Rabies

From Wikipedia, the free encyclopedia

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) is a viral neuroinvasive 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 but occasionally by other forms of contact. Generally fatal if left untreated, it is a significant killer of livestock in some countries.

The rabies virus travels 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.

Early-stage symptoms of rabies are malaise, headache and fever, later progressing to more serious ones, including acute pain, violent movements, uncontrolled excitement, depression and inability to swallow water. Finally, the patient may experience periods of mania and lethargy, followed by coma. The primary cause of death is usually 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 8 External links

[edit] 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]

[edit] Virology

The rabies virus is the type species of the Lyssavirus genus, which encompasses other similar viruses. 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. These genes are nucleoprotein (N), phosphoprotein (P), matrix protein (M), glycoprotein (G) and the viral RNA polymerase (L).^[4]

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.

[edit] Epidemiology

[edit] Transmission

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Any warm-blooded animal, including humans, may become infected with the rabies virus and develop symptoms. 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.^{[citation needed]} 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)^{[citation needed]} 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 between humans is extremely rare. A few cases have been recorded through transplant surgery.^[11]

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.^[12] 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, and is the beginning of the symptoms. Once it reaches this point and symptoms show, there is no treatment, and death is certain. Rabies may also inflame the spinal cord producing transverse myelitis.^[13][14]

[edit] 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.^[15] 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.^[16] India has been reported as having the highest rate of human rabies in the world, primarily because of stray dogs.^[17]

Rabies was once rare in the United States outside the Southern states^{[citation needed]}, but as of 2006, raccoons in the mid-Atlantic and northeast United States were suffering from a rabies epidemic since the 1970s, which was moving westwards into Ohio.^[18] In the midwestern United States, skunks are the primary carriers of rabies, comprising 134 of the 237 documented non-human cases in 1996^[update].

[edit] 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.^[19]

As recently as 2004, a new symptom of rabies has been observed in foxes. Probably at the beginning of the prodromal stage, foxes, who are extremely cautious by nature, seem to lose this instinct. Foxes will come into settlements, approach people, and generally behave as if tame. How long such "euphoria" lasts is not known. But even in this state such animals are extremely dangerous, as their saliva and excretions still contain the virus and they remain very unpredictable. ^[20].

[edit] Medical aspects

[edit] 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.^[21] Similar nerve tissue-derived vaccines are still used in some countries, as they are much cheaper than modern cell culture vaccines.^[22] 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.^[23] 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.^{[citation needed]}

In the U.S., 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 twentieth century, to 1–2 per year, mostly caused by bat bites, which may go unnoticed by the victim and hence untreated.^[24]

[edit] 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.^[25] 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 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. The disease itself was also once commonly known as hydrophobia, from this characteristic symptom.

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.

[edit] 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.^[26] 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.^[27] 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.^[28] 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.^[29]

[edit] Prognosis

In non-vaccinated 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.^[15] 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.^[30][31]

[edit] Treatments

[edit] 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...Exposed mucous membranes such as eyes, nose or mouth should be flushed well with water.”^[32] 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.

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]} The recommendation for the precautionary use of post-exposure prophylaxis in occult bat encounters where there is no recognized contact has been questioned in the medical literature based on a cost-benefit analysis.^[33]

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 100% effective against rabies.^[34] 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.^{[citation needed]} If there has been a delay between exposure and attempts at treatment, such that the possibility exists that the virus has already penetrated the nervous system, the possibility exists that amputation of the affected limb might thwart rabies, if the bite or exposure was on an arm or leg. This treatment should be combined with an intensive PEP regimen.^{[citation needed]}

[edit] 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.^[35] This aspect contributes to the pathogenicity of the virus and artificially increasing BBB permeability promotes viral clearance.^[36] 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.^{[citation needed]}

[edit] Induced coma

In 2005, American teenager Jeanna Giese survived an infection of rabies unvaccinated. She was placed into an induced coma upon onset of symptoms. Her doctors administered treatment based on the hypothesis that detrimental effects of rabies were caused by temporary dysfunctions in the brain and could be avoided by inducing 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, Giese was released from the hospital.^[37]

Giese's treatment regimen became known as the "Milwaukee protocol". To date only one other patient has survived under the protocol, despite numerous attempts at the treatment. Rodney Willoughby Jr., Giese's primary care physician, has asserted that subsequent failures occurred because patients were not given the same combination of drugs used in the initial incident.^{[citation needed]}

[edit] History

[edit] Cultural impact

This section requires expansion with: currently the following web page [1].

Because of its potentially violent nature, rabies has been known since 3500 B.C.^{[citation needed]} 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 a person was bitten by a rabid dog and later died, the owner was fined heavily.^[38]

Rabies was considered a scourge for its prevalence in the 19th century. Fear of rabies related to methods of transmissions was almost irrational;^[3] however, this gave Louis Pasteur ample opportunity to test post-exposure treatments in 1895.^{[citation needed]}

[edit] 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.
• 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 wild wolf.
• REC a 2007 Spanish horror film, along with the American remake Quarantine, both involve a new strain of rabies which causes its subjects to succumb to uncontrollable violence, rage, and cannibalism.
• 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 Nicolas 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.
• Mad Dogs and Servicemen, an episode of M*A*S*H in which Radar must receive a painful vaccine injection after being bitten by a stray dog.
• To Kill a Ladybird, an episode of King of the Hill in which Ladybird is bitten by a raccoon, then bites Dale Gribble, who becomes convinced he has rabies.
• 28 Days Later, A horror film where humans infect one another with a virus called rage, which happens to be the French word for rabies. In the movie, almost all the infected come down with the manic/violent form of the disease and transmit it to one another through biting or aerosolized saliva.
• Sunset Babies (All Got Rabies), a song by Alice Cooper, in which Cooper's twisted lyrical humor can be seen into a parallel being made between having rabies and some women's wicked sexual behavior.
• Quarantine, A horror film where a T.V. journalist reports on the events of disease outbreak from inside a quarantined building. A veteraniarian trapped inside the quarantine claims that the spreading disease is a mutated form of rabies.
• Rabid, A Canadian made horror film in which a character played by Marilyn Chambers undergoes experimental surgery that appears successful, but actually gave her a needlelike appendage in her armpit that feeds on human blood. Anyone that she feeds off of becomes infected with a particularly virulent and vaccine resistant strain of rabies, causing them to crave blood, and this passes the infection to their victim.
• Little House on the Prairie, In the Season 1 episode, The Raccoon, Laura adopts a stray raccoon whom she names Jasper. The raccoon bites her and the Ingalls family fear that she may have contracted rabies.

[edit] See also

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

[edit] References

[edit] External links

Wikimedia Commons has media related to: Rabies

Look up rabies in Wiktionary, the free dictionary.

• Aerophobia and Hydrophobia in Rabies Videos
• Rabies at the Open Directory Project

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