Rabies (from a Latin word meaning rage), is a viral disease that causes acute encephalitis in animals and people. It can affect most species of warm-blooded animal, but is rare among non-carnivores. In unvaccinated humans, rabies is almost invariably fatal once full-blown symptoms have developed, but post-exposure vaccination can prevent symptoms developing.
Transmission and symptoms
The stereotypical image of an infected ("rabid") animal is a "mad dog" foaming at the mouth, but cats, ferrets, raccoons, chipmunks, skunks, foxes and bats also become rabid. Squirrels, other rodents and rabbits are very seldom infected, perhaps because they would not usually survive an attack by a rabid animal. Rabies may also present in a so-called 'paralytic' form, rendering the infected animal unnaturally quiet and withdrawn.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. By causing the infected animal to be exceptionally aggressive, the virus ensures its transmission to the next host. 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 from person to person is extremely rare, and can happen through transplant surgery (see below for recent cases), or even more rarely through bites or kisses.
After a typical human infection by animal 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 pre-empt symptomatic rabies. Once the virus reaches the brain, it rapidly causes an 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 3-12 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 is known as "hydrophobia". Death almost invariably results 2-10 days after the first symptoms; the handful of people 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 Rabies virus is a Lyssavirus. This group of RNA viruses also includes the Australian bat lyssavirus, Duvenhage virus, two European bat lyssaviruses, Lagos bat virus and Mokola 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.
The Lyssaviruses are the only viruses known to travel along the nerves after infection. Biopsy shows typical "Negri bodies" in the infected neurons.
The Rabies virus has a bullet-like shape with a length of about 180 nm and a cross-sectional diameter of about 75 nm.
Longitudinal and cross-sectional schematic view of Rabies virus
There is no known cure for symptomatic rabies, but it can be prevented by vaccination, either of humans or of animals. Rabies originally doomed almost everyone who got it to die, until Louis Pasteur developed the first rabies vaccination in 1886 and used it to save the life of Joseph Meister, who had been bitten by a rabid dog.
Pasteur's vaccine was a virus grown in rabbits and then weakened by letting it dry. Similar nervous-tissue derived vaccines are still used today in poor countries; while they are much cheaper than modern cell-culture vaccines, they are not as effective and carry a certain risk of neurological complications.
Treatment after exposure (known as post-exposure prophylaxis or "PEP") is highly successful in preventing the disease if administered promptly. In the United States, the treatment consists of a regimen of one dose of immunoglobulin and five doses of rabies vaccine over a 28-day period. Rabies immunoglobulin and the first dose of rabies vaccine should be given as soon as possible after exposure, with additional doses on days 3, 7, 14, and 28 after the first. The vaccinations are relatively painless and are given in one's arm. In case of animal bites it is also helpful to remove, by thorough washing, as much infectious material as soon as possible.
PEP is possible in 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 and causing 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 time of travel is dependent on how far the infected area is from the brain by nerve: if bitten in the face, for example, the time until the brain is infected is very short and PEP may not be successful.
Between 40,000 and 70,000 die annually from rabies, most in Africa and Asia where rabies is endemic. About 10 million people receive treatment annually after suspected exposure to rabies.
Dog licensing, destruction of stray dogs, muzzling and other measures contributed to the eradication of rabies from Great Britain 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.
Rabies virus survives in widespread, varied, rural wildlife reservoirs. Mandatory vaccination of animals is less effective in rural areas. Especially in developing countries, animals may not be privately owned 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.
Since the development of effective human vaccines and immunoglobulin treatments the US death rate from rabies has dropped from 100 or more per year early in the 20th century, to 1-2 per year, mostly caused by bat bites, which may go unnoticed by the patient.
Australia is one of the few parts of the world where rabies has never been introduced. However, the Australian Bat Lyssavirus occurs naturally 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 and Guam, are free of rabies (although there may be a very low prevalence of rabies among bats in the UK; see below).
Recently publicised cases
Transmission by animal bites
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 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 person to contract rabies in the United Kingdom since 1902. He died from the disease on November 24 2002.
In October 2004 a wild female brown bear killed one person and injured several others near the city of Brasov, Central Romania. The bear was killed by hunters and diagnosed with rabies. More than one hundred people were vaccinated afterwards.
In November 2004, Jeanna Giese, a 15-year old girl from Fond du Lac, Wisconsin, became one of only six people known to have survived rabies after the onset of symptoms. 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, 37 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, becoming the first known instance of a person surviving rabies without vaccine treatment.
Transmission through organ transplants
Rabies is known to have been transmitted between humans by transplant surgery. The medical advisory web site Manbir Online notes "Under no circumstances should a cornea be transplanted from a donor, who died of an undiagnosed neurological disorder.".
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). The CDC documents the case in France in 1980. 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.
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 world-wide. Dozens of medical staff have been 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."
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.
Rabies and domestic skunks in the United States
Since there is no USDA-approved vaccine or quarantine period for skunks, pet skunks are frequently put down after biting a human.
The post-exposure rabies series must be administered to the bite victim before the disease progresses too far. For that reason, there has to be a means of determining whether the animal has rabies within a reasonable amount of time. Without a recognized quarantine period for skunks, there is no way of knowing how long to watch the animal for signs of the disease. That leaves no option but to kill the skunk and test its brain cells for rabies.
Skunk owners have recently organized to campaign for USDA approval of a vaccine and quarantine period for skunks in the United States.
Last updated: 06-01-2005 22:40:53
Last updated: 08-16-2005 12:36:29