Rabies (hydrophobia): causes and pathogenesis

The causes of rabies (hydrophobia)

Rabies causes the RNA-containing virus of the family Rhabdoviridae, the genus Lyssavirus. There are seven genotypes of the virus. Classical strains of the rabies virus (genotype 1) are highly pathogenic for all warm-blooded animals. The virion has the shape of a bullet, its diameter is 60-80 nm, consists of a core (associated with the RNA protein), surrounded by a lipoprotein membrane with glycoprotein spines. Glycoprotein G is responsible for the adsorption and introduction of the virus into the cell, has antigenic (type-specific antigen) and immunogenic properties. Antibodies to it neutralize the virus, they are determined in PH. There are wild (street) and fixed strains of the rabies virus. The wild strain of the virus circulates among animals and is pathogenic to humans. The fixed strain was obtained by Pasteur through repeated passaging of the wild virus through the brain of rabbits, as a result of which the virus acquired new properties: it lost pathogenicity for man, ceased to stand out with saliva, the incubation period decreased from 15-20 to 7 days and thereafter did not change. The resulting virus with a constant incubation period Pasteur was named fixed and used it as an antiplaque vaccine. Both viruses are identical in antigens. The rabies virus is unstable, quickly dies under the action of solar and ultraviolet rays, when heated to 60 ° C. It is sensitive to disinfectants, fat solvents, alkalis. It is stored at low temperatures (down to -70 ° C). The virus is cultured by intracerebral infection of laboratory animals (rabbits, white mice, rats, hamsters, guinea pigs, sheep, etc.) and in the culture of hamster kidney cells, mouse neuroblastoma, human fibroblasts and chicken embryo.

The pathogenesis of rabies (hydrophobia)

After a bite, the rabies virus penetrates the human body through the damaged epithelium, is introduced into the striated muscles; in the nervous system the virus enters through the neuromuscular synapses and tendon receptors of the Golgi (in these structures there are vulnerable to the virus the mothless neuronal endings). Further, the virus slowly, with a speed of about 3 mm / h, moves along the nerve fibers in the central nervous system, apparently with an axoplasmatic current. With natural infection with rabies, there is no viralemia, but in some animal experiments, the circulation of the virus in the blood is recorded. Having reached the central nervous system, the virus infects neurons, replication occurs almost exclusively in gray matter. After replication in brain neurons, the virus spreads in the opposite direction along the autonomic nerve fibers - into the salivary glands (this explains the presence of the virus in the saliva at the end of the incubation period), into the lacrimal glands, the cornea, the kidneys, the lungs, the liver, the intestine, the pancreas , skeletal muscles, skin, heart, papillae of the tongue, adrenals, hair follicles, etc. The presence of the virus in the hair follicles and the cornea is used for intravital diagnosis of the disease (the presence of a viral antigen is examined in a biopsy of the skin taken in austral area, and in the smear-print from the cornea). Death occurs due to the defeat of vital centers - the respiratory and vasomotor. A pathomorphological study of the brain of the deceased can reveal moderate inflammatory changes with a relatively unstable destruction of nerve cells, accompanied by edema-swelling of the brain substance. The histological pattern resembles that of other viral infections of the central nervous system: fullness, more or less pronounced chromatolysis, pycnosis of nuclei and neuronophagia, infiltration of perivascular spaces with lymphocytes and plasma cells, proliferation of microglia, hydrophilic dystrophy. Attention is drawn to the discrepancy between severe neurological manifestations of the disease and poor pathomorphological changes in the brain substance. In the brain cells, the rabies virus forms oxyphilic cytoplasmic inclusions (babesh-Negri bodies), most often found in the hippocampus, Purkinje cortex, cerebral cortex, hypothalamus and spinal ganglions. Inclusions have a size of about 10 nm, these are areas of the cytoplasm of nerve cells and the accumulation of viral particles. In 20% of the patients, the Babesh-Negri body can not be detected, but their absence does not exclude the diagnosis of rabies.

Epidemiology of rabies (hydrophobia)

The main reservoir of rabies in nature - wild mammals, different in different regions of the world. There are two epidemic forms of the disease:

• urban rabies (anthropurgic foci), the main reservoir - domestic dogs and cats;
• Forest rabies, a reservoir - various wild animals.

In natural foci of Russia, the main spreaders of the disease are fox (90%), wolf, raccoon dog, corsac, Arctic fox (in the tundra zone). In connection with the intensive circulation of the virus into epizootic foci, wild animals of other families are increasingly involved. In recent years, cases of rabies have been reported in badgers, ferrets, martens, beavers, elk, lynx, wild cats, gray rats, brown mice. The cases of protein, hamster, muskrat, nutria, and bear have been revealed. A pet is usually infected with rabies from wild animals. A person can meet with a source of infection both in the city and in nature, infection occurs when the animal is bitten, as well as when the skin is muzzled (if there are micro-traumas) and mucous membranes. Undamaged mucous membranes are permeable to rabies virus, and intact skin is not. Transmission of the virus is also possible with a bite of bats-vampires (more often in Mexico, Argentina and Central America), recently there have been cases of rabies after bites of insectivorous bats in the USA, Europe, Australia, Africa, India, Russia (Belgorod region ), in Ukraine. The possibility of an aerogenic infection (infection of speleologists, a case of laboratory infection as a result of an accident, etc.) is proved. There are cases of transmission of rabies from a donor to a recipient through an infected cornea transplant. In 2004, for the first time, the possibility of transmission of this disease was reported for the transplantation of solid organs: recipients of the kidneys, liver and segment of the artery from the same donor died from encephalitis of unknown etiology. From person to person, rabies is not transmitted, however, when working with sick people or animals, it is necessary to observe precautions, use protective clothing (robe, cap, gloves, glasses, etc.) and disinfect instruments, equipment, premises.

Susceptibility to rabies is not universal. The development of rabies in an infected person depends on whether a rabies virus is contained during a bite in the saliva of an animal and whether it has been caught by a bite or moulting towards a person. There are data that only 12-30% of people who are bitten by animals with proven rabies and not vaccinated with rabies vaccine become ill. According to modern data, almost 50% of dogs with proven rabies do not secrete the virus with saliva. Despite this. The special severity of the outcome of this infection (100% lethality) dictates the necessity of compulsory conducting (according to the current instruction) the whole complex of therapeutic and preventive measures in those cases when the fact of biting or moulting the sick animals is recorded.

Rabies is spread almost all over the world, except for Australia, Oceania and Antarctica. Annually in the world from rabies die from 40 to 70 thousand people. The most unfavorable regions are Asia, Africa and Latin America. According to WHO. Rabies for economic damage is the fifth most infectious disease. In recent years, the world has seen the activation of natural foci of this infection, which inevitably leads to an increase in the number of people who become ill.

[1], [2], [3], [4], [5], [6], [7], [8],