The first vaccine against this disease was manufactured by Louis Pasteur in 1885, but despite effective vaccines being available, more than 55,000 people still die from rabies each year throughout the world, with most of them in developing countries of Asia, the Middle East and Africa.
Genomic sequencing of the virus has established two major clades, one comprising those isolated from terrestrial animals around the world and the other containing viruses isolated from bats and raccoons in the Americas. Close homolog exists between differing continental strains.
Although the incidence of this disease has been steadily declining due to strict vaccination, quarantine and border control measures, sporadic cases still occur in endemic areas across Latin America, Asia, India, Middle-East, South America and Africa. Some countries are rabies-free, such as New Zealand, Australia, United Kingdom and parts of Europe. Reservoir hosts, such as bats, foxes, skunks and other wildlife are responsible for sporadic outbreaks in Europe and the Americas.
Transmission is by viral-laden saliva, usually by biting, with incubation periods of 3 - 6 weeks, although longer incubation periods have been reported (up to 25 years in humans). The virus reaches the brain via peripheral nerves, but also infects the salivary glands. Hematogenous spread does not occur.
Clinical signs are variable, but consistent findings are behavior changes and progressive paralysis. The behavioral changes are related to progressive neuropathy, particularly the regions responsible for emotional control. Dogs may become aggressive ('rabid form'), antisocial, hyperexcitable, fearful or mentally depressed and wander aimlessly ('dumb form'). Eventual collapse and respiratory paralysis occur, leading to death.
Diagnosis can be determined by rapid neutralizing antibody detection test, PCR assay testing of oral or hair swabs and formalin-fixed tissue but definitive confirmation requires histopathological confirmation of characteristic brain changes using histopathology and immunohistochemistry by a government reference laboratory. Samples of cerebellum and medulla oblongata are required from necropsied dogs.
No treatment is usually instituted in animals due to zoonotic risk, but humans infected by this virus receive amoxycillin/clavulanate, post-exposure vaccination and, in advanced cases, multiple intrathecal hyperimmune serum immunoglobulin injections. Every year, about 50,000 people die of rabies, usually due to lack of funding for education and preventative vaccinations. Once symptoms appear, human rabies is almost inevitably fatal.
This is a notifiable disease, and strict quarantine protocols are required for monitoring at-risk animals in the immediate vicinity. In most countries, widespread culling is required of animals in the vicinity to minimize spread of the disease. Control measures for canine rabies include vaccination and reducing population density through culling or sterilization. Despite the evidence that culling fails to control canine rabies, efforts to reduce canine population density continue in many parts of the world.
Vaccines are used worldwide as a preventative and control measure in dogs and humans and are mandatory in many countries such as the USA. Control of rabies vector populations utilizes a number of methods such as oral vaccine in food drops and trap-vaccinate-release programs.
Attenuated live vaccine is the main vaccine used against rabies infection, but recombinant bivalent canine distemper virus has shown efficacy against infection. The vaccine regimen involves two doses of rabies vaccine during the first six months of life. Booster immunizations must be administered every year. Testing for seroconversion is required in dogs shipped inter-country.
In humans, immunity provided by the three-dose series is long-lasting and should be considered an investment for at-risk veteriarians and those traveling to rabies-endemic regions.
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