species contaminate persons; it is also the only way to protect them and to save money in livestock. 9. Does rabies occur in all countries? Rabies occurs in all countries of the world. Only Antarctica, Australia, a few islands and some other countries do not have, or no longer have, the disease in its endemic form. The exact list is kept up to date by international organisations (World Organisation for Animal Health, World Health Organisation). However, little is known about the rabies situation in several African countries, and all countries in Africa are considered to be rabies endemic. The main vector for rabies may vary depending on the country. Generally there is only a single reservoir species in a given area. For instance, in African countries the main vector is the domestic dog, however, in North America skunks and raccoons are the main vectors as dog rabies has been eradicated. However, no matter the country, all mammals can be exposed. It is only the probability of exposure and the capability of transmitting the disease that varies between countries. 10.How does rabies enter a country and how can it be eliminated? How can rabies be eliminated from a country? If rabies has prevailed for a long period of time, it can be eliminated under certain conditions: • In the case of rabies maintained by dogs, measures for systematic vaccination of dogs and disease control must be applied simultaneously. The first action must be to implement mass vaccination programmes of dogs. In the same time, the dog population must be studied to estimate the proportion of stray animals and of dogs that cannot be vaccinated by injection. Domestic dogs 8/10 must be kept under control. Local culling measures may be efficient locally, when based on the results of the dog population survey. Other measures may be helpful to control dog population, such as sterilisation coupled with vaccination, have also been shown to be extremely useful and more humane. The reduced dog population and the prevention of further breeding have shown to reduce the time and money needed for an effective vaccination programme. • In the case of wildlife maintained rabies too, the only way to eradicate the disease is to vaccinate the reservoir. This time special vaccines safe and efficient orally are used. Some European countries have eradicated wildlife rabies by the use of oral vaccination campaigns. It should be emphasised that wildlife populations should not be targeted for culling due to them being vectors for rabies. As mentioned in question 8, unvaccinated domestic dogs pose the greatest threat to humans and their domestic animals both in case of dog mediated rabies and in case of wildlife rabies. If there is an isolated outbreak of rabies, immediate disease control measures such as restriction of movement of susceptible animals, euthanasia of unvaccinated infected or contact individuals and booster vaccinations should be implemented. This will reduce the risk of the rabies outbreak from spreading. These measures have shown their efficiency in freed or partially freed countries. How can rabies be prevented from entering a country? When no local case of rabies has been reported in a country for 2 years despite surveillance, the country is considered rabies free. The only possibility for such a rabies free country to become infected is the entry of a live rabid animal in the territory. In the case of wildlife rabies, this control is impossible. The preservation of the rabies free status is based on exchange of data on rabies situation with neighbouring countries and on an immune belt maintained with oral vaccination all along the borders with infected neighbouring countries when rabies is close to the border. All what is theoretically necessary to avoid rabies entry in a rabies free country is to prohibit the introduction of live mammals, except after a prolonged quarantine period and to vaccinate constantly all susceptible animals in the country. But these measures are very expensive and make difficult the cross-border travel of pets. That is why quarantine is most often replaced by compulsory anti-rabies vaccination associated with a reliable identification of pets with a control of the level of protection. 11.Does the danger of rabies justify the considerable measures set up for its control? The reputation of rabies is solely due to the fact that it is transmissible to man, as well as the fact that livestock can also be affected. Even in developing countries, rabies is nearly last in the statistics of causes of death by infectious disease. Although rabies kills 55,000 people each year (that is to say 6 persons every hour), it is still an under-reported and neglected disease, especially in Africa where some countries do not even monitor the disease. Although rabies is such a serious disease which costs many people their lives, it is 100% preventable through good vaccination campaigns as well as awareness and proper reporting of the disease. If people receive a full Post-exposure treatment in time when exposed, 9/10 the rate of human deaths will decrease dramatically to quite zero. It is also vital that animals are properly vaccinated and are boosted on a regular basis in order to prevent the spread of rabies through communities in rabies infected areas. Proper reporting of the disease is also vital in order to determine where vaccination campaigns are effective or not and where more focus should be placed in future eradication campaigns. 10/10