Search

In Russia, 131,590 cases of hemorrhagic fever with renal syndrome caused by 6 different hantaviruses were reported during 2000-2017. Most cases, 98.4%, were reported in western Russia. The average case-fatality rate was 0.4%, and strong regional differences were seen, depending on the predominant virus type.

267 Hemorrhagic fever with renal syndrome (HFRS) is a nontransmissible viral zoonosis that is widespread in Europe and ranks first among infections with natural focality in Russia. The agents of HFRS belong to the genus Hantavirus of the family Bunyaviridae, which currently comprises more than 30 genoand sero� types. Natural reservoir hosts for all hantaviruses pathogenic for humans are some small mammals of the families Muridae and Cricetidae, with virus-host relationships having been established in the course of longterm coevolution (Plyusnin and Morzunov, 2001). In the twocomponent parasitic system of han� taviral zoonoses, the main warmblooded hosts become directly involved in horizontal virus transmis� sion and are the only source of infection for humans. The absolute majority of HFRS cases in Russia are caused by Puumala virus (>95%), whose main reser� voir host (and source of human infection) in nature is the bank vole ( Myodes glareolus), a species widespread in the forest and forest-steppe zones of Europe, Euro� pean Russia, and Transural region. The most active foci of Puumala HFRS concentrate in the optimum of M. glareolus range. This optimum lies in broadleaf and conifer-broadleaf forest with a large proportion of lin� den, which, in particular, are characteristic of the Middle Volga and Cisural regions (Bashenina et al., 1981b; Bernshtein, Gavrilovskaya, and Apekina, 2010). More than 30 years have passed since the agent of HFRS was identified, and abundant data on the genetic structure, distribution, and evolution of differ� ent hantaviruses and their phylogenetic relationships with warmlooded hosts have been obtained during this period/ However, the mechanisms of functioning of natural hantavirus foci in forest subzones have not been studied adequately, and the task of making a reli� able forward prognosis of morbidity from zoonotic infections often remains unsolved (Zhigalski, 2012). Therefore, the purposes of our research were (1) to identify the main factors determining the activity of forest foci of HFRS associated with Puumala virus, and (2) to develop a prognostic model of the function� ing of HPRS foci and verify it with reference to the data of longterm monitoring of HFRS endemic areas in the Republic of Udmurtia. This paper is based on the results of integrated studies on HRFS foci in the Republic of Udmurtia, including zoological and epidemiological monitoring for 38 years (1973-2010) and epizootiological moni� toring performed in all seasons for 15 years (1981- 1995) and then in August for 10 years (1981-2005). Annual data on meteorological parameters and seed production in the main tree species were available for the entire observation period. Trapline censuses of bank voles were regularly taken four times a year by standard methods (Karaseva, Telitsina, and Zhigalski, 2008), recording animal age and reproductive status. The starting date of the breeding season was estimated from the reproductive status of females and the age composition of population in April. Animals with viral antigen in the lungs (active virus carriers) were identi� fied by an immunoenzyme assay (Bernshtein, Gavrilovskaya, and Apekina, 2010). On the whole, field work in sample plots amounted to about 20000 trap- days, and more than 10000 bank voles were examined. Analysis of HFRS incidence was based on the absolute numbers of confirmed human cases recorded per epi� demiological season. This parameter was also used to estimate epidemic activity in the endemic area of the

The frequency of chromosome damage was studied in the carriers of virus of the hemorrhagic fever with renal syndrome (Puumala virus) and in noninfected animals from two laboratory colonies and two natural populations of bank vole. In the laboratory colony, where Puumala virus persisted for three years, multiaberrant (“rogue”) cells were found in the bone marrow; the mean frequencies of both structural and numeral chromosome abnormalities were significantly enhanced. In the other laboratory colony, no Puumala virus was detected during all 30 years of its existence, but the mean frequencies of structural chromosome damage were increased to the same degree probably due to the prolonged breeding under laboratory conditions, which resulted in suppression of immunity and DNA repair. The voles from the natural populations were more resistant to the clastogenic viral effect, but they also had multiaberrant cells which served as indicators of viral infection. The data obtained support the hypothesis that viral infections increase mutation rate, contributing thereby to the evolution process.

Specific features of hantavirus infection in bank vole (Clethrionomys glareolus) were studied in the endemic area of hemorrhagic fever with renal syndrome (HFRS) in the foothills of the Ural mountains, using long-term observations on living animals by the capture-mark-recapture (CMR) method. The results demonstrated that the infection naturally circulating in the voles is chronic (lasting for up to 15 months) and asymptomatic, with a peak of Puumala virus accumulation and release from the organism during the first month after infection. It was shown that the bank vole population includes young animals with maternal immunity, which remain resistant to the Puumala virus infection for 3-3.5 months. The infection rate in voles depended on the age and sexual maturity of animals. The greatest proportion of seropositive animals was observed among overwintered males. Seroconversion in voles was more frequent during the period of high reproductive activity.

From 2000 to 2011 85 600 cases of hemorrhagic fever with renal syndrome (HFRS) were registered in Russian Federation. Epidemically active foci of HFRS infection are located generally in temperate latitudes of the European part and the Far East. In the Far East regions whose fraction of all the HFRS disease cases in Russia is around 2%, the causative agents of the infection are Hantaan, Amur, Seoul hantaviruses, the natural reservoir for those are striped field mouse, Korean field mouse and brown rat. In the European part of Russia the causative agent of the infection are Puumala hantavirus as well as 2 genetic subtypes of Dobrava virus, the main reservoirs of those in the nature are bank vole, striped field mouse and Black Sea field mouse, respectively. 9 strain of Puumala and 10 strains of Dobrava virus were isolated. Based on sequencing of Dobrava virus strains significant differences were detected between Dobrava virus strains isolated from Black Sea field mouse from Sochi and striped field mouse from Lipetsk Region. Cultural inactivated vaccine against HFRS was developed and completed preclinical trials.

An immunoglobulin G avidity assay was used to determine recent and past hantavirus infection in bank voles (Clethrionomys glareolus). Sera of experimentally infected bank voles were studied at different time intervals. The avidity of specific IgG increased over time after infection. This experimental data were used to estimate the time after onset of hantavirus infection in naturally infected bank voles caught in an endemic area. The possibility to discriminate between recently infected animals and animals infected some time ago is important since the proportion of recently infected bank voles represents the intensity of the epizootic which in turn correlates to the risk of humans to contract the disease.

Inapparent, persisting hantavirus infection was demonstrated in bank voles (Clethrionomys glareolus) after experimental infection with strain Kazan 6 C.g. isolated in the U.S.S.R. Virus, viral antigen, antibodies, and the capacity for horizontal transmission of infection were demonstrable throughout the period of observation (13 months), the highest titers being observed 10–20 days postinfection. Direct correlation was detected between the intensity of horizontal transmission and the level of humoral immunity. The progeny of infected females were shown to be passively immune for 30–45 days after birth and to be relatively resistant to infection with strain Kazan 6 C.g. during that period.

Data were analyzed on the dynamics of two neighbouring populations of Clethrionomys glareolus with a similar fluctuation pattern dwelling in broad-leaved forests north of the forest-steppe zone (54°45'N, 37°40'E). Censuses, using trap-lines, and investigation of the demographic structure were conducted simultaneously from April to October during 1966-1976 in Population 1 and during 1972-1981 in Population 2.

Four strains of haemorrhagic fever with renal syndrome virus (HFRSV) from rodents or patients in European U.S.S.R. foci of HFRS were isolated in laboratory bred C. glareolus. The sensitivity of these animals to HFRSV was compared with that of five other laboratory and wild animals.

The use of indirect fluorescent antibody testing (IFAT) and enzyme linked immunosorbant assay (ELISA) procedures allowed the hemorrhagic fever with renal syndrome (HFRS) virus antigen to be detected not only in the known reservoir host, Clethrionomys glareolus, but also in 7 other species of small mammals in European foci of the U.S.S.R. Marked viscerotropism of HFRS virus and the participation of brown fat in maintaining the infection in rodents were demonstrated. The frequency of detection of circulating antigen and antibody to HFRS virus in rodents is indicative of the high level of activity of the virus in its epizootic foci.