Rabies in humans and animals. Rabies

Rabies- acute infection of the central nervous system, accompanied by degeneration of neurons in the brain and spinal cord; The mortality rate for this disease reaches 100%. Rabies has been known since ancient times.

The causative agent of rabies is included in the genus Lyssavirus of the family Rhabdoviridae. Mature rabies virus virions are bullet-shaped and 75x180 in size; one end is rounded, the other is flat. The genome of the rabies virus is formed by a single-stranded, non-segmented RNA molecule. The core of the rabies virus virion is symmetrically twisted inside the shell along the longitudinal axis of the particle. The nucleocapsid of the rabies virus is complemented by molecules of the core protein NP) and viral transcriptase. The rabies virus enzyme includes large (L) and small (NS) proteins. The nucleocapsid covers a supercapsid, which includes surface glycoprotein “spikes”. Reproduction of the rabies virus occurs in the cytoplasm of the cell. The rabies virus is not stable in the external environment and is quickly inactivated by exposure to sunlight and high temperature. The rabies virus can survive in animal corpses for up to 3~4 months; sensitive to the action of various disinfectants.

Rabies virus antigens. Pathogenesis of rabies. Rabies clinic. Signs of rabies. The causative agent of rabies is represented by one antigenic variant. There are “fixed” (virus fixe) and “street” rabies viruses. The “fixed” type of rabies virus was obtained by Pasteur after repeated passages on laboratory animals; does not affect peripheral nerves. The “street” rabies virus causes disease. The antigens of the “fixed” and “street” types of rabies viruses are identical.

Epidemiology. Rabies is widespread everywhere, excluding island countries (England, the Caribbean, etc.). Rabies- typical zoonosis; The reservoir of the pathogen can be almost all mammals (dogs, cats, cattle, bats, foxes, wolves, rodents, etc.). Main route of transmission of rabies- through the bite of a sick animal; It is also possible for the pathogen to penetrate through damaged skin (for example, scratches) when salivated by a sick animal. The rabies virus appears in the saliva of animals several days before the onset of clinical manifestations, which increases the risk of developing rabies after a bite to 30-40%. After the rabies virus penetrates the central nervous system of a sick animal, the risk of infection through a bite is reduced to 10%. There are two types of rabies - forest and urban rabies.

Wild (forest) rabies. The main reservoir is wild animals specific to individual regions, such as skunks (USA), foxes (Russia, North America), vampire bats (Caribbean countries and South America).

Urban madness. The greatest epidemic danger is posed by sick dogs (up to 90% of all cases) and cats. In Nigeria, the latter transmit the Mokola virus, which is close to rabies, to humans, causing neurological diseases (paralysis) with a fatal outcome.

Pathogenesis. The rabies virus multiplies in muscle and connective tissue, where it persists for weeks or months. The rabies virus then migrates along the axons of peripheral nerves to the basal ganglia and central nervous system, where it multiplies in the gray matter, causing neuronal degeneration. The rabies virus then disseminates along centrifugal neurons to various tissues (including the salivary glands).

Clinical manifestations. The duration of the incubation period of rabies varies from 1-3 months to a year, but it can be reduced to 6 days, which depends on the distance from the place of entry of the virus from the brain. The main symptoms of the prodrome of rabies are irritability, insomnia, and sensory disturbances (eg, paresthesia) in the wound area. Rabies is manifested by impaired muscle tone, leading to difficulty swallowing (first liquid and then solid food), generalized convulsions, delirium and coma. In rare cases, the development of paralysis is observed. The prognosis of rabies is extremely unfavorable, mortality reaches 100%.

Microbiological diagnostics. Virusoscopic, biological and serological methods are used to isolate and identify the causative agent of rabies. The material for testing for the rabies virus is saliva, blood and sectional material (brain tissue and submandibular salivary glands). Using microscopy of stained sections or prints, eosinophilic Babes-Negri bodies 5-10 μm in size, formed by clusters of viral nucleocapsids, are detected in the cells of the cerebral cortex, ammon's mouth and cerebellum. Inclusion bodies are located near the nuclei and have uneven outlines. Sections and prints are also used to detect rabies virus Ag in these tissues using RIF or RNIF. The causative agent of rabies is isolated by intracerebral infection of mice and rabbits with the saliva of sick people or fresh sectional material. Animals develop paralysis with a fatal outcome, and inclusion bodies and virus Ag can be found in the brain tissues in RIF and RNIF. AT to the rabies virus in vaccinated individuals is detected in RSK, RN, RIF, etc.

Treatment and prevention. Initially, wounds or bites are treated with antiseptics; The areas of salivation are washed with soapy water. Then carry out specific immunoprophylaxis with rabies vaccine and rabies immunoglobulin. Before carrying out, you should pay attention to the nature of the lesion (bite or salivation), the type of animal suspected of rabies, the circumstances of the attack (provoked or not), the presence of previous rabies vaccine prevention (at least in humans), and other cases of rabies in the region.

For active immunization, live attenuated and killed vaccines have been proposed. Currently, vaccines made from weakened or killed rabies virus grown on nerve cells are replacing cultured vaccines from attenuated virus obtained on various cell lines. Such vaccines are free of side effects (encephalitis, paralysis as a result of cross-reactions with Ag neurons), are more immunogenic and do not require such repeated administration. As planned, the vaccine is administered on the 1st, 3rd, 7th, 14th and 28th days; the vaccine can be considered as a therapeutic and prophylactic agent, since specific protective reactions have time to develop during the incubation period. AT to surface glycoprotein Ags have a neutralizing effect on the rabies pathogen.

When clinical symptoms of rabies appear, it is not possible to save patients. Symptomatic treatment is carried out to alleviate the patient's suffering. Prevention of rabies includes control of the disease in nature and vaccine prevention. It is necessary to vaccinate all domestic and farm animals, combat natural foci of rabies (monitor the number of animals and destroy sick ones), introduce vaccine bait into reservoirs, and apply strict quarantine measures when importing animals. Mandatory vaccination is carried out in high-risk groups - trappers, veterinarians, etc.

The logic of rabies was proven in 1903 by P. Remlenger.

Taxonomy. The causative agent of rabies is an RNA virus that belongs to the family Rhabdoviridae (from the Greek rhabdos - twig), the genus Lyssavirus.

Morphology and chemical composition. Bullet-shaped virions (see Fig. 2.10), 170x70 nm in size, consist of a core surrounded by a lipoprotein shell with spines of a glycoprotein nature. RNA is single-stranded, minus-stranded.

Cultivation. The rabies virus is cultivated in the brain tissue of white mice, Syrian hamsters, rabbits, rats, guinea pigs, sheep, etc. Infected animals develop paralysis of the limbs and then die. The rabies virus can be adapted to primary and continuous cell cultures and chicken embryos. In the cytoplasm of virus-affected animal brain cells or tissue cultures, specific inclusions are formed, first described by V. Babesch (1892) and A. Negri (1903) and therefore called Babes-Negri bodies. Inclusions of spherical or oval shape, ranging in size from 0.5 to 20 microns, are easily stained with acidic dyes, contain viral antigen, and have diagnostic value.

Antigenic structure. The rabies virus contains core and surface antigens. Glycoprotein antigen (spine protein) has pronounced immunogenic properties. There are two rabies viruses that are identical in antigenic properties: a wild one, circulating among animals, pathogenic for humans, called a street virus, and a fixed virus (virus fixe), obtained by L. Pasteur in the laboratory through long-term passages of a street virus through the brain of rabbits. Due to the latter's loss of virulence for humans, L. Pasteur used this virus as an anti-rabies vaccine.

Resistance. The rabies virus is not stable in the environment: it quickly dies under the influence of sunlight and UV rays, disinfectants (phenol, chloramine, formaldehyde), and is sensitive to fat solvents and alkaline solutions. It can be stored for a long time at low temperatures (-20 °C).

Epidemiology. Rabies has been known since ancient times. This is a typical zoonotic infection that is widespread throughout the globe. All warm-blooded animals can get rabies. However, due to the peculiarities of the transmission mechanism (through a bite), the circulation of the virus in nature is ensured by wild and domestic carnivores, mainly dogs, wolves, foxes, raccoon dogs, jackals, and cats. Natural foci of rabies are found everywhere. A person is a random link in the epidemic process and does not take part in the circulation of the virus in nature.

The rabies virus accumulates and is released through the animal's salivary glands during illness and in the last days of the incubation period. The mechanism of transmission of the pathogen is direct contact, mainly through bites, to a lesser extent with excessive salivation of skin that has scratches and abrasions. The role of a sick person as a source of infection is minimal, although his saliva contains the rabies virus. There are only isolated cases of human-to-human infection.

Pathogenesis and clinical picture. The rabies virus has pronounced neurotropic properties. From the site of introduction, viruses enter the central nervous system along peripheral nerve fibers, multiply in it, and then spread centrifugally, affecting the entire nervous system, including the nerve ganglia of some glandular organs, especially the salivary glands. In the latter, viruses multiply and are released into the environment with saliva.

The incubation period for rabies in humans varies from 7 days to 1 year or more, depending on the location and nature of the damage, as well as the virulence of the strain. The shortest incubation is observed with extensive bites to the head.

In the clinical picture of rabies in humans, the following periods are distinguished: precursors (prodromal), excitement and paralysis. The disease begins with the appearance of a feeling of fear, anxiety, irritability, insomnia, general malaise, and an inflammatory reaction at the site of the bite. In the second period of the disease, reflex excitability sharply increases, hydrophobia (phobia of water), spasmodic contractions of the muscles of the pharynx and respiratory muscles appear, making breathing difficult; salivation increases, patients are excited, sometimes aggressive. After a few days, paralysis of the muscles of the limbs, face, and respiratory muscles occurs. The duration of the disease is 3-7 days. Mortality 100%.

Immunity. Naturally acquired immunity has not been studied, since the disease usually ends in death. Artificially acquired immunity occurs after vaccination of people bitten by rabid animals. It is caused by the production of antibodies that persist throughout the year, the formation of interferon, as well as cellular immunity factors.

Laboratory diagnostics. Laboratory studies are carried out posthumously. Pieces of the brain and spinal cord and submandibular salivary glands are used as test material in accordance with the rules provided for working with particularly dangerous infectious material.

Express diagnostics is based on the detection of a specific antigen using RIF and ELISA and Babes-Negri bodies. The virus is isolated using a bioassay on white mice.

Specific prevention and treatment. Vaccines against rabies were developed and proposed by L. Pasteur. Vaccines obtained from the brains of infected animals - rabbits, sheep - can cause complications, so they are rarely used. In our country, an anti-rabies culture concentrated vaccine is used, obtained from the Vnukovo-32 strain (derived from a fixed Pasteur virus), inactivated by UV or gamma rays.

Therapeutic and prophylactic vaccination is given to persons bitten or salivated by sick or suspected rabid animals. Vaccinations should begin as soon as possible after the bite. In severe cases, combined administration of rabies immunoglobulin and vaccine is used. Genetically engineered rabies vaccines are being developed. Treatment is symptomatic.

13.2.2. Herpes simplex virus

Herpes simplex is one of the most common human viral infections, characterized by a fever and blistering rashes, which are most often localized on the skin and mucous membranes. Important features of herpes infection are lifelong carriage of the virus and frequent relapses of the disease.

The viral nature of herpes simplex was established in 1912 by W. Grüter.

Taxonomy, morphology, chemical composition. The causative agent of herpes simplex is a DNA virus that belongs to the Herpesviridae family, genus Simplexvirus. In morphology and chemical composition it does not differ from the varicella zoster and herpes zoster viruses (see Fig. 2.10 in section 11.2.7).

Cultivation. Herpes simplex virus (HSV) is cultivated in chicken embryos, cell cultures and laboratory animals. On the chorioallantoic membrane of chick embryos, the virus forms small white dense plaque nodules; in infected cultures - causes a cytopathic effect: the formation of giant multinucleated cells with intranuclear inclusions.

Antigenic structure. The virus contains a number of antigens associated with both internal proteins and glycoproteins of the outer shell. The latter are the main immunogens that induce the production of antibodies and cellular immunity. There are two serotypes of the virus: HSV type 1 and HSV type 2.

Resistance. The virus can survive on the surface of objects at room temperature for several hours, is sensitive to UV rays, conventional disinfectants, fat solvents, and is heat labile.

Animal susceptibility. The herpes simplex virus is pathogenic for many animals, in which it causes encephalitis when the pathogen is introduced into the brain or a local inflammatory process when infected in the eye. Under natural conditions, animals do not get sick.

Epidemiology. Herpes simplex is one of the most common infections that affects various age groups of people, more often in the autumn-winter period. There are sporadic cases of the disease, sometimes small outbreaks in families, children's groups, and hospitals. There are no epidemics observed.

The source of infection is patients and carriers. The main transmission mechanism is contact, aerogenic. Infection occurs when viruses enter damaged skin or mucous membranes.

The epidemiology of herpes caused by viruses types 1 and 2 is different. HSV type 1 is transmitted through saliva, saliva-contaminated hands and household objects, and HSV type 2 is transmitted through sexual contact. Infection of the fetus through the placenta is possible.

Pathogenesis and clinical picture. Based on clinical manifestations, primary and recurrent herpes are distinguished. The entry gates of the pathogen during a primary herpetic infection are damaged areas of the skin and mucous membranes of the mouth, eyes, nose, and genitourinary tract, where viruses reproduce. Then the viruses enter the blood through the lymphatic vessels and are carried into various organs and tissues.

The incubation period for primary herpes is on average 6-7 days. The disease begins with burning, itching, redness, swelling in limited areas of the skin and mucous membranes, then vesicular rashes filled with liquid appear in this area. Sometimes the disease is accompanied by an increase in body temperature and a disturbance in the general condition. When the bubbles dry, no scars are formed. Primary herpes in newborns is severe and often ends in death. However, in most people the primary infection remains unrecognized because it is asymptomatic.

After a primary infection (overt and asymptomatic), 70-90% of people remain lifelong carriers of the virus, which remains latent in the nerve cells of the sensory ganglia. Carriers often experience relapses of the disease as a result of hypothermia, overheating, menstruation, intoxication, various infectious diseases, stress, and neuropsychic disorders. Recurrent herpes is characterized by repeated rashes on the skin and mucous membranes, often in the same places. Most common location

Structure and chemical composition. Virions are bullet- or rod-shaped, measuring 170 x 70 nm. Hence the name of the family (Greek. rhabdos- rod). On the outside there is a lipid-containing shell with processes extending from it; in the center there is a nucleocapsid of helical symmetry, separated from the outer shell by a matrix protein.

The genome contains single-stranded, non-fragmented minus RNA.

Refers to genus Lyssavirus(Greek Lyssa- rabies). Causes a fatal infection in animals and humans, characterized by irreversible damage to CNS neurons. In 1885, L. Pasteur experimentally substantiated a method for attenuating an as yet unknown pathogen and obtained an anti-rabies vaccine. In 1892, V. Babes and in 1903, A. Negri, described specific inclusions in the neurons of the brain of animals that died from rabies (Negri bodies). Several related biovars of the pathogen are known: the “wilding” virus of deer, arctic foxes and foxes in the Arctic, the bat virus in America, the “mad dog” virus in West Africa, etc.

Cultivation and reproduction. The rabies virus is cultivated in kidney cell cultures of newborn hamsters and in human diploid cells. Cytopathogenic activity is variable. The virus can be adapted to chicken and duck embryos when infected in the yolk sac.

Pathogenesis and immunity. The virus remains at the entrance gate of infection for several days. Primary reproduction appears to occur in muscle cells at the site of the bite. Then the viral particles reach the endings of the sensory peripheral nerves, move along their axial cylinders and perineural spaces (up to 3 mm per hour), affecting neurons of the spinal cord and brain. The different speeds at which the virus moves along the nerve trunks may explain the length of the incubation period of the infection. It is minimal (up to 10-14 days) when the pathogen penetrates through the skin of the head and face and the longest (1.5 months or more) with bites on the extremities (hands, feet). Intensive reproduction of the virus occurs in neurons, resulting in the appearance of cytoplasmic Babes-Negri bodies containing viral nucleocapsids. Neurons of the ammon's horn, medulla oblongata, and Purkinje cells of the cerebellum are especially intensively affected.

The body synthesizes virus-neutralizing antibodies, which may have a protective effect before the pathogen penetrates the cells of the central nervous system.

Laboratory diagnostics rabies is usually carried out after

death of an animal or person upon detection of Babes-Negri bodies in neurons of the brain and spinal cord, in the cells of the salivary glands, detection of viral antigen in affected tissues, using an immunofluorescence reaction. In the saliva of sick people and in the brains of the dead, the presence of the virus can be determined by intracerebral infection of white mice, which develop paralysis of the limbs and soon die.

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On the topic: “Rabies virus”

Moscow 2016

Introduction

Rabies is an acute, particularly dangerous viral disease that causes severe damage to the nervous system, usually with death. One of the most dangerous and severe infectious diseases of humans and animals. Rabies occurs with signs of damage to the central nervous system, characterized by unusual behavior, unprovoked aggressiveness, and paralysis. The disease in animals most often ends in death. Humans and all warm-blooded animals except birds are susceptible. Wild animals can become ill latently, without death.

Rabies was described by the ancient doctors of the East as early as 3000 years ago, Democritus as early as 500 years ago, and Aristotle as early as 300 years BC. The problem of combating rabies remains one of the most important in the world to this day. The particular danger of rabies is that to date no effective means of treating an already developed pathogenic process have been found. Therefore, it is prohibited to treat animals with rabies; their immediate destruction is legalized.

There is a natural type of rabies, the foci of which are formed by wild animals, and an urban type of rabies. Pets become infected with rabies after contact with sick wild animals.

Rabies is recorded on all continents of the globe (with the exception of Antarctica, Australia and New Zealand) and has been identified in animals belonging to more than 30 species. Every year, more than 50 thousand people and more than 1 million animals die from rabies in the world.

rabies virus antigenic diagnostics

1. Characteristics of the virus

1.1 Taxonomy of the virus

An RNA-containing rabies virus, it belongs to the family Rhabdoviridae (Greek Rhabdos - stick), genus Lyssavirus (from Greek lyssa - hydrophobia). In addition to the rabies virus, the genus Lyssavirus includes 5 more viruses (Lagos, Moсola, Duvenhage, Kotonkan, Obodhiang), isolated from bats and mosquitoes in Africa and causing diseases in dogs, cats, and farm animals, but without the clinical picture of rabies.

1.2 Virion morphology

The causative agent of rabies is characterized by a rod-shaped or bullet-shaped virion: with one flat and the other rounded end, covered with a supercapsid shell (peplos) with peplomer processes: between the supercapsid and the capsid there is an intermediate membrane (matrix), a spiral type of symmetry has 5 structural proteins: L (RNA polymerase ), G, M, NS, N . The virus is approximately 180 nanometers in length and has a cross-section of about 75 nanometers. Genome single-stranded linear minus RNA.

1.3 Sustainability

The rabies virus is not highly resistant in the external environment. It is stored at a temperature of 6°C for up to 1 week, at 23°C for 28-53 days, at 54-56°C for an hour, at 70°C for 1-2 minutes, at 100°C - it dies instantly. Ultraviolet radiation inactivates the virus in 5-10 minutes. It is resistant to low temperatures and survives for months in frozen brains; in rotting material remains viable for 2 - 3 weeks. In the brain of a dead animal buried in the ground, the virus persists for 45 days or more. Repeated freezing and thawing does not destroy the virus.

1-5% formalin solution, 5-7% iodine solution, bleach, 3-5% hydrochloric acid solution, 45-70% ethyl alcohol and 1% soap solution inactivates the virus after 5 minutes, 0.1% solution of sublimate - after 2-3 hours, 5% solution of phenol - after 5-10 minutes, ether - after 60-120 hours.

1.4 Stages of virus reproduction

Reproduction of viruses of the Rhabdoviridae family occurs in the cytoplasm of the host cell. Rhabdoviruses bind to host cell receptors via supercapsid G glycoproteins and enter the cell via endocytosis (1). Then, after removal of the supercapsid, the released ribonucleoprotein (RNP) enters the cell cytoplasm (2). In the cytoplasm of the host cell, with the help of RNA-dependent RNA polymerase (3), incomplete (4) plus RNA strands are synthesized (five individual mRNAs for the synthesis of viral proteins) and complete (6) plus RNA strands, which are the matrix for the synthesis of genomic RNA (7). During translation of mRNA by ribosomes (5) of the host cell, viral proteins are synthesized. Glycoprotein G is glycolyzed in the endoplasmic reticulum and then finally converted in the Golgi complex and incorporated into the host cell plasmalemma (8). The matrix protein (M protein), immediately after synthesis, is integrated into the plasmalemma from the inner cytoplasmic side of the lipid bilayer. The inclusion of matrix protein M into the plasmalemma is a signal for the formation of a virion. Ribonucleoprotein is formed by the interaction of genomic minus RNA and proteins N, NS and L (disjunctive type of virus reproduction). Once assembled, virions exit the host cell by budding (9).

1.5 Antigenic properties

Antigenic structure.

Rabies virus virions contain glycoprotein (external) and nucleocapsid (internal) antigens. The glycoprotein antigen induces the formation of virus-neutralizing and antihemagglutinating antibodies and ensures the development of immunity in animals, and the nucleocapsid antigen induces complement-fixing and precipitating antibodies.

The rabies virus has 4 serotypes (prototypes): rabies virus, Lagos, Mokola, Duvenhage. Epizootic strains of the rabies virus are immunobiologically related, but differ in virulence. All isolated virus strains are divided into 5 groups based on virulence. Strains of the first group are characterized by high, and the fifth group - low virulence.

The spectrum of pathogenicity of the virus is closely related to its ecology, which has its own characteristics. Thus, it is necessary to distinguish between two main and independent epizootic manifestations of lyssavirus infection:

1) rabies epizootics supported by terrestrial animals (foxes, wolves, raccoon dogs, jackals, mongooses, skunks, raccoons, etc.);

2) epizootics of chiropteric origin, supported by vampires, insectivorous and carnivorous bats.

Since the 1960s, rabies in wild animals has become prevalent. The main reservoir and source of infection were foxes and other wild animals. The disease in them can proceed latently, ensuring the persistence of the virus in natural conditions. Rabies in dogs during urban epizootics usually ends in their death.

Antigenic activity.

Animals immunized against rabies produce virus-neutralizing, complement-fixing, precipitating, antihemagglutinating and lytic (destroying cells infected with the virus in the presence of complement) antibodies.

1.6 Hemagglutinating and hemadsorbing properties

The hemadsorbing properties of the rabies virus in the culture of primary Syrian hamster kidney cells were described by M. A. Selimov and R. Sh. Ilyasova. The hemadsorption phenomenon was reproduced with erythrocytes of goose, chicken, Syrian hamster, guinea pig and monkey at a temperature of 4°C; the specificity of this phenomenon was confirmed by inhibition using immune serum; after three times washing, hemadsorption was not destroyed and was not reproduced with other strains of the rabies virus.

The virus has hemagglutinating properties against red blood cells of geese, chickens, guinea pigs, sheep, and humans (group 0). Typically, the hemagglutination reaction is performed with goose red blood cells at 0-4 °C, pH 6.2-6.4. There is a linear relationship between infectious and hemagglutinating activity.

1.7 Features of cultivation in various living systems

In laboratory conditions, the virus can be cultivated on laboratory animals (mice, rabbits, hamsters, guinea pigs, etc.) using the intracerebral method of infection. The virus reproduces in primary and continuous cell cultures (Syrian hamster kidneys, sheep embryos, calves, BHK-21, rat Gasserian ganglion neuroma cells, etc.). In the first passages, the virus multiplies slowly, without causing CPE. After preliminary adaptation, chicken embryos are also susceptible to the rabies virus.

Easily reproduced on all types of warm-blooded animals.

1.7 Organ pathogenesis

Stage 1 - penetration of the virus by contact through a bite or contact of a virus-containing secretion with a wound;

Stage 2 - primary reproduction and accumulation in the cells of the submucosal layer of the skin;

Stage 3 - primary dissemination along centripetal neurons in the central nervous system (neuroprosbasia);

Stage 4 - secondary reproduction and accumulation in brain cells;

Stage 5 - secondary dissemination along centrifugal neurons to peripheral organs (septineuria);

Stage 6 - isolation of the virus with secretions (saliva) and excreta (tear fluid, blood, urine, feces, etc.

2. Diagnosis of the disease

2.1 Making a preliminary diagnosis

Analysis of epizootic data.

According to the epizootological classification, the causative agent of rabies is included in the group of natural focal infections. There are currently three types of rabies infection in Russia:

1) Arctic (reservoir - arctic foxes);

2) natural focal forest-steppe (reservoir - foxes);

3) anthropourgic (reservoir - cats, dogs).

Taking into account the nature of the pathogen reservoir, rabies epizootics are distinguished between urban and natural types. In urban epizootics, the main sources of the pathogen and spreaders of the disease are stray and stray dogs. The scale of the epizootic depends on their numbers. In natural epizootics, the disease is spread mainly by wild predators. The localization of natural foci of the disease corresponds to the distribution patterns of foxes, corsac foxes, raccoon dogs, wolves, jackals, and arctic foxes. They are very sensitive to the virus, aggressive, often prone to long-distance migrations, and when sick, they intensively secrete the virus in their saliva. These circumstances, along with the significant population density of some predators (fox, raccoon dog), the rapid change of their generations and the length of the incubation period for rabies, ensure the continuity of the epizootic process, despite the relatively rapid death of each individual diseased animal.

Characteristics of clinical signs.

The incubation period varies from a few days to 1 year and averages 3-6 weeks. Its duration depends on the type, age, resistance of the animal, the amount of virus that has penetrated and its virulence, the location and nature of the wound.

The disease is often acute. The clinical picture is similar in all animal species, but has been better studied in dogs. Rabies usually manifests itself in two forms: violent and silent. With violent rabies, three periods are distinguished: prodromal, agitation and paralysis.

The prodromal period (precursor stage) lasts from 12 hours to 3 days. This period begins with a slight change in behavior. Sick animals become apathetic, boring, avoid people, try to hide in a dark place, and are reluctant to respond to the owner’s call. In other cases, the dog becomes affectionate towards its owner and acquaintances, and tries to lick its hands and face. Then anxiety and excitability gradually increase. The animal often lies down and jumps up, barks for no reason, there is increased reflex excitability (to light, noise, rustling, touch, etc.), shortness of breath appears, and the pupils are dilated. Sometimes severe itching occurs at the site of the bite, and the animal licks, scratches, and chews the area. As the disease progresses, a perverted appetite often appears. The dog eats inedible objects (stones, glass, wood, earth, its own feces, etc.). During this period, paresis of the pharyngeal muscles develops. Difficulty swallowing is noted (it seems that the dog has choked on something), drooling, hoarse and abrupt barking, an unsteady gait, and sometimes squint.

The second period is excitement, lasts 3-4 days and is characterized by an intensification of the symptoms described above. Aggression increases, the dog can bite another animal or person, even its owner, without a reason; it gnaws iron, sticks, the ground, often breaking its teeth and sometimes its lower jaw. Sick dogs have an increased desire to break free and run away; within a day, a rabid dog runs tens of kilometers, biting and infecting other dogs and people along the way. It is typical that the dog silently runs up to animals and people and bites them. Bouts of violence, lasting several hours, are followed by periods of oppression. Paralysis of individual muscle groups gradually develops. The change in the dog's voice is especially noticeable due to paralysis of the laryngeal muscles. The bark sounds hoarse, reminiscent of a howl. This sign has diagnostic value. The lower jaw is completely paralyzed and droops. The oral cavity is open all the time, the tongue falls out halfway, and there is profuse salivation. At the same time, paralysis of the swallowing muscles and tongue muscles occurs, as a result of which the animals cannot eat food. Strabismus appears.

The third period is paralytic, lasting 1-4 days. In addition to paralysis of the lower jaw, the hind limbs, the muscles of the tail, bladder and rectum are paralyzed, then the muscles of the trunk and forelimbs. The body temperature in the excited stage rises to 40-41 ° C, and in the paralytic stage it decreases below normal. Polymorphonuclear leukocytosis is noted in the blood, the number of leukocytes is reduced, and the sugar content in the urine is increased to 3%. The total duration of the disease is 8-10 days, but often death can occur after 3-4 days.

In the silent (paralytic) form of rabies (more often observed when dogs are infected by foxes), the excitement is weakly expressed or not expressed at all. In the complete absence of aggressiveness, the animal experiences severe drooling and difficulty swallowing. Then the dogs experience paralysis of the lower jaw, muscles of the limbs and torso. The illness lasts 2-4 days.

The atypical form of the disease does not have an excitation stage. Muscle wasting and atrophy are noted. Cases of rabies have been recorded that occurred only with symptoms of hemorrhagic gastroenteritis: vomiting, semi-liquid feces containing bloody mucous masses. Even less common are the abortive course of the disease, which ends with recovery, and recurrent rabies (after apparent recovery, clinical signs of the disease develop again).

Characteristics of pathological changes

Pathoanatomical changes are not specific, but together with clinical signs they can be of diagnostic value. The corpse is emaciated, the fur is disheveled, abundantly moistened in some places with saliva, the skin is often injured.

When autopsying the corpses of dogs that died from rabies, they find: an empty stomach or foreign objects in it; venous hyperemia, hemorrhages and erosions in the gastric mucosa; blood thickening (anhydremia), dry serous tissue, subcutaneous tissue and skin; general venous congestion: cyanosis of the mucous membranes, acute venous hyperemia of the liver, lungs, spleen, brain; histo: non-purulent lymphocytic encephalitis in the brain stem (quadrigemole, pons, medulla oblongata); rabies nodules in the brainstem and autonomic ganglia; Babes Negri bodies in the nerve cells of ammon's horns. Corpses suspected of being infected with rabies are prohibited from opening!

2.2 Types of pathological material

To test for rabies, fresh whole corpses of small animals are sent to the laboratory, and from large and medium-sized animals - the head with the first two cervical vertebrae. The corpses of small animals are treated with insecticides before being sent for research.

Pathological material is packaged in plastic bags and placed in tightly closed boxes with a moisture-absorbing pad impregnated with a disinfectant. The material and a covering letter, which indicates the sender and his address, the type of animal, anamnestic data and the basis for suspicion of the animal having rabies, the date and signature of the doctor, are sent by courier.

2.3 Stages of laboratory diagnostics

Laboratory diagnostics include: detection of viral antigen in ELISA (solid-phase, sandwich version), MFA (RIF, direct version), RDP, Babes-Negri bodies (no longer used) and bioassay on white mice.

MFA. For this reaction, the bioindustry produces fluorescent anti-rabies g-globulin.

Thin impressions or smears are prepared on fat-free glass slides from various parts of the brain on the left and right side (ammon's horn, cerebral cortex, cerebellum and medulla oblongata). At least two preparations of each part of the brain are prepared. You can also examine the spinal cord and submandibular salivary glands. For control, preparations are made from the brain of a healthy animal (usually a white mouse).

The preparations are dried in air, fixed in chilled acetone (minus 15–20 °C) for 4 to 12 hours, dried in air, a specific fluorescent g-globulin is applied, and placed in a humid chamber at 37 °C for 25–30 minutes. Then they are thoroughly washed with saline or phosphate buffer with a pH of 7.4, rinsed with distilled water, air dried, applied with non-fluorescent immersion oil and viewed under a fluorescent microscope. In preparations containing the rabies virus antigen, yellow-green fluorescent granules of varying sizes and shapes are observed in neurons, but more often outside cells. In control, there should be no such glow; nervous tissue usually glows with a dull grayish or greenish color. The intensity of the glow is assessed in crosses. The result is considered negative if there is no specific fluorescence.

Material from animals vaccinated against rabies cannot be examined in the RIF 3 months after vaccination, as there may be fluorescence of the vaccine virus antigen.

Tissues preserved with glycerin, formaldehyde, alcohol, etc., as well as material that shows signs of even slight decay, are not subject to examination in the RIF.

RDP in agar gel. The method is based on the property of antibodies and antigens to diffuse in an agar gel and, upon meeting, form visually visible precipitation lines (antigen + antibody complex). Used to detect antigen in the brain of animals that have died from street rabies virus, or during experimental infection (bioassay).

The reaction is carried out on glass slides, onto which 2.5-3 ml of molten 1.5% agar solution is poured.

Agar gel: Difko agar - 15 g, sodium chloride - 8.5 g, 1% solution of methyl orange in 50% ethyl alcohol - 10 ml, merthiolate - 0.01 g, distilled water - 1000 ml.

After hardening in agar, wells are made using a stencil with a diameter of 4-5 mm, placed under a glass slide with agar. Agar columns are removed with a student's pen. The wells in the agar are filled with components according to the diagram.

In large animals, all parts of the brain (left and right sides) are examined; in medium animals (rats, hamsters, etc.) - any three parts of the brain; in mice - the entire brain. Using tweezers, a paste-like mass is prepared from the brain, which is placed in the appropriate wells.

Controls with positive and negative antigens are placed on separate glass using the same stencil.

After filling the wells with the components, the preparations are placed in a humid chamber and placed in a thermostat at 37 ° C for 6 hours, then left at room temperature for 18 hours. Results are recorded within 48 hours.

The reaction is considered positive when one or two or three lines of precipitation of any intensity appear between the wells containing the brain suspension and anti-rabies g-globulin.

Bacterial contamination and brain decay do not prevent its use for RDP. Material preserved with glycerin, formalin and other means is unsuitable for RDP.

Detection of Babes-Negri bodies. Thin smears or prints are made on glass slides from all parts of the brain (as for RIF), at least two preparations from each part of the brain, and stained using one of the methods (according to Sellers, Muromtsev, Mann, Lenz, etc.).

A positive result is considered to be the presence of Babes-Negri bodies - clearly defined oval or oblong granular formations of pink-red color, located in the cytoplasm of cells or outside them.

This method has diagnostic value only when typical specific inclusions are detected.

Bioassay. It is more effective compared to all the above methods. It is placed when negative results are obtained by previous methods and in doubtful cases.

For the bioassay, white mice weighing 16-20 g are selected. Nervous tissue from all parts of the brain is ground in a mortar with sterile sand, physiological solution is added to obtain a 10% suspension, left for 30-40 minutes, and the supernatant is used to infect the mice. . If bacterial contamination is suspected, add 500 units of penicillin and streptomycin per 1 ml of suspension and leave for 30-40 minutes at room temperature.

For one bioassay, 10-12 mice are infected: half intracerebrally with 0.03 ml, half subcutaneously in the area of the nose or in the upper lip with 0.1-0.2 ml.

Infected mice are placed in glass jars (preferably aquariums) and monitored for 30 days, keeping daily records. The death of mice within 48 hours is considered nonspecific and is not taken into account in assessing the results. In the presence of the rabies virus in the pathological material, from the 7th to 10th day after infection, the following symptoms are observed in mice: ruffled fur, a peculiar hunchback of the back, impaired coordination of movements, paralysis of the hind limbs. In dead mice, the brain is examined in the RIF to detect Babes-Negri bodies and a RDP is placed.

A bioassay for rabies is considered positive if Babes Negri bodies are found in preparations from the brains of infected mice or the antigen is detected by RIF or RDP methods. A negative diagnosis is the absence of death of mice within 30 days.

It is recommended for early diagnosis using the bioassay method (this is especially important when the animal being studied has bitten a person) to use not 10-12, but 20-30 mice for infection, and from the third day after infection, kill 1-2 mice daily to study them brain in RIF. This allows (in positive cases) to reduce the study period by several days.

In laboratory practice, the so-called specific bioassay method is sometimes used. Its essence is that mice get sick when infected with the brain tissue of animals with rabies and do not get sick if this tissue is pre-treated (10 minutes at 37 ° C) with anti-rabies serum.

Usually in the laboratory a study is carried out in the following sequence: fingerprint smears are made from the brain for RIF and detection of Babes-Negri bodies, an RDP is placed, and if negative results are obtained, a bioassay is made.

When performed in a highly qualified manner, RIF results in 99-100% agreement with the bioassay. Babesh-Negri bodies are detected only in 65-85% of rabies cases, in RDP - from 45 to 70%.

3. Specific prevention

Immunity and specific prevention.

Currently, inactivated and live vaccines are used to prevent rabies. Conventionally, vaccines can be divided:

First generation vaccines, which are prepared from the brains of animals infected with a fixed rabies virus;

Second generation vaccines, which are prepared from strains of the rabies virus adapted to cell culture;

Third generation vaccines, which are obtained using genetic engineering methods.

There are no effective treatments for rabies, so specific prevention is of paramount importance. The following attenuated strains are currently used in various countries for the production of rabies vaccines: Pasteur's Paris strain, PV-11 or PM, CVS, Flury Lep, Flury Hep, Kelev, Era, Sad B-19, Vnukovo, Shchelkovo-51, C- 80.71 BelNIIEV-VGNKI, KMIEV-94, etc. Virus reproduction is carried out mainly in cell cultures using roller or suspension methods. The most commonly used are continuous cell cultures BHK-21, Wj-38, MRC-5, Vero, MDBK, saiga kidney, etc. All rabies vaccines used in the prevention of rabies are divided into live and inactivated. Inactivated vaccines are vaccines containing the rabies virus, the infectious properties of which are inactivated by one of the chemical or physical methods. Aluminum salts are mainly used as an adjuvant. When administered to animals or humans, the vaccine virus is unable to multiply and acts in the body only as an antigen. These vaccines are the safest. The mechanism of action of live vaccines is based on the fact that a weakened virus, multiplying in the body, affects the immune system, inducing the formation of immunity.

Currently, inactivated vaccines are mainly used for parenteral vaccination of animals. For the purpose of prevention, vaccines are administered 1-2 times; in forced cases after an infection has occurred, the number of injections is increased to 5 or more. They are produced according to certain schemes. Immunity occurs in 25-30 days and lasts up to a year or more. In the CIS countries, domestic vaccines from the Shchelkovo-51, S-80, 71 BelNIIEV-VGNKI virus strains, as well as vaccines produced in Holland, France and other countries, are used for preventive and compulsory vaccination of animals. Live vaccines are used mainly for oral vaccination of wild carnivores against rabies. In addition to whole-virion rabies vaccines, a highly effective genetically engineered vaccine containing the surface glycoprotein of the rabies virus and a recombinant vaccine based on the smallpox virus are currently used. The mechanism of post-vaccination immunity in rabies has not been fully deciphered. However, it has been proven that its intensity correlates with the titer of virus-neutralizing antibodies in the blood, for the determination of which the virus neutralization reaction is used in white mice or in cell culture, as well as the ELISA method.

Prevention and elimination measures.

The fight against rabies is carried out through the joint efforts of veterinary, medical and municipal services, police, forestry, nature conservation, hunting and economic organizations, and local councils. The system of measures to prevent rabies in animals and people includes the following main measures.

1. Specific prevention of rabies by expanding the scope of oral immunization of wild carnivores and improving the quality of vaccines used for this purpose. These measures are leading in the prevention of rabies and are used in all countries of the world. Oral vaccines in edible baits are distributed in areas unaffected and threatened by rabies. The experience of a number of countries (Czech Republic, Switzerland, France, Germany) shows that with mass use over a number of years, this measure can significantly reduce or even eliminate the incidence of rabies in animals.

2. Reducing the population of wild carnivores, especially foxes, by shooting them, ensuring the conservation of the species (1-2 individuals per 1000 hectares). Regulation of the number of wild carnivores is carried out by shooting, extermination of young animals in dens, the use of baits with sleeping pills or poisonous substances (luminal, barium fluoroacetate, etc.) and is carried out by hunting organizations.

3. The fight against stray dogs and cats by creating shelters for last resorts, sterilizing females, etc. The capture and destruction of stray dogs and cats, which are the main spreaders of rabies in populated areas, is carried out by city departments of public utilities, which organize special teams.

4. Streamline the keeping of domestic dogs and cats, universally vaccinate them against rabies. The rabies vaccine makes dogs immune to infection with the rabies virus. Immunity appears 3-4 weeks after vaccination and lasts about a year, so vaccinations must be repeated annually.

5. Conducting educational work among the population about the danger of rabies and measures to prevent it. All recent cases of illness and death of people from rabies are associated with their lack of basic knowledge on the prevention of this disease.

6. Preventive immunization against rabies for persons whose professional activities involve a high risk of contracting the rabies virus.

Measures in the outbreak of rabies.

Carrying out activities in a rabies outbreak largely depends on the timely diagnosis of the disease, therefore, in all cases of suspicion of rabies or the death of an animal from it, owners are obliged to urgently report to a veterinary institution or local council. The arriving veterinarian must make a diagnosis on the spot or send the material for examination to a veterinary laboratory and take appropriate measures. When rabies appears, the locality (or part of it) is declared unsafe and quarantine is introduced. Veterinary workers with the participation of sanitary and epidemiological services are taking measures to prevent the further spread of the disease and eliminate it. Animals with rabies are destroyed. Their corpses, without removing the skin, are burned or buried in a cattle burial ground to a depth of at least 2 m. The places where sick animals were located are disinfected with a 2-3% solution of sodium hydroxide or formaldehyde. Bedding and low-value animal care items are burned, metal objects are boiled or burned in a flame. To neutralize clothes, it is recommended to boil or iron them with a hot iron. By examining the outbreak, interviewing residents and door-to-door canvassing of the locality, all people and animals who had contact with sick animals are identified. People who have been in contact with a sick animal must be immediately sent to a medical facility for consultation. All suspected and infected dogs and cats are destroyed, and those who bite people or animals are subject to a 10-day quarantine. Farm animals suspected of being infected must be vaccinated with an anti-rabies vaccine according to a forced scheme. The slaughter of such animals for meat is permitted if they do not show signs of rabies. The meat is used without restriction, with the exception of the head and bitten areas of the body, which are destroyed. Milk can be consumed only after 5 minutes of boiling or pasteurization. The rabies quarantine is lifted after the end of two months from the date of the last case of the disease.

Conclusion

In a number of countries, incl. and in Russia, in recent years, the epizootic situation regarding rabies has tended to become more complicated. Some researchers note that, despite the ongoing anti-rabies measures in the regions and Russia as a whole, it was not possible to completely limit the spread of rabies.

According to Russian statistics for the first quarter of 2014, animal rabies was detected in 37 constituent entities of the Russian Federation, including Moscow and the Moscow region. Traditionally, St. Petersburg and the Leningrad region remain rabies-free. The sad leaders are Belgorod region (79 cases in animals), Saratov region (64 cases), Moscow region (40), Voronezh region (37) and Tambov region (36). In this quarter, two people fell ill (and died) - in the Kursk and Vladimir regions.

Despite the fact that the basic mechanisms of the spread of rabies are now well known, very reliable means of preventing the disease are available and a strategy to combat the infection has been developed, there is still a lot of work ahead in order to improve the effectiveness of protecting animals and humans from a deadly disease. It is important to timely identify sick animals and isolate those suspected of illness and infection. Protection of farm animals from attacks by sick people, disposal of corpses. In order to prevent “wild rabies” - trapping, shooting, degassing of burrows, oral immunization, aerosol immunization of bats in caves, immunization of cattle.

As a result, the main directions of protecting people and animals are the control and regulation of the epizootic situation, immunization of animals and people with drugs and the use of increasingly reliable and safe methods.

Bibliography:

1. R.V. Belousova, I.V. Tretyakova, M.S. Kalmykova, E.I. Yarygina Manual on veterinary virology. Moscow 2011

2. Makarov V.V. Real epizootology of rabies. Bulletin of the Russian Academy of Agricultural Sciences. 2002.

3. Movseyants A.A. Modern problems of rabies. Veterinary and medical aspects of zooanthroponoses. 2003.

4. http://news.sarbc.ru/main/2014/03/28/151713.html

5. http://www.bestreferat.ru/referat-182318.html

6. Baryshnikov, P.I. Veterinary virology [Text]: textbook / P.I. Baryshnikov.- M.: FORUM, 2009. - 96 s.

7. Gruzdev, K.N. Animal rabies [Text] / K.N. Gruzdev, V.V. Nedosekov. - M.: Aquarium LTD, 2001. - 304 s.

8. Rabies [Electronic resource] / Access mode: http://www.vetzverocenter.ru/index.php?catid=73&module=catalog.

9. Types of rabies [Electronic resource] / Access mode: http://www.medintime.ru/medtimes-57-1.html.

10. “Wilding” and rabies in the polar regions of Russia, Canada, the USA [Electronic resource] / Access mode: http://nepropadu.ru/blog/guestroom/5883.html.

11. http://viralzone.expasy.org/

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Rabies virus

The filterable rabies virus is a member of the genus Lyssavirus(from the Greek lyssa, which means rabies, demon) family Rhabdoviridae.

The rabies virus has a tropism for nervous tissue.

Rabies viruses are heat sensitive. They are quickly inactivated when exposed to solutions of alkalis, iodine, detergents (surfactant synthetic substances), and disinfectants (Lysol, chloramine, carbolic and hydrochloric acids).
Viruses are sensitive to ultraviolet irradiation, die quickly when dried, and die within 2 minutes when boiled.
At low temperatures and freezing, rabies viruses persist for a long time. They can be stored in animal corpses for up to 4 months.

Viruses are transmitted to humans through bites with saliva or through damaged skin that contains saliva from a sick animal. Damage to the central nervous system inevitably leads to the death of the patient. The presence of viruses in the central nervous system is indicated by the detection of “Babes-Negri bodies” in ganglion cells.

Rice. 2. The photo shows rabies viruses that resemble a bullet in appearance. One end is rounded, the other is flat. The synthesis of viral particles occurs in the cytoplasm of neurons.

Rice. 3. The photo shows the rabies virus. The virion is surrounded by a double shell. On the outer shell of viral particles there are spikes (protrusions) with knobby swellings at the ends. Inside the virions there is an internal component, which is a thread-like formation. The photo clearly shows transverse stripes representing a nucleoprotein.

Taurus Babesha-Negri

In 1892, V. Babes and in 1903, A. Negri, described specific inclusions in the cytoplasm of neurons in the brains of animals that died from rabies. They are called Babesh-Negri bodies. Large neurons of the ammon's horn, pyramidal cells of the cerebral hemispheres, Purkinje cells of the cerebellum, neurons of the thalamus optic, cells of the medulla oblongata and ganglia of the spinal cord are areas of the nervous system where Babes-Negri bodies are most often found.

Cytoplasmic inclusions are strictly specific for rabies disease

Babes Negri bodies are detected in the neurons of the brain of dogs that died from rabies in 90 - 95% of cases, in humans - in 70% of cases.

According to a number of researchers, Babes Negri bodies are:

sites where virion replication occurs
places where the production and accumulation of the specific antigen of the rabies pathogen occurs,
The internal granularity of Babes-Negri bodies represents viral particles associated with cellular elements.

Rice. 4. The photo shows nerve cells with cytoplasmic inclusions. Babes Negri bodies have different shapes - round, oval, spherical, amoeboid and fusiform.

Rice. 5. The photo shows the Babesh-Negri body. The internal granularity of the inclusions represents viral particles associated with cellular elements.

Rice. 6. The photo shows the Babes-Negri body in the light of a conventional microscope. They are surrounded by a light rim.

Replication of viral particles in rabies is always accompanied by the formation of specific inclusions - Babes-Negri bodies.

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