Volume 88, Issue 2
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645



Hepatitis E virus (HEV) causes an orofecal disease transmitted through poor hygiene environments, contaminated food (mainly pork products), or by contacts with infected animals. Very little data are currently available regarding the disease in the Southwestern Indian Ocean Islands. We report the first sero- and viro-survey for HEV in human and swine in Madagascar. A seroprevalence rate of 14.1% (60 of 427) was measured in slaughterhouse workers. Seroprevalence to HEV in pigs was estimated to 71.2% (178 of 250), strongly suggesting the existence of a zoonotic cycle. Three out of 250 pig livers (1.2%) tested HEV RNA-positive by quantitative polymerase chain reaction. Phylogenetic analyses based on 1-kb sequences of the ORF 2-3 identified these viruses as HEV genotype 3. Sequences clustered in a distinct Malagasy sub-clade, possibly representative of a new sub-genotype, for which the date of emergence was estimated around 1989. Further studies are needed to confirm other transmission routes of HEV to humans, especially through non-zoonotic cycles.


Article metrics loading...

The graphs shown below represent data from March 2017
Loading full text...

Full text loading...



  1. Meng XJ, Anderson DA, Arankalle VA, Emerson SU, Harrison TJ, Jameel S, Okamoto H, King AM, Carstens EB, Lefkowitz EJ, , 2011. Family Hepeviridae. , ed. Virus Taxonomy: 9th Report of the International Committee on Taxonomy of Viruses. San Diego, CA: Elsevier, 10211028. [Google Scholar]
  2. Purcell RH, Emerson SU, , 2010. Hidden danger: the raw facts about hepatitis E virus. J Infect Dis 202: 819821.[Crossref] [Google Scholar]
  3. Pavio N, Meng X-J, Renou C, , 2010. Zoonotic hepatitis E: animal reservoirs and emerging risks. Vet Res 41: 46.[Crossref] [Google Scholar]
  4. Zhang W, Shen Q, Hua X, Cui L, , 2011. Novel hepatitis E virus genotype in Norway rats, Germany. Emerg Infect Dis 17: 19811983.[Crossref] [Google Scholar]
  5. Cossaboom C, Córdoba L, Dryman B, Meng X-J, , 2011. Hepatitis E virus in rabbits, Virginia, USA. Emerg Infect Dis 17: 20472049.[Crossref] [Google Scholar]
  6. Colson P, Borentain P, Queyriaux B, Kaba M, Moal V, Gallian P, Heyries L, Raoult D, Gerolami R, , 2010. Pig liver sausage as a source of hepatitis E virus transmission to humans. J Infect Dis 202: 825834.[Crossref] [Google Scholar]
  7. Lu L, Li C, Hagedorn CH, , 2006. Phylogenetic analysis of global hepatitis E virus sequences: genetic diversity, subtypes and zoonosis. Rev Med Virol 16: 536.[Crossref] [Google Scholar]
  8. Johne R, Heckel G, Plenge-Bönig A, Kindler E, Maresch C, Reetz J, Schielke A, Ulrich R, , 2010. Novel hepatitis E virus genotype in Norway rats, Germany. Emerg Infect Dis 16: 14521455.[Crossref] [Google Scholar]
  9. Haqshenas G, Shivaprasad HL, Woolcock PR, Read DH, Meng X, , 2001. Genetic identification and characterization of a novel virus related to human hepatitis E virus from chickens with hepatitis-splenomegaly syndrome in the United States. J Gen Virol 82: 24492462.[Crossref] [Google Scholar]
  10. Marek A, Bilic I, Prokofieva I, Hess M, , 2010. Phylogenetic analysis of avian hepatitis E virus samples from European and Australian chicken flocks supports the existence of a different genus within the Hepeviridae comprising at least three different genotypes. Vet Microbiol 145: 5461.[Crossref] [Google Scholar]
  11. Zhao Q, Zhou EM, Dong SW, Qiu HK, Zhang L, Hu SB, Zhao FF, Jiang SJ, Sun YN, , 2010. Analysis of avian hepatitis E virus from chickens, China. Emerg Infect Dis 16: 14691472.[Crossref] [Google Scholar]
  12. Drexler JF, Seelen A, Corman VM, Fumie Tateno A, Cottontail V, Melim Zerbinati R, Gloza-Rausch F, Klose SM, Adu-Sarkodie Y, Oppong SK, Kalko EK, Osterman A, Rasche A, Adam A, Müller MA, Ulrich RG, Leroy EM, Lukashev AN, Drosten C, , 2012. Bats worldwide carry hepatitis E-related viruses that form a putative novel genus within the family Hepeviridae. J Virol 86: 91349147.[Crossref] [Google Scholar]
  13. Satou K, Nishiura H, , 2007. Transmission dynamics of hepatitis E among swine: potential impact upon human infection. BMC Vet Res 3: 9.[Crossref] [Google Scholar]
  14. Rose N, Lunazzi A, Dorenlor V, Merbah T, Eono F, Eloit M, Madec F, Pavio N, , 2011. High prevalence of Hepatitis E virus in French domestic pigs. Comp Immunol Microbiol Infect Dis 34: 419427.[Crossref] [Google Scholar]
  15. Montalvo Villalba M, Lay L, Chandra V, Bello Corredor M, Frometa S, Moreno A, Jameel SM, , 2008. Hepatitis E virus genotype 1, Cuba. Emerg Infect Dis 14: 13201322.[Crossref] [Google Scholar]
  16. Despierres L-A, Kaphan E, Attarian S, Cohen-Bacrie S, Pelletier J, Pouget J, Motte A, Charrel R, Gerolami R, Colson P, , 2010. Neurologic disorders and hepatitis E, France. Emerg Infect Dis 17: 15101512. [Google Scholar]
  17. Escribà J, Nakoune E, Recio C, Massamba P-M, Matsika-Claquin M, Goumba C, Rose AM, Nicand E, García E, Leklegban C, Koffi B, , 2008. Hepatitis E, Central African Republic. Emerg Infect Dis 14: 681683.[Crossref] [Google Scholar]
  18. Lewis H, Boisson S, Ijaz S, Hewitt K, Ngui S, Boxall E, Teo CG, Morgan D, , 2008. Hepatitis E in England and Wales. Emerg Infect Dis 14: 165167.[Crossref] [Google Scholar]
  19. Li R-C, Ge S-X, Li Y-P, Zheng Y-J, Nong Y, Guo Q-S, Zhang J, Ng M, Xia N, , 2006. Seroprevalence of hepatitis E virus infection, rural southern People's Republic of China. Emerg Infect Dis 12: 16821688.[Crossref] [Google Scholar]
  20. Rutjes S, Lodder W, Lodder-Verschoor F, van den Berg H, Vennema H, Duizer E, Koopmans M, de Roda Husman AM, , 2009. Sources of hepatitis E virus genotype 3 in the Netherlands. Emerg Infect Dis 15: 381387.[Crossref] [Google Scholar]
  21. Legrand-Abravanel F, Mansuy JM, Dubois M, Kamar N, Peron JM, Rostaing L, Izopet J, , 2009. Hepatitis E virus genotype 3 diversity, France. Emerg Infect Dis 15: 110114.[Crossref] [Google Scholar]
  22. Purcell RH, Emerson SU, , 2008. Hepatitis E: an emerging awareness of an old disease. J Hepatol 48: 494503.[Crossref] [Google Scholar]
  23. Boccia D, Guthmann J, Klovstad H, Hamid N, Tatay M, Ciglenecki I, Nizou J, Nicand E, Guerin P, , 2006. High mortality associated with an outbreak of hepatitis E among displaced persons in Darfur, Sudan. Clin Infect Dis 42: 16791684.[Crossref] [Google Scholar]
  24. Meng XJ, Wiseman B, Elvinger F, Guenette DK, Toth TE, Engle RE, Emerson SU, Purcell RH, , 2002. Prevalence of antibodies to hepatitis E virus in veterinarians working with swine and in normal blood donors in the United States and other countries. J Clin Microbiol 40: 117122.[Crossref] [Google Scholar]
  25. Pérez-Gracia M, Mateos M, Galiana C, Fernández-Barredo S, García A, Gómez M, Moreira V, , 2007. Autochthonous hepatitis E infection in a slaughterhouse worker. Am J Trop Med Hyg 77: 893896. [Google Scholar]
  26. Di Martino B, Di Profio F, Martella V, Di Felice E, Di Francesco C, Ceci C, Marsilio F, , 2010. Detection of hepatitis E virus in slaughtered pigs in Italy. Arch Virol 155: 103106.[Crossref] [Google Scholar]
  27. Epelboin L, Nicand E, Roussin C, Lernout T, Pettinelli M-E, Tesse S, Ali R, Aubry P, , 2011. A sporadic case of genotype 3f hepatitis E in Mayotte. Med Mal Infect 41: 392394.[Crossref] [Google Scholar]
  28. Nicand É, Bigaillon C, Tessé S, , 2009. Hepatitis E in France: surveillance data for human cases, 2006–2008. Bull Épidémiol Hebd 31–32: 337342. [Google Scholar]
  29. Milon A, , 2004. Hépatite E à la Réunion. Bull Soc Pathol Exot 96: 149150. [Google Scholar]
  30. Barnaud E, Rogee S, Garry P, Rose N, Pavio N, , 2012. Thermal inactivation of infectious hepatitis e virus in experimentally contaminated food. Appl Environ Microbiol 78: 51535159.[Crossref] [Google Scholar]
  31. Jothikumar N, Cromeans TL, Robertson BH, Meng XJ, Hill VR, , 2006. A broadly reactive one-step real-time RT-PCR assay for rapid and sensitive detection of hepatitis E virus. J Virol Methods 131: 6571.[Crossref] [Google Scholar]
  32. Gyarmati P, Mohammed N, Norder H, Blomberg J, Belák S, Widén F, , 2007. Universal detection of hepatitis E virus by two real-time PCR assays: TaqMan and Primer-Probe Energy Transfer. J Virol Methods 146: 226235.[Crossref] [Google Scholar]
  33. Cooper K, Huang FF, Batista L, Rayo CD, Bezanilla JC, Toth TE, Meng XJ, , 2005. Identification of genotype 3 hepatitis E virus (HEV) in serum and fecal samples from pigs in Thailand and Mexico, where genotype 1 and 2 HEV strains are prevalent in the respective human populations. J Clin Microbiol 43: 16841688.[Crossref] [Google Scholar]
  34. Kearse M, Moir R, Wilson A, Stones-Havas S, Cheung M, Sturrock S, Buxton S, Cooper A, Markowitz S, Duran C, Thierer T, Ashton B, Meintjes P, Drummond A, , 2012. Geneious basic: an integrated and extendable desktop software platform for the organization and analysis of sequence data. Bioinformatics 28: 16471649.[Crossref] [Google Scholar]
  35. Edgar RC, , 2004. MUSCLE: a multiple sequence alignment method with reduced time and space complexity. BMC Bioinformatics 5: 113.[Crossref] [Google Scholar]
  36. Posada D, , 2008. jModelTest: phylogenetic model averaging. Mol Biol Evol 25: 12531256.[Crossref] [Google Scholar]
  37. Tamura K, Peterson D, Peterson N, Stecher G, Nei M, Kumar S, , 2011. MEGA5: molecular evolutionary genetics analysis using maximum likelihood, evolutionary distance, and maximum parsimony methods. Mol Biol Evol 28: 27312739.[Crossref] [Google Scholar]
  38. Tajima F, Nei M, , 1984. Estimation of evolutionary distance between nucleotide sequences. Mol Biol Evol 1: 269285. [Google Scholar]
  39. Guindon S, Gascuel O, , 2003. A simple, fast, and accurate algorithm to estimate large phylogenies by maximum likelihood. Syst Biol 52: 696704.[Crossref] [Google Scholar]
  40. Ronquist F, Huelsenbeck JP, , 2003. MrBayes 3: Bayesian phylogenetic inference under mixed models. Bioinformatics 19: 15721574.[Crossref] [Google Scholar]
  41. R Development Core Team, 2008. R: a language and environment for statistical computing. Vienna. Available at: http://www.r-project.org. Accessed January 22, 2012.
  42. Tajima F, Nei M, , 1984. Estimation of evolutionary distance between nucleotide sequences. Mol Biol Evol 1: 269285. [Google Scholar]
  43. Vivek R, Kang G, , 2011. Hepatitis E virus infections in swine and swine handlers in Vellore, southern India. Am J Trop Med Hyg 84: 647649.[Crossref] [Google Scholar]
  44. Zhang W, Yang S, Ren L, Shen Q, Cui L, Fan K, Huang F, Kang Y, Shan T, Wei J, Xiu H, Lou Y, Liu J, Yang Z, Zhu J, Hua X, , 2009. Hepatitis E virus infection in central China reveals no evidence of cross-species transmission between human and swine in this area. PLoS ONE 4: e8156.[Crossref] [Google Scholar]
  45. Perez-Gracia MT, Mateos ML, Galiana C, Fernandez-Barredo S, Garcia A, Gomez MT, Moreira V, , 2007. Autochthonous hepatitis E infection in a slaughterhouse worker. Am J Trop Med Hyg 77: 893896. [Google Scholar]
  46. Adjei AA, Aviyase JT, Tettey Y, Adu-Gyamfi C, Mingle JA, Ayeh-Kumi PF, Adiku TK, Gyasi RK, , 2009. Hepatitis E virus infection among pig handlers in Accra, Ghana. East Afr Med J 86: 359363. [Google Scholar]
  47. Galiana C, Fernandez-Barredo S, Garcia A, Gomez MT, Perez-Gracia MT, , 2008. Occupational exposure to hepatitis E virus (HEV) in swine workers. Am J Trop Med Hyg 78: 10121015. [Google Scholar]
  48. Krumbholz A, Mohn U, Lange J, Motz M, Wenzel JJ, Jilg W, Walther M, Straube E, Wutzler P, Zell R, , 2012. Prevalence of hepatitis E virus-specific antibodies in humans with occupational exposure to pigs. Med Microbiol Immunol (Berl) 201: 239244.[Crossref] [Google Scholar]
  49. Kaufmann A, Kenfak-Foguena A, Andre C, Canellini G, Burgisser P, Moradpour D, Darling KE, Cavassini M, , 2011. Hepatitis E virus seroprevalence among blood donors in southwest Switzerland. PLoS ONE 6: e21150.[Crossref] [Google Scholar]
  50. Withers MR, Correa MT, Morrow M, Stebbins ME, Seriwatana J, Webster WD, Boak MB, Vaughn DW, , 2002. Antibody levels to hepatitis E virus in North Carolina swine workers, non-swine workers, swine, and murids. Am J Trop Med Hyg 66: 384388. [Google Scholar]
  51. Toole MJ, Claridge F, Anderson DA, Zhuang H, Morgan C, Otto B, Stewart T, , 2006. Hepatitis E virus infection as a marker for contaminated community drinking water sources in Tibetan villages. Am J Trop Med Hyg 74: 250254. [Google Scholar]
  52. Xiao P, Li R, She R, Yin J, Li W, Mao J, Sun Q, , 2012. Prevalence of hepatitis E virus in swine fed on kitchen residue. PLoS ONE 7: e33480.[Crossref] [Google Scholar]
  53. Di Bartolo I, Martelli F, Inglese N, Pourshaban M, Caprioli A, Ostanello F, Ruggeri FM, , 2008. Widespread diffusion of genotype 3 hepatitis E virus among farming swine in Northern Italy. Vet Microbiol 132: 4755.[Crossref] [Google Scholar]
  54. Nakai I, Kato K, Miyazaki A, Yoshii M, Li TC, Takeda N, Tsunemitsu H, Ikeda H, , 2006. Different fecal shedding patterns of two common strains of hepatitis E virus at three Japanese swine farms. Am J Trop Med Hyg 75: 11711177. [Google Scholar]
  55. Geng J, Wang L, Wang X, Fu H, Bu Q, Liu P, Zhu Y, Wang M, Sui Y, Zhuang H, , 2011. Potential risk of zoonotic transmission from young swine to human: seroepidemiological and genetic characterization of hepatitis E virus in human and various animals in Beijing, China. J Viral Hepat 18: 583590.[Crossref] [Google Scholar]
  56. 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. Vet Microbiol 139: 270278.[Crossref] [Google Scholar]
  57. Nakano T, Takahashi K, Pybus OG, Hashimoto N, Kato H, Okano H, Kobayashi M, Fujita N, Shiraki K, Takei Y, Ayada M, Arai M, Okamoto H, Mishiro S, , 2012. New findings regarding the epidemic history and population dynamics of Japan-indigenous genotype 3 hepatitis E virus inferred by molecular evolution. Liver Int 32: 675688.[Crossref] [Google Scholar]

Data & Media loading...

  • Received : 04 Oct 2012
  • Accepted : 31 Oct 2012
  • Published online : 06 Feb 2013

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error