Island Quarantine Management Rabies By Julia Hughes Introduction Rabies is a preventable virus, mainly transmitted through the bite of an unprovoked attack by a rabid animal. The rabies virus infects the CNS, causing encephalopathy and ultimately death within days of the first onset of symptoms. Rabies is a recognised disease worldwide, estimated to have been the cause of over 55,000 deaths per year, 56% of which occur in Asian and 44% in Africa, however some countries such as Japan, Norway, Iceland, Eire, Portugal and Sweden remain free of infection. The UK is mainly under threat of imported dogs from Asia, African and Latin America. (Lane & Cooper) Any mammal is capable of contracting rabies and it is a zoonosis. (Lane & Cooper) There are two forms of clinical rabies - furious rabies and dumb rabies. Furious rabies makes the infected animal progressively hyperexcitable lasting a few minutes to several hours. During this time, the animal may become more aggressive than normal, snapping at imaginary objects, chewing at anything in sight while in between these episodes, the animal will appear friendly, placid and calm. As the disease progresses there is difficulty in swallowing and distortion of the face and eventually the animal will die during a violent seizure. (Lane & Cooper) Dumb rabies shows less of the aggressive signs of furious rabies, however there is still paralysis of the limbs, face distortion where the jaws and eyelids droop and the animal drools (see picture overleaf). The animal will then become comatose and die. (Lane & Cooper)
A Rabid Dog Drooling Daff Diagnosis in animals is done through the direct florescent antibody test (dfa) and can only be performed post-mortem as it requires brain tissue from the animal suspected of being rabid. Treatment is determined by which animal has spread the infection but generally there is no effective treatment available and even though there are reports of cats and dogs recovering from rabies, these situations are extremely rare. (Lane & Cooper) The Rabies Virus Classification The rabies virus belong to the order Mononegavirales - viruses with a non-segmented, negative-stranded RNA genomes. This group of viruses are classified in the Rhabdoviridae family and have a distinct "bullet" shape (see diagram overleaf) of which there are at least three genera of animal viruses - Lyssavirus, Ephemerovirus, and Vesiculovirus. The rabies virus is included in the genus Lyssavirus together with Lagos bat, Mokola virus, Duvenhage virus, European bat virus 1 & 2 and Australian bat virus.
Structure The infection process is initiated by the fusion of the rabies virus envelope to the host cell membrane (adsorption). The virus then penetrates the host cell, entering the cytoplasm by pinocytosis. The virions group together in the large endosomes (cytoplasmic vesicles) where the viral membranes fuse to the endosomal membranes which causes the release of viral RNP into the cytoplasm (see diagram below on the cycle of infection and replication). Cycle of Infection and Replication
Symptoms of Rabies When bitten by an infected animal, the infection remains undetected while it travels from the muscle or site of inoculation to the Central Nervous System by axonal flow along nerve fibres and up into the brain. The speed of this process varies, lasting a few weeks to several months (see diagram of the infectious path below). 3. Rabies virus spreads through the nerves to the spinal cord and brain. The infectious path of rabies virus 4. The virus incubates in raccoon's body for approximately 3-12 weeks. The raccoon has no signs of illness during this time. 5. When it reaches the brain, the virus multiplies rapidly, passes to the salivary glands, and the raccoon begins to show signs of the disease. 2. Rabies virus enters the raccoon through infected saliva. 1. Raccoon is bitten by a rabid animal. 6. The infected animal usually dies within 7 days of becoming sick. Once the virus has reached the brain, it multiplies to cause inflammation or encephalitis where the first signs of rabies can be detected in the animals behaviour, symptoms of which include:- Malaise Fever Headache Insomnia Anxiety Fearfulness Confusion Delirium
Slight or partial paralysis - staggering and seizures Excitation Hallucinations Agitation Hyper-salivation Aggression Difficulty swallowing Hydrophobia (fear of water) - in humans only Depression Self mutilation Increase sensitivity to light. (AVMA) The speed of the development of these clinical signs depends on where the bite occurs, ie the virus will reach the CNS quicker if the bite occurred to the head or neck, the severity of the bite and how much of the virus was transferred (see diagram below). (Lane & Cooper) The Spread of Rabies (Symptom of Rabies)
When the infection matures and moves to the salivary glands and into the saliva, the virusinduced aggressive biting-behaviour (see picture below) maximises the chance of the infection being spread to a new host through a bite or less commonly through a nonbite where the saliva of a rabid animal comes in contact with an open cut or through the eyes, nose or mouth. An Aggressive Rabid Dog (Family Pet) What Animals that are Susceptible to Rabies It is most commonly found in wild mammals such as bats, raccoons, foxes, skunks and coyotes and according to The Center for Disease Control and Prevention in 2009 only about 10% of their reported cases are from domestic mammals - mainly cats, dogs and cattle. Small rodents such as rats, hamsters, gerbils, mice, guinea pigs, squirrels and lagomorphs such as rabbits and hares are rarely found to be infected. Wildlife infection is called sylvatic rabies and domestically spread rabies is called urban rabies. (Lane & Cooper) Bats and Rabies If a bat (see photo overleaf) is active during the day, in a place where bats are not usually seen, or is unable to fly, it is most likely to be rabid. If bitten by a bat, or infected saliva gets into the eyes, nose, mouth, or a wound, the affected area needs to be washed thoroughly and medical advice sought immediately. If possible, the bat should be captured and sent to a laboratory for rabies testing.
A Bat If a pet or domestic animal gets bitten by a bat, immediate assistance is required by a veterinarian. The bat will also need to be tested for rabies. Vaccinations are available for cats, dogs, and other animals. Bats in the Attic Bats should always discouraged from entering the home (see bats in the attic above). To bat-proof" homes, examine the house for holes larger than ¼ by ½ that might allow bats entry into living quarters (see drawing overleaf), fill them with stainless steel wool or caulking and block off entry points with bird netting. Common Bat Entry Points
Young bats are unable to fly so if the adult bats have their entries barred, the young will get trapped and die so the best times to bat-proof is during the autumn before they hibernate. Diagnosis Humans require several tests while they are still alive as no single test is sufficient. These tests include skin biopsies of hair follicles at the nape of the neck that are examined for the rabies antigen in the cutaneous nerves, serum and spinal fluid that are tested for antibodies and saliva that is tested by virus isolation followed by a polymerase chain reaction. These tests are performed rapidly and accurately, resulting in the crucial decision on whether to administer post-exposure prophylaxis or not saving a patient from any unnecessary psychological and physical trauma. Direct fluorescent antibody test (dfa) It has been observed that infected animals have rabies virus proteins (antigen) present in their nervous tissues so the ideal tissue test is on the brain and the most important part of the test is fluorescently-labelled anti-rabies antibody. The rabies antigen bind when labelled antibody is incubated with rabies-suspect brain tissue. The unbound antibody can then be washed away, leaving areas where the antigen is present. This can be seen as a florescent-apple-green area using a florescence microscope (see image overleaf). Antigen detection by dfa
Treatment The rabid animal should be tested immediately, thereby providing information if rabies postexposure prophylaxis is necessary. The table below shows the decisions made for each circumstance. Animal Type to Post-exposure Prophylaxis Table Animal Type Dogs, cats, and ferrets Raccoons, skunks, foxes, and most other carnivores; Bats Livestock, horses, rodents, rabbits and hares, and other mammals Evaluation and Disposition of Animal Healthy and available for 10 day observation Rabid or suspected rabid Unknown (escaped) Regarded as rabid unless animal is proven negative by laboratory test Consider individually Post-exposure Prophylaxis Recommendations Vaccination should not begin unless animal develops clinical signs of rabies Immediately vaccinate Consult public health officials Consider immediate vaccination Consult public health officials. Bites of squirrels, hamsters, guinea pigs, gerbils, chipmunks, rats, mice, other small rodents, rabbits, and hares almost never require rabies post-exposure prophylaxis. An unvaccinated animal that is bitten or scratched by a rabid animal should either be euthanized or placed in quarantine for at least six months. In the unlikely event that the infected animal survives, it should be vaccinated against rabies at least one months before it is allowed back to its normal environment. An infected animal that has up to date
vaccinations should be kept under observations for approximately 45 days, giving long enough for any signs to show up. Treatment of Wounds The treatment of any rabid bite wounds must be done in sterile conditions in order to avoid infection (both local and systemic). Immediate cleansing of the wound with gentle water irrigation and if available, a virucidal agent such as povidine-iodine solution, is very important to minimise the risk of any bacterial infection and reduce the likelihood of the spread of rabies. The Rabies Vaccine The Rabies Vaccine (Family Pet) A tetanus prophylaxis shot should be given if there has been more than 10 years since last immunised against rabies and for those who have never been vaccinated against rabies, an anti-rabies vaccine should be administered post exposure which includes a passive antibody. Those who have previously been vaccinated should receive only the vaccine (see picture above). For both bite and nonbite exposures, a combination of human rabies immune globulin (HRIG) which provides immediate antibodies and vaccine is recommended. For persons unvaccinated, a course of five 1ml doses of HDCV or PCEC vaccines should be administered intramuscularly, the first dose of which should be administered as soon as possible after exposure. The remaining doses should be administered on days 3, 7, 14, and 28 after first vaccination. Adults should be administered intramuscularly in the deltoid area or arm and children in the anterolateral aspect of the thigh. Previously vaccinated persons should receive two IM doses (1ml each) of vaccine, one immediately and the other three days
later. Pre-exposure rabies prophylaxis is administered for several reasons. While it does not totally eliminate the need for additional therapy, it does simplifies the management by decreasing the number of vaccine doses which is particularly important for people at high risk of exposure to rabies in areas where immunisation might not be available or where therapy could possibly be delayed. It also may provide protection to those who may unknowingly be exposed to the risk of rabies. The table below sets out these different risk factors. Rabies Pre-exposure Prophylaxis guide Risk Category Continuous Nature of Risk Typical Population Pre-exposure Recommendations High concentration of virus present - continuously. Specific exposures likely to go unrecognized. Bite, nonbite, or aerosol exposure. Rabies research laboratory workers; rabies biologics production workers. Primary course. Serologic testing every 6 months; booster vaccination if antibody titer is below acceptable level. Frequent Exposure usually episodic, with source recognized, but exposure also might be unrecognized. Bite, nonbite, or aerosol exposure. Rabies diagnostic lab workers, spelunkers, veterinarians and staff, and animal-control and wildlife workers in rabies-enzootic areas. All persons who frequently handle bats. Primary course. Serologic testing every 2 years; booster vaccination if antibody titer is below acceptable level. Infrequent Exposure nearly always episodic with source recognized. Bite or nonbite exposure. Veterinarians and terrestrial animal-control workers in areas where rabies is uncommon to rare. Veterinary students. Travellers visiting areas where rabies is enzootic and immediate access to appropriate medical care including biologics is limited. Primary course. No serologic testing or booster vaccination. Rare (population at large) Exposure always episodic with source recognized. Bite or nonbite exposure. Population at large, including persons in rabiesepizootic areas. No vaccination necessary Those who work in research laboratories or vaccine production facilities are at the highest
risk for unapparent exposures and should have a serum sample that has been tested for the rabies antibody every six months. Intramuscular booster doses of vaccine should be administered in order to maintain a serum titer. The frequent-risk category includes other laboratory workers, spelunkers, veterinarians and staff, animal-control and wildlife officers in areas where animal rabies is enzootic and bat handlers. This group should receive a serum sample tested for rabies antibody every two years and in some cases a single booster dose of vaccine. The infrequent exposure group, ie veterinarians, veterinary students, and terrestrial animalcontrol and wildlife officers, working in areas where rabies is uncommon to rare and at-risk international travellers do not require the routine pre-exposure booster doses of vaccine after completion of the primary pre-exposure vaccination. Prevention and Education Even though rabies occur mainly in wild animals, all pet cats, dogs, ferrets and any valuable livestock and horses should receive a rabies vaccination as it is possible that they could come into contact with a wild infected animal. Pets should be spayed or neutered as this decreases undesirable behaviour and will no only prevent them from contributing to the birth of unwanted animals but also keep away any unwanted animals that may not have been properly vaccinated. Stray animals should be rounded up by Animal Control as they may be unvaccinated or ill. (AVMA) If in doubt of whether an animal has the rabies virus or not, it should be kept in quarantine for 10 days, after which, rabid signs will show. To prevent the attraction of wild or stray animals to the home, food waste or pet food should not be left outside. Wild animals should not be brought into homes and keep as pets as this poses a potential rabies threat. Materials should be distributed throughout all veterinary clinics in order to educate their clients on rabies prevention. (AVMA) Cost of Rabies Prevention In America the annual estimated cost of rabies is US$ 583.5 million. (WHO) Vaccines have been available for more than 100 years and approximately 10 million people worldwide
receive post-exposure treatment, but it is mainly countries with inadequate public health resources that suffer from the most deaths from rabies as these countries lack diagnostic facilities and rabies surveillance which means that most cases go unreported. Surveillance and Monitoring of Rabies The surveillance work, diagnostics and all laboratory investigations on wildlife rabies controlled in Finland, includes serology testing and life vaccine titration and together with the Ministry of Agriculture and Forestry, the elaboration of baiting strategies is annually planned. (EC) Apart from one case of an imported horse from Estonia in 2003, no rabies cases have been found in Finland since 1989 and has been declared rabies free in 1991, however infection in Russia and the Baltic countries remained high and as a consequence still poses a risk of the reintroduction of the disease. (EC) In 1988 an oral vaccination field campaign of raccoon, dogs and foxes commenced. Local volunteer hunters distributed the bait in the first year together with aerial distribution. Vaccine baits have been distributed along the south eastern border of Russia over an area of 250 km long by 20 km wide since the beginning of the 1990s with an objective to prevent a rabies epidemic by maintaining adequate immunity in the wild raccoon, dog and fox population in Finland. From 2003 the adjacent area on the Russian territory has also received the rabies vaccine baits. (EC) Every year, tests are carried out by provincial veterinary and municipal veterinary officers in Finland on approximately 400 to 700 wildlife animals and 20 to 40 domestic animals. During an eleven month period in 2006 and using the WHO recommended techniques, a total of 473 wild animals and 19 domestic animals were examined for the rabies virus. All these tests had negative results. (EC) Any new outbreaks of rabies are detected early by using epidemiological screening. When human exposure occurs, there is an immediate submission of the suspected animals brain for diagnoses in a laboratory. If the suspected animal is a domestic one which cannot be killed, then it s isolated and kept under observation for 10 days. (WHO)
Conclusion If rabies became established in the UK, it would be extremely difficult to eradicate it, profoundly changing the way of life and how safe people would feel when approaching a stray cat or dog which is why all imported animals are subject to strict quarantine requirements, including vaccination for dogs and cats from all affected countries. In this case, the prevention is definitely better than the cure.
References Websites AVMA, 2008, http://www.avma.org/animal_health/brochures/rabies/rabies_brochure.asp [Accessed 26 th January 2010] CDC, http://www.cdc.gov/rabies/ [Accessed 26 th January 2010] Department of Agriculture, Fisheries and Forestry, Australian Government, http://www.daff.gov.au/animal-plant-health/pests-diseases-weeds/animal/rabies [Accessed 11 th April 2010] European Commission, http://ec.europa.eu/food/animal/diseases/eradication/rabies_pres_20.pdf, Finnish Food Safety Authority, Finland, Miia Jakava-Viljanen [Accessed 11 th April 2010] Family Pet Medical Centre, http://familypetmedicalcenter.com/medical_articles1.htm [Accessed 11 th April 2010] Symptoms of Rabies, http://symptomsofrabies.net/tag/rabies-facts/ [Accessed 11 th April 2010] World Health Organization, http://www.who.int/rabies/epidemiology/rabiessurveillance.pdf [Accessed 11 th April 2010] Books Lane & Cooper, 2002, Veterinary Nursing, Second Edition, Butterworth-Heinemann