Hemorrhagic fever virus with renal syndrome

Hemorrhagic fever with renal syndrome (HFRS) is an acute severe infectious disease characterized by systemic damage to small vessels, hemorrhagic diathesis, hemodynamic disorders and specific kidney damage (interstitial nephritis with the development of acute renal failure).

The causative agent of hemorrhagic fever with renal syndrome belongs to the genus Hantavirus of the Bunyaviridae family. Hantaviruses have a spherical shape, a lipid-containing membrane; the diameter of the virion is 90-120 nm. The membrane has protrusions formed by glycoproteins. The viral genome is a segmented single-stranded negative RNA. Three segments: large (L), medium (M) and small (S) encode viral RNA polymerase, envelope glycoproteins (G1 and G2) and nucleocapsid, respectively. Transcription initiation in hantaviruses occurs in the same way as in influenza A virus: with the help of virion endonuclease, which is part of the RNA polymerase complex, the cap is cut off from cellular mRNA. The cap serves as a primer - a primer for the synthesis of virion mRNA. The life cycle of hantaviruses is also similar to that of the influenza virus. Like all RNA-containing viruses, hantaviruses are subject to frequent mutations. To date, the genus Hantavirus includes more than 25 serologically and genetically distinct viruses. They are divided into Old World viruses (Hantaan, Seoul, Pumala, Dobrava/Belgrade, Khabarovsk, Thailand-Tottopalayam, etc.) and New World viruses (Prospect Hill, Sin Nombre, New York, Andes, Bayon, Laguna Negra, etc.). They cause two clinical forms of hantavirus infection in humans: hemorrhagic fever with renal syndrome (caused by Hantaan, Seoul, etc.) and hantavirus cardiopulmonary syndrome (HCPS), the causative agents of which are Sin Nombre, New York, Bayon, Andes, Laguna Negra and possibly others.

Hantaviruses are widespread.

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Pathogenesis of hemorrhagic fever with renal syndrome

Having penetrated the body, the virus circulates in the blood, affecting the walls of capillaries and small veins, especially in the vessels of the renal medulla. The virus multiplies in the cells of the kidneys, spleen, lungs and in the vascular endothelium. It is contained in the blood and urine of patients during the entire febrile period. Immune complexes of viral antigen + antibody are deposited in the cells of the glomeruli and convoluted tubules of the kidneys, which causes renal syndrome.

Immunity

After the disease, it is persistent, long-lasting, and caused by virus-neutralizing antibodies and immune memory cells.

Epidemiology of hemorrhagic fever with renal syndrome

Infection with hantaviruses occurs from rodents by airborne dust, contact or alimentary, but not by transmission. Viruses transmitted in this way are called roboviruses (from the English rodent - rodent and borne - born). The high incidence of hemorrhagic fever with renal syndrome (in 1997, 20,921 cases of the disease were registered in Russia) is due to the presence of active natural foci in the country, especially in the Volga region, the Ural and Volga-Vyatka regions, as well as in Primorsky Krai. Natural infection with hantaviruses has been established in more than 50 species of small mammals belonging to various families of the rodent and insectivorous orders. The hypothesis that each hantavirus in natural conditions is associated with a single species of small mammals has received wide recognition. However, the question of the actual number of hantaviruses existing in nature and the species of their main carriers requires further study.

Animals infected with hantaviruses develop an asymptomatic infection, during which viral antigens can be detected in many organs, primarily in the lungs. The virus is excreted in animals with saliva, feces and urine for a long time. Humans become infected through the air. The virus, together with an aerosol containing rodent waste products, enters the lungs through the upper respiratory tract, where the conditions for its reproduction are most favorable, and is then carried with the blood to other organs and tissues. Healthy people are not infected by a sick person.

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Symptoms of hemorrhagic fever with renal syndrome

The incubation period is 11-23 days. The disease begins with chills, a rise in temperature to 39-40 ° C. Severe headache, hyperemia of the face and neck, injection of scleral vessels are noted, from the 3rd to 5th day of the disease a hemorrhagic rash appears on the skin and oliguria occurs, in severe cases - anuria and uremia. Recovery is slow. Kidney function is completely restored in 1-3 months. Transition of hemorrhagic fever with renal syndrome to a chronic form does not occur. Along with the severe form of hemorrhagic fever with renal syndrome (hemorrhagic nephrosonephritis), erased, mild and moderate forms of the disease are observed. Mortality varies from 0 to 44%.

Laboratory diagnostics of hemorrhagic fever with renal syndrome

Hantaviruses reproduce poorly in cell culture, and there is no laboratory infection model for them, so they are difficult to isolate and identify. Almost the only method for direct detection of hantaviruses is PCR. All other methods can only indirectly indicate the presence of the virus in the material being studied. PCR allows for direct detection of the virus in various biological samples taken from both animals and humans.

Laboratory diagnostics of hantavirus infections is based on the isolation of viruses from blood and urine during the acute period of the disease, as well as the detection of antibodies in paired sera and urine of patients. Viruses are most often isolated from mice, since they do not cause cytopathic action in cell culture. Indication of viral antigen in the lungs of mice is carried out using RIF, ELISA. Identification of viruses is carried out using RIF, ELISA and RIGA. RIF, ELISA, RTNGA, RIGA and RIA are used for serological diagnostics of diseases. Early diagnostics of the disease is carried out by detecting viral antigens in urine using RIF and ELISA.

Treatment of hemorrhagic fever with renal syndrome

Use of interferon and its inducers. In acute renal failure, uremia and hemorrhagic nephrosonephritis, hemodialysis is necessary.

Ribovirin and amixin are used. Currently, a specific human immunoglobulin liquid of targeted action has been developed for the treatment and emergency prevention against the Hantaan virus. In Russia, a killed vaccine against HFRS based on the K-27 strain of the Puumala virus has been developed, which is used according to epidemiological indications. It is necessary to exercise caution when working with the test material and the blood of patients.