Rabies

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 animals, 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 from developing.

Transmission and symptoms
 
Micrograph with numerous rabies viruses (small dark-grey rod-like particles) and Negri bodies, larger cellular inclusions typical of Rabies infectionThe stereotypical image of an infected ("rabid") animal is a "mad dog" foaming at the mouth, but cats, ferrets, raccoons, skunks, fox, coyotes and bats also become rabid. Squirrels, chipmunks, other rodents and rabbits are very seldom infected, perhaps because they would not usually survive an attack by a rabid animal. Rabies may also be present in a so-called 'paralytic' form, rendering the infected animal unnaturally quiet and withdrawn.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, 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 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).

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 historically a death sentence, until Louis Pasteur developed the first rabies vaccination in 1886. Pasteur demonstrated its effectiveness by treating Joseph Meister, who had been bitten by a rabid dog.

Pasteur's 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 today in developing 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.

Treatment after exposure (known as post-exposure prophylaxis or "PEP") is highly successful in preventing the disease if administered promptly, within 14 days after infection. 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 contrast to previous treatments which were given through a large needle inserted into the abdomen. In case of animal bites it is also helpful to remove, by thorough washing, as much infectious material as soon as possible. Since the development of effective human vaccines and immunoglobulin treatments the US, death rate from rabies has dropped from 100 or more annually in the early 20th century, to 1-2 per year, mostly caused by bat bites, which may go unnoticed by the victim and hence untreated.

PEP 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 PEP may not be successful.