In 2017 Zagreb faced the largest outbreak of haemorrhagic fever with renal syndrome (HFRS) to date. We investigated to describe the extent of the outbreak and identify risk factors for infection. We compared laboratory-confirmed cases of Hantavirus infection in Zagreb residents with the onset of illness after 1 January 2017, with individually matched controls from the same household or neighbourhood. We calculated adjusted matched odds ratios (amOR) using conditional logistic regression. During 2017, 104 cases were reported: 11–81 years old (median 37) and 71% (73) male. Compared with 104 controls, cases were more likely to report visiting Mount Medvednica (amOR 60, 95% CI 6–597), visiting a forest (amOR 46, 95% CI 4.7–450) and observing rodents (amOR 20, 95% CI 2.6–159). Seventy per cent of cases (73/104) had visited Mount Medvednica prior to infection. Among participants who had visited Mount Medvednica, cases were more likely to have drunk water from a spring (amOR 22, 95% CI 1.9–265), observed rodents (amOR 17, 95% CI 2–144), picked flowers (amOR 15, 95% CI 1.2–182) or cycled (amOR 14, 95% CI 1.6–135). Our study indicated that recreational activity around Mount Medvednica was associated with HFRS. We recommend enhanced surveillance of the recreational areas during an outbreak.

Puumala hantavirus (PUUV) causes hemorrhagic fever with renal syndrome in humans, that is an endemic disease in Finland. We estimated the seroprevalence of PUUV in Finland and explored risk factors and disease associations by using unique survey data with health register linkage. A total of 2000 sera from a nationwide health survey from 2011, representative of the adult population, were screened for PUUV IgG by immunofluorescence assay. We performed statistical analysis adjusting for stratified cluster design and taking into account sampling weights. In total, 254 sera among 2000 tested were PUUV-IgG-positive resulting in a weighted seroprevalence of 12.5%, (95% CI 10.9–14.4), mirroring known age and regional variation in reported incidence. No associations between PUUV-seropositivity and chronic diseases including cardiovascular (including hypertension), pulmonary, kidney disease and cancer were observed. Smoking was significantly associated with seropositivity (adjusted OR 1.54; 95% CI 1.16–2.04). In addition, significant dose-response relations were found for the number of cigarettes smoked daily (OR 1.14; 95% CI 1.12–1.28). The results are important for disease burden assessment and guide intervention strategies, highlighting also the role of smoking prevention.

As part of further investigations into three linked haemorrhagic fever with renal syndrome (HFRS) cases in Wales and England, 21 rats from a breeding colony in Cherwell, and three rats from a household in Cheltenham were screened for hantavirus. Hantavirus RNA was detected in either the lungs and/or kidney of 17/21 (81%) of the Cherwell rats tested, higher than previously detected by blood testing alone (7/21, 33%), and in the kidneys of all three Cheltenham rats. The partial L gene sequences obtained from 10 of the Cherwell rats and the three Cheltenham rats were identical to each other and the previously reported UK Cherwell strain. Seoul hantavirus (SEOV) RNA was detected in the heart, kidney, lung, salivary gland and spleen (but not in the liver) of an individual rat from the Cherwell colony suspected of being the source of SEOV. Serum from 20/20 of the Cherwell rats and two associated HFRS cases had high levels of SEOV-specific antibodies (by virus neutralisation). The high prevalence of SEOV in both sites and the moderately severe disease in the pet rat owners suggest that SEOV in pet rats poses a greater public health risk than previously considered.

Recent cases of acute kidney injury due to Seoul hantavirus infection from exposure to wild or pet fancy rats suggest this infection is increasing in prevalence in the UK. We conducted a seroprevalence study in England to estimate cumulative exposure in at-risk groups with contact with domesticated and wild rats to assess risk and inform public health advice. From October 2013 to June 2014, 844 individual blood samples were collected. Hantavirus seroprevalence amongst the pet fancy rat owner group was 34.1% (95% CI 23·9–45·7%) compared with 3·3% (95% CI 1·6–6·0) in a baseline control group, 2·4% in those with occupational exposure to pet fancy rats (95% CI 0·6–5·9) and 1·7% with occupational exposure to wild rats (95% CI 0·2–5·9). Variation in seroprevalence across groups with different exposure suggests that occupational exposure to pet and wild rats carries a very low risk, if any. However incidence of hantavirus infection among pet fancy rat owners/breeders, whether asymptomatic, undiagnosed mild viral illness or more severe disease may be very common and public health advice needs to be targeted to this at-risk group.

Hantaviruses are globally distributed and cause severe human disease. Puumala hantavirus (PUUV) is the most common species in Northern Europe, and the only hantavirus confirmed to circulate in Sweden, restricted to the northern regions of the country. In this study, we aimed to further add to the natural ecology of PUUV in Sweden by investigating prevalence, and spatial and host species infection patterns. Specifically, we wanted to ascertain whether PUUV was present in the natural reservoir, the bank vole (Myodes glareolus) further south than Dalälven river, in south-central Sweden, and whether PUUV can be detected in other rodent species in addition to the natural reservoir. In total, 559 animals were collected at Grimsö (59°43′N; 15°28′E), Sala (59°55′N; 16°36′E) and Bogesund (59°24′N; 18°14′E) in south-central Sweden between May 2013 and November 2014. PUUV ELISA-reactive antibodies were found both in 2013 (22/295) and in 2014 (18/264), and nine samples were confirmed as PUUV-specific by focus reduction neutralization test. Most of the PUUV-specific samples were from the natural host, the bank vole, but also from other rodent hosts, indicating viral spill-over. Finally, we showed that PUUV is present in more highly populated central Sweden.

Puumala virus (PUUV) causes many human infections in large parts of Europe and can lead to mild to moderate disease. The bank vole (Myodes glareolus) is the only reservoir of PUUV in Central Europe. A commercial PUUV rapid field test for rodents was validated for bank-vole blood samples collected in two PUUV-endemic regions in Germany (North Rhine-Westphalia and Baden-Württemberg). A comparison of the results of the rapid field test and standard ELISAs indicated a test efficacy of 93–95%, largely independent of the origin of the antigens used in the ELISA. In ELISAs, reactivity for the German PUUV strain was higher compared to the Swedish strain but not compared to the Finnish strain, which was used for the rapid field test. In conclusion, the use of the rapid field test can facilitate short-term estimation of PUUV seroprevalence in bank-vole populations in Germany and can aid in assessing human PUUV infection risk.

Puumala hantavirus (PUUV) causes haemorrhagic fever with renal syndrome in humans, an endemic disease in Finland. We aimed to study recent trends in PUUV infections in Finland, to evaluate whether there are regional differences in seasonality and long-term cycles and whether the patterns have changed over time. We analysed serologically confirmed acute PUUV infections reported to the National Infectious Disease Register from 1 April 1995 to 31 March 2014. A total of 30 942 cases of PUUV infections were identified during the study period. The average annual incidence was 31 cases/100 000 person-years with the highest in Eastern Finland and the lowest in Southwestern Finland. Throughout Finland there was not an increasing trend in incidence but changes in incidence, seasonality and long-term cycles differed regionally. Long-term cycles supported by high Bayesian posterior probabilities (73–100%) differed between the south and the north, shifting from 3 to 4 years, respectively. Temporal changes in seasonality were most prominent in Southwestern Finland. The pattern of human PUUV infection epidemiology probably primarily reflects the spatio-temporal interaction between bank-vole population dynamics and climate.

This report summarizes epidemiological data on nephropathia epidemica (NE) in the Republic of Tatarstan, Russia. NE cases identified in the period 1997–2013 were investigated in parallel with the hantavirus antigen prevalence in small rodents in the study area. A total of 13 930 NE cases were documented in all but one district of Tatarstan, with most cases located in the central and southeastern districts. The NE annual incidence rate exhibited a cyclical pattern, with the highest numbers of cases being registered once in every 3–5 years. The numbers of NE cases rose gradually from July to November, with the highest morbidity in adult males. The highest annual disease incidence rate, 64·4 cases/100 000 population, was observed in 1997, with a total of 2431 NE cases registered. NE cases were mostly associated with visiting forests and agricultural activities. The analysis revealed that the bank vole Myodes glareolus not only comprises the majority of the small rodent communities in the region, but also consistently displays the highest hantavirus prevalence compared to other small rodent species.

Two global (re-)emerging zoonoses, leptospirosis and hantavirus infections, are clinically indistinguishable. Thirty-one patients, hospitalized in Sri Lanka for acute severe leptospirosis, were after exclusion of other potentially involved pathogens, prospectively screened with IgM ELISA for both pathogens. Of these, nine (29·0%) were positive for leptospirosis only, one (3·2%) for hantavirus only, seven (22·5%) for both pathogens concomitantly, whereas 13 (41·9%) remained negative for both. Moreover, in a retrospective study of 23 former patients, serologically confirmed for past leptospirosis, six (26·0%) were also positive in two different IgG ELISA hantavirus formats. Surprisingly, European Puumala hantavirus (PUUV) results were constantly higher, although statistically not significantly different, than Asian Hantaan virus (HTNV), suggesting an unexplained cross-reaction, since PUUV is considered absent throughout Asia. Moreover, RT–PCR on all hantavirus IgM ELISA positives was negative. Concomitant leptospirosis-hantavirus infections are probably heavily underestimated worldwide, compromising epidemiological data, therapeutical decisions, and clinical outcome.

Dobrava-Belgrade virus (DOBV) is the most pathogenic hantavirus in Europe with a case-fatality rate of up to 12%. To detect changes in risk for humans, the prevalence of antibodies to DOBV has been monitored in a population of Apodemus flavicollis in the province of Trento (northern Italy) since 2000, and a sudden increase was observed in 2010. In the 13-year period of this study, 2077 animals were live-trapped and mean hantavirus seroprevalence was 2·7% (s.e. = 0·3%), ranging from 0% (in 2000, 2002 and 2003) to 12·5% (in 2012). Climatic (temperature and precipitation) and host (rodent population density, rodent weight and sex, and larval tick burden) variables were analysed using Generalized Linear Models and multi-model inference to select the best model. Climatic changes (mean annual precipitation and maximum temperature) and individual body mass had a positive effect on hantavirus seroprevalence. Other possible drivers affecting the observed pattern need to be studied further.

The transmission of haemorrhagic fever with renal syndrome (HFRS) is deeply influenced by the reservoir and hantavirus prevalence rate. In this study, a surveillance on human HFRS cases, relative rodent abundance, and hantavirus infection prevalence was conducted in Shaanxi province, China, during 1984–2012. A generalized linear model with Poisson-distributed residuals and a log link was used to quantify the relationship between reservoir, virus and HFRS cases. The result indicated that there was a significant association of HFRS incidence with relative rodent density and the prevalence rate. This research provides evidence that the changes of infection prevalence in the reservoir could lead directly to the emergence of a new epidemic. It was concluded that the measurement of a number of these variables could be used in disease surveillance to give useful advance warning of potential disease epidemics.

An outbreak of haemorrhagic fever with renal syndrome (HFRS) started on Medvednica mountain near Zagreb in January 2012. In order to detect the aetiological agent of the disease in small rodents and to make the link with the human outbreak, rodents were trapped at four different altitudes. Using nested RT–PCR, Puumala virus (PUUV) RNA was detected in 41/53 (77·4%) bank voles (Myodes glareolus) and Dobrava virus (DOBV) RNA was found in 6/61 (9·8%) yellow-necked mice (Apodemus flavicollis). Sequence analysis of a 341-nucleotide region of the PUUV S segment, obtained from all infected bank voles and five HFRS patients, showed 98·8–100% sequence similarity, indicating that the patients were probably exposed to PUUV on Medvednica mountain. A very large bank-vole population combined with an extremely high infection rate of PUUV was responsible for this unusual winter outbreak of HFRS in Croatia.

Recent discovery of genetically distinct hantaviruses in shrews and moles (order Soricomorpha, family Soricidae and Talpidae) has challenged the conventional view that rodents serve as the principal reservoir hosts. Nova virus (NVAV), previously identified in archival liver tissue of a single European mole (Talpa europaea) from Hungary, represents one of the most highly divergent hantaviruses identified to date. To ascertain the spatial distribution and genetic diversity of NVAV, we employed RT–PCR to analyse lungs from 94 moles, captured in two locations in France, during October 2012 to March 2013. NVAV was detected in more than 60% of moles at each location, suggesting efficient enzootic virus transmission and confirming that this mole species serves as the reservoir host. Although the pathogenic potential of NVAV is unknown, the widespread geographical distribution of the European mole might pose a hantavirus exposure risk for humans.

To examine the prevalence of human pathogens carried by rats in urban areas in Hanoi and Hai Phong, Vietnam, we live-trapped 100 rats in January 2011 and screened them for a panel of bacteria and viruses. Antibodies against Leptospira interrogans (22·0%), Seoul virus (14·0%) and rat hepatitis E virus (23·0%) were detected in rats, but antibodies against Yersinia pestis were not detected. Antibodies against L. interrogans and Seoul virus were found only in adult rats. In contrast, antibodies to rat hepatitis E virus were also found in juvenile and sub-adult rats, indicating that the transmission mode of rat hepatitis E virus is different from that of L. interrogans and Seoul virus. Moreover, phylogenetic analyses of the S and M segments of Seoul viruses found in Rattus norvegicus showed that Seoul viruses from Hai Phong and Hanoi formed different clades. Human exposure to these pathogens has become a significant public health concern.

Puumala virus (PUUV) causes mild haemorrhagic fever with renal syndrome, a rodent-borne zoonosis. To evaluate the disease burden of PUUV infections in Finland, we analysed data reported by laboratories to the National Infectious Disease Registry during 1995–2008 and compared these with data from other national registries (death, 1998–2007; hospital discharge, 1996–2007; occupational diseases, 1995–2006). A total of 22 681 cases were reported (average annual incidence 31/100 000 population); 85% were in persons aged 20–64 years and 62% were males. There was an increasing trend in incidence, and the rates varied widely by season and region. We observed 13 deaths attributable to PUUV infection (case-fatality proportion 0·08%). Of all cases, 9599 (52%) were hospitalized. Only 590 cases (3%) were registered as occupational disease, of which most were related to farming and forestry. The wide seasonal and geographical variation is probably related to rodent density and human behaviour.

The extent of hantavirus seroprevalence in the healthy population from Bosnia and Herzegovina has not yet been investigated; therefore, the aim of this study was to assess the hantavirus seroprevalence in the population from different regions of Bosnia and Herzegovina and in different risk groups. The serosurvey included 1331 subjects from endemic and non-endemic regions in Bosnia and Herzegovina. All sera samples were examined using IgG ELISA, and Western blot (Bunyavirus IgG) tests. Hantavirus seroprevalence was 7·4% in the endemic region and 2·4% in the non-endemic region (P<0·05). Former soldiers from the endemic region had significantly the highest seroprevalence (16·1%) compared to the general population from the endemic region (6·2%), the occupational risk group from the non-endemic region (5·6%) and the general population from the non-endemic region (0·8%) (P<0·01). No difference in hantavirus seroprevalence between gender or age groups was observed. Hantavirus seroprevalence in different populations in Bosnia and Herzegovina was found to be highest compared to other central European countries.

Puumala hantavirus (PUUV) is apparently transmitted to humans by inhalation of aerosolized secretions of carrier rodents (bank voles). The means of transmission and the associated risk factors are poorly defined. An epidemiological study during the peak of an epidemic season in Finland was conducted based on 282 acute clinical PUUV infections and 204 controls without PUUV infection or immunity. The main risk factors adjusted by age, sex and living environment were cigarette smoking [odds ratio (OR) 3·6, 95% confidence interval (CI) 2·1–5·9, P<0·0001] and buildings with holes allowing rodents to enter (OR 3·3, 95% CI 2·0–5·6); these results were similar in two subsets. Further, use of rodent traps (OR3·5, 95% CI 2·2–5·7) and handling firewood (OR 2·7, 95% CI 1·6–4·4) were associated with a risk. The risk attributed to smoking also remained high using simulated population controls with average smoking habits. The results suggest that hantavirus transmission occurs by inhalation mainly indoors and is dependent on the condition of the respiratory tract.

Puumala virus (PUUV) is a zoonotic rodent-borne hantavirus in continental Europe. Its reservoir host, the bank vole (Myodes glareolus), is ubiquitous in Great Britain (GB); however, there has been no reported incidence of virus in either animals or humans. In northwest Europe, increases in bank vole numbers, stimulated by increases in production of beech/oak crops (mast), are associated with outbreaks of nephropathia epidemica (NE) in humans. These so-called ‘mast years’ are determined by sequential climatic events. This paper investigates the contribution of a number of ecological and environmental factors driving outbreaks of PUUV in northwest Europe and assesses whether such factors might also permit enzootic PUUV circulation in GB. Analysis of GB climate data, using regression models, confirms that mast years in GB are stimulated, and can be predicted, by the same climatic events as mast years in PUUV-endemic regions of northwest Europe. A number of other possible non-climatic constraints on enzootic cycles are discussed.