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Rabies: causes, transmission, symptoms, and prevention

Rabies is a viral zoonotic disease that causes acute encephalitis and is almost always fatal once symptoms start. This article covers its agent, spread, clinical signs, prevention, and public-health measures.

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Rabies is an infectious disease caused by lyssaviruses, most commonly the rabies virus, that attacks the nervous system and produces acute encephalitis. It is a zoonosis — an infection naturally transmitted between animals and people — and remains a major public-health concern in parts of the world where animal vaccination and access to medical care are limited. The illness is notable for its high case-fatality rate once neurological signs appear and for the proven effectiveness of prompt post-exposure vaccination.

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Rabid dog
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Agent and characteristics

The causative agents are members of the family Rhabdoviridae, genus Lyssavirus. The virus is neurotropic: it travels along peripheral nerves to the central nervous system, then spreads to salivary glands and other tissues. Incubation periods vary widely, commonly from a few weeks to several months, and depend on factors such as the location of inoculation, dose of virus, and host immunity.

Transmission and reservoirs

Transmission most often occurs when infectious saliva enters tissue via a bite or scratch from an infected mammal. Common reservoir species include dogs, bats, raccoons, foxes, and skunks, depending on the region. Bites are the classical route, but non-bite exposures (e.g., contamination of mucous membranes) are possible. Management of animal reservoirs through vaccination and control of stray populations is central to prevention.

Clinical features and diagnosis

Early symptoms are often nonspecific: fever, malaise, headache, and local paresthesia or pain at the exposure site. As disease progresses, patients may develop anxiety, agitation, hydrophobia (fear of water), aerophobia, paralysis, alterations in consciousness, and coma. Once clinical encephalitis is established, prognosis is poor. Diagnosis during life relies on specialized tests that detect virus or antibodies in saliva, serum, cerebrospinal fluid, or skin biopsies of hair follicles.

Treatment and prevention

There is no reliably effective cure after the onset of symptoms. However, prompt cleaning of wounds and timely post-exposure prophylaxis (PEP) — a combination of rabies immune globulin and a series of rabies vaccinations — is highly effective at preventing disease if given before symptom onset. Routine vaccination of domestic animals, wildlife management, public education, and rapid access to PEP are the pillars of rabies prevention.

Public-health importance and history

Historically feared because of its dramatic neurological manifestations and near-universal lethality, rabies has been largely controlled in many high-income countries through systematic dog vaccination and animal control. Worldwide, tens of thousands of human deaths still occur annually, most in Asia and Africa and primarily affecting people bitten by rabid dogs. Global elimination of dog-mediated human rabies is an achievable goal with coordinated vaccination and surveillance efforts.

Further reading and resources

Note: This article summarizes broadly known facts about rabies for educational purposes. In suspected exposures, immediate consultation with local health authorities or medical professionals is essential.

Pathogen

Rabies is caused by viruses of the genus Lyssaviruses from the family Rhabdoviridae. These are enveloped viruses of cylindrical shape whose genome is present as single-stranded RNA with negative polarity. This is in contrast to other viruses that infect humans, which normally have cubic symmetry. A total of seven genotypes are currently distinguished among all these pathogens:

  • Genotype 1: Rabies virus (RABV). This virus is the classic rabies virus.
  • Genotype 2: Lagos bat virus = Lagos bat virus (LBV)
  • Genotype 3: Mokola virus (MOKV)
  • Genotype 4: Duvenhage virus (DUVV)
  • Genotypes 5 and 6: European bat lyssavirus = European bat lyssavirus (EBLV 1, 2)
  • Genotype 7: Australian bat lyssavirus (ABLV)

Except for genotype 2, rabies cases in humans have been described for all genotypes listed above.

The transcription and replication of the viruses take place in the cytoplasm of the host cell within special "virus factories", the so-called Negri bodies or Negri inclusion bodies (named after their discoverer, the pathologist Adelchi Negri, who was involved in research into rabies from 1903 onwards and found the bodies named after him in the ganglion cells of the brain). They have a diameter of 2-10 µm and are typical of rabies infection, so they serve as a pathognomonic feature.

Rabies viruses in a cell, EM. Clearly visible are the Negri bodies.
Rabies viruses in a cell, EM. Clearly visible are the Negri bodies.

Transmission

99% of human cases worldwide are transmitted by dogs. In the USA, however, most cases in recent years have been due to bites from bats and these also pose some health risk in Australia, Latin America and Western Europe. Contact with wild rabies-infected predators such as fox, raccoon, skunk, jackal, coyote, wolf, or mongoose can also cause this disease in humans.

The virus is present in the saliva of a rabid animal and the route of infection is usually via a bite or scratch wound. Transmission is also possible through direct contact of infected saliva with mucous membranes.

In vitro transmission through mucous membranes has occurred. It is possible that transmission in this form occurred in humans exploring caves populated by bats. Except for organ transplantation (three cases in the USA at the beginning of 2004 and three cases in Germany at the beginning of 2005), human-to-human transmission has not been observed so far.

From the point of entry, the virus travels rapidly along neurons into the central nervous system (CNS). Retrograde axonal transport is the most important step in natural rabies infection. The exact molecular basis of this transport has not yet been elucidated, but rabies virus protein P has been shown to interact with the dynein light chain protein DYNLL1 (LC8). P also acts as an interferon antagonist, thereby attenuating the immune response.

From the CNS, the virus also spreads to other organs, so it appears in the saliva of infected animals and can thus spread further. Often there is increased aggressiveness with increased biting behaviour, which increases the likelihood of spreading the virus further.

Questions and answers

Q: What is rabies?

A: Rabies is a viral zoonotic disease that causes acute encephalitis and is almost always fatal when the symptoms appear.

Q: How does rabies spread to humans?

A: Rabies can spread to humans through the saliva and blood of a rabid mammal, usually through a bite.

Q: Is there a cure for rabies?

A: There is no cure for rabies once symptoms appear, but vaccines can increase the chance of survival if administered soon after infection.

Q: How can pets like dogs be protected from rabies?

A: In most countries, pets like dogs need to be vaccinated against rabies to protect them from the disease.

Q: What is acute encephalitis?

A: Acute encephalitis is a condition where the brain becomes inflamed and can cause a variety of symptoms including fever, headache, seizures, and confusion.

Q: Is rabies contagious?

A: No, rabies is not contagious from person to person, only through contact with the saliva and blood of an infected animal.

Q: Can people survive rabies without treatment?

A: It is almost always fatal when symptoms appear, so prompt treatment with vaccines is necessary for survival.

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