Abstract
Highly endemic and outbreak regions for human hantavirus infections are located in the southern, southeastern, and western parts of Germany. The dominant hantavirus is the bank vole transmitted Puumala virus (PUUV). In the eastern part of Germany, previous investigations revealed Tula virus (TULV) and Dobrava–Belgrade virus (DOBV) infections in the respective rodent reservoirs. Here, we describe a seroprevalence study in forestry workers from Brandenburg, eastern Germany, using IgG ELISA and immunoblot tests based on recombinant TULV, DOBV, and PUUV antigens. Out of the 563 sera tested, 499 from male and 64 from female workers, we found 41 out of the 499 (8.2%) sera from men (mean age 47 years) and 10 out of 64 (15.6%) from the women (mean age 48 years) anti-hantavirus-positive. The majority of the 51 seropositive samples reacted exclusively in the TULV (n = 22) and DOBV tests (n = 17). Focus reduction neutralization assay investigations on selected sera confirmed the presence of TULV- and DOBV-specific antibodies in the forestry workers. These investigations demonstrated a potential health threat for forestry workers and also the average population in non-endemic geographical regions where TULV and DOBV are circulating in the corresponding reservoir hosts. The infections in this region might be frequently overlooked due to their unspecific and mild symptoms.
References
Kruger DH, Ulrich R, Lundkvist A (2001) Hantavirus infections and their prevention. Microbes Infect 3(13):1129–1144
Maes P, Klempa B, Clement J, Matthijnssens J, Gajdusek DC, Krüger DH, Van Ranst M (2009) A proposal for new criteria for the classification of hantaviruses, based on S and M segment protein sequences. Infect Genet Evol 9:813–820
Avsic-Zupanc T, Petrovec M, Furlan P, Kaps R, Elgh F, Lundkvist A (1999) Hemorrhagic fever with renal syndrome in the Dolenjska region of Slovenia–a 10-year survey. Clin Infect Dis 28(4):860–865
Klempa B, Tkachenko EA, Dzagurova TK, Yunicheva YV, Morozov VG, Okulova NM, Slyusareva GP, Smirnov A, Kruger DH (2008) Hemorrhagic fever with renal syndrome caused by 2 lineages of Dobrava hantavirus, Russia. Emerg Infect Dis 14(4):617–625
Golovljova I, Vasilenko V, Mittzenkov V, Prükk T, Seppet E, Vene S, Settergren B, Plyusnin A, Lundkvist A (2007) Characterization of hemorrhagic fever with renal syndrome caused by hantaviruses, Estonia. Emerg Infect Dis 13:1773–1776
Sibold C, Ulrich R, Labuda M, Lundkvist A, Martens H, Schutt M, Gerke P, Leitmeyer K, Meisel H, Kruger DH (2001) Dobrava hantavirus causes hemorrhagic fever with renal syndrome in central Europe and is carried by two different Apodemus mice species. J Med Virol 63(2):158–167
Antoniadis A, Pilaski J, Klein H, Zöller L, Gorschewski O (1985) Serologic evidence for Korean haemorrhagic fever in western Germany. Zbl Bakt Hyg A 260:459
Pilaski J, Ellerich C, Kreutzer T, Lang A, Benik W, Pohl-Koppe A, Bode L, Vanek E, Autenrieth IB, Bigos K et al (1991) Haemorrhagic fever with renal syndrome in Germany. Lancet 337(8733):111
Zoller L, Faulde M, Meisel H, Ruh B, Kimmig P, Schelling U, Zeier M, Kulzer P, Becker C, Roggendorf M et al (1995) Seroprevalence of hantavirus antibodies in Germany as determined by a new recombinant enzyme immunoassay. Eur J Clin Microbiol Infect Dis 14(4):305–313
Abu Sin M, Stark K, van Treeck U, Dieckmann H, Uphoff H, Hautmann W, Bornhofen B, Jensen E, Pfaff G, Koch J (2007) Risk factors for hantavirus infection in Germany, 2005. Emerg Infect Dis 13(9):1364–1366
Essbauer S, Schmidt J, Conraths FJ, Friedrich R, Koch J, Hautmann W, Pfeffer M, Wolfel R, Finke J, Dobler G, Ulrich R (2006) A new Puumala hantavirus subtype in rodents associated with an outbreak of Nephropathia epidemica in South-East Germany in 2004. Epidemiol Infect 134(6):1333–1344
Essbauer SS, Schmidt-Chanasit J, Madeja EL, Wegener W, Friedrich R, Petraityte R, Sasnauskas K, Jacob J, Koch J, Dobler G, Conraths FJ, Pfeffer M, Pitra C, Ulrich RG (2007) Nephropathia epidemica in metropolitan area, Germany. Emerg Infect Dis 13(8):1271–1273
Hofmann J, Meisel H, Klempa B, Vesenbeckh SM, Beck R, Michel D, Schmidt-Chanasit J, Ulrich RG, Grund S, Enders G, Krüger DH (2008) Molecular epidemiology of a large hantavirus outbreak in Germany, 2007. Emerg Infect Dis 14:850–852
Schilling S, Emmerich P, Klempa B, Auste B, Schnaith E, Schmitz H, Kruger DH, Gunther S, Meisel H (2007) Hantavirus disease outbreak in Germany: limitations of routine serological diagnostics and clustering of virus sequences of human and rodent origin. J Clin Microbiol 45(9):3008–3014
Faber MS, Ulrich RG, Frank C, Brockmann SO, Pfaff GM, Jacob J, Krüger DH, Stark K (2010) Steep rise in notified hantavirus infections in Germany, April 2010. Eurosurveill 15:19574
Ulrich RG, Schmidt-Chanasit J, Schlegel M, Jacob J, Pelz HJ, Mertens M, Wenk M, Buchner T, Masur D, Sevke K, Groschup MH, Gerstengarbe FW, Pfeffer M, Oehme R, Wegener W, Bemmann M, Ohlmeyer L, Wolf R, Zoller H, Koch J, Brockmann S, Heckel G, Essbauer SS (2008) Network Rodent-borne pathogens in Germany: longitudinal studies on the geographical distribution and prevalence of hantavirus infections. Parasitol Res 103(Suppl 1):S121–S129
Meisel H, Lundkvist A, Gantzer K, Bar W, Sibold C, Kruger DH (1998) First case of infection with hantavirus Dobrava in Germany. Eur J Clin Microbiol Infect Dis 17(12):884–885
Mentel R, Bordihn N, Wegner U, Wendel H, Niklasson B (1999) Hantavirus Dobrava infection with pulmonary manifestation. Med Microbiol Immunol (Berl) 188:51–53
Klempa B, Schutt M, Auste B, Labuda M, Ulrich R, Meisel H, Kruger DH (2004) First molecular identification of human Dobrava virus infection in central Europe. J Clin Microbiol 42(3):1322–1325
Schlegel M, Klempa B, Auste B, Bemmann M, Schmidt-Chanasit J, Buchner T, Groschup MH, Meier M, Balkema-Buschmann A, Zoller H, Kruger DH, Ulrich RG (2009) Dobrava-Belgrade virus spillover infections, Germany. Emerg Infect Dis 15(12):2017–2020
Klempa B, Meisel H, Rath S, Bartel J, Ulrich R, Kruger DH (2003) Occurrence of renal and pulmonary syndrome in a region of northeast Germany where Tula hantavirus circulates. J Clin Microbiol 41(10):4894–4897
Schmidt-Chanasit J, Essbauer S, Petraityte R, Yoshimatsu K, Tackmann K, Conraths FJ, Sasnauskas K, Arikawa J, Thomas A, Pfeffer M, Scharninghausen JJ, Splettstoesser W, Wenk M, Heckel G, Ulrich RG (2010) Extensive host sharing of central European Tula virus. J Virol 84(1):459–474
Kimmig P, Silva-Gonzalez R, Backe H, Brockmann S, Oehme R, Ernst E, Mackenstedt U (2001) Epidemiology of hantaviruses in Baden-Wurttemberg. Gesundheitswesen 63(2):107–112
Mertens M, Wolfel R, Ullrich K, Yoshimatsu K, Blumhardt J, Romer I, Esser J, Schmidt-Chanasit J, Groschup MH, Dobler G, Essbauer SS, Ulrich RG (2009) Seroepidemiological study in a Puumala virus outbreak area in south-east Germany. Med Microbiol Immunol 198:83–91
Heider H, Ziaja B, Priemer C, Lundkvist A, Neyts J, Kruger DH, Ulrich R (2001) A chemiluminescence detection method of hantaviral antigens in neutralisation assays and inhibitor studies. J Virol Method 96(1):17–23
Klempa B, Stanko M, Labuda M, Ulrich R, Meisel H, Kruger DH (2005) Central European Dobrava hantavirus isolate from a striped field mouse (Apodemus agrarius). J Clin Microbiol 43(6):2756–2763
Mertens M, Kindler E, Emmerich P, Esser J, Wagner-Wiening C, Wölfel R, Petraityte-Burneikiene R, Schmidt-Chanasit J, Zvirbliene A, Groschup MH, Dobler G, Pfeffer M, Heckel G, Ulrich RG, Essbauer SS (2011) Phylogenetic analysis of Puumala virus subtype Bavaria, characterization and diagnostic use of its recombinant nucleocapsid protein. Virus Genes (in press)
Plyusnin A, Cheng Y, Vapalahti O, Pejcoch M, Unar J, Jelinkova Z, Lehväslaiho H, Lundkvist A, Vaheri A (1995) Genetic variation in Tula hantaviruses: sequence analysis of the S and M segments of strains from Central Europe. Virus Res 39:237–250
Razanskiene A, Schmidt J, Geldmacher A, Ritzi A, Niedrig M, Lundkvist A, Kruger DH, Meisel H, Sasnauskas K, Ulrich R (2004) High yields of stable and highly pure nucleocapsid proteins of different hantaviruses can be generated in the yeast Saccharomyces cerevisiae. J Biotechnol 111(3):319–333
R Development Core Team (2008) R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. ISBN 3-900051-07-0. URL: http://www.R-project.org
Ulrich R, Meisel H, Schutt M, Schmidt J, Kunz A, Klempa B, Niedrig M, Pauli G, Kruger DH, Koch J (2004) Prevalence of hantavirus infections in Germany. Bundesgesundheitsbl Gesundheitsforsch Gesundheitsschutz 47(7):661–670
Elgh F, Linderholm M, Wadell G, Tarnvik A, Juto P (1998) Development of humoral cross-reactivity to the nucleocapsid protein of heterologous hantaviruses in nephropathia epidemica. FEMS Immunol Med Microbiol 22(4):309–315
Sjolander KB, Lundkvist A (1999) Dobrava virus infection: serological diagnosis and cross-reactions to other hantaviruses. J Virol Method 80(2):137–143
Schmidt J, Meisel H, Hjelle B, Kruger DH, Ulrich R (2005) Development and evaluation of serological assays for detection of human hantavirus infections caused by Sin Nombre virus. J Clin Virol 33(3):247–253
Schmidt J, Meisel H, Capria SG, Petraityte R, Lundkvist A, Hjelle B, Vial PA, Padula P, Kruger DH, Ulrich R (2006) Serological assays for the detection of human Andes hantavirus infections based on its yeast-expressed nucleocapsid protein. Intervirology 49(3):173–184
Meisel H, Wolbert A, Razanskiene A, Marg A, Kazaks A, Sasnauskas K, Pauli G, Ulrich R, Kruger DH (2006) Development of novel immunoglobulin G (IgG), IgA, and IgM enzyme immunoassays based on recombinant Puumala and Dobrava hantavirus nucleocapsid proteins. Clin Vaccine Immunol 13(12):1349–1357
Martens H (2000) Serologic study of the prevalence and course of hantavirus infections in Mecklenburg-Vorpommern. Gesundheitswesen 62(2):71–77
Sandmann S, Meisel H, Razanskiene A, Wolbert A, Pohl B, Krüger DH, Sasnauskas K, Ulrich R (2005) Detection of human hantavirus infections in Lithuania. Infection 33:66–72
Lundkvist Å, Vapalahti O, Henttonen H, Vaheri A, Plyusnin A (2000) Hantavirus infections among mammalogists studied by focus reduction neutralisation test. Eur J Clin Microbiol Infect Dis 19:802–803
Golovljova I, Sjolander KB, Lindegren G, Vene S, Vasilenko V, Plyusnin A, Lundkvist Å (2002) Hantaviruses in Estonia. J Med Virol 68:589–598
Acknowledgments
The work was supported by Research-Project M/SAB1/5/A017 for the Bundeswehr Medical Service. We would like to thank Carsten Leßner, Jürgen Rubach, Roberto Drexler, Jürgen Rinno, Ramona Huth, Viola Kunze, Albert Ulonska, Bernd Friedrich, Pierre Gulz, Rosemarie Augsten, Elvira Pohle, Monika Prechel, Siegfred Zernick, Ausra Razanskiene, and all forestry workers for support and Bernd Köllner and Anke Wiethölter for helpful discussions. The excellent technical assistance of Brigitte Pohl, Beate Becker-Ziaja, and Anna Hegele is kindly acknowledged.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Mertens, M., Hofmann, J., Petraityte-Burneikiene, R. et al. Seroprevalence study in forestry workers of a non-endemic region in eastern Germany reveals infections by Tula and Dobrava–Belgrade hantaviruses. Med Microbiol Immunol 200, 263–268 (2011). https://doi.org/10.1007/s00430-011-0203-4
Received:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00430-011-0203-4