Rabies

Rabies (pronounced /ˈreɪbiz/. From Latin: rabies. Also known as “hydrophobia”) is a viral zoonotic neuroinvasive disease that causes acute encephalitis (inflammation of the brain) in mammals. It is most commonly caused by a bite from an infected animal, but occasionally by other forms of contact. If left untreated in humans it is usually fatal. In some countries it is a significant killer of livestock.

The rabies virus makes its way 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.[1] Once the infection reaches the central nervous system and symptoms begin to show, the untreated infection is usually fatal within days.

In the beginning stages of rabies, the symptoms are malaise, headache, and fever, while in later stages it includes acute pain, violent movements, uncontrolled excitements, depressions, and the inability to swallow water (hence the name hydrophobia). In the final stages, the patient begins to have periods of mania and lethargy, and coma. Death generally occurs due to respiratory insufficiency.[1]
The rabies virus is the type species of the Lyssavirus genus, which encompasses similar viruses such as Australian bat lyssavirus, Mokola virus, Lagos bat virus, and Duvenhage virus. Lyssaviruses have helical symmetry, with a length of about 180 nm and a cross-sectional diameter of about 75 nm. 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 to be further transmitted.he rabies vi

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, 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.[verification needed]

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 infected animal is exceptionally aggressive, may attack without provocation, and exhibits otherwise uncharacteristic behavior.[4] 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 that will bite.

Transmission between humans is extremely rare. A few cases have been recorded through transplant surgery,[5] or, even more rarely, through bites, kisses or sexual relations.[citation needed]

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. At this time, treatment is useless. Then symptoms appear. Rabies may also inflame the spinal cord producing myelitis.

The rabies virus survives in wide-spread, 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.[6] 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.[7] India has been reported as having the highest rate of human rabies in the world, primarily because of stray dogs.[8]

Rabies was once rare in the United States outside the Southern states[citation needed] , 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.[9] In the midwestern United States, skunks are the primary carriers of rabies, composing 134 of the 237 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.[citation needed]

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.[10]

Recently[provide time reference] new symptoms of rabies of wild animals have been observed, namely in foxes. Probably at the beginning of the prodromal stage foxes, who are extremely cautious by nature, absolutely lose wild instincts. Animals come into settlements, reach for people, and behave as if tame. How long such "euphoria" lasts is not known. But even in such status the animal is extremely dangerous, as its saliva and excretions still contain the virus. In an August 2008 blog article[unreliable source?], one author observed and photographed such a subject.
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.[11] Similar nerve tissue-derived vaccine are still used in some countries, as they are much cheaper than modern cell culture vaccines.[12] 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.[citation needed] 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.[13] Currently pre-exposure immunization has been used in both human and non-human populations, where as in many jurisdictions domesticated animals are required to be vaccinated.[citation needed]

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.[citation needed] 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 because the throat and jaw become slowly paralyzed, shows panic when presented with liquids to drink, and cannot quench his or her thirst. The disease itself was also once commonly known as hydrophobia, from this characteristic symptom. The patient experiences the response of “foaming at the mouth” as a result of the body's inability to quench its thirst; essentially, the overproduction of saliva as a last-resort attempt at retaining fluids.

Death almost invariably results two to ten days after the first symptoms; the few humans who are known to have survived the disease[citation needed] were all left with severe brain damage, with the exception of Jeanna Giese (see below). It is neurotropic in nature.

The reference method for diagnosing rabies is by performing PCR or viral culture on brain samples taken after death. The diagnosis can also be reliably made from skin samples taken before death.[14] It is also possible to make the diagnosis from saliva, urine and cerebrospinal fluid samples, but this is not as sensitive. Inclusion bodies called Negri bodies are 100% diagnostic for rabies infection, but found only in 20% of cases.

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. 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.[15] 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.[16] 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.

Cheaper rabies diagnosis will be possible for low-income settings according to research reported on the Science and Development Network website in 2008. Accurate rabies diagnosis can be done ten times more cheaply, according to researchers from the Farcha Veterinary and Livestock Research Laboratory and the Support International Health Centre in N'Djamena, Chad. The scientists evaluated a method using light microscopy, cheaper than the standard tests, and say this could provide better rabies control across Africa.[17]