Rabies

Rabies (from "rage"), also Rabies (from Latin rabere, 'to be mad', 'to rage', 'to rage'), Lyssa (Greek), dog rage or rage disease, formerly also called hydrophobia ("water shyness"), is an acute infectious disease caused by the Rabies virus, known since ancient times, which causes infausal encephalitis in animals of the same temperature and is usually transmitted by the bite of a rabid animal.

Most mammals and many bird species can become infected with the rabies virus, but the infection is less frequently transmitted to herbivores than to carnivores. Red foxes, dogs, cats, bats, ferrets, badgers, raccoons and wolves are classic rabies vectors. Until the disease was largely eradicated by oral wildlife vaccination in European countries, the main vector was the red fox, while in India, for example, stray dogs are a major source of infection. The stereotypical image of a rabid animal in Europe is the aggressive red fox foaming at the mouth. However, rabies can also manifest itself in a "paralytic" form, in which the diseased animal behaves calmly, withdrawnly or unnaturally tame, without the usual shyness towards humans.

Squirrels, other rodents and rabbits, on the other hand, are very rarely infected. Birds also rarely get rabies, as their body temperature is usually higher than necessary for optimal reproduction of the virus. It is possible that these smaller species rarely survive predatory attacks and thus do not reach the first stage of the disease.

According to a WHO estimate, 59,000 people die from rabies every year, 60% of them in Asia and 36% in Africa. India is the country with the most rabies-related deaths, accounting for 35 % of all cases worldwide. In Germany, five cases of rabies were registered between 1977 and 2000, three of which originated abroad. In Europe as a whole, there were 281 cases during this period. Worldwide, more than 15 million people are vaccinated annually on suspicion of rabies infection, preventing an estimated 327,000 rabies-related deaths. Without vaccination or post-exposure prophylaxis (PEP), rabies infection is fatal within 15 to 90 days, except in very rare isolated cases. Post-exposure prophylaxis is only effective within 24 hours of infection, the sooner the better.

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.

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.