European Hantavirus Research Articles

Cardiopulmonary involvement in Puumala hantavirus infection

BackgroundHantavirus infections cause potentially life-threatening disease in humans world-wide. Infections with American hantaviruses may lead to hantavirus pulmonary syndrome characterised by severe cardiopulmonary distress with high mortality. Pulmonary involvement in European Puumala hantavirus (PUUV) infection has been reported, whereas knowledge of potential cardiac manifestations is limited. We aimed to comprehensively investigate cardiopulmonary involvement in patients with PUUV-infection.MethodsTwenty-seven hospitalised patients with PUUV-infection were examined with lung function tests, chest high-resolution CT (HRCT), echocardiography including speckle tracking strain rate analysis, ECG and measurements of cardiac biomarkers N-terminal pro-B-type natriuretic peptide (NT-ProBNP) and troponin T. Patients were re-evaluated after 3 months. Twenty-five age and sex-matched volunteers acted as controls for echocardiography data.ResultsTwo-thirds of the patients experienced respiratory symptoms as dry cough or dyspnoea. Gas diffusing capacity was impaired in most patients, significantly improving at follow-up but still subnormal in 38%. HRCT showed thoracic effusions or pulmonary oedema in 46% of the patients. Compared to controls, the main echocardiographic findings in patients during the acute phase were significantly higher pulmonary vascular resistance, higher systolic pulmonary artery pressure, lower left ventricular ejection fraction and impaired left atrial myocardial motion. Pathological ECG, atrial fibrillation or T-wave changes, was demonstrated in 26% of patients. NT-ProBNP concentrations were markedly increased and were inversely associated with gas diffusing capacity but positively correlated to pulmonary vascular resistance. Furthermore, patients experiencing impaired general condition at follow-up had significantly lower gas diffusing capacity and higher pulmonary vascular resistance, compared to those feeling fully recovered.ConclusionsIn a majority of patients with PUUV-infection, both cardiac and pulmonary involvement was demonstrated with implications on patients’ recovery. The results demonstrate vascular leakage in the lungs that most likely is responsible for impaired gas diffusing capacity and increased pulmonary vascular resistance with secondary pulmonary hypertension and right heart distress. Interestingly, NT-ProBNP was markedly elevated even in the absence of overt ventricular heart failure. The method of simultaneous investigations of important cardiac and respiratory measurements improves the interpretation of the underlying pathophysiologic mechanisms.

Molecular characterization of Dobrava and Kurkino genotypes of Dobrava-Belgrade hantavirus detected in Hungary and Northern Croatia

Among the Hantavirus genus, Saaremaa virus (SAAV) has been the subject of taxonomical debates. While the International Committee on Taxonomy of Viruses declares SAAV as a distinct species, several European hantavirus experts proposed that SAAV is in fact a genotype of Dobrava-Belgrade virus (DOBV). In the present study we performed S-segment-based phylogenetic analysis of eight DOBV strains identified in rodents in Hungary and Northern Croatia. These new sequences considerably increase the number of complete nucleoprotein gene sequences deposited in the NCBI database. Our phylogenetic analysis clearly support the taxonomical nomenclature recently proposed for DOBV, i.e., genotypes such as Dobrava, Saaremaa, Kurkino, and Sochi should indeed be classified within the DOBV hantavirus species. Moreover, we found that only the Dobrava and Kurkino genotypes of DOBV species are circulating in Hungary while currently there is no evidence for the presence of Saaremaa genotype.

Another case of “European hantavirus pulmonary syndrome” with severe lung, prior to kidney, involvement, and diagnosed by viral inclusions in lung macrophages

Puumala virus (PUUV) is considered a classic Old World etiologic agent of nephropathia epidemica (NE), or hemorrhagic fever with renal syndrome (HFRS). HFRS is considered to be distinct from hantavirus (cardio-)pulmonary syndrome (HPS or HCPS), described in the New World. Here, we report a severe case, which fulfilled most, if not all, Centers for Disease Control and Prevention (CDC) criteria for HPS, needing non-invasive ventilation and subsequent acute hemodialysis. However, the etiological agent was PUUV, as proved by serological testing, real-time polymerase chain reaction (PCR), and sequencing. Viral antigen was detected by specific anti-PUUV immunostaining, showing, for the first time, greenish intracytoplasmic inclusions in bronchoalveolar lavage (BAL) macrophages. This case definitely confirms that HPS can be encountered during PUUV infections. Interestingly, special findings could render the diagnosis easier, such as greenish homogeneous cytoplasmic inclusions, surrounded by a fine clear halo in BAL macrophages. Therefore, although the diagnosis remains difficult before the onset of renal involvement, the occurrence of severe respiratory failure mimicking community-acquired pneumonia must alert the clinician for possible HPS, especially in endemic areas.

Novel Hantavirus in Wildlife, United Kingdom

Novel Hantavirus in Wildlife, United Kingdom

Données récentes sur les hantavirus et perspectives de recherche

Les virus du genre Hantavirus sont les seuls représentants de la famille des Bunyaviridae qui ne sont pas transmis par des vecteurs arthropodes mais par des petits mammifères. Les hantavirus transmis par les rongeurs (Ordre Rodentia) ont été les premiers découverts en raison de leur pouvoir pathogène chez l’homme. Les premières études phylogénétiques ont suggéré une coévolution entre chaque hantavirus et son espèce de rongeur réservoir. Toutefois, l’exploration d’autres réservoirs animaux a montré que des hantavirus circulent aussi chez les insectivores (Ordre Soricomorpha) et les chauvessouris (Ordre Chiroptera), sans qu’aucune transmission pathogène à l’homme n’ait pu être mise en évidence jusqu’à aujourd’hui. Des observations naturelles de cocirculation d’un même hantavirus au sein de plusieurs espèces de rongeurs sympatriques, ainsi que de nouvelles données phylogénétiques qui soulignent des changements d’hôte (host-switching) entre hantavirus très proches, remettent actuellement en cause la cospéciation stricte. De même, l’observation plus fine de cas cliniques suggère de modérer le dogme d’une maladie distincte chez l’homme, les hantavirus de l’Ancien Monde (Europe-Asie) provoquant une fièvre hémorragique à syndrome rénal (FHRS) et ceux du Nouveau Monde (Amériques) conduisant à une hantavirose à syndrome cardio-pulmonaire (HSCP). Ces points sont discutés car ils ouvrent d’importantes perspectives en matière de recherche transdisciplinaire, depuis l’immunologie comparée chez les mammifères jusqu’à la modélisation de la dynamique des réservoirs dans leur milieu naturel, en passant par la sociologie des populations à risque. Les données récentes sur la circulation et le pouvoir pathogène des hantavirus en Europe et dans le monde sont aussi présentées, ainsi que les nouveaux outils d’investigation sérologique et génétique permettant la découverte sans a priori de nouveaux virus «dormants» dans des réservoirs et l’évaluation de leur potentiel d’émergence chez l’homme.

The broad spectrum of hantaviruses and their hosts in Central Europe

Hantaviruses are considered to be emerging viruses due to their increasing significance as human pathogens and their cyclic reappearance during outbreaks. Central Europe is an important endemic region for hantavirus infections. Reflecting the presence of all relevant small mammals serving as reservoir hosts, close to all recognized European hantaviruses occur also in Central Europe. Important human pathogens, Puumala and Dobrava-Belgrade viruses, are present and cause hemorrhagic fever with renal syndrome of various severities. Moreover, several of the newly recognized shrew- and mole-borne hantaviruses are present. In this review, we summarize current data on molecular detection of hantaviruses in reservoir hosts as well as on molecular epidemiology of human hantavirus infections in Central Europe.

Hantavirus infections by Puumala or Dobrava-Belgrade virus in pregnant women

BackgroundHantavirus infection in humans usually occurs via inhalation of infectious aerosolized excreta of rodents. Horizontal human-to-human transmission was reported only for the highly virulent Andes virus. The likelihood of vertical transmission and the clinical outcome of hantavirus infections in pregnancy is still unpredictable. ObjectivesVery few data were published about the impact of hantaviruses in pregnancy. Here we present four cases of pregnant women infected by European hantaviruses. The risk of vertical virus transmission was investigated. Study designFour pregnant women with clinical signs of acute hantavirus disease were investigated for hantavirus IgM and IgG after onset of clinical symptoms. Furthermore, the newborns were tested for presence of viral RNA and antibodies in cord blood and, if any parameter was found positive, 8–12 months after delivery. ResultsFour women suffered from a hantavirus infection, two of them due to infection by Puumala virus and two by Dobrava-Belgrade virus. Three women delivered healthy babies by vaginal route and one woman by Caesarean section (week 28). In no case hantavirus RNA was detected in cord blood after delivery or in the 8–12 month old babies. Hantavirus IgG was detectable in the cord blood of 3 babies (but not in the preterm child); these antibodies disappeared after 8–12 months indicating a passive transfer of immunoglobulins. No child had any clinical sign of hantavirus infection. ConclusionsIn this study, the absence of vertical hantavirus transmission was demonstrated for pregnant women with onset of hantavirus disease between gestation weeks 14 and 28.

Dobrava-Belgrade Hantavirus from Germany Shows Receptor Usage and Innate Immunity Induction Consistent with the Pathogenicity of the Virus in Humans

BackgroundDobrava-Belgrade virus (DOBV) is a European hantavirus causing hemorrhagic fever with renal syndrome (HFRS) in humans with fatality rates of up to 12%. DOBV-associated clinical cases typically occur also in the northern part of Germany where the virus is carried by the striped field mouse (Apodemus agrarius). However, the causative agent responsible for human illness has not been previously isolated.Methodology/Principal FindingsHere we report on characterization of a novel cell culture isolate from Germany obtained from a lung tissue of “spillover” infected yellow necked mouse (A. flavicollis) trapped near the city of Greifswald. Phylogenetic analyses demonstrated close clustering of the new strain, designated Greifswald/Aa (GRW/Aa) with the nucleotide sequence obtained from a northern German HFRS patient. The virus was effectively blocked by specific antibodies directed against β3 integrins and Decay Accelerating Factor (DAF) indicating that the virus uses same receptors as the highly pathogenic Hantaan virus (HTNV). In addition, activation of selected innate immunity markers as interferon β and λ and antiviral protein MxA after viral infection of A549 cells was investigated and showed that the virus modulates the first-line antiviral response in a similar way as HTNV.Conclusions/SignificanceIn summary, our study reveals novel data on DOBV receptor usage and innate immunity induction in relationship to virus pathogenicity and underlines the potency of German DOBV strains to act as human pathogen.

The N-terminus of the Montano virus nucleocapsid protein possesses broadly cross-reactive conformation-dependent epitopes conserved in rodent-borne hantaviruses

The hantavirus nucleocapsid (N) protein is an important immunogen that stimulates a strong and cross-reactive immune response in humans and rodents. A large proportion of the response to N protein has been found to target its N-terminus. However, the exact nature of this bias towards the N-terminus is not yet fully understood. We characterized six monoclonal antibodies (mAbs) against the N protein of Montano virus (MTNV), a Mexican hantavirus. Five of these mAbs recognized eight American hantaviruses and six European and Asian hantaviruses, but not the Soricomorpha-borne Thottapalayam hantavirus. The N protein-reactive binding regions of the five mAbs were mapped to discontinuous epitopes within the N-terminal 13–51 amino acid residues, while a single serotype-specific mAb was mapped to residues 1–25 and 49–75. Our findings suggest that discontinuous epitopes at the N-terminus are conserved, at least in rodent-borne hantaviruses, and that they contribute considerably to N protein cross-reactivity.

Second External Quality Assurance Study for the Serological Diagnosis of Hantaviruses in Europe

Hantaviruses are endemic throughout the world and hosted by rodents and insectivores. Two human zoonoses, hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS), are caused by hantaviruses and case fatality rates have reached 12% for HFRS and 50% for HPS in some outbreaks. Symptomatic hantavirus infections in Europe are summarised as HFRS mainly due to Puumala, Dobrava-Belgrade and Saaremaa virus. While HFRS has an overall low incidence in Europe, the number of cases varies from 100 per year in all Eastern and Southern Europe up to 1,000 per year only in Finland. To assess the quality of hantavirus diagnostics, the European Network for the Diagnostics of “Imported” Viral Diseases (ENIVD) organised a first external quality assurance (EQA) in 2002. The purpose of this second EQA study is to collect updated information on the efficiency and accurateness of hantavirus serological methods applied by expert laboratories. A serum panel of 14 samples was sent to 28 participants in Europe of which 27 sent results. Performance in hantavirus diagnosis varied not only on the method used but also on the laboratories and the subclass of antibodies tested. Commercial and in-house assays performed almost equally. Enzyme immunoassays were mainly used but did not show the best performances while immunoblot assays were the less employed and showed overall better performances. IgM antibodies were not detected in 61% of the positive IgM samples and IgM detection was not performed by 7% of the laboratories indicating a risk of overlooking acute infections in patients. Uneven performances using the same method is indicating that there is still a need for improving testing conditions and standardizing protocols.

Development and optimization of a PCR assay for detection of Dobrava and Puumala hantaviruses in Bosnia and Herzegovina

Hantavirus-specific serology tests are the main diagnostic technique for detection of hantavirus infection in Bosnia and Herzegovina. In order to enhance hantavirus infections monitoring a sensitive PCR based assay was developed to detect Dobrava (DOBV) and Puumala (PUUV) hantaviruses. Nested primer sets were designed within three different regions of the viral RNA (S and M segment of DOBV and M segment of PUUV) based on highly similar regions from a number of different European hantavirus strains. Assay conditions were optimized using cell cultures infected with DOBV Slovenia, PUUV Sotkamo and PUUV CG 18-20. This sensitive and specific assay has proven to be useful for detection of both Puumala and Dobrava hantaviruses.

Tula Virus Infections in the Eurasian Water Vole in Central Europe

Recent reports of novel hantaviruses in shrews and moles and the detection of rodent-borne hantaviruses in different rodent species raise important questions about their host range and specificity, evolution, and host adaptation. Tula virus (TULV), a European hantavirus, is believed to be slightly or non-pathogenic in humans and was initially detected in the common vole Microtus arvalis, the East European vole M. levis (formerly rossiaemeridionalis), and subsequently in other Microtus species. Here we report the first multiple RT-PCR detection and sequence analyses of TULV in the Eurasian water vole Arvicola amphibius from different regions in Germany and Switzerland. Additional novel TULV S-, M-, and L-segment sequences were obtained from M. arvalis and M. agrestis trapped in Germany at sites close to trapping sites of TULV-RT-PCR-positive water voles. Serological investigations using a recombinant TULV nucleocapsid protein revealed the presence of TULV-reactive antibodies in RT-PCR-positive and a few RT-PCR-negative water voles. Phylogenetic analyses revealed a geographical clustering of the novel S-, M-, and L-segment sequences from A. amphibius with those of M. arvalis- and M. agrestis-derived TULV lineages, and may suggest multiple TULV spillover or a potential host switch to A. amphibius. Future longitudinal studies of sympatric Microtus and Arvicola populations and experimental infection studies have to prove the potential of A. amphibius as an additional TULV reservoir host.

Concomitant influence of helminth infection and landscape on the distribution of Puumala hantavirus in its reservoir, Myodes glareolus

BackgroundPuumala virus, the agent of nephropathia epidemica (NE), is the most prevalent hantavirus in Europe. The risk for human infection seems to be strongly correlated with the prevalence of Puumala virus (PUUV) in populations of its reservoir host species, the bank vole Myodes glareolus. In humans, the infection risks of major viral diseases are affected by the presence of helminth infections. We therefore proposed to analyse the influence of both helminth community and landscape on the prevalence of PUUV among bank vole populations in the Ardennes, a PUUV endemic area in France.ResultsAmong the 313 voles analysed, 37 had anti-PUUV antibodies. Twelve gastro-intestinal helminth species were recorded among all voles sampled. We showed that PUUV seroprevalence strongly increased with age or sexual maturity, especially in the northern forests (massif des Ardennes). The helminth community structure significantly differed between this part and the woods or hedgerows of the southern cretes pre-ardennaises. Using PUUV RNA quantification, we identified significant coinfections between PUUV and gastro-intestinal helminths in the northern forests only. More specifically, PUUV infection was positively associated with the presence of Heligmosomum mixtum, and in a lesser extent, Aonchotheca muris-sylvatici. The viral load of PUUV infected individuals tended to be higher in voles coinfected with H. mixtum. It was significantly lower in voles coinfected with A. muris-sylvatici, reflecting the influence of age on these latter infections.ConclusionsThis is the first study to emphasize hantavirus - helminth coinfections in natural populations. It also highlights the importance to consider landscape when searching for such associations. We have shown that landscape characteristics strongly influence helminth community structure as well as PUUV distribution. False associations might therefore be evidenced if geographic patterns of helminths or PUUV repartition are not previously identified. Moreover, our work revealed that interactions between helminths and landscape enhance/deplete the occurrence of coinfections between PUUV and H. mixtum or A. muris-sylvatici. Further experimental analyses and long-term individual surveys are now required to confirm these correlative results, and to ascertain the causal links between helminth and PUUV infection risks.

Hantavirus infection during a stay in a mountain hut in Northern Slovakia

Hantaviruses in Europe cause human hemorrhagic fever with renal syndrome (HFRS) with various degree of severity. The most severe form is caused by the Dobrava/Belgrade virus (DOBV), associated with the rodent Apodemus flavicollis. During the last decade cases of infection caused by DOBV have been reported in Central Europe. The present study is a report on two Czech patients with severe HFRS who were infected during their stay in a mountain hut in Northern Slovakia. The two patients, combined with a third case observed in the same year in a nearby village in the Czech Republic, suggest that this region in Central Europe has to be considered as endemic for HFRS.

Time to revise the paradigm of hantavirus syndromes? Hantavirus pulmonary syndrome caused by European hantavirus

Hantaviruses have previously been recognised to cause two separate syndromes: hemorrhagic fever with renal syndrome in Eurasia, and hantavirus pulmonary syndrome (HPS) in the Americas. However, increasing evidence suggests that this dichotomy is no longer fruitful when recognising human hantavirus disease and understanding the pathogenesis. Herein are presented three cases of severe European Puumala hantavirus infection that meet the HPS case definition. The clinical and pathological findings were similar to those found in American hantavirus patients. Consequently, hantavirus infection should be considered as a cause of acute respiratory distress in all endemic areas worldwide.

Specific humoral reaction of hemorrhagic fever with renal syndrome (HFRS) patients in China to recombinant nucleocapsid proteins from European hantaviruses

Hemorrhagic fever with renal syndrome (HFRS) is endemic in East Asia and Europe. This study was initiated to investigate the reactivity of antibodies in sera of Chinese HFRS patients with the recombinant nucleocapsid proteins (rNPs) of Hantaan virus (HTNV), Dobrava-Belgrade virus (DOBV), and Puumala virus (PUUV), which are the prevalent hantavirus strains in Europe. Forty-eight pairs of acute and convalescent sera were collected from HFRS patients in Hubei, China (1985-2002) and tested by indirect IgG, IgA, and IgM enzyme-linked immunosorbent assays with six rNPs of European hantaviruses as coated antigens, respectively. The results showed that the sensitivity of rNPs against IgG was HTNV-rNP > DOBV-rNP > PUUV-rNP, while the sensitivity against IgA was DOBV-rNP > HTNV-rNP > PUUV-rNP. Quantitative analysis revealed both acute and convalescent sera from HFRS patients predominantly exhibit high levels of IgA. Although PUUV-rNPs showed very weak reactivity to the three kinds of immunoglobulins in all samples, three pairs of sera unexpectedly cross-reacted strongly to all three PUUV-rNP subtypes. We first observe that HFRS patients' sera from Hubei Province show new prevalent characteristics of cross-reacting with PUUV-rNPs and continued high level of IgA in convalescent phase, as well as in China.

Genetic evidence for the presence of two distinct hantaviruses associated with Apodemus mice in Croatia and analysis of local strains

In Europe, Dobrava-Belgrade (DOBV), Saaremaa (SAAV), and Puumala (PUUV) viruses are known to cause hemorrhagic fever with renal syndrome (HFRS). All three hantaviruses are now found in Croatia. Lung tissue samples of 315 Apodemus mice trapped in 2003-2004 were screened for the presence of hantaviral N-Ag and 20 mice (6.3%) were found either strongly positive or weak/suspected-positive. Partial sequences of hantavirus M and S segments were recovered by RT-PCR from six mice and subjected to (phylo)genetic analysis that revealed the presence of four novel strains of DOBV and one of SAAV. Curiously, one of the newly described DOBV strains was found in Apodemus agrarius mouse, that is, not in the traditional host, A. flavicollis mice, suggesting a spillover event. S segment sequences recovered previously from HFRS cases [Markotić et al., 2002] were confirmed as DOBV sequences; one of which appeared particularly close to the prototype Slovenian DOBV isolate. Taken together with earlier data on PUUV in Croatia, these results show a co-circulation of three European hantavirus pathogens in this country. So far, not a single SAAV sequence has been recovered from HFRS patients either in Croatia or neighboring Slovenia and Hungary nor in Slovakia suggesting a somewhat lower fequency of acute SAAV infection in humans in this part of Europe than for example in the Baltics.

Hantaviruses and Their Hosts in Europe: Reservoirs Here and There, But Not Everywhere?

Five hantaviruses are known to circulate among rodents in Europe, and at least two among insectivores. Four (Dobrava, Saaremaa, Seoul, and Puumala [PUUV] viruses) are clearly associated with hemorrhagic fever with renal syndrome (HFRS). PUUV, the most common etiological agent of HFRS in Europe, is carried by the bank vole (Myodes glareolus), one of the most widespread and abundant mammal species in Europe. This host-virus system is among hantaviruses also the most studied one in Europe. However, HFRS incidence varies throughout the continent. The spatial as well as temporal variation in the occurrence of HFRS is linked to geographic differences in the population dynamics of the reservoir rodents in different biomes of Europe. While rodent abundance may follow mast seeding events in many parts of temperate Europe, in northern (N) Europe multiannual cycles in population density exist as the result of the interaction between rodent populations and specialist predator populations in a delayed density-dependent manner. The spatial distribution of hantaviruses further depends on parameters such as forest patch size and connectivity of the most suitable rodent habitats, and the conditions for the survival of the virus outside the host, as well as historical distribution patterns (phylogeographies) of hosts and viruses. In multiannually fluctuating populations of rodents, with population increases of great amplitude, one should expect a simultaneous build-up of recently hantavirus-infected (shedding) rodents. The increasing number of infectious, virus-shedding rodents leads to a rapid transmission of hantavirus across the rodent population, and to humans. Our review discusses these aspects for PUUV, the only European hantavirus for which there is a reasonable, yet still far from complete, ecological continental-wide understanding. We discuss how this information could translate to other European hantavirus-host systems, and where the most important questions lie for further research.

Hemorrhagic fever with renal syndrome caused by 2 lineages of Dobrava hantavirus, Russia.

Dobrava-Belgrade virus (DOBV) is a European hantavirus that causes hemorrhagic fever with renal syndrome (HFRS); case-fatality rates in Balkan countries are as high as 12%. To determine causative agents, we examined 126 cases of DOBV-associated HFRS in central and southern European Russia. In central Russia (Lipetsk, Voronezh, Orel regions), outbreaks were caused by a DOBV variant (DOBV-Aa) carried by Apodemus agrarius. In southern Russia (Sochi district), where HFRS is endemic, HFRS cases were caused by a new DOBV variant (DOBV-Ap), found in A. ponticus, a novel hantavirus natural host. Both viruses, DOBV-Aa/Lipetsk and DOBV-Ap/Sochi, were isolated through Vero E6 cells, genetically characterized, and used for serotyping of the HFRS patients' serum. The clinical severity of HFRS caused by DOBV-Aa resembles that of HFRS caused by Puumala virus (mild to moderate); clinical severity of disease caused by DOBV-Ap infections is more often moderate to severe.

Emerging zoonoses: Hantavirus infections

ZusammenfassungDie weltweite Verbreitung und die jährlich steigende Zahl der Infektion mit Hantaviren lässt die Bedeutung der Hantaviren unter den „emerging viruses“ ansteigen. Die Ansteckung verläuft über das Einatmen von Staub oder Aerosolen, die mit Ausscheidungen infizierter Nagetiere kontaminiert sind. Krankheitsbild und Schwere des Verlaufs hängen vom Virustyp ab, dessen geographisch begrenztes Auftreten vom Vorkommen des virustypspezifischen Nagerreservoirs bestimmt wird. Die Infektion mit in Asien und Europa beheimateten Stämmen löst das hämorrhagische Fieber mit renalem Syndrom (HFRS) aus. Die in Deutschland vorherrschende Virusspezies Puumala löst eine mildere Verlaufsform des HFRS, die Nephropathia epidemica (NE), aus. Infektionen mit Hantavirus-Stämmen des amerikanischen Kontinents hingegen führen zu einem Krankheitsbild mit vorwiegend pulmonaler Symptomatik (hantavirales pulmonales Syndrom, HPS). Da für keinen der humanpathogenen Vertreter eine spezifische antivirale Therapie oder ein zugelassener Impfstoff zur Verfügung steht, bleibt zur Eindämmung und Vermeidung der Infektion nur die Kontrolle der Nagerpopulationen und Präventionsmaßnahmen des expositionsgefährdeten Personenkreises.