Rabies (hydrophobia) - Causes and pathogenesis

Causes of rabies (hydrophobia)

Rabies is caused by an RNA-containing virus of the Rhabdoviridae family, genus Lyssavirus. There are seven genotypes of the virus. Classic strains of the rabies virus (genotype 1) are highly pathogenic for all warm-blooded animals. The virion is bullet-shaped, its diameter is 60-80 nm, consists of a core (RNA associated with protein), surrounded by a lipoprotein membrane with glycoprotein spikes. Glycoprotein G is responsible for the adsorption and penetration of the virus into the cell, has antigenic (type-specific antigen) and immunogenic properties. Antibodies to it neutralize the virus, they are determined in RN. A distinction is made between wild (street) and fixed strains of the rabies virus. The wild strain of the virus circulates among animals and is pathogenic for humans. The fixed strain was obtained by Pasteur by repeated passage of the wild virus through the brain of rabbits, as a result of which the virus acquired new properties: it lost pathogenicity for humans, stopped being excreted with saliva, the incubation period was reduced from 15-20 to 7 days and subsequently did not change. Pasteur called the resulting virus with a constant incubation period fixed and used it as an antirabies vaccine. Both viruses are identical in antigens. The rabies virus is unstable, quickly dies under the influence of sunlight and ultraviolet rays, when heated to 60 ° C. Sensitive to disinfectants, fat solvents, alkalis. Preserved at low temperatures (up to -70 ° C). The virus is cultivated 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 ferroblasts, and chicken embryos.

Pathogenesis of rabies (hydrophobia)

After a bite, the rabies virus enters the human body through damaged epithelium, penetrates into striated muscles; the virus enters the nervous system through neuromuscular synapses and Golgi tendon receptors (these structures contain unmyelinated nerve endings that are vulnerable to the virus). Then the virus slowly, at a speed of about 3 mm/h, moves along the nerve fibers into the CNS, apparently with axoplasmic flow. There is no viremia in natural rabies infection, but in some animal experiments, circulation of the virus in the blood was recorded. Having reached the CNS, the virus infects neurons, replication occurs almost exclusively in the gray matter. After replication in the neurons of the brain, the virus spreads in the opposite direction along the autonomic nerve fibers - to the salivary glands (this explains the presence of the virus in saliva already at the end of the incubation period), to the lacrimal glands, to the cornea, kidneys, lungs, liver, intestines, pancreas, skeletal muscles, skin, heart, papillae of the tongue, adrenal glands, hair follicles, etc. The presence of the virus in the hair follicles and cornea is used for lifetime diagnosis of the disease (the presence of the viral antigen is examined in a skin biopsy taken in the area behind the ear and in a smear-imprint from the cornea). Death occurs due to damage to vital centers - respiratory and vasomotor. Pathomorphological examination of the brain of the deceased allows us to identify moderate inflammatory changes with relatively mild destruction of nerve cells, accompanied by edema-swelling of the brain matter. The histological picture resembles that of other viral infections of the central nervous system: plethora, more or less pronounced chromatolysis, pyknosis of nuclei and neuronophagia, infiltration of perivascular spaces by lymphocytes and plasma cells, proliferation of microglia, hydropic dystrophy. The discrepancy between the severe neurological manifestations of the disease and the scanty pathomorphological changes in the brain tissue is noteworthy. In brain cells, the rabies virus forms oxyphilic cytoplasmic inclusions (Babes-Negri bodies), most often found in the hippocampus, Purkinje cells of the cerebellar cortex, brainstem, hypothalamus and spinal ganglia. The inclusions are about 10 nm in size, these are areas of the cytoplasm of nerve cells and accumulations of viral particles. In 20% of patients, Babes-Negri bodies cannot be detected, but their absence does not exclude a diagnosis of rabies.

Epidemiology of rabies (hydrophobia)

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

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

In natural foci of Russia, the main carriers of the disease are foxes (90%), wolves, raccoon dogs, corsac foxes, and Arctic foxes (in the tundra zone). Due to the intensive circulation of the virus, wild animals of other families are increasingly involved in epizootic foci. In recent years, cases of rabies have been registered in badgers, ferrets, martens, beavers, elks, lynxes, wild cats, gray rats, and house mice. Cases of the disease have been identified in squirrels, hamsters, muskrats, nutrias, and bears. Domestic animals usually become infected with rabies from wild animals. A person can encounter a source of infection both in the city and in nature; infection occurs through a bite from a sick animal, as well as through drooling on the skin (if there are microtraumas) and mucous membranes. Intact mucous membranes are permeable to the rabies virus, but intact skin is not. The virus can also be transmitted by bites of vampire bats (most often in Mexico, Argentina and Central America); recently, cases of rabies have been registered after bites of insectivorous bats in the USA, Europe, Australia, Africa, India, Russia (Belgorod Region), and Ukraine. The possibility of airborne infection has been proven (infection of speleologists; a case of laboratory infection as a result of an accident, etc.). Cases of rabies transmission from donor to recipient through an infected corneal transplant have been described. In 2004, the possibility of transmission of this disease during solid organ transplantation was reported for the first time: recipients of kidneys, liver and an arterial segment obtained from the same donor died of encephalitis of unknown etiology. Rabies is not transmitted from person to person, however, when working with sick people or animals, it is necessary to take precautions, use protective clothing (gown, cap, gloves, glasses, etc.) and disinfect tools, equipment, and premises.

Susceptibility to rabies is not universal. The development of rabies in an infected person depends on whether the rabies virus is present in the animal's saliva during the bite and whether it was transmitted to a person as a result of the bite or drooling. There is evidence that only 12-30% of people bitten by animals with proven rabies and not vaccinated with an anti-rabies vaccine become ill. According to modern data, almost 50% of dogs with proven rabies do not excrete the virus with saliva. Despite this, the particular severity of the outcome of this infection (100% mortality) dictates the need for mandatory implementation (according to the current instructions) of the entire range of therapeutic and preventive measures in cases where the fact of bites or drooling by sick animals is recorded.

Rabies is widespread throughout the world, with the exception of Australia, Oceania and Antarctica. Every year, 40 to 70 thousand people die from rabies worldwide. The most disadvantaged regions are Asia, Africa and Latin America. According to WHO, rabies ranks fifth among infectious diseases in terms of economic damage. In recent years, the world has seen an increase in natural foci of this infection, which inevitably leads to an increase in the number of people who become ill.

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