Hemorrhagic fever virus with renal syndrome

Hemorrhagic fever with renal syndrome (HFRS) is an acute serious infectious disease characterized by systemic lesions of small vessels, hemorrhagic diathesis, hemodynamic disorders and peculiar 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 family Bunyaviridae. Hantaviruses have a spherical shape, a lipid-containing membrane; the diameter of the virion is 90-120 nm. The shell has protuberances formed by glycoproteins. The genome of the virus is a segmented single-stranded negative RNA. Three segments: large (L), medium (M) and small (S) encode viral RNA polymerase, enveloped glycoproteins (G1 and G2), and nucleocapsid, respectively. The initiation of transcription in hantaviruses occurs in the same way as in influenza A virus: a cap (cap) from cell mRNA is cut off with the help of a virion endonuclease entering the RNA polymerase complex. The cap serves as primer - 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 prone to frequent mutations. To date, the genus Hantavirus includes more than 25 serologically and genetically different from each other viruses. They are divided into viruses of the Old World (Hantaan, Seoul, Pumala, Dobrava / Belgrade, Khabarovsk, Thailand-Tottopalayama, etc.) and viruses of the New World (Prospect Hill, Sin Nombre, New York, Andes, Bayon, Laguna Negra, ). They cause two clinical forms of hantavirus infection in humans: hemorrhagic fever with kidney syndrome (pathogens - Hantaan, Seoul, etc.) and hantavirus cardiopulmonary syndrome (HCPS), the causative agents of which are the viruses of Sin Nombre, New York, Bayon, Andes, Laguna Negra and, perhaps, others.

Hantaviruses are ubiquitous.

[1], [2], [3], [4], [5], [6], [7], [8], [9], [10]

Pathogenesis of hemorrhagic fever with renal syndrome

Penetrating into the body, the virus circulates in the blood, affecting the walls of capillaries and small veins, especially in the vessels of the medulla of the kidneys. 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 throughout the febrile period. Immune complexes of viral antigen + antibody are deposited in glomerular cells and convoluted tubules of the kidneys, which causes renal syndrome.

Immunity

After the disease, a persistent, prolonged, is caused by virus neutralizing antibodies and immune memory cells.

Epidemiology of hemorrhagic fever with renal syndrome

Infection with hantaviruses comes from rodents airborne, contact or alimentary, but not transmissive. Viruses transmitted in this way are called roboviruses (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, Ural and Volgo-Vyatsky regions, and also in Primorsky Krai. Natural infection with hantaviruses of more than 50 species of small mammals belonging to different families from orders of rodents and insectivores has been established. A widely accepted hypothesis was that each hantavirus in natural conditions is associated with a single species of small mammals. However, the question of the actual number of hantaviruses existing in nature and the types of their main carriers requires further study.

In animals, infection with hantaviruses develops an asymptomatic infection, during which viral antigens can be detected in many organs, mainly in the lungs. The virus is for a long time allocated in animals with saliva, feces and urine. Infection of a person occurs through the air. The virus, together with the aerosol containing the products of the rodents' vital activity, enters the lungs through the upper respiratory tract, where the conditions for its reproduction are most favorable, then it is transferred to the blood with other organs and tissues. Infections of healthy people from the patient does not occur.

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Symptoms of hemorrhagic fever with kidney syndrome

The incubation period is 11-23 days. The disease begins with a chill, raising the temperature to 39-40 ° C. There is a severe headache, hyperemia of the face and neck, injection of scleral vessels, from the 3-5th day of the disease there is a hemorrhagic rash on the skin and oliguria occurs, in severe cases - anuria and uremia. Recovery is slow. Renal function is restored in 1-3 months. Completely. There is no transition of hemorrhagic fever with renal syndrome into a chronic form. Along with the severe form of hemorrhagic fever with renal syndrome (hemorrhagic nephrozonephritis), erased, light and moderate forms of the disease are observed. The lethality varies from 0 to 44%.

Laboratory diagnostics of hemorrhagic fever with renal syndrome

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

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

Apply ribovirin and amixin. Currently, for the treatment and emergency prophylaxis against the Hantaan virus, a specific human immunoglobulin has been developed. In Russia, a deadly vaccine against HFRS was developed based on the K-27 strain of the Puumala virus, which is used for epidemiological reasons. Care must be taken when working with the test material and blood of patients.