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Rabies | Understanding and definition of Rabies | Symptoms caused by Rabies | The risk is borne by Rabies

Rabies is a viral disease that causes acute encephalitis (inflammation of the brain) in warm-blooded animals. It is zoonotic (i.e., transmitted by animals), most commonly by a bite from an infected animal. For a human rabies is almost invariably fatal if post-exposure prophylaxis is not administered prior to the onset of severe symptoms. The rabies virus infects the central nervous system, ultimately causing disease in the brain and death. The early symptoms of rabies in people are similar to that of many other illnesses, including fever, headache, and general weakness or discomfort. As the disease progresses, more specific symptoms appear and may include insomnia, anxiety, confusion, slight or partial paralysis, excitation, hallucinations, agitation, hypersalivation (increase in saliva), difficulty swallowing, and hydrophobia (fear of water). Death usually occurs within days of the onset of these symptoms.

The rabies virus travels to the brain by following the peripheral nerves. The incubation period of the disease is usually a few months in humans, depending on the distance the virus must travel to reach the central nervous system. Once the rabies virus reaches the central nervous system and symptoms begin to show, the infection is effectively untreatable and usually fatal within days.

Early-stage symptoms of rabies are malaise, headache and fever, progressing to acute pain, violent movements, uncontrolled excitement, depression, and hydrophobia. Finally, the patient may experience periods of mania and lethargy, eventually leading to coma. The primary cause of death is usually respiratory insufficiency. Worldwide, roughly 97% of rabies cases come from dog bites. In the United States, however, animal control and vaccination programs have effectively eliminated domestic dogs as reservoirs of rabies. In several countries, including the United Kingdom, Estonia and Japan, rabies carried by animals that live on the ground has been eradicated entirely. Concerns exist about airborne and mixed-habitat animals including bats. A small number of bats of three species in the U.K and in some other countries have been found to have European Bat Lyssavirus 1 and European Bat Lyssavirus 2. The symptoms of these viruses are similar to those of rabies and so the viruses are both known as bat rabies. An unvaccinated Scottish bat handler died from an EBLV infection in 2002.

The economic impact is also substantial, as rabies is a significant cause of death of livestock in some countries.

The period between infection and the first flu-like symptoms is normally two to twelve weeks, but can be as long as two years. Soon after, the symptoms expand to slight or partial paralysis, cerebral dysfunction, anxiety, insomnia, confusion, agitation, abnormal behavior, paranoia, terror, hallucinations, progressing to delirium. The production of large quantities of saliva and tears coupled with an inability to speak or swallow are typical during the later stages of the disease; this can result in hydrophobia, in which the patient has difficulty swallowing because the throat and jaw become slowly paralyzed, shows panic when presented with liquids to drink, and cannot quench his or her thirst.

Death almost invariably results two to ten days after first symptoms. In 2005, the first patient was treated with the Milwaukee protocol, and Jeanna Giese became the first person ever recorded to survive rabies without receiving successful post-exposure prophylaxis. An intention to treat analysis has since found that this protocol has a survival rate of about 8%.

The rabies virus is the type species of the Lyssavirus genus, in the family Rhabdoviridae, order Mononegavirales. Lyssaviruses have helical symmetry, with a length of about 180 nm and a cross-sectional diameter of about 75 nm. These viruses are enveloped and have a single stranded RNA genome with negative-sense. The genetic information is packaged as a ribonucleoprotein complex in which RNA is tightly bound by the viral nucleoprotein. The RNA genome of the virus encodes five genes whose order is highly conserved: nucleoprotein (N), phosphoprotein (P), matrix protein (M), glycoprotein (G) and the viral RNA polymerase (L).

From the point of entry, the virus is neurotropic, traveling quickly along the neural pathways into the central nervous system (CNS), and then further into other organs. The salivary glands receive high concentrations of the virus thus allowing further transmission.

The reference method for diagnosing rabies is by performing PCR or viral culture on brain samples taken after death. The diagnosis can also be reliably made from skin samples taken before death. It is also possible to make the diagnosis from saliva, urine and cerebrospinal fluid samples, but this is not as sensitive. Inclusion bodies called Negri bodies are 100% diagnostic for rabies infection, but are found in only about 80% of cases. If possible, the animal from which the bite was received should also be examined for rabies.

The differential diagnosis in a case of suspected human rabies may initially include any cause of encephalitis, particularly infection with viruses such as herpesviruses, enteroviruses, and arboviruses (e.g., West Nile virus). The most important viruses to rule out are herpes simplex virus type 1, varicella-zoster virus, and (less commonly) enteroviruses, including coxsackieviruses, echoviruses, polioviruses, and human enteroviruses 68 to 71. In addition, consideration should be given to the local epidemiology of encephalitis caused by arboviruses belonging to several taxonomic groups, including eastern and western equine encephalitis viruses, St. Louis encephalitis virus, Powassan virus, the California encephalitis virus serogroup, and La Crosse virus.

New causes of viral encephalitis are also possible, as was evidenced by the recent outbreak in Malaysia of some 300 cases of encephalitis (mortality rate, 40%) caused by Nipah virus, a newly recognized paramyxovirus. Similarly, well-known viruses may be introduced into new locations, as is illustrated by the recent outbreak of encephalitis due to West Nile virus in the eastern United States. Epidemiologic factors (e.g., season, geographic location, and the patient’s age, travel history, and possible exposure to animal bites, rodents, and ticks) may help direct the diagnostic workup.

Cheaper rabies diagnosis will be possible for low-income settings: accurate rabies diagnosis can be done at a tenth of the cost of traditional testing using basic light microscopy techniques.

All human cases of rabies were fatal until a vaccine was developed in 1885 by Louis Pasteur and Émile Roux. Their original vaccine was harvested from infected rabbits, from which the virus in the nerve tissue was weakened by allowing it to dry for five to ten days. Similar nerve tissue-derived vaccines are still used in some countries, as they are much cheaper than modern cell culture vaccines. The human diploid cell rabies vaccine was started in 1967; however, a new and less expensive purified chicken embryo cell vaccine and purified vero cell rabies vaccine are now available. A recombinant vaccine called V-RG has been successfully used in Belgium, France, Germany, and the United States to prevent outbreaks of rabies in wildlife. Currently pre-exposure immunization has been used in both human and non-human populations, whereas in many jurisdictions domesticated animals are required to be vaccinated.

In the USA, since the widespread vaccination of domestic dogs and cats and the development of effective human vaccines and immunoglobulin treatments, the number of recorded deaths from rabies has dropped from one hundred or more annually in the early 20th century, to 1–2 per year, mostly caused by bat bites, which may go unnoticed by the victim and hence untreated.

The Missouri Dept. of Health and Senior Services Communicable Disease Surveillance 2007 Annual Report states that the following can help reduce the risk of exposure to rabies by :
  1. Vaccinating dogs, cats, and ferrets against rabies
  2. Keeping pets under supervision
  3. Not handling wild animals or strays
  4. Contacting an animal control officer, if you see a wild animal or a stray, especially if the animal is acting strangely.
  5. Washing the wound with soap and water between 10–15 minutes, if you do get bitten by an animal, and contacting your health care provider to see if you need rabies post-exposure prophylaxis.
  6. Getting pets spayed or neutered. Pets that are fixed are less likely to leave home, become strays, and make more stray animals.
September 28 is World Rabies Day, which promotes information on, and prevention and elimination of the disease.

In unvaccinated humans, rabies is almost always fatal after neurological symptoms have developed, but prompt post-exposure vaccination may prevent the virus from progressing. Rabies kills around 55,000 people a year, mostly in Asia and Africa. There are only six known cases of a person surviving symptomatic rabies, and only one known case of survival in which the patient received no rabies-specific treatment either before or after illness onset.

Any warm-blooded animal (including humans) may become infected with the rabies virus and develop symptoms (although birds have only been known to be experimentally infected). Indeed the virus has even been adapted to grow in cells of poikilothermic ("cold-blooded") vertebrates. Most animals can be infected by the virus and can transmit the disease to humans. Infected bats, monkeys, raccoons, foxes, skunks, cattle, wolves, coyotes, dogs, mongoose (normally yellow mongoose) or cats present the greatest risk to humans. Rabies may also spread through exposure to infected domestic farm animals, groundhogs, weasels, bears and other wild carnivores. Small rodents such as squirrels, hamsters, guinea pigs, gerbils, chipmunks, rats, and mice and lagomorphs like rabbits and hares are almost never found to be infected with rabies and are not known to transmit rabies to humans.

The virus is usually present in the nerves and saliva of a symptomatic rabid animal. The route of infection is usually, but not always, by a bite. In many cases the infected animal is exceptionally aggressive, may attack without provocation, and exhibits otherwise uncharacteristic behavior.

After a typical human infection by bite, the virus enters the peripheral nervous system. It then travels along the nerves towards the central nervous system. During this phase, the virus cannot be easily detected within the host, and vaccination may still confer cell-mediated immunity to prevent symptomatic rabies. When the virus reaches the brain, it rapidly causes encephalitis. This is called the prodromal phase, and is the beginning of the symptoms. Once the patient becomes symptomatic, treatment is almost never effective and mortality is over 99%. Rabies may also inflame the spinal cord producing transverse myelitis.

The rabies virus survives in widespread, varied, rural fauna reservoirs. It is present in the animal populations of almost every country in the world, except in Australia and New Zealand. In some countries like those in western Europe and Oceania, rabies is considered to be prevalent among bat populations only.

Because of its potentially violent nature, rabies has been known since c.2000 B.C. The first written record of rabies is in the Codex of Eshnunna (ca. 1930 BC), which dictates that the owner of a dog showing symptoms of rabies should take preventive measure against bites. If another person was bitten by a rabid dog and later died, the owner was heavily fined.

Rabies was considered a scourge for its prevalence in the 19th century. In France and Belgium, where Saint Hubert was venerated, the "St Hubert's Key" was heated and applied to cauterize the wound; by an application of magical thinking, dogs were branded with the key in hopes of protecting them from rabies. Fear of rabies related to methods of transmissions was almost irrational; however, this gave Louis Pasteur ample opportunity to test post-exposure treatments from 1885.

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Related : Rabies | Understanding and definition of Rabies | Symptoms caused by Rabies | The risk is borne by Rabies