Abstract
In the last few years it has been realized that the hepatitis E virus (HEV) is endemic in most industrialized countries and that it is a zoonotic disease. Potential reservoirs for HEV have been identified to be wild boars and deers, but HEV has also been found in domestic pigs and other animals. Due to the probable spread of the virus via contaminated food or contact to infected animals, HEV antibodies are present in more than 16% of the German adult population and rates are increasing with age. We collected blood from 104 wild boars in southern Germany and the border region of Alsace. We found an anti-HEV seroprevalence of 11.5% in our cohort, using ELISA. Furthermore, we observed active infection in 3.85% of the animals by positive HEV PCR in the sera of the boars. In our cohort, no regional differences of seroprevalence or active infection were seen. Sequencing revealed rather close homology of some detected HEV sequences to genotypes isolated from patients in Germany. Hence wild boars are a potential source of HEV infection in Middle Europe and the rate of infectious animals is quite high.
Similar content being viewed by others
References
Acharya, S. K., & Panda, S. K. (2006). Hepatitis E virus: Epidemiology, diagnosis, pathology and prevention. Tropical Gastroenterology, 27(2), 63–68.
Adlhoch, C., Wolf, A., Meisel, H., Kaiser, M., Ellerbrok, H., & Pauli, G. (2009). High HEV presence in four different wild boar populations in East and West Germany. Veterinary Microbiology, 139(3–4), 270–278. https://doi.org/10.1016/j.vetmic.2009.06.032.
Al-Shukri, I., Davidson, E., Tan, A., Smith, D. B., Wellington, L., Johannessen, I., et al. (2013). Rash and arthralgia caused by hepatitis E. Lancet, 382(9907), 1856. https://doi.org/10.1016/S0140-6736(13)62074-7.
Anheyer-Behmenburg, H. E., Szabo, K., Schotte, U., Binder, A., Klein, G., & Johne, R. (2017). Hepatitis E virus in wild boars and spillover infection in red and roe deer, Germany, 2013–2015. Emerging Infectious Diseases, 23(1), 130–133. https://doi.org/10.3201/eid2301.161169.
Balayan, M. S., Andjaparidze, A. G., Savinskaya, S. S., Ketiladze, E. S., Braginsky, D. M., Savinov, A. P., et al. (1983). Evidence for a virus in non-A, non-B hepatitis transmitted via the fecal-oral route. Intervirology, 20(1), 23–31.
Baumann-Popczyk, A., Popczyk, B., Golab, E., Rozej-Bielicka, W., & Sadkowska-Todys, M. (2017). A cross-sectional study among Polish hunters: Seroprevalence of hepatitis E and the analysis of factors contributing to HEV infections. Medical Microbiology and Immunology. https://doi.org/10.1007/s00430-017-0515-0.
Brost, S., Wenzel, J. J., Ganten, T. M., Filser, M., Flechtenmacher, C., Boehm, S., et al. (2010). Sporadic cases of acute autochthonous hepatitis E virus infection in Southwest Germany. Journal of Clinical Virology, 47(1), 89–92. https://doi.org/10.1016/j.jcv.2009.10.011.
Chauhan, A., Jameel, S., Dilawari, J. B., Chawla, Y. K., Kaur, U., & Ganguly, N. K. (1993). Hepatitis E virus transmission to a volunteer. Lancet, 341(8838), 149–150.
Colson, P., Borentain, P., Queyriaux, B., Kaba, M., Moal, V., Gallian, P., et al. (2010). Pig liver sausage as a source of hepatitis E virus transmission to humans. Journal of Infectious Diseases, 202(6), 825–834. https://doi.org/10.1086/655898.
Dalton, H. R., Hunter, J. G., & Bendall, R. P. (2013). Hepatitis E. Current Opinion in Infectious Diseases, 26(5), 471–478. https://doi.org/10.1097/01.qco.0000433308.83029.97.
Dalton, H. R., Stableforth, W., Thurairajah, P., Hazeldine, S., Remnarace, R., Usama, W., et al. (2008). Autochthonous hepatitis E in Southwest England: Natural history, complications and seasonal variation, and hepatitis E virus IgG seroprevalence in blood donors, the elderly and patients with chronic liver disease. European Journal of Gastroenterology and Hepatology, 20(8), 784–790. https://doi.org/10.1097/MEG.0b013e3282f5195a.
Dremsek, P., Wenzel, J. J., Johne, R., Ziller, M., Hofmann, J., Groschup, M. H., et al. (2012). Seroprevalence study in forestry workers from eastern Germany using novel genotype 3- and rat hepatitis E virus-specific immunoglobulin G ELISAs. Medical Microbiology and Immunology, 201(2), 189–200. https://doi.org/10.1007/s00430-011-0221-2.
Engle, R. E., Yu, C., Emerson, S. U., Meng, X. J., & Purcell, R. H. (2002). Hepatitis E virus (HEV) capsid antigens derived from viruses of human and swine origin are equally efficient for detecting anti-HEV by enzyme immunoassay. Journal of Clinical Microbiology, 40(12), 4576–4580.
Faber, M. S., Wenzel, J. J., Jilg, W., Thamm, M., Hohle, M., & Stark, K. (2012). Hepatitis E virus seroprevalence among adults, Germany. Emerging Infectious Diseases, 18(10), 1654–1657. https://doi.org/10.3201/eid1810.111756.
Geng, Y., & Wang, Y. (2016). Epidemiology of hepatitis E. Advances in Experimental Medicine and Biology, 948, 39–59. https://doi.org/10.1007/978-94-024-0942-0_3.
Hartl, J., Otto, B., Madden, R. G., Webb, G., Woolson, K. L., Kriston, L., et al. (2016). Hepatitis E seroprevalence in Europe: A meta-analysis. Viruses, 8(8). doi:10.3390/v8080211.
Hewitt, P. E., Ijaz, S., Brailsford, S. R., Brett, R., Dicks, S., Haywood, B., et al. (2014). Hepatitis E virus in blood components: A prevalence and transmission study in southeast England. Lancet, 384(9956), 1766–1773. https://doi.org/10.1016/S0140-6736(14)61034-5.
Hoerning, A., Hegen, B., Wingen, A. M., Cetiner, M., Lainka, E., Kathemann, S., et al. (2012). Prevalence of hepatitis E virus infection in pediatric solid organ transplant recipients–a single-center experience. Pediatric Transplantation, 16(7), 742–747. https://doi.org/10.1111/j.1399-3046.2012.01740.x.
Hoofnagle, J. H., Nelson, K. E., & Purcell, R. H. (2012). Hepatitis E. New England Journal of Medicine, 367(13), 1237–1244. https://doi.org/10.1056/NEJMra1204512.
Huzly, D., Umhau, M., Bettinger, D., Cathomen, T., Emmerich, F., Hasselblatt, P., et al. (2014). Transfusion-transmitted hepatitis E in Germany, 2013. Euro Surveill, 19(21), 20812. https://doi.org/10.2807/1560-7917.ES2014.19.21.20812.
Ivanova, A., Tefanova, V., Reshetnjak, I., Kuznetsova, T., Geller, J., Lundkvist, A., et al. (2015). Hepatitis E Virus in domestic pigs, wild boars, pig farm workers, and hunters in Estonia. Food and Environmental Virology, 7(4), 403–412. https://doi.org/10.1007/s12560-015-9210-8.
Kaci, S., Nockler, K., & Johne, R. (2008). Detection of hepatitis E virus in archived German wild boar serum samples. Veterinary Microbiology, 128(3–4), 380–385. https://doi.org/10.1016/j.vetmic.2007.10.030.
Kamar, N., Bendall, R., Legrand-Abravanel, F., Xia, N. S., Ijaz, S., Izopet, J., et al. (2012). Hepatitis E. Lancet, 379(9835), 2477–2488. https://doi.org/10.1016/S0140-6736(11)61849-7.
Khuroo, M. S. (1980). Study of an epidemic of non-A, non-B hepatitis. Possibility of another human hepatitis virus distinct from post-transfusion non-A, non-B type. American Journal of Medicine, 68(6), 818–824.
Krumbholz, A., Mohn, U., Lange, J., Motz, M., Wenzel, J. J., Jilg, W., et al. (2012). Prevalence of hepatitis E virus-specific antibodies in humans with occupational exposure to pigs. Medical Microbiology and Immunology, 201(2), 239–244. https://doi.org/10.1007/s00430-011-0210-5.
Legrand-Abravanel, F., Kamar, N., Sandres-Saune, K., Lhomme, S., Mansuy, J. M., Muscari, F., et al. (2011). Hepatitis E virus infection without reactivation in solid-organ transplant recipients, France. Emerging Infectious Diseases, 17(1), 30–37. https://doi.org/10.3201/eid1701.100527.
Li, T. C., Chijiwa, K., Sera, N., Ishibashi, T., Etoh, Y., Shinohara, Y., et al. (2005). Hepatitis E virus transmission from wild boar meat. Emerging Infectious Diseases, 11(12), 1958–1960. https://doi.org/10.3201/eid1112.051041.
Mansuy, J. M., Gallian, P., Dimeglio, C., Saune, K., Arnaud, C., Pelletier, B., et al. (2016). A nationwide survey of hepatitis E viral infection in French blood donors. Hepatology, 63(4), 1145–1154. https://doi.org/10.1002/hep.28436.
Mansuy, J. M., Peron, J. M., Abravanel, F., Poirson, H., Dubois, M., Miedouge, M., et al. (2004). Hepatitis E in the south west of France in individuals who have never visited an endemic area. Journal of Medical Virology, 74(3), 419–424. https://doi.org/10.1002/jmv.20206.
Mansuy, J. M., Saune, K., Rech, H., Abravanel, F., Mengelle, C., L Homme, S., et al. (2015). Seroprevalence in blood donors reveals widespread, multi-source exposure to hepatitis E virus, southern France, October 2011. Eurosurveillance Weekly, 20(19), 27–34.
Matsuda, H., Okada, K., Takahashi, K., & Mishiro, S. (2003). Severe hepatitis E virus infection after ingestion of uncooked liver from a wild boar. Journal of Infectious Diseases, 188(6), 944. https://doi.org/10.1086/378074.
Meng, X. J. (2000). Novel strains of hepatitis E virus identified from humans and other animal species: Is hepatitis E a zoonosis? Journal of Hepatology, 33(5), 842–845.
Meng, X. J., Purcell, R. H., Halbur, P. G., Lehman, J. R., Webb, D. M., Tsareva, T. S., et al. (1997). A novel virus in swine is closely related to the human hepatitis E virus. Proceedings of the National Academy of Sciences of the United States of America, 94(18), 9860–9865.
Michitaka, K., Takahashi, K., Furukawa, S., Inoue, G., Hiasa, Y., Horiike, N., et al. (2007). Prevalence of hepatitis E virus among wild boar in the Ehime area of western Japan. Hepatology Research, 37(3), 214–220. https://doi.org/10.1111/j.1872-034X.2007.00030.x.
Montagnaro, S., De Martinis, C., Sasso, S., Ciarcia, R., Damiano, S., Auletta, L., et al. (2015). Viral and antibody prevalence of hepatitis E in European wild boars (Sus scrofa) and hunters at zoonotic risk in the Latium Region. Journal of Comparative Pathology, 153(1), 1–8. https://doi.org/10.1016/j.jcpa.2015.04.006.
Oliveira-Filho, E. F., Bank-Wolf, B. R., Thiel, H. J., & Konig, M. (2014). Phylogenetic analysis of hepatitis E virus in domestic swine and wild boar in Germany. Veterinary Microbiology, 174(1–2), 233–238. https://doi.org/10.1016/j.vetmic.2014.09.011.
Pina, S., Buti, M., Cotrina, M., Piella, J., & Girones, R. (2000). HEV identified in serum from humans with acute hepatitis and in sewage of animal origin in Spain. Journal of Hepatology, 33(5), 826–833.
Pischke, S., Behrendt, P., Bock, C. T., Jilg, W., Manns, M. P., & Wedemeyer, H. (2014). Hepatitis E in Germany—an under-reported infectious disease. Deutsches Ärzteblatt International, 111(35–36), 577–583. https://doi.org/10.3238/arztebl.2014.0577.
Pischke, S., Hartl, J., Pas, S. D., Lohse, A. W., Jacobs, B. C., & van der Eijk, A. A. (2016). Hepatitis E virus infection beyond the liver? Journal of Hepatology. https://doi.org/10.1016/j.jhep.2016.11.016.
Pischke, S., Heim, A., Bremer, B., Raupach, R., Horn-Wichmann, R., Ganzenmueller, T., et al. (2011). Hepatitis E: An emerging infectious disease in Germany? Zeitschrift fur Gastroenterologie, 49(9), 1255–1257. https://doi.org/10.1055/s-0031-1273394.
Pischke, S., Potthoff, A., Hauroder, B., Schlue, J., Manns, M. P., Cornberg, M., et al. (2010). Hepatitis E virus infection: A paradigm shift? Deutsche Medizinische Wochenschrift, 135(22), 1129–1133. https://doi.org/10.1055/s-0030-1255136.
Purcell, R. H., & Emerson, S. U. (2000). Hepatitis E virus infection. Lancet, 355(9203), 578. https://doi.org/10.1016/S0140-6736(05)73231-1.
Purcell, R. H., & Emerson, S. U. (2008). Hepatitis E: An emerging awareness of an old disease. Journal of Hepatology, 48(3), 494–503. https://doi.org/10.1016/j.jhep.2007.12.008.
Rein, D. B., Stevens, G. A., Theaker, J., Wittenborn, J. S., & Wiersma, S. T. (2012). The global burden of hepatitis E virus genotypes 1 and 2 in 2005. Hepatology, 55(4), 988–997. https://doi.org/10.1002/hep.25505.
Romano, L., Paladini, S., Tagliacarne, C., Canuti, M., Bianchi, S., & Zanetti, A. R. (2011). Hepatitis E in Italy: A long-term prospective study. Journal of Hepatology, 54(1), 34–40. https://doi.org/10.1016/j.jhep.2010.06.017.
Schielke, A., Ibrahim, V., Czogiel, I., Faber, M., Schrader, C., Dremsek, P., et al. (2015). Hepatitis E virus antibody prevalence in hunters from a district in Central Germany, 2013: A cross-sectional study providing evidence for the benefit of protective gloves during disembowelling of wild boars. BMC Infectious Diseases, 15, 440. https://doi.org/10.1186/s12879-015-1199-y.
Schielke, A., Sachs, K., Lierz, M., Appel, B., Jansen, A., & Johne, R. (2009). Detection of hepatitis E virus in wild boars of rural and urban regions in Germany and whole genome characterization of an endemic strain. Virology Journal, 6, 58. https://doi.org/10.1186/1743-422X-6-58.
Smith, D. B., Simmonds, P., Izopet, J., Oliveira-Filho, E. F., Ulrich, R. G., Johne, R., et al. (2016). Proposed reference sequences for hepatitis E virus subtypes. Journal of General Virology, 97(3), 537–542. https://doi.org/10.1099/jgv.0.000393.
Takahashi, M., Nishizawa, T., Sato, H., Jirintai, Y., Nagashima, S., et al. (2011). Analysis of the full-length genome of a hepatitis E virus isolate obtained from a wild boar in Japan that is classifiable into a novel genotype. Journal of General Virology, 92(Pt 4), 902–908. https://doi.org/10.1099/vir.0.029470-0.
Tam, A. W., Smith, M. M., Guerra, M. E., Huang, C. C., Bradley, D. W., Fry, K. E., et al. (1991). Hepatitis E virus (HEV): Molecular cloning and sequencing of the full-length viral genome. Virology, 185(1), 120–131.
Tamada, Y., Yano, K., Yatsuhashi, H., Inoue, O., Mawatari, F., & Ishibashi, H. (2004). Consumption of wild boar linked to cases of hepatitis E. Journal of Hepatology, 40(5), 869–870. https://doi.org/10.1016/j.jhep.2003.12.026.
Tei, S., Kitajima, N., Takahashi, K., & Mishiro, S. (2003). Zoonotic transmission of hepatitis E virus from deer to human beings. Lancet, 362(9381), 371–373. https://doi.org/10.1016/S0140-6736(03)14025-1.
Teshale, E. H., Hu, D. J., & Holmberg, S. D. (2010). The two faces of hepatitis E virus. Clinical Infectious Diseases, 51(3), 328–334. https://doi.org/10.1086/653943.
van den Berg, B., van der Eijk, A. A., Pas, S. D., Hunter, J. G., Madden, R. G., Tio-Gillen, A. P., et al. (2014). Guillain-Barre syndrome associated with preceding hepatitis E virus infection. Neurology, 82(6), 491–497. https://doi.org/10.1212/WNL.0000000000000111.
Vina-Rodriguez, A., Schlosser, J., Becher, D., Kaden, V., Groschup, M. H., & Eiden, M. (2015). Hepatitis E virus genotype 3 diversity: Phylogenetic analysis and presence of subtype 3b in wild boar in Europe. Viruses, 7(5), 2704–2726. https://doi.org/10.3390/v7052704.
Wenzel, J. J., Preiss, J., Schemmerer, M., Huber, B., Plentz, A., & Jilg, W. (2011). Detection of hepatitis E virus (HEV) from porcine livers in Southeastern Germany and high sequence homology to human HEV isolates. Journal of Clinical Virology, 52(1), 50–54. https://doi.org/10.1016/j.jcv.2011.06.006.
Wenzel, J. J., Sichler, M., Schemmerer, M., Behrens, G., Leitzmann, M. F., & Jilg, W. (2014). Decline in hepatitis E virus antibody prevalence in southeastern Germany, 1996-2011. Hepatology, 60(4), 1180–1186. https://doi.org/10.1002/hep.27244.
Wichmann, O., Schimanski, S., Koch, J., Kohler, M., Rothe, C., Plentz, A., et al. (2008). Phylogenetic and case-control study on hepatitis E virus infection in Germany. Journal of Infectious Diseases, 198(12), 1732–1741. https://doi.org/10.1086/593211.
Acknowledgements
This study was only possible since many hunters were willing to sample blood from culled wild boar. We thank all hunters who contributed. The majority of samples were obtained from the following hunters: Alfred Baumhauer, Fürst zu Oettingen-Spielberg, Ulrich Gann, F. Vaas, and Josef Lemmermeier to whom we are particularly grateful. We also thank Barbara Hottenträger and Monika Erl for expert technical assistance.
Author information
Authors and Affiliations
Contributions
Concept of the study: Kilian Weigand, Kurt Weigand. Writing the manuscript: Kilian Weigand, Kurt Weigand. Sequencing, genotyping, and ELISA: Mathias Schemmerer and Juergen Wenzel. Data acquirement, Statistical, and data analysis: Kilian Weigand and Juergen Wenzel. Scientific support: Martina Mueller. Critical review of the manuscript: all authors.
Corresponding author
Ethics declarations
Conflict of interests
The authors have no conflict of interest regarding this study.
Rights and permissions
About this article
Cite this article
Weigand, K., Weigand, K., Schemmerer, M. et al. Hepatitis E Seroprevalence and Genotyping in a Cohort of Wild Boars in Southern Germany and Eastern Alsace. Food Environ Virol 10, 167–175 (2018). https://doi.org/10.1007/s12560-017-9329-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12560-017-9329-x