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Rabies

2007 Schools Wikipedia Selection. Related subjects: Health and medicine

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   Rabies virus
       Virus classification

   Group:   Group V ( (-)ssRNA)
   Order:   Mononegavirales
   Family:  Rhabdoviridae
   Genus:   Lyssavirus
   Species: Rabies virus

   CAPTION: Rabies
   Classifications and external resources

     ICD- 10   A 82.-
     ICD- 9    071
   DiseasesDB  11148
   MedlinePlus 001334
    eMedicine  med/1374  emerg/493 ped/1974

   Rabies (Latin, rabies, "madness, rage, fury") is a viral zoonotic
   disease that causes acute encephalitis in animals. In non-vaccinated
   humans, rabies is almost invariably fatal after neurological symptoms
   have developed, but prompt post-exposure vaccination may prevent the
   virus from progressing.

Transmission and symptoms

   Micrograph with numerous rabies virions (small dark-grey rod-like
   particles) and Negri bodies, larger pathognomonic cellular inclusions
   of rabies infection.
   Enlarge
   Micrograph with numerous rabies virions (small dark-grey rod-like
   particles) and Negri bodies, larger pathognomonic cellular inclusions
   of rabies infection.

   Cats, dogs, ferrets, raccoons, skunks, foxes, wolves, coyotes, bears,
   bats, and horses can become rabid. Squirrels, chipmunks, other rodents
   (except beavers), and rabbits are very seldom infected. Rabies may also
   be present in a so-called "paralytic" form, rendering the victim
   abnormally quiet and withdrawn.

   The virus is usually present in the saliva of a symptomatic rabid
   animal; the route of infection is nearly always by a bite, and in many
   cases in animals, causes the victim to be exceptionally aggressive,
   attack without provocation, and exhibit otherwise uncharacteristic
   behaviour . Transmission has occurred via an aerosol through mucous
   membranes; transmission in this form may have happened in people
   exploring caves populated by rabid bats. Transmission between humans is
   extremely rare, though it can happen through transplant surgery (see
   below for recent cases), or even more rarely through bites or kisses.

   After a typical human infection by bite, the virus directly or
   indirectly 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 preempt symptomatic rabies. Once
   the virus reaches the brain, it rapidly causes encephalitis and
   symptoms appear. It may also inflame the spinal cord producing
   myelitis.

   The period between infection and the first flu-like symptoms is
   normally three to twelve weeks, but can be as long as two years. Soon
   after, the symptoms expand to cerebral dysfunction, anxiety, insomnia,
   confusion, agitation, abnormal behaviour, 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". Death
   almost invariably results two to ten days after the first symptoms; the
   few humans who are known to have survived the disease were all left
   with severe brain damage, with the recent exception of Jeanna Giese
   (see below).

The virus

   The rabies virus is a Lyssavirus. This genus of RNA viruses also
   includes the Aravan virus, Australian bat lyssavirus, Duvenhage virus,
   European bat lyssavirus 1, European bat lyssavirus 2, Irkut virus,
   Khujand virus, Lagos bat virus, Mokola virus and West Caucasian bat
   virus. Lyssaviruses have helical symmetry, so their infectious
   particles are approximately cylindrical in shape. This is typical of
   plant-infecting viruses; human-infecting viruses more commonly have
   cubic symmetry and take shapes approximating regular polyhedra.

   Biopsy shows typical Negri bodies in the infected neurons.

   The virus has a bullet-like shape with a length of about 180 nm and a
   cross-sectional diameter of about 75 nm. One end is rounded or conical
   and the other end is planar or concave. The lipoprotein envelope
   carries knob like spikes, composed of Glycoprotein G. Spikes do not
   cover the planar end of the virion. Beneath the envelope is the
   membrane or matrix (M) protein layer which may be invaginated at the
   planar end. The core of the Virion consists of helically arranged
   ribonucleoprotein. The genome is unsegmented linear antisense R.N.A.
   Also present in the nucleocapsid are RNA dependent R.N.A. transcriptase
   and some structural proteins.

    Longitudinal schematic view of Rabies virus   Cross section of Rabies
                                    virus
       Longitudinal and cross-sectional schematic view of Rabies virus

Prevention

   There is no known cure for symptomatic rabies, but it can be prevented
   by vaccination, both in humans and other animals. Virtually every
   infection with rabies was a death sentence, until Louis Pasteur and
   Emile Roux developed the first rabies vaccination in 1885. This vaccine
   was first used on nine-year old boy Joseph Meister (1876-1940), on July
   6, 1885, after the boy was mauled by a rabid dog.

   Their vaccine consisted of a sample of the virus harvested from
   infected (and necessarily dead) rabbits, which was weakened by allowing
   it to dry. Similar nerve tissue-derived vaccines are still used now in
   some countries, and while they are much cheaper than modern cell
   culture vaccines, they are not as effective and carry a certain risk of
   neurological complications.

   The human diploid cell rabies vaccine (H.D.C.V.) was started in 1967.
   Human diploid cell rabies vaccines are made using the attenuated
   Pitman-Moore L503 strain of the virus. Human diploid cell rabies
   vaccines have been given to more than 1.5 million humans as of 2006.
   Newer and less expensive purified chick embryo cell vaccine, and
   purified Vero cell rabies vaccine are now available. The purified Vero
   cell rabies vaccine uses the attenuated Wistar strain of the rabies
   virus, and uses the Vero cell line as its host.

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, within fourteen days after infection. The first
   step is immediately washing the wound with soap and water, which is
   very effective at reducing the number of viral particles. In the United
   States, patients receive one dose of immunoglobulin and five doses of
   rabies vaccine over a twenty-eight day period. One-half the dose of
   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 to when immunoglobulin was administered through
   the abdominal wall with a large needle. 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 preexposure vaccination do not
   receive the immunogolbulin, only the post-exposure vaccinations. Since
   the wide-spread 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.

   P.E.P. is effective in treating rabies because the virus must travel
   from the site of infection through the peripheral nervous system
   (nerves in the body) before infecting the central nervous system (brain
   and spinal cord) and glands to cause lethal damage. This travel along
   the nerves is usually slow enough that vaccine and immunoglobulin can
   be administered to protect the brain and glands from infection. The
   amount of time this travel requires is dependent on how far the
   infected area is from the brain: if the victim is bitten in the face,
   for example, the time between initial infection and infection of the
   brain is very short and P.E.P. may not be successful.

Preexposure prophylaxis

   Currently preexposure immunization has been used on domesticated and
   normal non-human populations. In many jurisdictions, domestic dogs,
   cats, and ferrets are required to be vaccinated. A new, orally active,
   genetically recombined virus vaccine for raccoon rabies awaits
   licensing by the U.S. Department of Agriculture as of 2006. A gene that
   produces a protein in the rabies virus outer coat was inserted into a
   live vaccinia virus using recombinant D.N.A. technology. When the
   modified vaccinia virus infects a normal animal, it produces the
   antigenic protein normally made by the rabies virus. The victim's
   systems recognize the protein as foreign, and the animal develops
   active immunity. The plan for immunization of normal populations
   involves dropping bait containing food wrapped around a small dose of
   the live virus. The bait would be dropped by helicopter concentrating
   on areas that have not been infected yet.

   A preexposure vaccination is also available for humans, most commonly
   given to veterinarians and those traveling to regions where the disease
   is common, such as India. (Most tourists would not need such a
   vaccination, just those doing substantial non-urban activities.)
   However, should a vaccinated human be bitten by a possible victim, they
   must have subsequent post-exposure treatment. Failure to do so could be
   fatal. Such post-exposure treatment is far less extensive than what
   would normally be required by one with no preexposure vaccination.

Induced coma treatment

   In 2005, the case of a girl of 15 who survived acute, unvaccinated
   rabies was reported, indicating the successful treatment of rabies
   through induction of a coma. This treatment approach was based on the
   theory that rabies' detrimental effects were caused by temporary
   dysfunctions of the brain, and that the induction of a coma, by
   producing a temporary partial stop in brain function, would protect the
   brain from damage while the body built up an immune response to the
   virus. After thirty-one days of isolation and seventy-six days of
   hospitalization, she was released from the hospital, having survived
   rabies. Later attempts to use the same treatment have failed.

Prevalence

   Countries with Rabies-Free status (in red), as of January 2006
   Enlarge
   Countries with Rabies-Free status (in red), as of January 2006

   More than 99% of all human deaths from rabies occur in Africa, Asia and
   South America; India alone reports thirty thousand deaths annually.
   China recorded 2,254 rabies cases in the first nine months of 2006, up
   30% on the same period in 2005 and had overtaken tuberculosis and AIDS
   as the country's most deadly disease. One of the sources of resent
   flourishing of rabies in the East Asia is the pet boom. China
   introduced the "One-dog policy" in November 2006 to control the issue.

   Dog licensing, killing of stray dogs, muzzling and other measures
   contributed to the eradication of rabies from the United Kingdom in the
   early 20th century. More recently, large-scale vaccination of cats,
   dogs and ferrets has been successful in combating rabies in some
   developed countries.

   Rabies virus survives in wide-spread, varied, rural fauna reservoirs.
   However, in Asia, parts of Latin America and large parts of Africa,
   dogs remain the principal host. Mandatory vaccination of non-human
   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 impacted rabies in rural areas of France,
   Ontario, Texas, Florida and elsewhere. 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.

   Rabies was once rare in the United States outside the Southern states,
   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.
   Cases of animal rabies in the United States in 2001
   Enlarge
   Cases of animal rabies in the United States in 2001

   The particular variant of the virus has been identified in the
   southeastern United States raccoon population since the 1950s, and is
   believed to have traveled to the northeast as the result of infected
   raccoons being among those caught and transported from the southeast to
   the northeast by human hunters attempting to replenish the declining
   northeast raccoon population. As a result, urban residents of these
   areas have become more wary of the large but normally unseen urban
   raccoon population. It has become the common assumption that any
   raccoon seen diurnally is infected; certainly the reported behaviour of
   most such animals appears to show some sort of illness, and autopsies
   usually confirm rabies. Whether as a result of increased vigilance or
   only the common human avoidance reaction to any other animal not
   normally seen, such as a raccoon, there has only been one documented
   human rabies case as a result of this variant. This does not include,
   however, the greatly increasing rate of prophylactic rabies treatments
   in cases of possible exposure, which numbered fewer than one hundred
   humans annually in New York State before 1990, for instance, but rose
   to approximately ten thousand annually between 1990 and 1995. At
   approximately $1500 per course of treatment, this represents a
   considerable public health expenditure. Raccoons do constitute
   approximately 50% of the approximately eight thousand documented
   non-human rabies cases in the United States. Domestic animals
   constitute only 8% of rabies cases, but are increasing at a rapid rate.
   A rabid dog, with saliva dropping out of the mouth
   Enlarge
   A rabid dog, with saliva dropping out of the mouth

   In the midwestern United States, skunks are the primary carriers of
   rabies, comprising one hundred and thirty-four of the two hundred and
   thirty-seven 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. Nineteen of the
   twenty-two human rabies cases documented in the United States between
   1980 and 1997 have been identified genetically as bat rabies. In many
   cases, victims are not even aware of having been bitten by a bat,
   assuming that a small puncture wound found after the fact was the bite
   of an insect or spider; in some cases, no wound at all can be found,
   leading to the hypothesis that in some cases the virus can be
   contracted via inhaling airborne aerosols from the vicinity of a bat or
   bats. For instance, the Centers for Disease Control and Prevention
   warned on May 9, 1997, that a woman who died in October, 1996 in
   Cumberland County, Kentucky and a man who died in December, 1996 in
   Missoula County, Montana were both infected with a rabies strain found
   in silver-haired bats; although bats were found living in the chimney
   of the woman's home and near the man's place of employment, neither
   victim could remember having had any contact with them. This inability
   to recognize a potential infection, in contrast to a bite from a dog or
   raccoon, leads to a lack of proper prophylactic treatment, and is the
   cause of the high mortality rate for bat bites.

   In case of an attack by a possibly rabid non-human, most states in the
   United States allow the killing of the attacker. Because a rabies
   diagnosis requires that the brain tissue be preserved, it is
   recommended that rabid non-humans are not to be shot in the head.

   Australia is one of the few regions where rabies has never been
   introduced. However, the Australian Bat Lyssavirus occurs normally in
   both insectivorous and fruit eating bats (flying foxes) from most
   mainland states. Scientists believe it is present in bat populations
   throughout the range of flying foxes in Australia.

   Many territories, such as the United Kingdom, Ireland, Hawaii,
   Mauritius and Guam, are free of rabies (although there may be a very
   low prevalence of rabies among bats in the UK; see below).

Recently publicized cases

Transmission by bite

   Several recently publicised cases have stemmed from bats, which are
   known to be a vector for rabies.

   The United Kingdom, which has stringent regulations on the importation
   of non-human animals, had also been believed to be entirely free from
   rabies until 1996 when a single Daubenton's bat was found to be
   infected with a rabies-like virus usually found only in bats – European
   Bat Lyssavirus 2 (EBL2). There were no more known cases in the British
   Isles until September 2002 when another Daubenton's bat tested positive
   for EBL2 in Lancashire. A bat conservationist who was bitten by the
   infected bat received post-exposure treatment and did not develop
   rabies.

   Then in November 2002 David McRae, a Scottish bat conservationist from
   Guthrie, Angus who was believed to have been bitten by a bat, became
   the first human to contract rabies in the United Kingdom since 1902. He
   died from the disease on November 24, 2002.

   In October 2004 a female brown bear killed one human and injured
   several others near the city of Braşov, Central Romania. The bear was
   killed by human hunters and diagnosed with rabies. More than one
   hundred humans were vaccinated afterwards.

   In November 2004, Jeanna Giese, a fifteen-year old girl from Fond du
   Lac, Wisconsin, became one of only six humans known to have survived
   rabies after the onset of symptoms, and the first known instance of a
   human surviving rabies without vaccine treatment. All of the other five
   received vaccination before symptoms developed. Giese's disease was
   already too far progressed for the vaccine to help, and she was
   considered too weak to tolerate it. Doctors at the Children's Hospital
   of Wisconsin in Wauwatosa, a suburb of Milwaukee, achieved her survival
   with an experimental treatment that involved putting the girl into a
   drug-induced coma, and administering a cocktail of antiviral drugs.
   Giese had symptoms of full-blown rabies when she sought medical help,
   thirty-seven days after being bitten by a bat. Her family did not seek
   treatment at the time because the bat seemed healthy. Jeanna regained
   her weight, strength, and coordination while in the hospital. She was
   released from the Children's Hospital of Wisconsin on January 1, 2005.

   On May 12, 2006 Harris County Health Department officials reported that
   a teenage boy, Zach Jones, in Houston, Texas had died of rabies after a
   bat flew in his bedroom while he took a nap and somehow brushed itself
   upon the boy's skin, allowing Jones to feel it as he woke up. He died
   at Texas Children's Hospital after an attempt to cure the disease
   through a drug-induced coma, similar to that of Jeanna Giese.

   On August 6, 2006, 950 Girl Scouts were urged to receive rabies shots
   by the Girl Scouts of America. The nine hundred and fifty girls had
   attended a camp in Virginia in July, and had reported seeing bats in
   their cabins. Even though infections were relatively unlikely, the
   G.S.A. offered to pay for the shots, at a cost of nearly two million
   dollars. The Centers for Disease Control reports 27 cases of human
   rabies caused by the bat variant rabies virus in the United States from
   1990 to 2002.

Transmission through organ transplants

   Rabies is known to have been transmitted between humans by transplant
   surgery.
   A patient with rabies, 1959
   Enlarge
   A patient with rabies, 1959

   Infections by corneal transplant have been reported in Thailand (2
   cases), India (2 cases), Iran (2 cases), the United States (1 case),
   and France (1 case). Details of two further cases of infection
   resulting from corneal transplants were described in 1996.

   In June 2004, three organ recipients died in the United States from
   rabies transmitted in the transplanted kidneys and liver of an infected
   donor from Texarkana. There are bats near the donor's home, but he did
   not mention having been bitten. The donor is now reported to have died
   of a cerebral hemorrhage, the culmination of an unidentified
   neurological disorder, although recipients are said to have been told
   the cause of death had been a car crash. Marijuana and cocaine were
   found in the donor's urine at the time of his death, according to a
   report in The New England Journal of Medicine. The surgeons

     "thought he had suffered a fatal crack-cocaine overdose, which can
     produce symptoms similar to those of rabies. 'We had an explanation
     for his condition,' says Dr. Goran Klintmalm, a surgeon who oversees
     transplantation at Baylor University Medical Centre, where the
     transplants occurred. 'He'd recently smoked crack cocaine. He'd
     hemorrhaged around the brain. He'd died. That was all we needed to
     know.' … Because of doctor-patient confidentiality rules, doctors
     involved with this case would not talk about it on the record, but a
     few did say that no cocaine was found in the donor's blood, the E.R.
     doctors might have investigated his symptoms more aggressively
     instead of assuming he had overdosed. (Because no autopsy was done,
     doctors have not been able to establish whether the rabies or the
     drugs actually killed him.)"

   In February 2005, three German patients in Mainz and Heidelberg were
   diagnosed with rabies after receiving various organs and cornea
   transplants from a female donor. Two of the infected people died. Three
   other patients who received organs from the woman have not yet shown
   rabies symptoms. The 26 year old donor had died of heart failure in
   December 2004 after consuming cocaine and ecstasy. In October 2004, she
   had visited India, one of the countries worst affected by rabies
   worldwide. Dozens of medical staff were vaccinated against rabies in
   the two hospitals as a precautionary measure.

   Associated Press reports that "Donated organs are never tested for
   rabies. The strain detected in the victims' bodies is one commonly
   found in bats, health officials said." According to CNN "Rabies tests
   are not routine donor screening tests, Virginia McBride, public health
   organ donation specialist with the Health Resources and Services
   Administration, said. The number of tests is limited because doctors
   have only about six hours from the time a patient is declared
   brain-dead until the transplantation must begin for the organs to
   maintain viability." The tragedy inspired an episode in the American TV
   show 'Scrubs'.

Transport of pet animals between countries

   Rabies is endemic to many parts of the world, and one of the reasons
   given for quarantine periods in international animal transport has been
   to try to keep the disease out of uninfected regions. However, most
   developed countries, pioneered by Sweden, now allow unencumbered travel
   between their territories for pet animals that have demonstrated an
   adequate immune response to rabies vaccination.

   Such countries may limit movement to animals from countries where
   rabies is considered to be under control in pet animals. There are
   various lists of such countries. The United Kingdom has developed a
   list, and France has a rather different list, said to be based on a
   list of the Office International des Epizooties (OIE). The European
   Union has a harmonised list. No list of rabies-free countries is
   readily available from OIE.

   However, the recent spread of rabies in the northeastern United States
   and further may cause a restrengthening of precautions against movement
   of possibly rabid animals between countries.

Rabies and domestic skunks in the United States

   There is currently no USDA-approved vaccine for the strain of rabies
   that afflicts skunks. When cases are reported of pet skunks biting a
   human, the animals are frequently killed in order to be tested for
   rabies.

   Humans exposed to the rabies virus must begin post-exposure prophylaxis
   before the disease can progress to the central nervous system. For this
   reason, it is necessary to determine whether the animal, in fact, has
   rabies as quickly as possible. Without a definitive quarantine period
   in place for skunks, quarantining the animals is not advised as there
   is no way of knowing how long it may take the animal to show symptoms.
   Euthanasia of the skunk is recommended and the brain is then tested for
   presence of rabies virus.

   Skunk owners have recently organized to campaign for USDA approval of
   both a vaccine and an officially recommended quarantine period for
   skunks in the United States.

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