Hemorrhagic fever with renal syndrome: causes and epidemiology

Causes of hemorrhagic fever with renal syndrome

The cause of hemorrhagic fever with renal syndrome is arbovirus family Bunyaviridae. Of the genus Hantavirus, including about 30 serotypes, 4 of which (Hantaan, Puumala, Seul and Dobrava / Belgrad) cause a disease known as hemorrhagic fever with kidney syndrome. The hemorrhagic fever virus with renal syndrome has a spherical shape: a diameter of 85-120 nm. Contains four polypeptides: nucleocapsid (N), RNA polymerase and glycoproteins of the membrane - G1 and G2. The genome of the virus includes three segments (L-, M-, S-) of single-stranded "minus" -RNA; replicates in the cytoplasm of infected cells (monocytes, lung cells, kidneys, liver, salivary glands). Antigenic properties are due to the presence of nucleocapsid antigens and surface glycoproteins. Surface glycoproteins stimulate the formation of viral neutralizing antibodies, while antibodies to the nucleocapsid protein are not capable of neutralizing the virus. The causative agent of hemorrhagic fever with kidney syndrome is able to reproduce in chick embryos, passivated in field mice, golden and Dzhungar hamsters, rats Fisher and Wistar. The virus is sensitive to chloroform, acetone, ether, benzene, ultraviolet radiation; inactivated at 50 ° C for 30 minutes, acid-labile (completely inactivated at pH below 5.0). Relatively stable in the external environment at 4-20 ° C, well preserved at a temperature below -20 ° C. In the blood serum taken from patients, it persists up to 4 days at 4 ° C.

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

Pathogenesis of hemorrhagic fever with renal syndrome

Hemorrhagic fever with renal syndrome and its pathogenesis have not been studied enough. The pathological process proceeds in stages; several stages are distinguished.

• Infection. The virus is introduced through the mucous membranes of the respiratory, digestive tracts, damaged skin and reproduced in the lymph nodes and mononuclear-phagocytic system.
• Viralemia and generalization of infection. There is a dissemination of the virus and its infectious-toxic effects on the receptors of blood vessels and the nervous system, which clinically corresponds to the incubation period of the disease.
• Toxico-allergic and immunological reactions (correspond to the febrile period of the disease). The virus circulating in the blood captures the cells of the mononuclear-phagocytic system and is removed from the body with normal immunoreactivity. But in violation of regulatory mechanisms, antigen-antibody complexes damage arteriolar walls. Increasing the activity of hyaluronidase, kallikrein-kinin system, as a result of which vascular permeability increases and hemorrhagic diathesis develops with plasmorea in the tissue. The leading place in pathogenesis also belongs to cellular immunity factors: cytotoxic lymphocytes, NK cells and proinflammatory cytokines (IL-1, TNF-a, IL-6). Which have a damaging effect on virus-infected cells.
• Visceral lesions and metabolic disorders (clinically consistent with the oliguric period of the disease). The result of the developed under the influence of the virus are hemorrhagic, dystrophic and necrobiotic changes in the pituitary gland, adrenal glands, kidneys and other parenchymal organs (manifestation of DIC syndrome). The greatest changes are noted in the kidneys - a decrease in glomerular filtration and a violation of tubular reabsorption, which leads to oliguria. Azotemia, proteinuria, acid-base and water-electrolyte imbalance, as a result of which OPN develops.
• Anatomical reparation, the formation of persistent immunity, restoration of impaired renal function.

Epidemiology of hemorrhagic fever with renal syndrome

The main source and reservoir of the causative agent of hemorrhagic fever with renal syndrome are mouse rodents (red vole, forest mouse, red-gray vole, Asian forest mouse, house mice and rats) that tolerate an asymptomatic infection and excrete the virus with urine and feces. Infection of people takes place mainly by airborne dust (with aspiration of the virus from dried feces of infected rodents), as well as by contact (through damaged skin and mucous membranes, in contact with rodents or infected objects of the environment - hay, straw, brushwood), as well as alimentary (with the use of products contaminated with secretions of infected rodents and those who have not undergone thermal treatment). Transmission of infection from person to person is impossible. The natural susceptibility of people is high, diseases are affected by all age groups. Men are more often ill (70-90% of patients) from 16 to 50 years. Mainly agricultural workers, tractor drivers, drivers. Less often, HFRS is registered in children (3-5%), women and the elderly. The transferred infection leaves persistent lifelong type-specific immunity. Natural foci of hemorrhagic fever with renal syndrome are common all over the world, in Scandinavian countries (Sweden, Norway, Finland), Bulgaria, Czech Republic, Slovakia, Yugoslavia. Belgium, France, Austria, Poland. Serbia, Slovenia, Croatia, Bosnia, Albania, Hungary, Germany, Greece, the Far East (China, North Korea, South Korea). The seasonality of the morbidity is clearly expressed: from May to December.

[7], [8], [9], [10], [11]