Many zoonotic diseases are caused by rodent-borne viruses. Major fluctuations in the transmission of these viruses have been related to large changes in reservoir host population numbers due to external factors. However, the impact of the pathogen itself on the demography of its reservoir host is often overlooked. We investigated the impact of Puumala virus (PUUV) on survival and reproductive maturation probability of its reservoir host, the bank vole (Myodes glareolus). Three years (2004-06) of data from nine independent sites in southern Belgium were collected and analyzed with a capture-mark-recapture (CMR) method that includes statistical correction for the variation in capture probability of voles. A multistate model based on four states of reproductive activity and PUUV immunoglobulin G (IgG) antibody status was used to estimate survival and probability of transition from one reproductive or infection state to another. Although survival estimates for reproductively active voles were similar between infected and noninfected individuals, PUUV infection in reproductively inactive voles decreased mean monthly survival by 14%. PUUV infection was associated with a threefold increase in the probability of reproductive maturation in bank voles. Moreover, the probability of PUUV IgG seroconversion was three times higher for reproductively active voles compared to reproductively inactive voles. Our model indicates that PUUV infection may alter bank vole population dynamics by affecting both survival and maturation in its host. Additional studies, using CMR methodology with shorter time intervals between trapping sessions and possibly a longer duration, are needed to confirm these findings.

Differences between male and female individuals in response to infectious diseases are an overlooked global health problem.The relationship between sex and disease outcome was examined in populations of patients with hemorrhagic fever with renal syndrome (HFRS) in mainland China, where most cases of hantavirus exposure occur. HFRS in China is diagnosed on the basis of symptoms and is confirmed with serological testing. The geographical distribution, incidence, and case fatality rates (CFRs) of HFRS in China were estimated and compared by patient sex and age. In a subset of patients with HFRS, clinical manifestations of HFRS were assessed using latent class analysis and compared by sex.There were 80,671 HFRS cases reported during the period 2004-2008, with a majority of HFRS cases (39.2%) occurring among individuals 20-39 years of age. The incidence of HFRS was higher among male patients than among female patients for all individuals >10 years of age. There were 945 deaths (CFR, 1.17%) due to HFRS in China during the period 2004-2008. CFRs were higher among women than among men between the ages of 20-39 and ≥ 50 years of age. There were no sex differences in the geographical distribution of HFRS cases or deaths. Although the prevalence of each clinical marker did not differ by sex, 2 profiles of clinical markers were identified that were related to both severity of disease and sex.These data illustrate a paradox in which the incidence of disease is greater for males, but the severity of disease outcome is worse for females. Several behavioral, societal, and biological factors are hypothesized to be involved.

Hemorrhagic fever with renal syndrome (HFRS) is a serious public health problem in China, and is primarily caused by either the Hantaan virus (HTNV) or Seoul virus (SEOV) strains. However, the causative hantavirus has only been definitively identified in a few HFRS cases, and detailed comparisons of patient data for the 2 strains are limited.We conducted a 1-y prospective study in Heilongjiang Province, China. A total of 152 patients from 3 hospitals met the HFRS diagnostic criteria used in China. The diagnosis was further confirmed by specific immunoglobulin M to HTNV or SEOV. In addition, serum samples were tested for the presence of HTNV or SEOV using a reverse transcription-polymerase chain reaction (RT-PCR). Clinical manifestations and laboratory findings in patients with the 2 hantaviruses were subsequently compared.Eighty (61.1%) HTNV and 51 (38.9%) SEOV infections were identified. Fever and proteinuria, key to the diagnosis of HFRS, were observed in all patients. The clinical manifestations of hemorrhage and renal injury from SEOV infection were milder than those of HTNV infection. Interestingly, compared to patients with HTNV infection, patients with SEOV presented with a significantly longer febrile period, more normal white blood cell counts or even transient leukocytopenia, a higher incidence of liver injury related to disease severity, and a lower occurrence of the 5 typical phases of HFRS. The mortality was 6.3% in HTNV infections and 0% in SEOV infections.Clinical manifestations of SEOV infection appear to be milder and less typical than HTNV. This information may help us to improve the diagnosis of SEOV-infected patients.

Puumala virus (PUUV), the causal agent of nephropathia epidemica in humans, is one of the many hantaviruses included in the list of emerging pathogens. Hantavirus infection is not distributed evenly among PUUV reservoir hosts (i.e., bank voles [Myodes glareolus]). Besides environmental factors and local population features, individual characteristics play an important role in vole PUUV infection risk. Identifying the relative importance of these individual characteristics can provide crucial information on PUUV transmission processes. In the present study, bank voles were monitored during the nephropathia epidemica outbreak of 2005 in Belgium. Vole sera were tested for presence of immunoglobulin G against PUUV, and a logistic mixed model was built to investigate the temporal variation in individual characteristics and their relative importance to PUUV infection risk in bank voles. Relative risk calculations for individual vole characteristics related to PUUV infection in the reservoir host show that reproductive activity dominates infection risk. The gender effect is only found in reproductively active voles, where reproductively active males have the highest infection risk. Results also revealed a clear seasonal variation in the importance of reproductive activity linked to PUUV infection. In contrast to the main effect found in other trapping sessions, no difference in infection risk ratio was found between reproductively active and nonactive voles in the spring period. Combined with increased infection risk for the reproductively nonactive group at that time, these results indicate a shift in the transmission process due to changes in bank vole behavior, physiology, or climate conditions. Hence, our results suggest that mathematical models should take into account seasonal shifts in transmission mechanisms. When these results are combined with the seasonal changes in population structure during the epizootic period, we identify vole reproductive activity and length of the breeding season as potential drivers of PUUV epizootics in west-central European regions.

The clinical course and outcome of patients with haemorrhagic fever with renal syndrome (HFRS) caused by Puumala (PUUV) and Dobrava viruses (DOBV) were analyzed and whether it left long-term consequences on kidney function after 10 years was evaluated.Cross-sectional studies were conducted to test the kidney function and blood pressure of HFRS-affected patients and to follow them up 10 years after. Eighty-two PUUV- and 53 DOBV-induced HFRS patients and 14 and 31 participants 10 years after having contracted PUUV- and DOBV-related diseases, respectively were evaluated.Serum creatinine concentrations were 279.5 and 410 mcmol/L in PUUV and DOBV groups, respectively (P = 0.005). There were six and 13 anuric (P < 0.05), none and seven dialysis-dependant (P < 0.05), and nine and 18 hypotensive patients (P < 0.05) in PUUV and DOBV groups, respectively. After 10 years, glomerular filtration rates were 122.1 + or - 11.1 and 104.7 + or - 20.2 mL/min (P < 0.05) in PUUV and DOBV groups, respectively.During the acute phase, DOBV causes more severe renal impairment than PUUV infection. After 10 years follow up, renal function was found within normal limits, although after DOBV infection glomerular filtration rate (GFR) was significantly lower than after PUUV infection.

Study of hantavirus infections in India is in its early stages. As early symptoms of hantavirus disease can be non-specific and the diagnosis confirmed only by laboratory testing, use of appropriate diagnostic tools is important. To improve the diagnosis of hantavirus infections in India, commercial ELISA systems followed by indirect immunofluorescence assays were used to detect anti-hantavirus IgM and IgG in samples from patients with acute febrile illness. Of 347 patients tested, 5.2% showed serological evidence of hantavirus infection. Sequences obtained from patients showing molecular evidence of hantavirus infection were related to Hantaan virus. In the absence of mu-capture ELISA, we recommend the use of combination testing systems in areas non-endemic for hantavirus infections. In India there is an increased risk of rodent-borne infections and the differential diagnosis of undifferentiated febrile illness should include hantavirus infection.

Hemorrhagic fever with renal syndrome (HFRS) is an important public health problem in the People's Republic of China, accounting for 90% of human cases reported globally. In this study, a landscape epidemiologic approach, combined with geographic information system and remote sensing techniques, was applied to increase our understanding of HFRS due to Hantaan virus and its relationship with landscape elements in China. The landscape elements considered were elevation, normalized difference vegetation index (NDVI), precipitation, annual cumulative air temperature, land surface temperature, soil type, and land use. Multivariate logistic regression analysis showed that HFRS incidence was remarkably associated with elevation, NDVI, precipitation, annual cumulative air temperature, semihydromorphic soils, timber forests, and orchards. These findings have important applications for targeting HFRS interventions in mainland China.

Results of the serologic confirmation of hemorrhagic fever with renal syndrome (HFRS) in patients with clinical picture and overt symptoms of the disease from particular areas in Bosnia and Herzegovina during 2002 are presented.A total of 146 sera from 100 clinically suspected patients were tested. The sera were tested for the presence of specific IgM antibodies to Hantaan and Puumala antigens by Elisa IgM "capture" test, and for the presence of specific antibodies to Hantaan, Puumala and Dobrava antigens by Elisa IgG test.Most of the positive IgM reactions were recorded as cross reactions to Hantaan and Puumala antigens, and most of the positive IgG reactions as cross reactions to Hantaan and Dobrava antigens. The finding of antibodies in the sera of patients from Europe that react with Hantaan antigen are not associated with the infection with Hantaan, but with the infection with viruses that are genetically related with Hantaan. To date, HFRS caused by Puumala and Dobrava viruses has been verified in Bosnia and Herzegovina.Using Elisa IgM "capture" test, acute hantavirus infection was serologically confirmed in 38% of clinically suspected patients with manifested symptoms from different areas of Bosnia and Herzegovina in 2002. The distribution of human hantavirus infection in Bosnia and Herzegovina was confirmed by the presence of specific hantavirus antibodies in patient sera.

Bosnia and Herzegovina has been known as a highly endemic region for Hantavirus infections for more than 50 years. Previous studies have shown that at least two different hantaviruses, the murine Dobrava (DOB) and avricoline Puumala (PUU) viruses, each carried by a different rodent species, have been circulating in the area. However, there is little information on rodent population density fluctuations in Bosnia over the past years as well as on the ratio of Puumala to Dobrava infection in humans.The aims of our study were: to identify the rodent species which may serve as hantavirus reservoirs in the north-east and central Bosnia; to assess the geographical distribution, density and population dynamics of rodent species in the area; to assess the influence of climatic conditions on the size of rodent population; and to determine the ratio of Puumala to Dobrava infection in humans.The epidemiologic and epizootic study in the north-east and central Bosnia was conducted during the 8-year period (1995-2003). The average yearly and monthly temperatures, air humidity and precipitation during the study period were analyzed. A total of 381 small rodents were caught during the epidemic years (1995 and 2002), and in-between the epidemic periods (1999 and 2000). The animals were caught by live-traps and identified by morphometric methods. The density of animals was estimated by counting the number of holes per 1000 m2. Sera of 311 patients with clinical signs and symptoms of hemorrhagic fever with renal syndrome (HFRS) were tested for the presence of antibodies reactive to the Dobrava, Puumala and Seoul viruses by using indirect immunofluorescence test (IIF), and IgG and IgM ELIS. Sera of 84 patients were tested using only IIF, and 227 sera were tested by IIF and -capture IgM ELIS tests.During the epidemic years, the average monthly temperatures in February were by 4.3 times higher than the average temperatures during the nonepidemic years, which may have influenced the early reproduction of rodents and development of "mouse years". The rodents were identified as: Apodemus flavicollis (n = 139), Apodemus sylvaticus (n = 89), Apodemus agrarius (n = 4), Clethrionomys glareolus (n = 117), Sorex araneus (n = 5), Pytimus subterraneus (n = 23), Mus musculus (n = 1), Mycrotus arvalis (n = 1) and Rattus norvegicus (n = 2). Clethrionomys glareolus was predominant in the regions with the altitude higher than 1160 meters and Apodemus species in the regions with the altitude lower than 670 meters. The rodent population density changes seasonally and cyclically. During the epidemic years, the rodent population density was marked as very high, whereas during the nonepidemic years it was designated from low to moderate. Well-known natural hosts of Hantaviruses (A. flavicolis and C. glareolus) are most widely spread species of small rodents, and the increase in their population is closely related with outbreaks of epidemics of HVBS-a. Puumala virus caused HVBS-a in 49.84% (155/311); Dobrava virus in 23.15% (72/311) of cases, whereas Hantaviruses serotype was not identified in 27.00% (84/311) of cases. Infections caused by Puumala virus were more frequent than the infections caused by Dobrava virus during both epidemic and nonepidemic periods. The proportion of humans infected with Puumala and Dobrava viruses correlated with the number of natural hosts of Hantaviruses in the areas of HVBS outbreaks. The study of the prevalence of hantavirus antibodies in the populations of rodents and humans, which had been under way, should elucidate these relationships.

Hemorrhagic fever with renal syndrome (HFRS) is endemic in East Asia and Europe. The disease is caused by several viruses belonging to the genus Hantavirus, including the Hantaan virus (HTNV), Seoul virus (SEOV), Dobrava Belgrade virus (DOBV), and Puumala virus (PUUV). Recently, HTNV-related viruses, Amur (AMR) and Far East (FE) genotypes were identified as causative agents of HFRS in Far Eastern Russia. To investigate the epidemiology of HFRS and virus transmission, we collected sera from 17 acute and 32 convalescent patients who were clinically diagnosed with HFRS in the Khabarovsk region of Far Eastern Russia, and detected anti-hantavirus antibodies using an ELISA that can differentiate the infected virus serotype using truncated hantavirus nucleocapsid protein antigen. Sixteen of the 17 acute phase patients had antibodies to hantavirus, and all the positive sera had higher optical densities for HTNV-specific antigen than for SEOV-, DOBV-, or PUUV-specific antigens. The partial M segment of the viral genome was amplified from blood clots from three acute patients by PCR. The nucleotide sequences had closer identities to the FE genotype (>96%) than to the prototype HTNV (88 to 89%) or AMR genotype (81 to 83%). A phylogenetic analysis found that the virus sequences from the patients clustered with the FE type, and were distinct from the AMR type. Thirty-one of 32 convalescent patient sera had antibodies to HTNV-specific antigen. These data suggest that our ELISA system can detect HTNV-specific antibodies to the FE type, which may be responsible for most of the HFRS in Khabarovsk.