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Rabies (pronounced /ˈreɪbiːz/. From Latin: rabies) or hydrophobia 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. 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 (hence the name hydrophobia). Finally, the patient may experience periods of mania and lethargy, followed by coma. The primary cause of death is usually respiratory insufficiency.

Etymology

The term is derived from the Latin rabies, "madness". 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.

Virology

Main article: Rabies virus

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).

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.

Epidemiology

Transmission

Main article: Rabies transmission

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 though natural transmission has only been documented among mammals. 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) 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.

The virus is usually present in the nerves and saliva of a symptomatic rabid animal. 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.

Transmission between humans is extremely rare. A few cases have been recorded through transplant surgery.

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. 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.

Prevalence

Main article: Prevalence of rabies

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. 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. India has been reported as having the highest rate of human rabies in the world, primarily because of stray dogs.

Rabies was once rare in the United States outside the Southern states, 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. In the midwestern United States, skunks are the primary carriers of rabies, comprising 134 of the 237 documented non-human cases in 1996.

Rabies in animals

Main article: Rabies in animals

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.

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. .

Medical aspects

Prevention

Main article: Rabies vaccine

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. Similar nerve tissue-derived vaccines are still used in some countries, as they are much cheaper than modern cell culture vaccines. 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. 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. 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.

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.

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. The production of large quantities of saliva and tears coupled with an inabil

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