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Detlev H. Kruger - One of the best experts on this subject based on the ideXlab platform.

  • Proteinuria and the Clinical Course of Dobrava-Belgrade HantaVirus Infection.
    Nephron extra, 2018
    Co-Authors: Markus Meier, Detlev H. Kruger, Jörg Hofmann, Jan Kramer, Wolfram J. Jabs, Claudia Nolte, Hendrik Lehnert, Martin Nitschke
    Abstract:

    Purpose: Human infection with Dobrava-Belgrade Virus (DOBV) in Northern Germany causes a mild form of hantaVirus disease predominantly characterized by acute kidney injury due to interstitial nephritis. We evaluated the largest number of DOBV-infected patients so far regarding clinical course, proteinuria, and prognostic markers. Patients and Methods: Patients with DOBV-associated hantaVirus disease admitted to the Renal Division of the University of Lubeck (Germany) between 1997 and 2012 were included in this study. Symptoms, clinical course, laboratory parameters, and urinary protein analysis were investigated at admission (baseline, t0), 3-5 days (t3-5), 10-17 days (t10-17), and after 1 year of follow-up (t365). Results: Of the 34 patients (male/female ratio: 23/11; age: 41 ± 14 years) included in the study, 4 underwent hemodialysis (HD). Glomerular filtration rate was 17 ± 14 mL/min at t0 and increased to 27 ± 26 mL/min (t3-5), 57 ± 20 mL/min (t10-17), and 84 ± 16 mL/min (t365). Albuminuria and tubular proteinuria (α1- and β2-microglobulin) decreased during follow-up; the urinary α1-microglobulin concentration in patients who required HD was significantly higher than that in patients not requiring HD (t0: 186 ± 51 vs. 45 ± 26 mg/g creatinine; t3-5: 87 ± 14 vs. 32 ± 16 mg/g creatinine; t10-17: 63 ± 18 vs. 28 ± 12 mg/g creatinine; p < 0.001). Conclusions: DOBV infection of inpatients in Northern Germany is associated with severe kidney injury that recovers within a few weeks and normalizes within 1 year. Tubular proteinuria is associated with the severity of kidney injury and the necessity of renal replacement therapy in these DOBV-infected patients.

  • Clinical characterization of two severe cases of hemorrhagic fever with renal syndrome (HFRS) caused by hantaViruses Puumala and Dobrava-Belgrade genotype Sochi.
    BMC Infectious Diseases, 2016
    Co-Authors: Ellen Krautkramer, Alexandra Baumann, Christian Nusshag, Paul Schnitzler, Boris Klempa, Detlev H. Kruger, Jörg Hofmann, Peter T. Witkowski, Julia Schäfer, Martin Zeier
    Abstract:

    HantaVirus disease belongs to the emerging infections. The clinical picture and severity of infections differ between hantaVirus species and may even vary between hantaVirus genotypes. The mechanisms that lead to the broad variance of severity in infected patients are not completely understood. Host- and Virus-specific factors are considered. We analyzed severe cases of hantaVirus disease in two young women. The first case was caused by Puumala Virus (PUUV) infection in Germany; the second case describes the infection with Dobrava-Belgrade Virus (DOBV) in Russia. Symptoms, laboratory parameters and cytokine levels were analyzed and compared between the two patients. Serological and sequence analysis revealed that PUUV was the infecting agent for the German patient and the infection of the Russian patient was caused by Dobrava-Belgrade Virus genotype Sochi (DOBV-Sochi). The symptoms in the initial phase of the diseases did not differ noticeably between both patients. However, deterioration of laboratory parameter values was prolonged and stronger in DOBV-Sochi than in PUUV infection. Circulating endothelial progenitor cells (cEPCs), known to be responsible for endothelial repair, were mobilized in both infections. Striking differences were observed in the temporal course and level of cytokine upregulation. Levels of angiopoietin-2 (Ang-2), vascular endothelial growth factor (VEGF), and stromal derived factor-1 (SDF-1α) were increased in both infections; but, sustained and more pronounced elevation was observed in DOBV-Sochi infection. Severe hantaVirus disease caused by different hantaVirus species did not differ in the general symptoms and clinical characteristics. However, we observed a prolonged clinical course and a late and enhanced mobilization of cytokines in DOBV-Sochi infection. The differences in cytokine deregulation may contribute to the observed variation in the clinical course.

  • Clinical characterization of two severe cases of hemorrhagic fever with renal syndrome (HFRS) caused by hantaViruses Puumala and Dobrava-Belgrade genotype Sochi
    BMC Infectious Diseases, 2016
    Co-Authors: Ellen Krautkramer, Alexandra Baumann, Christian Nusshag, Paul Schnitzler, Boris Klempa, Detlev H. Kruger, Jörg Hofmann, Peter T. Witkowski, Julia Schäfer, Martin Zeier
    Abstract:

    Background HantaVirus disease belongs to the emerging infections. The clinical picture and severity of infections differ between hantaVirus species and may even vary between hantaVirus genotypes. The mechanisms that lead to the broad variance of severity in infected patients are not completely understood. Host- and Virus-specific factors are considered. Case presentation We analyzed severe cases of hantaVirus disease in two young women. The first case was caused by Puumala Virus (PUUV) infection in Germany; the second case describes the infection with Dobrava-Belgrade Virus (DOBV) in Russia. Symptoms, laboratory parameters and cytokine levels were analyzed and compared between the two patients. Serological and sequence analysis revealed that PUUV was the infecting agent for the German patient and the infection of the Russian patient was caused by Dobrava-Belgrade Virus genotype Sochi (DOBV-Sochi). The symptoms in the initial phase of the diseases did not differ noticeably between both patients. However, deterioration of laboratory parameter values was prolonged and stronger in DOBV-Sochi than in PUUV infection. Circulating endothelial progenitor cells (cEPCs), known to be responsible for endothelial repair, were mobilized in both infections. Striking differences were observed in the temporal course and level of cytokine upregulation. Levels of angiopoietin-2 (Ang-2), vascular endothelial growth factor (VEGF), and stromal derived factor-1 (SDF-1α) were increased in both infections; but, sustained and more pronounced elevation was observed in DOBV-Sochi infection. Conclusions Severe hantaVirus disease caused by different hantaVirus species did not differ in the general symptoms and clinical characteristics. However, we observed a prolonged clinical course and a late and enhanced mobilization of cytokines in DOBV-Sochi infection. The differences in cytokine deregulation may contribute to the observed variation in the clinical course.

  • Infection of human airway epithelial cells by different subtypes of Dobrava-Belgrade Virus reveals gene expression patterns corresponding to their virulence potential.
    Virology, 2016
    Co-Authors: Peter T. Witkowski, Brita Auste, Detlev H. Kruger, Daniel Bourquain, Katrin Bankov, Piotr Wojtek Dabrowski, Andreas Nitsche, Lars Schaade
    Abstract:

    Dobrava-Belgrade Virus (DOBV) is a pathogen causing hemorrhagic fever with renal syndrome in Europe. Virulence and case fatality rate are associated with Virus genotype; however the reasons for these differences are not well understood. In this work we present Virus-specific effects on the gene expression profiles of human lung epithelial cells (A549) infected with different genotypes of DOBV (Dobrava, Kurkino, and Sochi), as well as the low-virulent Tula Virus (TULV). The data was collected by whole-genome gene expression microarrays and confirmed by quantitative real-time PCR. Despite their close genetic relationship, the expression profiles induced by infection with different hantaViruses are significantly varying. Major differences were observed in regulation of immune response genes, which were especially induced by highly virulent DOBV genotypes Dobrava and Sochi in contrast to less virulent DOBV-Kurkino and TULV. This work gives first insights into the differences of Virus - host interactions of DOBV on genotype level.

  • Does proficiency testing improve the quality of hantaVirus serodiagnostics? Experiences with INSTAND EQA schemes.
    International Journal of Medical Microbiology, 2015
    Co-Authors: Jörg Hofmann, Hans-peter Grunert, Oliver Donoso-mantke, Heinz Zeichhardt, Detlev H. Kruger
    Abstract:

    Abstract HantaVirus infections in Germany appear periodically with peak numbers every 2–3 years. The reported cases in the years 2007, 2010 and 2012 exceeded many times over those in the years in-between. In order to reveal faults of certain in vitro diagnostic assays (IVDs), to harmonize the performances of the individual assays and to improve the users’ competence in interpreting the results, the National Consiliary Laboratory for HantaViruses and INSTAND e.V. (Society for Promoting Quality Assurance in Medical Laboratories e.V.) established an external quality assessment (EQA) scheme for proficiency testing of hantaVirus serodiagnostics. The first EQA scheme (pilot study) started in March 2009 with 58 participating laboratories from Germany and neighboring countries. Twice a year four serum samples were sent out to the participants to investigate whether the sample reflects an acute or past infection and to distinguish between infections with the hantaVirus types Puumala Virus (PUUV) and Dobrava-Belgrade Virus (DOBV), both endemic in Central Europe. In addition, samples negative for anti-hantaVirus antibodies were tested in order to examine the specificity of the IVDs applied in the participating laboratories. An increasing number of laboratories participated, with a maximum of 92 in March 2014. When summarizing in total 2592 test results, the laboratories reached an overall specificity of 96.7% and a sensitivity of 95% in their detection of a hantaVirus infection. A correct distinction between acute and past infections was forwarded in 90–96% of replies of laboratories. Exact serotyping (PUUV vs. DOBV) of the infection was reported in 81–96% of replies with the lowest accuracy for past DOBV infections; cross-reactivities between diagnostic antigens of the two Viruses as well as persistent IgM titers in humans may interfere with exact testing. The EQAs revealed acceptable results for the serodiagnostic of hantaVirus infection including serotyping but further improvement is still needed.

Anna Papa - One of the best experts on this subject based on the ideXlab platform.

  • Molecular epidemiology of Dobrava-Belgrade Virus in Greece
    Infection Genetics and Evolution, 2018
    Co-Authors: Katerina Tsergouli, Elpida Papadopoulou, Katerina Tsioka, Anna Papa
    Abstract:

    Abstract In order to gain an insight into the genetic relatedness of the Dobrava-Belgrade Virus (DOBV) in Greece, a phylogenetic analysis was performed based on all currently available DOBV sequences obtained from hospitalized cases with hemorrhagic fever with renal syndrome (HFRS). Most cases occurred in northwestern and north central part of the country. Two sequence datasets consisted of 41 S and 12 M partial DOBV RNA segment sequences were analyzed. All DOBV strains belong to Dobrava genotype which is associated with the rodent Apodemus flavicollis. In both phylogenetic trees (S and M segments), two main clusters of Greek strains could be distinguished. Phylogenetic analysis showed a spatial rather than temporal relation of the strains, since their genetic clustering was highly associated with the geographic distribution of the cases. Besides previous characterized endemic foci, novel ones have been identified, expanding our knowledge on the epidemiology of HFRS in Greece.

  • Immune response in Dobrava-Belgrade Virus infections
    Archives of Virology, 2016
    Co-Authors: Katerina Tsergouli, Anna Papa
    Abstract:

    Dobrava-Belgrade Virus (DOBV) is a hantaVirus that causes a disease in humans known as hemorrhagic fever with renal syndrome. Hallmarks of hantaviral infections are increased vascular permeability due to dysregulation of the endothelial cell barrier and acute thrombocytopenia. In order to gain insight into the immune response in DOBV infections, the serum levels of 27 cytokines in 24 hospitalized Greek HFRS patients were evaluated. Compared to the control group, significantly higher IL-1ra, IL-6, IL-8, IL-9, IL-10, GM-CSF, IP-10, MIP-1b, TNF-α and VEGF levels were found in severe cases, while in non-severe cases, IL-13 and TNF-α levels were significantly higher ( p  

  • Genetic detection of hantaViruses in rodents, Albania.
    Journal of Medical Virology, 2016
    Co-Authors: Anna Papa, Elton Rogozi, Enkelejda Velo, Evangelia Papadimitriou, Silvia Bino
    Abstract:

    : In order to have a first insight into the epidemiology of hantaViruses in Albania, 263 small mammals (248 rodents, 15 insectivores) were captured in 352 locations in 29 districts and tested for hantaVirus infection. Dobrava-Belgrade Virus (DOBV) was detected in 10 of 148 (6.7%) Apodemus flavicollis rodents. DOBV-positive A. flavicollis were detected in six districts (Diber, Korce, Kolonje, Librazhd, Pogradec, and Vlore). The obtained nucleotide sequences were highly similar to each other and to DOBV sequences from northwestern Greece. Understanding the epidemiology of hantaViruses and identifying the endemic foci enables the public health strategies to minimize the risk of human infection. J. Med. Virol. 88:1309-1313, 2016. © 2016 Wiley Periodicals, Inc.

  • Vascular Endothelial Growth Factor Levels in Dobrava/Belgrade Virus Infections
    Viruses, 2013
    Co-Authors: Katerina Tsergouli, Anna Papa
    Abstract:

    The levels of vascular endothelial growth factor-A (VEGF) were estimated in 102 serum samples from 63 hospitalized Greek patients with hemorrhagic fever with renal syndrome (HFRS) caused by Dobrava/Belgrade Virus. Significantly higher VEGF levels were seen in the severe when compared with non-severe cases (mean values 851.96 pg/mL and 326.75 pg/mL, respectively; p = 0.003), while a significant difference was observed among groups based on the day after the onset of illness. In both severe and non-severe cases, VEGF peaked in the second week of illness; however, elevation of VEGF in the severe cases started later and remained high until convalescence, suggesting that the role of VEGF was associated with repair of vascular damage rather than with increased permeability.

  • Serum TNF-α, sTNFR1, IL-6, IL-8 and IL-10 levels in hemorrhagic fever with renal syndrome.
    Virus Research, 2013
    Co-Authors: Ioannis Kyriakidis, Anna Papa
    Abstract:

    Abstract It is generally accepted that the pathogenesis of hantaVirus infections is the result of Virus-mediated host immune response. HantaViruses, and mainly Dobrava–Belgrade Virus, are present in Greece, and cause to humans hemorrhagic fever with renal syndrome (HFRS). Serum IL-6, IL-8, IL-10, TNF-α and sTNFR1 levels were measured in 29 HFRS Greek patients. Significant higher sTNFR1, IL-6, IL-8 and IL-10 levels were observed in severe than in mild/moderate cases, while TNF-α did not seem to be associated with disease severity. Correlations between cytokine levels and their fluctuation over time after onset of the illness, along with comparisons from previously published data on the field, led in building an immune response pattern for HFRS.

Boris Klempa - One of the best experts on this subject based on the ideXlab platform.

  • Hemorrhagic Fever with Renal Syndrome Caused by 2 Lineages of
    2020
    Co-Authors: Dobrava Hantavirus, Boris Klempa, Tamara K. Dzagurova, Evgeniy A. Tkachenko, Vyacheslav G. Morozov, Yulia V. Yunicheva, Natalia M. Okulova, Galina P. Slyusareva, Aleksey Smirnov, D. H. Krüger
    Abstract:

    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.

  • Reassortment events in the evolution of hantaViruses
    Virus Genes, 2018
    Co-Authors: Boris Klempa
    Abstract:

    HantaViruses (order Bunyavirales , family Hantaviridae ), known as important zoonotic human pathogens, possess the capacity to exchange genome segments via genetic reassortment due to their tri-segmented genome. Although not as frequent as in the arthropod-borne bunyaViruses, reports indicating reassortment events in the evolution of hantaViruses have been recently accumulating. The intra- and inter-lineage reassortment between closely related variants has been repeatedly reported for several hantaViruses including the rodent-borne human pathogens such as Sin Nombre Virus, Puumala Virus, Dobrava-Belgrade Virus, or Hantaan Virus as well as for the more recently recognized shrew-borne hantaViruses, Imjin and Seewis. Reassortment between more distantly related Viruses was rarely found but seems to play a beneficial role in the process of crossing the host species barriers. Besides the findings based on phylogenetic studies of naturally occurring strains, hantaVirus reassortants were generated also in in vitro studies. Interestingly, only reassortants with exchanged M segments could be generated suggesting that a high degree of genetic compatibility is required for the S and L segments while the exchange of M segment is better tolerated or is particularly beneficial. Altogether, the numerous reports on hantaVirus reassortment, summarized in this review, clearly demonstrate that reassortment events play a significant role in hantaVirus evolution and contributed to the currently recognized hantaVirus diversity.

  • Clinical characterization of two severe cases of hemorrhagic fever with renal syndrome (HFRS) caused by hantaViruses Puumala and Dobrava-Belgrade genotype Sochi
    BMC Infectious Diseases, 2016
    Co-Authors: Ellen Krautkramer, Alexandra Baumann, Christian Nusshag, Paul Schnitzler, Boris Klempa, Detlev H. Kruger, Jörg Hofmann, Peter T. Witkowski, Julia Schäfer, Martin Zeier
    Abstract:

    Background HantaVirus disease belongs to the emerging infections. The clinical picture and severity of infections differ between hantaVirus species and may even vary between hantaVirus genotypes. The mechanisms that lead to the broad variance of severity in infected patients are not completely understood. Host- and Virus-specific factors are considered. Case presentation We analyzed severe cases of hantaVirus disease in two young women. The first case was caused by Puumala Virus (PUUV) infection in Germany; the second case describes the infection with Dobrava-Belgrade Virus (DOBV) in Russia. Symptoms, laboratory parameters and cytokine levels were analyzed and compared between the two patients. Serological and sequence analysis revealed that PUUV was the infecting agent for the German patient and the infection of the Russian patient was caused by Dobrava-Belgrade Virus genotype Sochi (DOBV-Sochi). The symptoms in the initial phase of the diseases did not differ noticeably between both patients. However, deterioration of laboratory parameter values was prolonged and stronger in DOBV-Sochi than in PUUV infection. Circulating endothelial progenitor cells (cEPCs), known to be responsible for endothelial repair, were mobilized in both infections. Striking differences were observed in the temporal course and level of cytokine upregulation. Levels of angiopoietin-2 (Ang-2), vascular endothelial growth factor (VEGF), and stromal derived factor-1 (SDF-1α) were increased in both infections; but, sustained and more pronounced elevation was observed in DOBV-Sochi infection. Conclusions Severe hantaVirus disease caused by different hantaVirus species did not differ in the general symptoms and clinical characteristics. However, we observed a prolonged clinical course and a late and enhanced mobilization of cytokines in DOBV-Sochi infection. The differences in cytokine deregulation may contribute to the observed variation in the clinical course.

  • Clinical characterization of two severe cases of hemorrhagic fever with renal syndrome (HFRS) caused by hantaViruses Puumala and Dobrava-Belgrade genotype Sochi.
    BMC Infectious Diseases, 2016
    Co-Authors: Ellen Krautkramer, Alexandra Baumann, Christian Nusshag, Paul Schnitzler, Boris Klempa, Detlev H. Kruger, Jörg Hofmann, Peter T. Witkowski, Julia Schäfer, Martin Zeier
    Abstract:

    HantaVirus disease belongs to the emerging infections. The clinical picture and severity of infections differ between hantaVirus species and may even vary between hantaVirus genotypes. The mechanisms that lead to the broad variance of severity in infected patients are not completely understood. Host- and Virus-specific factors are considered. We analyzed severe cases of hantaVirus disease in two young women. The first case was caused by Puumala Virus (PUUV) infection in Germany; the second case describes the infection with Dobrava-Belgrade Virus (DOBV) in Russia. Symptoms, laboratory parameters and cytokine levels were analyzed and compared between the two patients. Serological and sequence analysis revealed that PUUV was the infecting agent for the German patient and the infection of the Russian patient was caused by Dobrava-Belgrade Virus genotype Sochi (DOBV-Sochi). The symptoms in the initial phase of the diseases did not differ noticeably between both patients. However, deterioration of laboratory parameter values was prolonged and stronger in DOBV-Sochi than in PUUV infection. Circulating endothelial progenitor cells (cEPCs), known to be responsible for endothelial repair, were mobilized in both infections. Striking differences were observed in the temporal course and level of cytokine upregulation. Levels of angiopoietin-2 (Ang-2), vascular endothelial growth factor (VEGF), and stromal derived factor-1 (SDF-1α) were increased in both infections; but, sustained and more pronounced elevation was observed in DOBV-Sochi infection. Severe hantaVirus disease caused by different hantaVirus species did not differ in the general symptoms and clinical characteristics. However, we observed a prolonged clinical course and a late and enhanced mobilization of cytokines in DOBV-Sochi infection. The differences in cytokine deregulation may contribute to the observed variation in the clinical course.

  • HantaVirus disease in Germany due to infection with Dobrava-Belgrade Virus genotype Kurkino
    Clinical Microbiology and Infection, 2014
    Co-Authors: Jörg Hofmann, Boris Klempa, Sabrina Schmidt, Markus Meier, Martin Enders, A. Führer, Jakob Ettinger, Rainer G. Ulrich, Detlev H. Kruger
    Abstract:

    Members of the Dobrava-Belgrade Virus (DOBV) species are hantaViruses carried by different Apodemus mice as reservoir hosts and causing haemorrhagic fever with renal syndrome (HFRS) in humans. In Central Europe, the Kurkino genotype of DOBV, associated with the striped field mouse, Apodemus agrarius, is prevalent. This paper presents the first extensive study of the serological and molecular diagnostics, epidemiology and clinics of DOBV-Kurkino infections in Central Europe. Serum samples from 570 German patients living in the habitat of A. agrarius (north and northeast Germany) and exhibiting febrile disease, were analysed. All samples were tested by ELISA, subsets of samples were also analysed by immunoblot, neutralization assay, and RT-PCR. A group of 86 individuals was confirmed as DOBV-infected. The Virus neutralization assay allowed a reliable identification of DOBV antibodies during both acute and convalescent phases of infection. However, differentiation of relevant DOBV genotypes was not possible by neutralization test but required molecular analysis. Whereas DOBV IgM antibodies tend to persist in the infected organism, RNAaemia seems to be short. Nucleotide sequences were amplified from four patients, and their analysis demonstrated infection by DOBV-Kurkino. With respect to the initial results, the high degree of identity of local patient-derived and A. agrarius-derived Virus sequences may allow a closer allocation of the geographical place where the human infection occurred. In contrast to moderate/severe HFRS caused by the DOBV genotypes Dobrava or Sochi, all available data showed a mild clinical course of HFRS caused by DOBV-Kurkino infection without lethal outcomes.

Annapaola Rizzoli - One of the best experts on this subject based on the ideXlab platform.

  • A49 Emerging rodent-borne viral pathogens in Italy: Overview of seroprevalence and genomic investigations
    Virus Evolution, 2019
    Co-Authors: Niccolò Alfano, Valentina Tagliapietra, Roberto Rosà, Heidi C. Hauffe, C. Rossi, Daniele Arnoldi, F. Rosso, Annapaola Rizzoli
    Abstract:

    Abstract Rodents play a key role as reservoirs of many zoonotic pathogens which represent an emerging public health threat worldwide. Among these, Dobrava-Belgrade Virus (DOBV) is the most pathogenic hantaVirus in Europe with a case-fatality rate of up to 12 per cent, while Lymphocytic choriomeningitis Virus (LCMV) has a mortality rate below 1 per cent. Both Viruses are predominantly transmitted to humans through the inhalation of infected particles in aerosolized urine, feces, or saliva that are shed in the environment by chronically infected hosts, such as the yellow-necked mouse Apodemus flavicollis. Although no human cases of DOBV or LCMV have been reported in the Province of Trento (northeastern Italy) thus far, in order to evaluate the human hazard for these Viruses, the prevalence of antibodies to DOBV and LCMV has been monitored using a specific immunofluorescence assay test in a wild population of A. flavicollis since 2000. These investigations have shown that the two RNA Viruses circulate silently in this species in the study area. In particular, a sudden increase (up to 12.5%) in DOBV seroprevalence was observed in this rodent species between 2010 and 2012. Several efforts have been undertaken to isolate these Viruses and characterize their genomes, but it has not yet been possible to detect viral RNA from seropositive mice using traditional methods such as RT-PCR. Since RNA Viruses are very diverse and often difficult to isolate, innovative molecular methods based on viral targeted enrichment and high-throughput sequencing have been applied. We intend to report on this long-term seroprevalence study and provide an overview of the molecular approaches adopted in the attempt to confirm the presence of these Viruses, and identify which variants are circulating in the region, as well as their pathogenicity.

  • Emerging Rodent-Borne Viral Zoonoses in Trento, Italy
    EcoHealth, 2018
    Co-Authors: Valentina Tagliapietra, Roberto Rosà, Chiara Rossi, Fausta Rosso, Heidi Christine Hauffe, Michele Tommasini, Walter Versini, Attilio Fabio Cristallo, Annapaola Rizzoli
    Abstract:

    Rodent-borne hanta- and arenaViruses are an emerging public health threat in Europe; however, their circulation in human populations is usually underestimated since most infections are asymptomatic. Compared to other European countries, Italy is considered ‘low risk’ for these Viruses, yet in the Province of Trento, two pathogenic hantaViruses (Puumala and Dobrava-Belgrade Virus) and one arenaVirus (Lymphocytic Choriomeningitis Virus) are known to circulate in rodent reservoirs. In this paper, we performed a follow-up serological screening in humans to detect variation in the prevalence of these three Viruses compared to previous analyses carried out in 2002. We also used a statistical model to link seropositivity to risk factors such as occupational exposure, cutting firewood, hunting, collecting mushrooms, having a garden and owning a woodshed, a dog or a companion rodent. We demonstrate a significant increase in the seroprevalence of all three target Viruses between 2002 and 2015, but no risk factors that we considered were significantly correlated with this increase. We conclude that the general exposure of residents in the Alps to these Viruses has probably increased during the last decade. These results provide an early warning to public health authorities, and we suggest more detailed diagnostic and clinical investigations on suspected cases.

  • Recent increase in prevalence of antibodies to Dobrava-Belgrade Virus (DOBV) in yellow-necked mice in Northern Italy.
    Epidemiology and Infection, 2014
    Co-Authors: Annapaola Rizzoli, Valentina Tagliapietra, Roberto Rosà, Heidi C. Hauffe, Giovanni Marini, Liina Voutilainen, Tarja Sironen, C. Rossi, Daniele Arnoldi, Heikki Henttonen
    Abstract:

    : 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.

Jörg Hofmann - One of the best experts on this subject based on the ideXlab platform.

  • Proteinuria and the Clinical Course of Dobrava-Belgrade HantaVirus Infection.
    Nephron extra, 2018
    Co-Authors: Markus Meier, Detlev H. Kruger, Jörg Hofmann, Jan Kramer, Wolfram J. Jabs, Claudia Nolte, Hendrik Lehnert, Martin Nitschke
    Abstract:

    Purpose: Human infection with Dobrava-Belgrade Virus (DOBV) in Northern Germany causes a mild form of hantaVirus disease predominantly characterized by acute kidney injury due to interstitial nephritis. We evaluated the largest number of DOBV-infected patients so far regarding clinical course, proteinuria, and prognostic markers. Patients and Methods: Patients with DOBV-associated hantaVirus disease admitted to the Renal Division of the University of Lubeck (Germany) between 1997 and 2012 were included in this study. Symptoms, clinical course, laboratory parameters, and urinary protein analysis were investigated at admission (baseline, t0), 3-5 days (t3-5), 10-17 days (t10-17), and after 1 year of follow-up (t365). Results: Of the 34 patients (male/female ratio: 23/11; age: 41 ± 14 years) included in the study, 4 underwent hemodialysis (HD). Glomerular filtration rate was 17 ± 14 mL/min at t0 and increased to 27 ± 26 mL/min (t3-5), 57 ± 20 mL/min (t10-17), and 84 ± 16 mL/min (t365). Albuminuria and tubular proteinuria (α1- and β2-microglobulin) decreased during follow-up; the urinary α1-microglobulin concentration in patients who required HD was significantly higher than that in patients not requiring HD (t0: 186 ± 51 vs. 45 ± 26 mg/g creatinine; t3-5: 87 ± 14 vs. 32 ± 16 mg/g creatinine; t10-17: 63 ± 18 vs. 28 ± 12 mg/g creatinine; p < 0.001). Conclusions: DOBV infection of inpatients in Northern Germany is associated with severe kidney injury that recovers within a few weeks and normalizes within 1 year. Tubular proteinuria is associated with the severity of kidney injury and the necessity of renal replacement therapy in these DOBV-infected patients.

  • Clinical characterization of two severe cases of hemorrhagic fever with renal syndrome (HFRS) caused by hantaViruses Puumala and Dobrava-Belgrade genotype Sochi
    BMC Infectious Diseases, 2016
    Co-Authors: Ellen Krautkramer, Alexandra Baumann, Christian Nusshag, Paul Schnitzler, Boris Klempa, Detlev H. Kruger, Jörg Hofmann, Peter T. Witkowski, Julia Schäfer, Martin Zeier
    Abstract:

    Background HantaVirus disease belongs to the emerging infections. The clinical picture and severity of infections differ between hantaVirus species and may even vary between hantaVirus genotypes. The mechanisms that lead to the broad variance of severity in infected patients are not completely understood. Host- and Virus-specific factors are considered. Case presentation We analyzed severe cases of hantaVirus disease in two young women. The first case was caused by Puumala Virus (PUUV) infection in Germany; the second case describes the infection with Dobrava-Belgrade Virus (DOBV) in Russia. Symptoms, laboratory parameters and cytokine levels were analyzed and compared between the two patients. Serological and sequence analysis revealed that PUUV was the infecting agent for the German patient and the infection of the Russian patient was caused by Dobrava-Belgrade Virus genotype Sochi (DOBV-Sochi). The symptoms in the initial phase of the diseases did not differ noticeably between both patients. However, deterioration of laboratory parameter values was prolonged and stronger in DOBV-Sochi than in PUUV infection. Circulating endothelial progenitor cells (cEPCs), known to be responsible for endothelial repair, were mobilized in both infections. Striking differences were observed in the temporal course and level of cytokine upregulation. Levels of angiopoietin-2 (Ang-2), vascular endothelial growth factor (VEGF), and stromal derived factor-1 (SDF-1α) were increased in both infections; but, sustained and more pronounced elevation was observed in DOBV-Sochi infection. Conclusions Severe hantaVirus disease caused by different hantaVirus species did not differ in the general symptoms and clinical characteristics. However, we observed a prolonged clinical course and a late and enhanced mobilization of cytokines in DOBV-Sochi infection. The differences in cytokine deregulation may contribute to the observed variation in the clinical course.

  • Clinical characterization of two severe cases of hemorrhagic fever with renal syndrome (HFRS) caused by hantaViruses Puumala and Dobrava-Belgrade genotype Sochi.
    BMC Infectious Diseases, 2016
    Co-Authors: Ellen Krautkramer, Alexandra Baumann, Christian Nusshag, Paul Schnitzler, Boris Klempa, Detlev H. Kruger, Jörg Hofmann, Peter T. Witkowski, Julia Schäfer, Martin Zeier
    Abstract:

    HantaVirus disease belongs to the emerging infections. The clinical picture and severity of infections differ between hantaVirus species and may even vary between hantaVirus genotypes. The mechanisms that lead to the broad variance of severity in infected patients are not completely understood. Host- and Virus-specific factors are considered. We analyzed severe cases of hantaVirus disease in two young women. The first case was caused by Puumala Virus (PUUV) infection in Germany; the second case describes the infection with Dobrava-Belgrade Virus (DOBV) in Russia. Symptoms, laboratory parameters and cytokine levels were analyzed and compared between the two patients. Serological and sequence analysis revealed that PUUV was the infecting agent for the German patient and the infection of the Russian patient was caused by Dobrava-Belgrade Virus genotype Sochi (DOBV-Sochi). The symptoms in the initial phase of the diseases did not differ noticeably between both patients. However, deterioration of laboratory parameter values was prolonged and stronger in DOBV-Sochi than in PUUV infection. Circulating endothelial progenitor cells (cEPCs), known to be responsible for endothelial repair, were mobilized in both infections. Striking differences were observed in the temporal course and level of cytokine upregulation. Levels of angiopoietin-2 (Ang-2), vascular endothelial growth factor (VEGF), and stromal derived factor-1 (SDF-1α) were increased in both infections; but, sustained and more pronounced elevation was observed in DOBV-Sochi infection. Severe hantaVirus disease caused by different hantaVirus species did not differ in the general symptoms and clinical characteristics. However, we observed a prolonged clinical course and a late and enhanced mobilization of cytokines in DOBV-Sochi infection. The differences in cytokine deregulation may contribute to the observed variation in the clinical course.

  • Does proficiency testing improve the quality of hantaVirus serodiagnostics? Experiences with INSTAND EQA schemes.
    International Journal of Medical Microbiology, 2015
    Co-Authors: Jörg Hofmann, Hans-peter Grunert, Oliver Donoso-mantke, Heinz Zeichhardt, Detlev H. Kruger
    Abstract:

    Abstract HantaVirus infections in Germany appear periodically with peak numbers every 2–3 years. The reported cases in the years 2007, 2010 and 2012 exceeded many times over those in the years in-between. In order to reveal faults of certain in vitro diagnostic assays (IVDs), to harmonize the performances of the individual assays and to improve the users’ competence in interpreting the results, the National Consiliary Laboratory for HantaViruses and INSTAND e.V. (Society for Promoting Quality Assurance in Medical Laboratories e.V.) established an external quality assessment (EQA) scheme for proficiency testing of hantaVirus serodiagnostics. The first EQA scheme (pilot study) started in March 2009 with 58 participating laboratories from Germany and neighboring countries. Twice a year four serum samples were sent out to the participants to investigate whether the sample reflects an acute or past infection and to distinguish between infections with the hantaVirus types Puumala Virus (PUUV) and Dobrava-Belgrade Virus (DOBV), both endemic in Central Europe. In addition, samples negative for anti-hantaVirus antibodies were tested in order to examine the specificity of the IVDs applied in the participating laboratories. An increasing number of laboratories participated, with a maximum of 92 in March 2014. When summarizing in total 2592 test results, the laboratories reached an overall specificity of 96.7% and a sensitivity of 95% in their detection of a hantaVirus infection. A correct distinction between acute and past infections was forwarded in 90–96% of replies of laboratories. Exact serotyping (PUUV vs. DOBV) of the infection was reported in 81–96% of replies with the lowest accuracy for past DOBV infections; cross-reactivities between diagnostic antigens of the two Viruses as well as persistent IgM titers in humans may interfere with exact testing. The EQAs revealed acceptable results for the serodiagnostic of hantaVirus infection including serotyping but further improvement is still needed.

  • HantaVirus disease in Germany due to infection with Dobrava-Belgrade Virus genotype Kurkino
    Clinical Microbiology and Infection, 2014
    Co-Authors: Jörg Hofmann, Boris Klempa, Sabrina Schmidt, Markus Meier, Martin Enders, A. Führer, Jakob Ettinger, Rainer G. Ulrich, Detlev H. Kruger
    Abstract:

    Members of the Dobrava-Belgrade Virus (DOBV) species are hantaViruses carried by different Apodemus mice as reservoir hosts and causing haemorrhagic fever with renal syndrome (HFRS) in humans. In Central Europe, the Kurkino genotype of DOBV, associated with the striped field mouse, Apodemus agrarius, is prevalent. This paper presents the first extensive study of the serological and molecular diagnostics, epidemiology and clinics of DOBV-Kurkino infections in Central Europe. Serum samples from 570 German patients living in the habitat of A. agrarius (north and northeast Germany) and exhibiting febrile disease, were analysed. All samples were tested by ELISA, subsets of samples were also analysed by immunoblot, neutralization assay, and RT-PCR. A group of 86 individuals was confirmed as DOBV-infected. The Virus neutralization assay allowed a reliable identification of DOBV antibodies during both acute and convalescent phases of infection. However, differentiation of relevant DOBV genotypes was not possible by neutralization test but required molecular analysis. Whereas DOBV IgM antibodies tend to persist in the infected organism, RNAaemia seems to be short. Nucleotide sequences were amplified from four patients, and their analysis demonstrated infection by DOBV-Kurkino. With respect to the initial results, the high degree of identity of local patient-derived and A. agrarius-derived Virus sequences may allow a closer allocation of the geographical place where the human infection occurred. In contrast to moderate/severe HFRS caused by the DOBV genotypes Dobrava or Sochi, all available data showed a mild clinical course of HFRS caused by DOBV-Kurkino infection without lethal outcomes.