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Rabies Classification and external resources
Rabies virus
ICD-10	A82.
ICD-9	071
DiseasesDB	11148
MedlinePlus	001334
eMedicine	med/1374  emerg/493 ped/1974
MeSH	D011818

Rabies (pronounced /ˈreɪbiːz/. From Latin: rabies. Also known as “hydrophobia”) is a viral neuroinvasive disease that causes acute encephalitis (inflammation of the brain) in warm-blooded animals. It is zoonotic, that is transmitted by mammals, most commonly by a bite from an infected animal, but occasionally by other forms of contact. It is fatal if left untreated. In some countries it is a significant killer of livestock.

The rabies virus makes its way to the brain by following the peripheral nerves. The incubation period of the disease depends on how far the virus must travel to reach the central nervous system, usually taking a few months.^[1] Once the infection reaches the central nervous system and symptoms begin to show, the untreated infection is usually fatal within days.

In the beginning stages of rabies, the symptoms are malaise, headache, and fever, while in later stages it includes acute pain, violent movements, uncontrolled excitements, depressions, and the inability to swallow water (hence the name hydrophobia). In the final stages, the patient begins to have periods of mania and lethargy, and coma. Death generally occurs due to respiratory insufficiency.^[1]

Contents 1 Etymology 2 Virology 3 Epidemiology 3.1 Transmission 3.2 Prevalence 3.3 Rabies in animals 4 Medical aspects 4.1 Prevention 4.2 Symptoms 4.3 Diagnosis 4.4 Prognosis 4.5 Treatments 4.5.1 Post-exposure prophylaxis 4.5.2 Blood-brain barrier 4.5.3 Induced coma 5 History 5.1 Cultural impact 5.2 Cultural references 6 See also 7 References 7.1 Notes 7.2 Bibliography 8 External links

Etymology

The term is derived from the Latin rabies, "madness".^[2] This, in turn, may have come from the Sanskrit rabhas, "to do violence". The Greeks derived the word "lyssa", which is derived from "lud" or "violent", this terminology is used in the name of the genus of rabies lyssavirus.^[3]

Virology

The rabies virus is the type species of the Lyssavirus genus, which encompasses similar viruses such as Australian bat lyssavirus, Mokola virus, Lagos bat virus, and Duvenhage virus. Lyssaviruses have helical symmetry, with a length of about 180 nm and a cross-sectional diameter of about 75 nm. From the point of entry, the virus travels 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.

Epidemiology

Transmission

This article may require cleanup to meet Wikipedia's quality standards. Please improve this article if you can. (January 2009)

Any warm-blooded animal may become infected with the rabies virus and develop symptoms, including humans (though birds have only been known to be experimentally infected^[4]). Indeed the virus has even been adapted to grow in cells of poikilothermic vertebrates^[5][6]though natural transmission has only been documented among mammals. Most animals can be infected by the virus and can transmit the disease to humans. Infected bats, monkeys, raccoons, foxes, skunks, cattle, wolves, dogs, mongoose (normally yellow mongoose) or cats provide the greatest risk to humans. Rabies may also spread through exposure to infected domestic farm animals, groundhogs, weasels, bears and other wild carnivores. Rodents (mice, squirrels etc) are seldom infected.^[7]

The virus is usually present in the nerves and saliva of a symptomatic rabid animal.^[8][9] The route of infection is usually, but not necessarily, by a bite. In many cases the infected animal is exceptionally aggressive, may attack without provocation, and exhibits otherwise uncharacteristic behavior.^[10] Transmission may also occur via an aerosol through mucous membranes; transmission in this form may have happened in people exploring caves populated by rabid bats that will bite.

Transmission between humans is extremely rare. A few cases have been recorded through transplant surgery,^[11] or, even more rarely, through bites, kisses or sexual relations.^{[citation needed]}

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. Once the virus reaches the brain, it rapidly causes encephalitis. This is called the “prodromal” phase. At this time, treatment is useless. Then symptoms appear. Rabies may also inflame the spinal cord producing myelitis.^{[citation needed]}

Prevalence

The rabies virus survives in widespread, varied, rural fauna reservoirs. However, in Asia, parts of America and large parts of Africa, dogs remain the principal host. Mandatory vaccination of animals is less effective in rural areas. Especially in developing countries, pets may not be privately kept and their destruction may be unacceptable. Oral vaccines can be safely distributed in baits, and this has successfully reduced rabies in rural areas of France, Ontario, Texas, Florida and elsewhere, like in the City of Montréal (Québec) where baits are successfully used among raccoons in the Mont-Royal park area. Vaccination campaigns may be expensive, and a cost-benefit analysis can lead those responsible to opt for policies of containment rather than elimination of the disease.

There are an estimated 55,000 human deaths annually from rabies worldwide, with about 31,000 in Asia, and 24,000 in Africa.^[12] One of the sources of recent flourishing of rabies in East Asia is the pet boom. China introduced in the city of Beijing the “one-dog policy” in November 2006 to control the problem.^[13] India has been reported as having the highest rate of human rabies in the world, primarily because of stray dogs.^[14]

Rabies was once rare in the United States outside the Southern states^{[citation needed]} , but raccoons in the mid-Atlantic and northeast United States have been suffering from a rabies epidemic since the 1970s, which is now moving westwards into Ohio.^[15] In the midwestern United States, skunks are the primary carriers of rabies, composing 134 of the 237 documented non-human cases in 1996. The most widely distributed reservoir of rabies in the United States, however, and the source of most human cases in the U.S., are bats.^{[citation needed]}

Rabies in animals

This section requires expansion with: information from the main article.

Rabies is infectious to mammals. Three stages of rabies are recognized in dogs and other animals. The first stage is a one to three day period characterized by behavioral changes and is known as the prodromal stage. The second stage is the excitative stage, which lasts three to four days. It is this stage that is often known as furious rabies due to the tendency of the affected dog to be hyperreactive to external stimuli and bite at anything near. The third stage is the paralytic stage and is caused by damage to motor neurons. Incoordination is seen due to rear limb paralysis and drooling and difficulty swallowing is caused by paralysis of facial and throat muscles. Death is usually caused by respiratory arrest.^[16]

Recently^{[provide time reference]} new symptoms of rabies of wild animals have been observed, namely in foxes. Probably at the beginning of the prodromal stage foxes, who are extremely cautious by nature, absolutely lose wild instincts. Animals come into settlements, reach for people, and behave as if tame. How long such "euphoria" lasts is not known. But even in such status the animal is extremely dangerous, as its saliva and excretions still contain the virus. In an August 2008 blog article^{[unreliable source?]}, one author observed and photographed such a subject.

Medical aspects

Prevention

Almost every infected case with rabies resulted in death until a vaccine was developed by Louis Pasteur and Emile Roux in 1885. Their original vaccine was harvested from infected rabbits, from which the nerve-tissue was weakened by allowing to dry for five to ten days.^[17] Similar nerve tissue-derived vaccine are still used in some countries, as they are much cheaper than modern cell culture vaccines.^[18] The human diploid cell rabies vaccine (H.D.C.V.) was started in 1967, however a new and less expensive purified chicken embryo cell vaccine and purified vero cell rabies vaccine are now available.^{[citation needed]} A recombinant vaccine called V-RG has been successfully used in the field of Belgium, France, Germany and the United States to prevent outbreaks of rabies in wildlife.^[19] Currently pre-exposure immunization has been used in both human and non-human populations, where as in many jurisdictions domesticated animals are required to be vaccinated.^{[citation needed]}

Symptoms

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.^{[citation needed]} 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”, where patients have 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. The disease itself was also once commonly known as hydrophobia, from this characteristic symptom. The patient experiences the response of “foaming at the mouth” as a result of the body's inability to quench its thirst; essentially, the overproduction of saliva as a last-resort attempt at retaining fluids.

Death almost invariably results two to ten days after the first symptoms; the few humans who are known to have survived the disease^{[citation needed]} were all left with severe brain damage, with the exception of Jeanna Giese (see below). It is neurotropic in nature.

Diagnosis

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.^[20] 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 found only in 20% of cases.

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.^[21] 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.^[22] 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 according to research reported on the Science and Development Network website in 2008. Accurate rabies diagnosis can be done ten times more cheaply, according to researchers from the Farcha Veterinary and Livestock Research Laboratory and the Support International Health Centre in N'Djamena, Chad. The scientists evaluated a method using light microscopy, cheaper than the standard tests, and say this could provide better rabies control across Africa.^[23]

Prognosis

In non-vaccinated humans, rabies is usually 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.^[12] There are only six known cases of a person surviving symptomatic rabies, and only two known cases of survival in which the patient received no rabies-specific treatment either before or after illness onset.^[24]

Treatments

Post-exposure prophylaxis

Treatment after exposure, known as post-exposure prophylaxis or “P.E.P.”, is highly successful in preventing the disease if administered promptly, generally within ten days of infection. Thoroughly washing the wound as soon as possible with soap and water for approximately five minutes is very effective at reducing the number of viral particles. “If available, a virucidal antiseptic such as povidone-iodine, iodine tincture, aqueous iodine solution or alcohol (ethanol) should be applied after washing.”^[25] Exposed mucous membranes such as eyes, nose or mouth should be flushed well with water. In the United States, patients receive one dose of human rabies immunoglobulin (HRIG) and five doses of rabies vaccine over a twenty-eight day period. One-half the dose of the immunoglobulin is injected in the region of the bite, if possible, with the remainder injected intramuscularly away from the bite. This is much less painful compared with administering the immunoglobulin through the abdominal wall with a large needle, as was done in the past. The first dose of rabies vaccine is given as soon as possible after exposure, with additional doses on days three, seven, fourteen, and twenty-eight after the first. Patients that have previously received pre-exposure vaccination do not receive the immunoglobulin, only the post-exposure vaccinations on day 0 and 3. Since the widespread vaccination of domestic dogs and cats and the development of effective human vaccines and immunoglobulin treatments, the number of recorded deaths in the U.S. from rabies has dropped from one hundred or more annually in the early twentieth century, to 1–2 per year, mostly caused by bat bites, which may go unnoticed by the victim and hence untreated.^[26]

In instances when post-exposure prophylaxis is administered as a precaution (e.g. a person wakes up and finds a bat in the room they were sleeping in), it is now mainly given in the gluteal region and deltoid (upper arm). The number of shots delivered to the gluteal area on the first day is determined by weight, and it is not uncommon to require three of these shots. Subsequent shots of the immunoglobulin (to build longer term immunity to rabies) are given to the arm. Recipients of the vaccine have reported that these shots are no more painful than normal shots (such as tetanus boosters).^{[citation needed]}

Most official documentation on rabies on the internet and otherwise warn that treatment becomes futile with the onset of prodrome (when symptoms begin to appear). These texts are written to convince the layman not to delay seeking treatment (and rightly so).^{[citation needed]} However, this may also lead them to falsely conclude that their situation is not an urgency and that treatment is possible up until the very end of the incubation period, as it may last 1 to 3 months on average; or it may at least convince them that it is safe to delay treatment by a few days. While the virus is treatable only during the incubation period, it is important to note that it is not treatable during its entirety. Rabies is fully treatable while the virus is present in tissues composed of cells other than neurons, such as skin and muscle. However, once the infection spreads to a neuron, the virus is sequestered from the immune system and will eventually make its way to the spinal cord and then to the brain. Treatment at this point may not be effective, even though symptoms may begin to appear weeks or even months later. Therefore, it is highly recommended that P.E.P. be administered as soon as possible. Begun without delay, or very little delay, P.E.P. is highly effective against rabies.^{[citation needed]} In the case where there has been a significant delay in administering P.E.P., the treatment should be administered regardless of that delay, as it may still be effective if it is not too late.

Blood-brain barrier

Some recent works have shown that during lethal rabies infection, the blood-brain barrier (BBB) does not allow anti-viral immune cells to enter the brain, the primary site of rabies virus replication.^[27] This aspect contributes to the pathogenicity of the virus and artificially increasing BBB permeability promotes viral clearance.^[28] Opening the BBB during rabies infection has been suggested as a possible novel approach to treat the disease, even though no attempts have yet been made to determine whether or not this treatment could be successful.

Induced coma

In 2005, Wisconsin teenager Jeanna Giese survived an acute, unvaccinated infection of rabies. Based on the theory that the detrimental effects of rabies were caused by temporary dysfunctions in the brain, Giese was placed into an induced coma, which was intended to produce a temporary partial halt in brain function that would protect the brain from damage while giving the immune system time to defeat the virus. After thirty-one days of isolation and seventy-six days of hospitalization, she was released from the hospital.^[29]

Giese's treatment regimen became known as the Milwaukee protocol. However, to date (March 2009), no confirmed case of a second successful treatment using the protocol has been recorded, despite several attempts. Rodney Willoughby Jr., Giese's primary care physician, has asserted that subsequent failures occurred because patients were not given the same combinations of drugs used in the initial incident. In April, 2008, in Cali, Colombia, local newspapers reported that an 11-year-old had recovered after induction of coma.^[30] This patient was infected on February 15, when several children were bitten by a cat in Santander de Quilichao, a small town near Cali. The claim has not been verified.

History

Cultural impact

This section requires expansion with: currently the following web page [2].

Because of its potentially violent nature, rabies has been known since 3000 B.C.^{[citation needed]} The term is derived from the Latin rabies, "madness".^[2] This, in turn, may have come from the Sanskrit rabhas, "to do violence". The Greeks derived the word "lyssa", which is derived from "lud" or "violent", this terminology is used in the name of the genus of rabies lyssavirus.^[3] 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 preventative measure against bites. If a person was bitten by a rabid dog and later died, the owner was fined heavily.^[31]

Rabies was considered a scourge for its prevalence in the 19th century. Fear of rabies related to methods of transmissions was almost irrational. This, however, gave Louis Pasteur ample opportunity to test post-exposure treatments in 1895. It was not until 1960 when the virus itself was isolated.^[32]

Cultural references

• Cujo, a Stephen King novel and film about a mother and son being terrorized by a rabid dog.
• Fun Run, an episode from the television sitcom The Office in which Meredith discovers that she may have been exposed to rabies via several animal bites.
• Histories (House), an episode of the television medical drama House where a homeless woman suffers from rabies.
• I Drink Your Blood, a 1970s cult horror film about a gang of Satanic hippies who get infected with rabies.
• Left 4 Dead, A first person shooter focused around a zombie apocalypse in which the aforementioned zombies are in fact living humans suffering from a mutated rabies virus.
• My Lunch, an episode of the comedy-drama Scrubs which refers to a case involving rabies transmitted by organ transplants.
• Old Yeller, a novel and film that involves a frontier dog becoming infected by a rabid hog.
• Quarantine, a 2008 horror film involving a new strain of rabies which causes its subjects to succumb to uncontrollable violence, rage, and cannibalism.
• Rant (book), a Chuck Palahniuk novel about killing with the rabies virus.
• Their Eyes Were Watching God, Tea Cake, a character in the novel, is mentally affected by a bite from a rabid dog.
• The Mad Death, a 1983 BBC TV series in which Britain is gripped by an outbreak of rabies after an afflicted pet cat is illegally smuggled into the country.
• To Kill a Mockingbird, A novel and film in which a main character, Atticus Finch, is called upon to shoot a 'mad,' presumably rabid, dog.
• Vampire's Kiss, a 1989 film in which the main character (portrayed by Nicholas Cage) slowly goes insane after discovering a bat in his apartment, implying a rabies infection.
• "Rant", a novel by Chuck Palahniuk in which the main character inflicts those around him with rabies.

See also

• Alliance for Rabies Control
• Neurotropic virus
• World Rabies Day

References

Notes

Bibliography

External links

Wikimedia Commons has media related to: Rabies

Wikinews has related news: Rabies

Look up rabies in Wiktionary, the free dictionary.

• Rabies at the Open Directory Project

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