RABIES

'Rabies' (, "madness, rage, fury") is a viral zoonotic disease that causes acute encephalitis (inflammation of the brain) in mammals. 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. There are only six known cases of a person surviving rabies after the onset of symptoms. ^[1]

Structure

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. ''Negri bodies'' in the infected neurons are pathognomonic.
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 (virus particle). 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 RNA. Also present in the nucleocapsid are RNA dependent RNA 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''

Differential diagnosis

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. A specific diagnosis may be made by a variety of diagnostic techniques, including polymerase chain reaction (PCR) testing of cerebrospinal fluid, viral culture, and serology. 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.

Transmission and symptoms

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

Any mammal may become infected with the rabies virus and develop symptoms, including humans. Most animals can be infected by the virus and can transmit the disease to humans. Infected bats, monkeys, raccoons, foxes, skunks, cattle, wolves, dogs or cats provide the greatest risk to humans. Rabies may also spread through exposure to infected domestic farm animals, groundhogs, weasels and other wild carnivores. Squirrels, rodents and rabbits are seldom infected.
The virus is usually present in the nerves and saliva of a symptomatic rabid animal.^[2]^[3] The route of infection is usually, but not necessarily, by a bite. In many cases the affected animal is exceptionally aggressive, may attack without provocation, and exhibits otherwise uncharacteristic behaviour[1]. 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. Transmission between humans is extremely rare, although 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 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, 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", where the victim has difficulty swallowing, shows panic when presented with liquids to drink, and cannot quench his or her thirst. The disease itself was also once commonly known as '', from these characteristic symptoms. 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).

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 a human on July 6, 1885 – nine-year old boy Joseph Meister (1876–1940) had been mauled by a rabid dog.[2] [3]
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 chicken 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 with administering immunoglobulin through the abdominal wall with a large needle, which is how it 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. 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.
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.

Pre-exposure prophylaxis

Currently pre-exposure 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 pre-exposure 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 do not need such a vaccination, just those doing substantial non-urban activities. However, should a vaccinated human be bitten by a carrier, failure to receive subsequent post-exposure treatment could be fatal, although post-exposure treatment for a vaccinated human is far less extensive than which would normally be required by one with no pre-exposure vaccination.
In 1984 researchers at the Wistar Institute developed a recombinant vaccine called V-RG by inserting the glycoprotein gene from rabies into a vaccinia virus. Protection from rabies by a vaccinia virus recombinant containing the rabies virus glycoprotein gene, Wiktor TJ, Macfarlan RI, Reagan KJ, Dietzschold B, Curtis PJ, Wunner WH, Kieny MP, Lathe R, Lecocq JP, Mackett M, , , Proc. Natl. Acad. Sci. U.S.A., 1984 The V-RG vaccine has since been commercialised by Merial under the trademark Raboral. It is harmless to humans and has been shown to be safe for various species of animals that might accidentally encounter it in the wild, including birds (gulls, hawks, and owls). Vaccinia recombinant virus expressing the rabies virus glycoprotein: safety and efficacy trials in Canadian wildlife, Artois M, Charlton KM, Tolson ND, Casey GA, Knowles MK, Campbell JB, , , Can. J. Vet. Res., 1990
V-RG has been successfully used in the field in Belgium, France, and the United States to prevent outbreaks of rabies in wildlife. The virus is stable under relatively high temperatures and can be delivered orally, making mass vaccination of wildlife possible by putting it in tasty baits. 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. Just such a strategy of oral immunization of foxes in Europe has already achieved substantial reductions in the incidence of human rabies. A strategy of vaccinating "neighborhood dogs" in Jaipur, India, (combined with a sterilization program) has also resulted in a large reduction in the number of human cases. Control of rabies in Jaipur, India, by the sterilisation and vaccination of neighbourhood dogs., Reece JF, Chawla SK., , , Vet Rec, 2006

Induced coma treatment

Main articles: Jeanna Giese

In 2005, the case of Jeanna Giese, a girl of 15 who survived acute, unvaccinated rabies was reported, indicating the successful treatment of rabies through induction of a coma. Survival after treatment of rabies with induction of coma, Willoughby RE, Tieves KS, Hoffman GM, Ghanayem NS, Amlie-Lefond CM, Schwabe MJ, Chusid MJ, Rupprecht CE, , , N. Engl. J. Med., 2005 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 hospitalisation, she was released from the hospital, having survived rabies. Later attempts to use the same treatment have failed.
The primary care physician in this case published in the April 2007 issue of ''Scientific American''.^[4] He notes that subsequent failures of what he calls the ''Milwaukee protocol'' did not use the cocktail of drugs used during the treatment. A point he makes for future research is the relationship of the virus to depletion of biopterin in the brain.

Prevalence

Rabies-free jurisdictions, as of January 2006:
Australia, New Zealand, Fiji, Guam, Hawaii, the United Kingdom, Ireland, Norway, Sweden, Iceland, Japan and Taiwan/ROC.

More than 99% of all human deaths from rabies occur in Africa, Asia, South America and India; which reports thirty thousand deaths annually. Rabies vaccine One of the sources of recent flourishing of rabies in the East Asia is the pet boom. China introduced the "One-dog policy" in November 2006 to control the problem.^[5]
The English Channel, 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 combatting rabies in some developed countries.
The 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 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. 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.
Many territories, such as the United Kingdom, Ireland, Taiwan, Japan, 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.
New Zealand and Australia have never had rabies.[4] However, in Australia, 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.

Rabies in the United States

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. Compendium of animal rabies prevention and control, 2006, , , , MMWR Recomm Rep, 2006

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. Rabies in translocated raccoons, Nettles VF, Shaddock JH, Sikes RK, Reyes CR, , , Am J Public Health, 1979 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 behavior of most such animals appears to show some sort of illness, and necropsies can 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. First Human Death Associated with Raccoon Rabies --- Virginia, 2003, Dietzschold, B, Proniak, M, , , Morbidity and Mortality Weekly Report, Rabies and Wildlife 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 the state of New York before 1990, for instance, but rose to approximately ten thousand annually between 1990 and 1995. At approximately $1,500 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. Rabies surveillance in the United States during 1995, Krebs JW, Strine TW, Smith JS, Noah DL, Rupprecht CE, Childs JE, , , J Am Vet Med Assoc, 1996 Domestic animals constitute only 8% of rabies cases, but are increasing at a rapid rate.

A rabid dog, with saliva dripping out of the mouth

In the midwestern United States, skunks are the primary carriers of rabies, composing 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 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.
On September 7, 2007, rabies expert Dr. Charles Rupprecht of Atlanta-based U.S. Centers for Disease Control and Prevention said that canine rabies disappeared from the United States.^[6]

Recently publicized cases

Transmission by bite

Several recently publicized cases have stemmed from bats, which are known to be a vector for rabies. See the Rabies and bats section below.
In October 2004 a female brown bear killed one human and injured several others near the city of Braşov in Central Romania. The bear was killed by human hunters and diagnosed with rabies. More than one hundred humans were vaccinated afterwards.

Transmission through organ transplants

Rabies is known to have been transmitted between humans by transplant surgery.

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).^[7] 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 were bats near the donor's home, and the donor had told others that he had 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''. Transmission of rabies virus from an organ donor to four transplant recipients, Srinivasan A, Burton EC, Kuehnert MJ, Rupprecht C, Sutker WL, Ksiazek TG, Paddock CD, Guarner J, Shieh WJ, Goldsmith C, Hanlon CA, Zoretic J, Fischbach B, Niezgoda M, El-Feky WH, Orciari L, Sanchez EQ, Likos A, Klintmalm GB, Cardo D, LeDuc J, Chamberland ME, Jernigan DB, Zaki SR, , , N Engl J Med, 2005

"[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 Center, 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 if 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.)"^[8]

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 caused by the Texarkana donor inspired the episode "My Lunch" in the American TV show ''Scrubs''.

Transport of pet animals between countries

Main articles: Pet passport

Sign at a UK port showing rabies prevention measures aimed at merchant seamen

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 dogs

Main articles: Dog health#Rabies

Rabies has a long history of association with dogs. The first written record of rabies is in the the Codex of Eshnunna (ca. 1930 BC) (written prior to the Code of Hammurabi), which dictates that the owner of a dog showing symptoms of rabies should take preventative measure against bites. If a person is bitten by a rabid dog and later died, the owner was fined heavily.^[9]
Three stages of rabies are recognized in dogs. 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. Textbook of Veterinary Internal Medicine, Ettinger, Stephen J.;Feldman, Edward C., , , W.B. Saunders Company, 1995, ISBN 0-7216-6795-3

Rabies and opossums

Cases have been reported across the United States from California to New York ^[10]^[11]. Rabies cases in the Virginia opossum are spillover cases from other wildlife species such as bats,skunks and the raccoon epizootic in the eastern United States^[12]. In New York state, the Wadsworth Center lists laboratory confirmed cases in opossums 5 years out of 10 from 1989 to 1998.

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.
or
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. Destruction 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.

Rabies and bats

The problem of bat-transmitted rabies is found over most of North and South America but was first closely studied in Trinidad in the West Indies which had a dreadful reputation for bat rabies, which took a significant toll of livestock and humans alike. In the 10 years from 1925 and 1935, 89 people and thousands of livestock had died from it - "the highest human mortality from rabies-infected bats thus far recorded anywhere.".^[13]
In early 1931, Dr. H. Metivier, a Veterinary surgeon, established the connection between the bites of bats and paralytic rabies. In September 1931, Dr. J. L. Pawan, a Government Bacteriologist found Negri bodies in the brain of a bat with unusual habits. In 1934 the Trinidad and Tobago Government began a program of vampire bat control, shooting, netting, trapping and poisoning, while encouraging the screening off of livestock buildings and free vaccination programs for exposed livestock.
After the opening of the Trinidad Regional Virus Laboratory in 1953, basic research on bats and rabies progressed rapidly under the able direction of Arthur Greenhall, who demonstrated that at least 8 species of bats in Trinidad had been infected with rabies - particularly the Common Vampire Bat, ''Desmodus rotundus'' (which "will attack any warm blooded creature"), the rare White-winged Vampire Bat, ''Diaemus youngi'', (which "appears to have a special preference for birds and goats"), as well as two abundant species of Fruit Bats: the Seba's Short-tailed Bat or Short-tailed Fruit Bat, ''Carollia perspicillata'', which commonly roosts with Vampires, and the Jamaican Fruit Bat, ''Artibeus jamaicensis''.^[14]
Non-bite transmission of rabies to susceptible animals placed in bat-proof cages in a cave with bat colonies was demonstrated by Constantine in Frio Cave, Texas, as early as 1960.^[15] In 1967, rabies virus was isolated from the air in the same cave,^[16] presumably passed by the bats urinating, potentially forming a source for infection of other susceptible animals, and presenting a hazard to researchers and spelunkers. While the risks may be low, they are deserving of further study and monitoring.^[17]
The United Kingdom, which has stringent regulations on the importation of 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 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. 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 Texas. U.S.A. Health Department officials reported that a teenage boy, Zachary Jones of Humble, Texas, had died of rabies at Texas Children's Hospital in Houston, Texas. Zachary had contracted the disease after a bat flew in his bedroom and bit him in his sleep. He was unware he had been bitten and was not hospitalized until he developed symptoms several weeks later. 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 November 2, 2006 a 10 year old girl in Bourbon, Indiana, U.S.A. died of rabies. The ''Indianapolis Star'' reports that she was bitten by a bat in June 2006.
In August of 2006, a 73 year old rural resident located east of Edmonton, Alberta, Canada was bitten by a bat while he slept. He ignored the bite and became symptomatic in January 2007. Diagnosed with rabies in March of 2007, he was treated with the Milwaukee protocol, but died April 26, 2007.
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, U.S.A. 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. Rabies Surveillance

References

1. VIROLOGY - CHAPTER TWENTY RABIES pathmicro.med.sc.edu
2. The ''Merck Manual'', Eleventh Edition (1983), p. 183
3. ''The Merck manual of Medical Information. Second Home Edition'', (2003), p. 484.
4. Rodney E. Willoughby, Jr., "A Cure for Rabies?" ''Scientific American'', V. 256, No. 4, April 2007, p. 95 (online link)
5. The Toronto Star "China cracks down on rabid dog menace"
6. Reuters, U.S. free of canine rabies virus
7. Human-to-human transmission of rabies via a corneal transplant -- France, CDC, , , MMWR, 1980
8. Will Any Organ Do?, Reynolds G, , , The New York Times Magazine, 2005
9. Veterinary Medicine:An Illustrated History, , Robert H., Dunlop, Mosby, , ISBN 0-8016-3209-9
10. Krebs JW, Smith JS, Rupprecht CE, Childs JE.Rabies surveillance in the United States during 1996.
J Am Vet Med Assoc. (1997) 211(12):1525-39. Review. Erratum in: J Am Vet Med Assoc. (1998) 212(8):1280.
PMID: 9412679
11. Krebs JW, Smith JS, Rupprecht CE, Childs JE.(1999) Rabies surveillance in the United States during 1998. J Am Vet Med Assoc. (1999) 215(12):1786-98. Erratum in: J Am Vet Med Assoc 2000 216(8):1223
12. Krebs JW, Smith JS, Rupprecht CE, Childs JE.Rabies surveillance in the United States during 1996.
J Am Vet Med Assoc. (1997) 211(12):1525-39. Review. Erratum in: J Am Vet Med Assoc. (1998) 212(8):1280.
PMID: 9412679
13. Goodwin G. G., and A. M. Greenhall. 1961. "A review of the bats of Trinidad and Tobago." ''Bulletin of the American Museum of Natural History'', 122, p. 196
14. Greenhall, Arthur M. 1961. ''Bats in Agriculture''. Ministry of Agriculture, Trinidad and Tobago.
15. Constantine, D. G. 1962. "Rabies transmission by nonbite route." ''Public Health Reports'' 77, pp. 287–289.
16. Winkler, W. G. 1968. "Airborne Rabies Virus Isolation." ''Bull. Wildlife Disease Assoc''. Vol. 4, April, 1968, pp. 37-40. Available online at: http://www.jwildlifedis.org/cgi/reprint/4/2/37
17. Messenger, Sharon L., Jean S. Smith, and Charles E. Rupprecht. 2002. "Emerging Epidemiology of Bat-Associated Cryptic Cases of Rabies in Humans in the United States." ''Clinical Infectious Diseases''. 2002; 35, pp. 738–747. Available on line at: journals.uchicago.edu

External links

★ History of Rabies in Los Angeles

Sources

★ Manbir Online

★ CNN News report of CDC news release - July 1, 2004.

★ Associated Press report: ''Families of rabies transplant victims react to deaths'' - July 3, 2004

★ BBC News Europe Report: Romanian killer bear had rabies - 19 October, 2004.

★ First Unvaccinated Rabies Survivor Goes Home - January 3, 2005

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