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The Epidemiology and Prevention of Hepatitis E Virus Infection

  • Infectious Disease Epidemiology (A Reingold, Section Editor)
  • Published:
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Abstract

Purpose of Review

Hepatitis E virus (HEV) infections are a global public health problem. These viruses were originally identified as the cause of large waterborne outbreaks with increased mortality in pregnant women in developing countries in Asia and Africa in 1983. A decade later, locally acquired cases of acute hepatitis were reported in industrialized countries after food-borne transmission from an animal reservoir, especially swine, wild boar, and deer. However, the knowledge about the clinical features of HEV infection, the animal reservoirs, and virus characteristics has expanded substantially in recent years.

Recent Findings

HEV infections in patients who are immunosuppressed after a solid organ transplant and AIDS or cancer chemotherapy frequently develop chronic hepatitis. Some patients with chronic HEV infection develop extra-hepatic manifestations, especially neurologic symptoms. Clinical observations support the effectiveness of ribavirin therapy from chronic HEV. Recent research has found an expanded animal reservoir of Hepeviridae that are human pathogens and strains that are only animal pathogens. A consensus classification of Hepeviridae has been published recently. The risk of transfusion transmission of HEV has been quantified and selected donor screening implemented in two countries in the last few years.

Summary

Recent research has greatly expanded scientific information on the diversity and zoonotic reservoirs of Hepeviridae as well as the epidemiology and clinical features of HEV infection in humans.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Findlay GM, Dunlop JL. Observations on an epidemic of catarrhal jaundice. Trans R Soc Trop Med Hyg. 1931;25:7–28.

    Article  Google Scholar 

  2. Krugman S, Giles JP, Hammond J. Infectious hepatitis. Evidence for two distinctive clinical, epidemiological, and immunological types of infection. JAMA. 1967;200:365–73.

    Article  CAS  PubMed  Google Scholar 

  3. Teo CG. Fatal outbreaks of jaundice in pregnancy and the epidemic history of hepatitis E. Epidemiology and infection 2012; 2012/01/26: 1–21.

  4. Viswanathan R. Infectious hepatitis in Delhi (1955-56). Indian J Med Res. 1957;45:1–29.

    CAS  PubMed  Google Scholar 

  5. Khuroo MS. 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. Am J Med. 1980;68:818–24.

    Article  CAS  PubMed  Google Scholar 

  6. Wong DC, Purcell RH, Sreenivasan MA, et al. Epidemic and endemic hepatitis in India: evidence for a non-A, non-B hepatitis virus aetiology. Lancet. 1980;2:876–9.

    Article  CAS  PubMed  Google Scholar 

  7. Balayan MS, Andjaparidze AG, Savinskaya SS, et al. Evidence for a virus in non-A, non-B hepatitis transmitted via the fecal-oral route. Intervirology. 1983;20:23–31.

  8. Reyes GR, Purdy MA, Kim JP, et al. Isolation of a cDNA from the virus responsible for enterically transmitted non-A, non-B hepatitis. Science. 1990;247:1335–9.

    Article  CAS  PubMed  Google Scholar 

  9. Tam AW, Smith MM, Guerra ME, et al. Hepatitis E virus (HEV): molecular cloning and sequencing of the full-length viral genome. Virology. 1991;185:120–31.

    Article  CAS  PubMed  Google Scholar 

  10. Kuniholm MH, Purcell RH, McQuillan GM, et al. Epidemiology of hepatitis E virus in the United States: results from the Third National Health and Nutrition Examination Survey, 1988-1994. J Infect Dis. 2009;200:48–56.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Dalton HR, Bendall R, Ijaz S, et al. Hepatitis E: an emerging infection in developed countries. Lancet Infect Dis. 2008;8:698–709.

    Article  PubMed  Google Scholar 

  12. Hoofnagle JH, Nelson KE, Purcell RH. Hepatitis E. N Engl J Med. 2012;367:1237–44.

    Article  CAS  PubMed  Google Scholar 

  13. Purcell RH, Emerson SU. Hepatitis E: an emerging awareness of an old disease. J Hepatol. 2008;48:494–503.

    Article  CAS  PubMed  Google Scholar 

  14. Mushahwar IK. Hepatitis E virus: molecular virology, clinical features, diagnosis, transmission, epidemiology, and prevention. J Med Virol. 2008;80:646–58.

    Article  PubMed  Google Scholar 

  15. Emerson SU, Nguyen H, Torian U, et al. ORF3 protein of hepatitis E virus is not required for replication, virion assembly, or infection of hepatoma cells in vitro. J Virol. 2006;80:10457–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Yin X, Li X, Feng Z. Role of envelopment in the HEV life cycle. Viruses. 2016; doi:10.3390/v8080229.

    Google Scholar 

  17. Kanai Y, Tsujikawa M, Yunoki M, et al. Long-term shedding of hepatitis E virus in the feces of pigs infected naturally, born to sows with and without maternal antibodies. J Med Virol. 2010;82:69–76.

    Article  CAS  PubMed  Google Scholar 

  18. Meng XJ. From barnyard to food table: the omnipresence of hepatitis E virus and risk for zoonotic infection and food safety. Virus Res. 2011;161:23–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Sanford BJ, Emerson SU, Purcell RH, et al. Serological evidence for a hepatitis e virus-related agent in goats in the United States. Transbound Emerg Dis. 2013; doi:10.1111/tbed.12001.

    PubMed  Google Scholar 

  20. Meng XJ. Expanding host range and cross-species infection of hepatitis E virus. PLoS Pathog. 2016;12:e1005695.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  21. Meng XJ. Hepatitis E virus: animal reservoirs and zoonotic risk. Vet Microbiol. 2010;140:256–65.

    Article  CAS  PubMed  Google Scholar 

  22. Xu F, Pan Y, Baloch AR, et al. Hepatitis E virus genotype 4 in yak, northwestern China. Emerging Infect Dis. 2014; doi:10.3201/eid2012.131599.

    Google Scholar 

  23. Geng Y, Wang C, Zhao C, et al. Serological prevalence of hepatitis E virus in domestic animals and diversity of genotype 4 hepatitis E virus in China. Vector Borne Zoonotic Dis. 2010; doi:10.1089/vbz.2009.0168.

    PubMed  Google Scholar 

  24. •• Huang F, Li Y, Yu W, et al. Excretion of infectious hepatitis E virus into milk in cows imposes high risks of zoonosis. Hepatology. 2016;64:350–9. This important paper documents a newly recognized, and likely important, zoonotic reservoir for the transmission of HEV to humans and cow’s milk. It is concerning that infectivity persisted even after pasteurization of the milk

    Article  CAS  PubMed  Google Scholar 

  25. •• Lee GH, Tan BH, Chi-Yuan Teo E, et al. Chronic infection with camelid hepatitis E virus in a liver transplant recipient who regularly consumes camel meat and milk. Gastroenterology. 2016;150:7.e3. This paper describes the first human infection of HEV genotype 7 from a newly recognized zoonotic reservoir, camels

    Google Scholar 

  26. •• Smith DB, Simmonds P, Jameel S, et al. Consensus proposals for classification of the family Hepeviridae. J Gen Virol. 2014; doi:10.1099/vir.0.068429-0. This paper presents the new classification and animal reservoirs of the Hepeviridae family of viruses

    Google Scholar 

  27. Smith DB, Simmonds P, Izopet J, et al. Proposed reference sequences for hepatitis E virus subtypes. J Gen Virol. 2016; doi:10.1099/jgv.0.000393.

    Google Scholar 

  28. Mast EE, Alter MJ, Holland PV, et al. Evaluation of assays for antibody to hepatitis E virus by a serum panel. Hepatitis E Virus Antibody Serum Panel Evaluation Group Hepatology. 1998;27:857–61.

    CAS  PubMed  Google Scholar 

  29. Drobeniuc J, Meng J, Reuter G, et al. Serologic assays specific to immunoglobulin M antibodies against hepatitis E virus: pangenotypic evaluation of performances. Clin Infect Dis. 2010;51:24.

    Article  Google Scholar 

  30. Sue PK, Pisanic N, Heaney CD, et al. Variability of hepatitis E serologic assays in a pediatric liver transplant recipient: challenges to diagnosing hepatitis E virus infection in the United States. Transpl Infect Dis. 2015;17:284–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Yoo N, Bernstein J, Caldwell C, et al. Hepatitis E virus infection in a liver transplant recipient: delayed diagnosis due to variable performance of serologic assays. Transpl Infect Dis. 2013;15:166.

    Article  Google Scholar 

  32. Zhang F, Li X, Li Z, et al. Detection of HEV antigen as a novel marker for the diagnosis of hepatitis E. J Med Virol. 2006;78:1441–8.

    Article  CAS  PubMed  Google Scholar 

  33. Trémeaux P, Lhomme S, Chapuy-Regaud S, et al. Performance of an antigen assay for diagnosing acute hepatitis E virus genotype 3 infection. J Clin Virol. 2016; doi:10.1016/j.jcv.2016.03.019.

    PubMed  Google Scholar 

  34. Labrique AB, Zaman K, Hossain Z, et al. An exploratory case control study of risk factors for hepatitis E in rural Bangladesh. PLoS One. 2013;8:e61351.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Kmush B, Wierzba T, Krain L, et al. Epidemiology of hepatitis E in low- and middle-income countries of Asia and Africa. Semin Liver Dis. 2013;33:15–29.

    Article  PubMed  Google Scholar 

  36. Gurley ES, Hossain MJ, Paul RC, et al. Outbreak of hepatitis E in urban Bangladesh resulting in maternal and perinatal mortality. Clin Infect Dis. 2014;59:658–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Guthmann JP, Klovstad H, Boccia D, et al. A large outbreak of hepatitis E among a displaced population in Darfur, Sudan, 2004: the role of water treatment methods. Clin Infect Dis. 2006;42:1685–91.

    Article  PubMed  Google Scholar 

  38. Teshale EH, Grytdal SP, Howard C, et al. Evidence of person-to-person transmission of hepatitis E virus during a large outbreak in Northern Uganda. Clin Infect Dis. 2010;50:1006–10.

    Article  PubMed  Google Scholar 

  39. Labrique AB, Sikder SS, Krain LJ, et al. Hepatitis e, a vaccine-preventable cause of maternal deaths. Emerg Infect Dis. 2012;18:1401–4.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Gurley ES, Halder AK, Streatfield PK, et al. Estimating the burden of maternal and neonatal deaths associated with jaundice in Bangladesh: possible role of hepatitis E infection. Am J Public Health. 2012;102:2248–54.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Krain LJ, Nelson KE, Labrique AB. Host immune status and response to hepatitis E virus infection. Clin Microbiol Rev. 2014;27:139–65.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  42. • Lachish T, Erez O, Daudi N, et al. Acute hepatitis E virus in pregnant women in Israel and in other industrialized countries. J Clin Virol. 2015; doi:10.1016/j.jcv.2015.10.011. This paper documents the risk of severe complicated HEV genotype 3 infections among pregnant women in industrialized countries. Severe complicated HEV infections during pregnancy are not limited to developing country populations who are infected with HEV genotype 1; pregnant women are at risk of severe complicated HEV everywhere.

    PubMed  Google Scholar 

  43. Navaneethan U, Mohajer MA, Shata MT. Hepatitis E and pregnancy: understanding the pathogenesis. Liver Int. 2008;28:1190–9.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Krain LJ, Atwell JE, Nelson KE, et al. Fetal and neonatal health consequences of vertically transmitted hepatitis E virus infection. AmJTrop Med Hyg. 2014;90:365–70.

    Article  Google Scholar 

  45. Patra S, Kumar A, Trivedi SS, et al. Maternal and fetal outcomes in pregnant women with acute hepatitis E virus infection. Ann Intern Med. 2007;147:28–33.

    Article  PubMed  Google Scholar 

  46. Bose PD, Das BC, Hazam RK, et al. Evidence of extrahepatic replication of hepatitis E virus in human placenta. J Gen Virol. 2014;95:1266–71.

    Article  CAS  PubMed  Google Scholar 

  47. Khuroo MS, Kamili S. Aetiology, clinical course and outcome of sporadic acute viral hepatitis in pregnancy. J Viral Hepat. 2003;10:61–9.

    Article  CAS  PubMed  Google Scholar 

  48. Geng Y, Yang J, Huang W, et al. Virus host protein interaction network analysis reveals that the HEV ORF3 protein may interrupt the blood coagulation process. PLoS One. 2013;8:e56320.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Kmush BL, Labrique A, Li W, et al. The association of cytokines and micronutrients with hepatitis E virus infection during pregnancy and the postpartum period in rural Bangladesh. AmJTrop Med Hyg. 2016;94:203–11.

    Article  CAS  Google Scholar 

  50. Heaney CD, Kmush B, Navas-Acien A, et al. Arsenic exposure and hepatitis E virus infection during pregnancy. Environ Res. 2015;142:273–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Kamar N, Selves J, Mansuy JM, et al. Hepatitis E virus and chronic hepatitis in organ-transplant recipients. N Engl J Med. 2008;358:811–7.

    Article  CAS  PubMed  Google Scholar 

  52. Kamar N, Mansuy JM, Cointault O, et al. Hepatitis E virus-related cirrhosis in kidney- and kidney-pancreas-transplant recipients. Am J Transplant. 2008;8:1744–8.

    Article  CAS  PubMed  Google Scholar 

  53. Kamar N, Rostaing L, Izopet J. Hepatitis E virus infection in immunosuppressed patients: natural history and therapy. Semin Liver Dis. 2013;33:62–70.

    Article  CAS  PubMed  Google Scholar 

  54. Kamar N, Garrouste C, Haagsma EB, et al. Factors associated with chronic hepatitis in patients with hepatitis E virus infection who have received solid organ transplants. Gastroenterology 2011.

  55. Kamar N, Izopet J, Tripon S, et al. Ribavirin for chronic hepatitis E virus infection in transplant recipients. N Engl J Med. 2014;370:1111–20. This paper reviews the issues concerning the ribavirin treatment of chronic HEV infection.

    Article  CAS  PubMed  Google Scholar 

  56. Dalton HR, Bendall RP, Keane FE, et al. Persistent carriage of hepatitis E virus in patients with HIV infection. N Engl J Med. 2009;361:1025–7.

    Article  CAS  PubMed  Google Scholar 

  57. Curry JA, Adams N, Crum-Cianflone N. Acute hepatitis E virus infection in an HIV-infected person in the United States. Ann Intern Med. 2009;150:226–7.

    Article  PubMed  PubMed Central  Google Scholar 

  58. Crum-Cianflone N, Curry J, Drobeniuc J, et al. Hepatitis E virus infection in HIV-infected persons. Emerg Infect Dis. 2012;18:502–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Geng Y, Zhang H, Huang W, et al. Persistent hepatitis e virus genotype 4 infection in a child with acute lymphoblastic leukemia. Hepat Mon. 2014;14:e15618.

    PubMed  PubMed Central  Google Scholar 

  60. Neukam K, Barreiro P, Macias J, et al. Chronic hepatitis E in HIV patients: rapid progression to cirrhosis and response to oral ribavirin. Clin Infect Dis. 2013;57:465–8.

    Article  CAS  PubMed  Google Scholar 

  61. Pineda JA, Cifuentes C, Parra M, et al. Incidence and natural history of hepatitis E virus coinfection among HIV-infected patients. AIDS. 2014;28:1931–7.

    Article  CAS  PubMed  Google Scholar 

  62. Lhomme S, Kamar N, Nicot F, et al. Mutation in the hepatitis E virus polymerase and outcome of ribavirin therapy. Antimicrob Agents Chemother. 2015; doi:10.1128/AAC.02496-15.

    PubMed  Google Scholar 

  63. Sue PK, Pisanic N, Heaney CD, et al. Hepatitis E virus infection among solid organ transplant recipients at a North American Transplant Center. Open Forum Infect Dis. 2016;3:ofw006.

    Article  PubMed  PubMed Central  Google Scholar 

  64. Kuniholm MH, Ong E, Hogema BM, et al. Acute and chronic hepatitis E virus infection in human immunodeficiency virus-infected U.S. women. Hepatology. 2016;63:712–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Caron M, Bouscaillou J, Kazanji M. Acute risk for hepatitis E virus infection among HIV-1-positive pregnant women in central Africa. Virol J. 2012;9:254.

    Article  PubMed  PubMed Central  Google Scholar 

  66. Jacobs C, Chiluba C, Phiri C, et al. Seroepidemiology of hepatitis E virus infection in an urban population in Zambia: strong association with HIV and environmental enteropathy. J Infect Dis. 2014;209:652–7.

    Article  PubMed  Google Scholar 

  67. Ramachandran J, Eapen CE, Kang G, et al. Hepatitis E superinfection produces severe decompensation in patients with chronic liver disease. J Gastroenterol Hepatol. 2004;19:134–8.

    Article  PubMed  Google Scholar 

  68. Fontana RJ, Engle RE, Scaglione S, et al. The role of hepatitis E virus infection in adult Americans with acute liver failure. Hepatology. 2016; doi:10.1002/hep.28649.

    Google Scholar 

  69. Dalton HR, Kamar N, van Eijk JJ, et al. Hepatitis E virus and neurological injury. Nat Rev Neurol. 2016;12:77–85.

    Article  CAS  PubMed  Google Scholar 

  70. Bazerbachi F, Haffar S, Garg SK, et al. Extra-hepatic manifestations associated with hepatitis E virus infection: a comprehensive review of the literature. Gastroenterol Rep (Oxf). 2016; doi:10.1093/gastro/gov042.

    Google Scholar 

  71. Kamar N, Bendall RP, Peron JM, et al. Hepatitis E virus and neurologic disorders. Emerg Infect Dis. 2011;17:173–9.

    Article  PubMed  PubMed Central  Google Scholar 

  72. Shukla P, Nguyen HT, Torian U, et al. Cross-species infections of cultured cells by hepatitis E virus and discovery of an infectious virus-host recombinant. Proc Natl Acad Sci U S A. 2011;108:2438–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Labrique AB, Thomas DL, Stoszek SK, et al. Hepatitis E: an emerging infectious disease. Epidemiol Rev. 1999;21:162–79.

    Article  CAS  PubMed  Google Scholar 

  74. Howard CM, Handzel T, Hill VR, et al. Novel risk factors associated with hepatitis E virus infection in a large outbreak in northern Uganda: results from a case-control study and environmental analysis. AmJTrop Med Hyg. 2010;83:1170–3.

    Article  Google Scholar 

  75. Rein DB, Stevens G, Theaker J, et al. The global burden of hepatitis E virus. Hepatology. 2012;55:988–97.

    Article  PubMed  Google Scholar 

  76. Hakim MS, Wang W, Bramer WM, et al. The global burden of hepatitis E outbreaks: a systematic review. Liver Int. 2017; doi:10.1111/liv.13237.

    PubMed  Google Scholar 

  77. Kim J, Nelson KE, Panzner U, et al. A systematic review of the epidemiology of hepatitis E virus in Africa. BMC Infect Dis. 2014; doi:10.1186/1471-2334-14-308.

    Google Scholar 

  78. Rab MA, Bile MK, Mubarik MM, et al. Water-borne hepatitis E virus epidemic in Islamabad, Pakistan: a common source outbreak traced to the malfunction of a modern water treatment plant. AmJTrop Med Hyg. 1997;57:151–7.

    Article  CAS  Google Scholar 

  79. Tei S, Kitajima N, Takahashi K, et al. Zoonotic transmission of hepatitis E virus from deer to human beings. Lancet. 2003;362:371–3.

    Article  PubMed  Google Scholar 

  80. Takahashi K, Kitajima N, Abe N, et al. Complete or near-complete nucleotide sequences of hepatitis E virus genome recovered from a wild boar, a deer, and four patients who ate the deer. Virology. 2004;330:501–5.

    Article  CAS  PubMed  Google Scholar 

  81. Colson P, Borentain P, Queyriaux B, et al. Pig liver sausage as a source of hepatitis E virus transmission to humans. J Infect Dis. 2010;202:825–34.

    Article  PubMed  Google Scholar 

  82. Yapa CM, Furlong C, Rosewell A, et al. First reported outbreak of locally acquired hepatitis E virus infection in Australia. Med J Aust. 2016;204:274.

    Article  PubMed  Google Scholar 

  83. Said B, Ijaz S, Kafatos G, et al. Hepatitis E outbreak on cruise ship. Emerg Infect Dis. 2009;15:1738–44.

    Article  PubMed  PubMed Central  Google Scholar 

  84. Brassard J, Gagne MJ, Genereux M, et al. Detection of human food-borne and zoonotic viruses on irrigated, field-grown strawberries. Appl Environ Microbiol. 2012;78:3763–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Dong C, Meng J, Dai X, et al. Restricted enzooticity of hepatitis E virus genotypes 1 to 4 in the United States. J Clin Microbiol. 2011; doi:10.1128/JCM.05481-11.

    Google Scholar 

  86. Meng XJ. Zoonotic and foodborne transmission of hepatitis E virus. Semin Liver Dis. 2013;33:41–9.

    Article  CAS  PubMed  Google Scholar 

  87. Feagins AR, Opriessnig T, Guenette DK, et al. Detection and characterization of infectious hepatitis E virus from commercial pig livers sold in local grocery stores in the USA. J Gen Virol. 2007;88:912–7.

    Article  CAS  PubMed  Google Scholar 

  88. Bouwknegt M, Lodder-Verschoor F, Van DP, et al. Hepatitis E virus RNA in commercial porcine livers in The Netherlands. J Food Prot. 2007;70:2889–95.

    Article  CAS  PubMed  Google Scholar 

  89. Wenzel JJ, Preiss J, Schemmerer M, et al. Detection of hepatitis E virus (HEV) from porcine livers in Southeastern Germany and high sequence homology to human HEV isolates. J Clin Virol. 2011;52:50–4.

    Article  PubMed  Google Scholar 

  90. • Satake M, Matsubayashi K, Hoshi Y, et al. Unique clinical courses of transfusion-transmitted hepatitis E in patients with immunosuppression. Transfusion. 2017; doi:10.1111/trf.13994. This paper reviews the experience of transfusion transmitted HEV infections in Japan, which was the first country to report transfusion transmitted HEV infections

    Google Scholar 

  91. Matsubayashi K, Nagaoka Y, Sakata H, et al. Transfusion-transmitted hepatitis E caused by apparently indigenous hepatitis E virus strain in Hokkaido, Japan. Transfusion. 2004;44:934–40.

    Article  PubMed  Google Scholar 

  92. Mitsui T, Tsukamoto Y, Yamazaki C, et al. Prevalence of hepatitis E virus infection among hemodialysis patients in Japan: evidence for infection with a genotype 3 HEV by blood transfusion. J Med Virol. 2004;74:563–72.

    Article  CAS  PubMed  Google Scholar 

  93. Nelson KE. Transmission of hepatitis E virus by transfusion: what is the risk? Transfusion. 2014;54:8–10.

    Article  PubMed  Google Scholar 

  94. Hewitt PE, Ijaz S, Brailsford SR, et al. Hepatitis E virus in blood components: a prevalence and transmission study in southeast England. Lancet. 2014;

  95. • Tedder RS, Ijaz S and Kitchens S. Hepatitis E risks: pigs or blood-that is the question. Transfusion 2017. This paper provides quantitative estimates of the risk of transfusion-transmitted HEV and food-borne-transmitted HEV in the UK.

  96. Singh S, Mohanty A, Joshi YK, et al. Mother-to-child transmission of hepatitis E virus infection. Indian J Pediatr. 2003;70:37–9.

    Article  PubMed  Google Scholar 

  97. Jaiswal SP, Jain AK, Naik G, et al. Viral hepatitis during pregnancy. Int J Gynaecol Obstet. 2001;72:103–8.

    Article  CAS  PubMed  Google Scholar 

  98. • Rivero-Juarez A, Frias M, Rodriguez-Cano D, et al. Isolation of hepatitis E virus from breast milk during acute infection. Clin Infect Dis. 2016;62:1464. This paper suggests that infants may acquire HEV through human breast milk.

    Article  PubMed  Google Scholar 

  99. Ippagunta SK, Naik S, Sharma B, et al. Presence of hepatitis E virus in sewage in Northern India: frequency and seasonal pattern. J Med Virol. 2007;79:1827–31.

    Article  CAS  PubMed  Google Scholar 

  100. Meng XJ, Wiseman B, Elvinger F, et al. 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. 2002;40:117–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Vaidya SR, Tilekar BN, Walimbe AM, et al. Increased risk of hepatitis E in sewage workers from India. Journal of occupational and environmental medicine/American College of Occupational and Environmental Medicine. 2003;45:1167–70.

    Article  Google Scholar 

  102. De Schryver A, De Schrijver K, François G, et al. Hepatitis E virus infection: an emerging occupational risk? Occup Med (Lond). 2015; doi:10.1093/occmed/kqv154.

    Google Scholar 

  103. Schielke A, Ibrahim V, Czogiel I, et al. 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 Infect Dis. 2015; doi:10.1186/s12879-015-1199-y.

    Google Scholar 

  104. Sarkar S, Rivera EM, Engle RE, et al. An epidemiologic investigation of a case of acute hepatitis E. J Clin Microbiol. 2015; doi:10.1128/JCM.01189-15.

    PubMed  PubMed Central  Google Scholar 

  105. Anheyer-Behmenburg HE, Szabo K, Schotte U, et al. Hepatitis E virus in wild boars and spillover infection in red and roe deer, Germany, 2013-2015. Emerging Infect Dis. 2017; doi:10.3201/eid2301.161169.

    PubMed  PubMed Central  Google Scholar 

  106. Wilhelm BJ, Rajić A, Greig J, et al. A systematic review/meta-analysis of primary research investigating swine, pork or pork products as a source of zoonotic hepatitis E virus. Epidemiol Infect. 2011; doi:10.1017/S0950268811000677.

    PubMed  Google Scholar 

  107. Emerson SU, Arankalle VA, Purcell RH. Thermal stability of hepatitis E virus. J Infect Dis. 2005;192:930–3.

    Article  PubMed  Google Scholar 

  108. Barnaud E, Rogée S, Garry P, et al. Thermal inactivation of infectious hepatitis E virus in experimentally contaminated food. Appl Environ Microbiol. 2012; doi:10.1128/AEM.00436-12.

    PubMed  PubMed Central  Google Scholar 

  109. Feagins AR, Opriessnig T, Guenette DK, et al. Inactivation of infectious hepatitis E virus present in commercial pig livers sold in local grocery stores in the United States. Int J Food Microbiol. 2008; doi:10.1016/j.ijfoodmicro.2007.11.068.

    PubMed  Google Scholar 

  110. Reuter G, Fodor D, Forgach P, et al. Characterization and zoonotic potential of endemic hepatitis E virus (HEV) strains in humans and animals in Hungary. J Clin Virol. 2009;44:277–81.

    Article  PubMed  Google Scholar 

  111. Woo PCY, Lau SKP, Teng JLL, et al. New hepatitis E virus genotype in camels, the Middle East. Emerging Infect Dis. 2014; doi:10.3201/eid2006.140140.

    Google Scholar 

  112. •• Rasche A, Saqib M, Liljander AM, et al. Hepatitis E virus infection in dromedaries, North and East Africa, United Arab Emirates, and Pakistan, 1983-2015. Emerging Infect Dis. 2016; doi:10.3201/eid2207.160168. This paper describes a major newly recognized zoonotic reservoir for HEV, camels. The camel reservoir may be an important source of infection in populations who have no exposure to swine

    PubMed  PubMed Central  Google Scholar 

  113. Woo PCY, Lau SKP, Teng JLL, et al. New hepatitis E virus genotype in Bactrian camels, Xinjiang, China. Emerging Infect Dis 2016. 2013; doi:10.3201/eid2212.160979.

    Google Scholar 

  114. Cossaboom CM, Córdoba L, Dryman BA, et al. Hepatitis E virus in rabbits, Virginia, USA. Emerging Infect Dis. 2011; doi:10.3201/eid1711.110428.

    PubMed  PubMed Central  Google Scholar 

  115. Izopet J, Dubois M, Bertagnoli S, et al. Hepatitis E virus strains in rabbits and evidence of a closely related strain in humans, France. Emerg Infect Dis 2012; serial on the Internet].

  116. Purcell RH, Engle RE, Rood MP, et al. Hepatitis E virus in rats, Los Angeles, California, USA. Emerging Infect Dis. 2011;17:2216–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Lack JB, Volk K and Van DB. Hepatitis E virus genotype 3 in wild rats, United States. Emerg Infect Dis 2012; serial on the Internet].

  118. • Sazzad HMS, Labrique AB, Teo C, et al. Surveillance at private laboratories identifies small outbreaks of hepatitis E in urban Bangladesh. AmJTrop Med Hyg. 2017; doi:10.4269/ajtmh.16-0411. This paper reports that isolated endemic HEV infections are common throughout the year in a developing country, where large waterborne epidemics occur during the monsoon season

    Google Scholar 

  119. Aggarwal R, Kumar R, Pal R, et al. Role of travel as a risk factor for hepatitis E virus infection in a disease-endemic area. Indian J Gastroenterol. 2002;

  120. Lapa D, Capobianchi MR, Garbuglia AR. Epidemiology of hepatitis E virus in European countries. Int J Mol Sci. 2015; doi:10.3390/ijms161025711.

    PubMed  PubMed Central  Google Scholar 

  121. Stoszek SK, Abdel-Hamid M, Saleh DA, et al. High prevalence of hepatitis E antibodies in pregnant Egyptian women. Trans R Soc Trop Med Hyg. 2006;100:95–101.

    Article  PubMed  Google Scholar 

  122. Labrique AB, Zaman K, Hossain Z, et al. Population seroprevalence of hepatitis E virus antibodies in rural Bangladesh. AmJTrop Med Hyg. 2009;81:875–81.

    Article  Google Scholar 

  123. Kamar N, Bendall R, Legrand-Abravanel F, et al. Hepatitis E. Lancet. 2012;379:2477–88.

    Article  PubMed  Google Scholar 

  124. Kamar N, Lhomme S, Abravanel F, et al. An early viral response predicts the virological response to ribavirin in hepatitis E virus organ transplant patients. Transplantation. 2015;99:2124–31.

    Article  CAS  PubMed  Google Scholar 

  125. Dalton HR, Kamar N. Treatment of hepatitis E virus. Curr Opin Infect Dis. 2016; doi:10.1097/QCO.0000000000000316.

    PubMed  Google Scholar 

  126. Donnelly MC, Imlach SN, Abravanel F, et al. Sofosbuvir and daclatasvir anti-viral therapy fails to clear HEV viremia and restore reactive T cells in a HEV/HCV co-infected liver transplant recipient. Gastroenterology. 2017; doi:10.1053/j.gastro.2016.05.060.

    PubMed  Google Scholar 

  127. Zhu FC, Zhang J, Zhang XF, et al. Efficacy and safety of a recombinant hepatitis E vaccine in healthy adults: a large-scale, randomised, double-blind placebo-controlled, phase 3 trial. Lancet. 2010;376:895–902.

    Article  CAS  PubMed  Google Scholar 

  128. Li SW, Zhang J, Li YM, et al. A bacterially expressed particulate hepatitis E vaccine: antigenicity, immunogenicity and protectivity on primates. Vaccine. 2005;23:2893–901.

    Article  CAS  PubMed  Google Scholar 

  129. Wu T, Zhu FC, Huang SJ, et al. Safety of the hepatitis E vaccine for pregnant women: a preliminary analysis. Hepatology. 2011;

  130. Zhang J, Zhang XF, Huang SJ, et al. Long-term efficacy of a hepatitis E vaccine. N Engl J Med. 2015;372:914–22.

    Article  CAS  PubMed  Google Scholar 

  131. Nelson KE, Shih JW, Zhang J, et al. Hepatitis e vaccine to prevent morbidity and mortality during epidemics. Open Forum Infect Dis. 2014;1:ofu098.

    Article  PubMed  PubMed Central  Google Scholar 

  132. SAGE Working Group on Hepatitis, E. Hepatitis E vaccine: WHO position paper, May 2015. Wkly Epidemiol Rec. 2015;90:185–200.

    Google Scholar 

  133. Girones R, Carratala A, Calgua B, et al. Chlorine inactivation of hepatitis E virus and human adenovirus 2 in water. J Water Health. 2014;12:436–42.

    Article  PubMed  Google Scholar 

  134. Guerrero-Latorre L, Gonzales-Gustavson E, Hundesa A, et al. UV disinfection and flocculation-chlorination sachets to reduce hepatitis E virus in drinking water. Int J Hyg Environ Health. 2016; doi:10.1016/j.ijheh.2016.04.002.

    PubMed  Google Scholar 

  135. Nelson KE, Heaney CD, Labrique AB, et al. Hepatitis E: prevention and treatment. Curr Opin Infect Dis. 2016; doi:10.1097/QCO.0000000000000294.

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, 615 N. Wolfe Street, Baltimore, MD, 21205, USA

    Kenrad E. Nelson

  2. Department of Environmental Health and Engineering and Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, 615 N. Wolfe Street, Baltimore, MD, 21205, USA

    Christopher D. Heaney

  3. Department of Public Health, Food Studies, and Nutrition, Falk College of Sport and Human Dynamics, Syracuse University, 150 Crouse Dr, Syracuse, NY, 13244, USA

    Brittany L. Kmush

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  1. Kenrad E. Nelson
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  2. Christopher D. Heaney
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Correspondence to Kenrad E. Nelson.

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Kenrad E. Nelson, Chris Heaney, and Brittany L. Kmush each declare no potential conflicts of interest.

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This article is part of the Topical Collection on Infectious Disease Epidemiology

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Nelson, K.E., Heaney, C.D. & Kmush, B.L. The Epidemiology and Prevention of Hepatitis E Virus Infection. Curr Epidemiol Rep 4, 186–198 (2017). https://doi.org/10.1007/s40471-017-0109-9

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