Rabies (Hydrophobia)

What is Rabies?

Rabies 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. Rabies is almost invariably fatal if post-exposure prophylaxis is not administered prior to the onset of severe symptoms. 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 infection is practically untreatable and 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. Finally, the patient may experience periods of mania and lethargy, followed by coma. The primary cause of death is usually respiratory insufficiency.

The term is derived from the Latin ''rabies'', "madness". This, in turn, may be related to the Sanskrit ''rabhas'', "to do violence". The Greeks derived the word "lyssa", from "lud" or "violent"; this root is used in the name of the genus of rabies ''lyssavirus''.

In unvaccinated humans, rabies is almost always fatal after neurological symptoms have developed, but prompt post-exposure vaccination may prevent the virus from progressing. Rabies kills around 55,000 people a year, mostly in Asia and Africa. There are only six known cases of a person surviving symptomatic rabies, and only three known cases of survival in which the patient received no rabies-specific treatment either before or after illness onset.

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Rabies Virology

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.

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Rabies Prevention

Every infected case with rabies resulted in death until a vaccine was developed by Louis Pasteur and Émile Roux in 1885. Their original vaccine was harvested from infected rabbits, from which the nerve tissue was weakened by allowing it 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 in 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.

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Rabies Epidemiology

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 present 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. When the virus reaches the brain, it rapidly causes encephalitis. This is called the ''prodromal'' phase, and is the beginning of the symptoms. Once the patient becomes symptomatic, treatment is almost never effective and mortality is near 100%. Rabies may also inflame the spinal cord producing transverse myelitis.

Prevalence

The rabies virus survives in widespread, varied, rural fauna reservoirs. However, in Asia, parts of the Americas 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 the City of Montréal, Québec, where baits are successfully used on 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. India has been reported as having the highest rate of human rabies in the world, primarily because of stray dogs. As of 2007, Vietnam had the second-highest rate, followed by Thailand; in these countries too the virus is primarily transmitted through canines (feral dogs and other wild canine species). Recent reports suggest that wild rabid dogs are roaming the streets. Because much cheaper pre-vaccination is not commonly administered in places like Thailand, the expense for lack of preparation with far more costly post-exposure prophylaxis can hit families hard. In the midwestern United States, skunks are the primary carriers of rabies, comprising 134 of the 237 documented non-human cases .

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Rabies History

Cultural impact

Because of its potentially violent nature, rabies has been known since 3500 B.C. The first written record of rabies is in the Codex of Eshnunna (ca. 1930 BC), which dictates that the owner of a dog showing symptoms of rabies should take preventive measure against bites. If a person was bitten by a rabid dog and later died, the owner was fined heavily.

Rabies was considered a scourge for its prevalence in the 19th century. Fear of rabies related to methods of transmissions was almost irrational;

Cultural references

  • ''Cujo'', a Stephen King novel and film about a mother and son being terrorized by a rabid dog.
  • ''I Drink Your Blood'', a 1970s cult horror film about a gang of Satanic hippies who get infected with rabies.
  • ''Old Yeller'', a novel and film that involves a frontier dog becoming infected by a rabid wild wolf.
  • ''The Mad Death'', a 1983 BBC TV series in which Britain is gripped by an outbreak of rabies after an afflicted pet cat is illegally smuggled into the country.
  • ''Rant'', a novel by Chuck Palahniuk in which the main character infects those around him with rabies.
  • ''Rabies'', a novel by Borislav Pekic about a genetically engineered Rabies virus with a double protein envelope, thus becoming extremely easy to transmit (biting is not neccessary any more), which spreads from one victim to another extremely fast. The virus gets turned loose at the London's Heathrow Airport.
  • ''Quarantine_'', a Hollywood horror movie about mutated variation of rabies.

In the Season 1 episode of House M.D. entitled "Histories", Dr. House works to diagnose a homeless woman's illness, and it turns out that the woman is infected with rabies, from an untreated bat bite.

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Rabies Diagnosis

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. 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. 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.

Cheaper rabies diagnosis will be possible for low-income settings according to research reported on the Science Development Network website in 2008. Accurate rabies diagnosis can be done at a tenth of the cost, 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.

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Rabies 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'' for 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 owing 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.

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Rabies 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 inability to speak or swallow are typical during the later stages of the disease; this can result in “hydrophobia”, in which the patient 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'' (or aquaphobia), from this characteristic symptom.

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 one recorded exception purportedly resulting from implementation of the Milwaukee protocol. It is neurotropic in nature.

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