Hemorrhagic fever with renal syndrome - Causes and epidemiology

Causes of hemorrhagic fever with renal syndrome

The cause of hemorrhagic fever with renal syndrome is an arbovirus of the Bunyaviridae family. The genus Hantavirus includes about 30 serotypes, 4 of which (Hantaan, Puumala, Seul and Dobrava/Belgrad) cause a disease known as hemorrhagic fever with renal syndrome. The hemorrhagic fever with renal syndrome virus has a spherical shape: 85-120 nm in diameter. It contains four polypeptides: nucleocapsid (N), RNA polymerase and membrane glycoproteins - G1 and G2. The viral genome includes three segments (L-, M-, S-) of single-stranded "minus" RNA; it 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 virus-neutralizing antibodies, while antibodies to the nucleocapsid protein are not able to neutralize the virus. The causative agent of hemorrhagic fever with renal syndrome can reproduce in chicken embryos, and is passaged on field mice, golden and Djungarian hamsters, and Fischer and Wistar rats. The virus is sensitive to chloroform, acetone, ether, benzene, and ultraviolet radiation; it is inactivated at 50 °C for 30 minutes, and is acid-labile (completely inactivated at pH below 5.0). It is relatively stable in the external environment at 4-20 °C and is well preserved at temperatures below -20 °C. It persists in blood serum taken from patients for up to 4 days at 4 °C.

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Pathogenesis of hemorrhagic fever with renal syndrome

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

• Infection. The virus enters through the mucous membranes of the respiratory and digestive tracts, damaged skin, and reproduces in the lymph nodes and mononuclear phagocytic system.
• Viremia and generalization of infection. The virus disseminates and has an infectious-toxic effect on the receptors of the vessels and nervous system, which clinically corresponds to the incubation period of the disease.
• Toxic-allergic and immunological reactions (correspond to the febrile period of the disease). The virus circulating in the blood is captured by cells of the mononuclear-phagocytic system and, with normal immunoreactivity, is removed from the body. But if regulatory mechanisms are disrupted, antigen-antibody complexes damage the walls of arterioles, increasing the activity of hyaluronidase, the kallikrein-kinin system, resulting in increased vascular permeability and the development of hemorrhagic diathesis with plasmorrhea in the tissue. The leading place in the 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 correspond to the oliguric period of the disease). The result of the disorders developed under the influence of the virus are hemorrhagic, dystrophic and necrobiotic changes in the pituitary gland, adrenal glands, kidneys and other parenchymatous 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, resulting in the development of acute renal failure.
• Anatomical reparation, formation of stable immunity, restoration of impaired renal functions.

Epidemiology of hemorrhagic fever with renal syndrome

The main source and reservoir of the causative agent of hemorrhagic fever with renal syndrome are mouse-like rodents (bank vole, wood mouse, red-sided vole, Asian wood mouse, house mice and rats), which carry an asymptomatic infection and excrete the virus with urine and feces. Humans become infected mainly through airborne dust (when aspirating the virus from dried excrement of infected rodents), as well as through contact (through damaged skin and mucous membranes, when in contact with rodents or infected objects in the environment - hay, straw, brushwood), and through food (when consuming products contaminated with excrement of infected rodents and not heat-treated). Transmission of infection from person to person is impossible. The natural susceptibility of people is high, all age groups are susceptible to the disease. Men (70-90% of patients) aged 16 to 50 years are more likely to get sick, mainly agricultural workers, tractor drivers, and drivers. HFRS is less common in children (3-5%), women, and the elderly. The infection leaves a strong lifelong type-specific immunity. Natural foci of hemorrhagic fever with renal syndrome are widespread throughout the world, in the Scandinavian countries (Sweden, Norway, Finland), Bulgaria, the Czech Republic, Slovakia, Yugoslavia, Belgium, France, Austria, Poland, Serbia, Slovenia, Croatia, Bosnia, Albania, Hungary, Germany, Greece, and the Far East (China, North Korea, South Korea). The seasonality of the disease is clearly expressed: from May to December.

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