Abstract
Background and Objectives
Hepatitis E virus (HEV) is a major public health concern in developing countries. HEV transmission occurs primarily by the fecal-oral route. It has also been reported that blood donors are potentially able to cause transfusion-associated hepatitis E in endemic areas. This study aimed to determine the seroprevalence of HEV infection among volunteer blood donors in Central province of Iran in 2012.
Material and Methods
A total of 530 consecutive blood donor samples collected from Blood Transfusion Organization, Central Province of Iran. All samples were tested for the presence of IgG Hepatitis E antibody (anti-HEV) using enzyme-linked immunosorbent assay (ELISA).
Results
From 530 blood donors, 91.9% were male and 8.1% were female. Overall, anti-HEV was found in 76 of 530 samples (14.3%). There was no significant difference in HEV seropositivity between the subjects regarding gender and area of residence (urban vs. rural). Anti-HEV was distributed among all age groups. Although people aged 31-50 years had the highest prevalence, but there was no statistical difference between the age groups.
Conclusion
This study shows a relatively high prevalence of anti-HEV in the blood donors of Central province of Iran. More investigations are needed to assess the potential benefit of adding HEV screening of blood products to the current blood donor selection criteria.
Keywords: Hepatitis E virus (HEV), Seroprevalence, Blood donor
INTRODUCTION
Hepatitis E virus (HEV) appears to be the second most frequent cause of enteric hepatitis after hepatitis A virus infection (1). Some studies showed that HEV hepatitis is a major public health concern in developing countries (2–4).
HEV is an unclassified nonenveloped virus belongs to genus Hepevirus of the family Hepeviridae (3, 5). Its genome is a single-stranded, positive-sense RNA of approximately 7.2 kb (5). HEV isolates are classified into five major genotypes which belong to one serotype (6). Genotypes 1 and 2 exclusively infect humans and are endemic in many parts of Asia, Africa and South America and often associated with outbreaks and epidemics in developing countries (7–9). Genotypes 3 and 4 infect humans, pigs and other animal species and have been responsible for sporadic cases of disease. Genotype 5 infects avian species (7–9).
Transmission of HEV occurs primarily by the fecal-oral route through fecal contamination of drinking water in developing countries. HEV may also be transmitted parenterally as well as vertically particularly in endemic areas (10), but person to person transmission is uncommon (1). Recent studies have indicated that zoonosis is involved in the transmission of HEV, especially in industrialized countries (11, 12). It has also been reported that blood donors are potentially able to cause transfusion-associated hepatitis E in high endemic areas (13, 14).
The prevalence of HEV antibodies (anti-HEV) has been described in different populations. Iran is an endemic country for hepatitis E disease and its seroprevalence increased significantly with age, from 3.3% in subjects less than 30 years of age to 37.5% in individuals of 50 years (15, 16). A population-based study indicated that the prevalence rate of anti-HEV IgG among healthy population was 9.6% (17).
Providing a safer blood and blood products is a major concern of blood banks in the world. HEV infection is emerging as a potential new threat to blood safety after several cases of transfusion-transmission were reported from different countries (18–20). HEV is endemic in Iran; however limited data are available for HEV seroprevalence in blood donors of different parts of the country (2, 15, 21, 22). This study aimed to determine the seroprevalence of HEV infection among volunteer blood donors in Central province of Iran in 2012.
MATERIALS AND METHODS
In this cross-sectional study, blood samples of 530 volunteer blood donors residing in urban and rural areas of Central province of Iran were collected consecutively from Iranian Blood Transfusion Organization in September 2012. Informed consent was obtained from all cases. The study was approved by Iranian Society for Support Patients with Infectious Diseases Ethics Committee.
Plasma samples were tested for IgG Hepatitis E antibody (anti-HEV) using enzyme-linked immunosorbent assay (ELISA) test.
Anti-HEV was detected by Dia.Pro Diagnostic BioProbes, Milan, Italy ELISA kit. This assay uses HEV-specific synthetic antigens derived from open reading frame (ORF) 2 and ORF3 of all 4 HEV subtypes. The procedure was followed as indicated by the manufacturer. Positive and negative controls were included in all the ELISA microplates assays. The anti-HEV detection sensitivity and specificity were 100%.
Statistical Analysis
The Chi-square were used with the SPSS 16 Package program for statistical analysis (Chicago, IL, USA). A p-value of <0.05 was considered significant. Data was presented as mean ± SD or, when indicated, as an absolute number and percentage.
RESULTS
A total of 530 volunteer blood donors were enrolled in the study. Of the study subjects, 91.9% were male and 8.1% were female. Their age ranged from 18 to 71 years with mean age 36.3 ± 11.7 years. 195 donors (36.8%) were aged 18-30 years, 266 cases (50.2%) were aged 31-50 years and 69 (13%) were older than 50 years. 10.4% of cases were habitant in rural areas and the remaining were resident in urban areas.
76 blood donors showed positive anti-HEV IgG antibodies, corresponding to an overall seroprevalence rate of 14.3%. There was no significant difference in HEV seropositivity between the subjects regarding gender (89.5% in males and 10.5% in females, p = 0.37). No significant differences were detected between the prevalence of anti-HEV antibodies in rural (6.6%) and urban (93.4%) areas (p = 0.24).
Anti-HEV was distributed among all age groups. Although people aged 31-50 years had the highest prevalence, but there was no statistical difference between the age groups (p = 0.3). General characteristics of the 530 examined blood donors are summarized in Table 1.
Table 1.
Variables | All donors n: 530 | Anti-HEV positive n: 76 | Anti-HEV negative n: 454 |
---|---|---|---|
Sex | |||
Male | 487 (91.9%) | 68 (89.5%) | 419 (92.3%) |
Female | 43 (8.1%) | 8 (10.5%) | 35 (7.7%) |
Area of residence | |||
Urban | 475 (89.6%) | 71 (93.4%) | 404 (89%) |
Rural | 55 (10.4%) | 5 (6.6%) | 50 (11%) |
Age group | |||
18-30 | 195 (36.8%) | 28 (36.9%) | 167 (36.8%) |
31-50 | 266 (50.2%) | 34 (44.7%) | 232 (51.1%) |
>50 | 69 (13%) | 14 (18.4%) | 55 (12.1%) |
Data indicated as absolute number (%); HEV: Hepatitis E Virus
DISCUSSION
HEV is an important cause of epidemic hepatitis in developing countries. HEV hepatitis also occurs sporadically in some developed countries. The main transmission route of HEV is fecal-oral specially in endemic areas, but other transmission routes like parenteral exposure, vertical transmission, blood transfusion and dialysis were also reported, which are more common in non endemic areas (7, 23–25).
Iran is an endemic country for hepatitis E disease (26). Previous studies have demonstrated a variety of seroprevalence rates in different parts of Iran. In a population-based study conducted by Taremi et al. (17) the prevalence of anti-HEV IgG among healthy population in Iran was reported as 9.6%. Another general survey in Mazendaran (North of Iran) showed that 1.1% of children younger than 10 years old and 7.2% of population between 20-25 years old had anti-HEV IgG (27). Another study from this area reported that the prevalence of HEV between adults was 11.8% (28). Ataei et al. (1) showed 3.8% anti-HEV seroprevalence rate in Isfahan province. They reported that HEV seroprevalence increased with age from 0.9% in children aged 6-9 years to 8.1% in people over 50 years old. A recent study in general population of Tehran demonstrated that IgG anti-HEV seroprevalence rate was 9.3% (29).
The results of few studies on blood donors in Iran showed different seroprevalence rates. In two independent performed studies, the prevalence of HEV was 12.9% in Hamedan province (30) and 7.8% in Tabriz city, East Azerbaijan Province (31). Another investigation in Khuzestan Province (Southwest Iran) showed that 11.5% of urban healthy blood donors had IgG anti-HEV (21). In two different studies on blood donors of Tehran, anti-HEV was detected in 7.8% and 4.5% of cases, respectively (2, 22).
The HEV seroprevalence in blood donors in other countries were reported as 0.95% to 20.6% in Europe (32, 33), 2.3% in Brazil (34), 3.7% in Japan (5), 32.6% in China (35) and 4% to 45.2% in the Middle East (36, 37).
In this study we investigated the seroprevalence of HEV infection among volunteer blood donors in Central province of Iran. Anti-HEV was detected in 14.3% of the cases. So the prevalence of anti-HEV in current study is higher than reported in previous studies from other parts of Iran (2, 21, 22, 30, 31) and in the range of other studies in the Middle East (36, 37). It can be due to differences in the demographics of studied population, the size of the samples, the public health services situation and used anti-HEV detection assays. Because HEV-RNA was not examined in our study, we cannot draw conclusions regarding active HEV prevalence in our blood donors. As both HEV epidemiology and cost effectiveness of a test are important in deciding whether adding a screening test to current blood product screening tests is appropriate or not, this topic merits further study.
In conclusion, this study shows a relatively high prevalence of anti-HEV in the blood donors of Central Province of Iran. Further studies on HEV prevalence rates in blood donors in different parts of the country are required to evaluate the safety of blood products and potential benefit of HEV screening in blood banks.
ACKNOWLEDGEMENT
The authors are grateful to Iranian Society for Support Patients with Infectious Diseases for financial support of this study.
REFERENCES
- 1.Ataei B, Nokhodian Z, Javadi AA, Kassaian N, Shoaei P, Farajzadegan Z, et al. Hepatitis E virus in Isfahan Province: a population-based study. Int J Infect Dis. 2009;13:67–71. doi: 10.1016/j.ijid.2008.03.030. [DOI] [PubMed] [Google Scholar]
- 2.Keyvani H, Shamsi Shahrabadi M, Najafifard S, Hajibeigi B, Fallahian F, Alavian SM. Seroprevalence of anti-HEV and HEV RNA among volunteer blood donors and patients with Hepatitis B and C in Iran. Bangladesh Liver Journal. 2009;1:34–37. [Google Scholar]
- 3.Ahn J, Kang SG, Lee DY, Shin SJ, Yoo HS. Identification of HEV isolates and determination of the seroprevalence of HEV in Korea. J Clin Microbiol. 2005;43:3042–3048. doi: 10.1128/JCM.43.7.3042-3048.2005. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Cheng XF, Wen YF, Zhu M, Zhan SW, Zheng JX, Dong C, et al. Serological and molecular study of hepatitis E virus among illegal blood donors. World J Gastroenterol. 2012;18:986–990. doi: 10.3748/wjg.v18.i9.986. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Fukuda S, Sunaga J, Saito N, Fujimura K, Itoh Y, Sasaki M, et al. Prevalence of antibodies to hepatitis E virus among Japanese blood donors: identification of three blood donors infected with a genotype 3 hepatitis E virus. J Med Virol. 2004;73:554–561. doi: 10.1002/jmv.20125. [DOI] [PubMed] [Google Scholar]
- 6.Kaufmann A, Kenfak-Foguena A, André C, Canellini G, Bürgisser P, Moradpour D, et al. Hepatitis E virus seroprevalence among blood donors in southwest Switzerland. PLoS One. 2011;6:e21150. doi: 10.1371/journal.pone.0021150. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Purcell RH, Emerson SU. Hepatitis E: an emerging awareness of an old disease. J Hepatol. 2008;48:494–503. doi: 10.1016/j.jhep.2007.12.008. [DOI] [PubMed] [Google Scholar]
- 8.Okamoto H. Genetic variability and evolution of hepatitis E virus. Virus Res. 2007;127:216–228. doi: 10.1016/j.virusres.2007.02.002. [DOI] [PubMed] [Google Scholar]
- 9.Aggarwal R. The Global Prevalence of Hepatitis E Virus Infection and Susceptibility: A Systematic Review. Geneva, Switzerland: WHO; 2010. [Google Scholar]
- 10.Acharya SK, Panda SK. Hepatitis E virus: epidemiology, diagnosis, pathology and prevention. Trop Gastroenterol. 2006;27:63–68. [PubMed] [Google Scholar]
- 11.Yazaki Y, Mizuo H, Takahashi M, Nishizawa T, Sasaki N, Gotanda Y, et al. Sporadic acute or fulminant hepatitis E in Hokkaido, Japan, may be food-borne, as suggested by the presence of hepatitis E virus in pig liver as food. J Gen Virol. 2003;84:2351–2357. doi: 10.1099/vir.0.19242-0. [DOI] [PubMed] [Google Scholar]
- 12.Tei S, Kitajima N, Takahashi K, Mishiro S. Zoonotic transmission of hepatitis E virus from deer to human beings. Lancet. 2003;362:371–373. doi: 10.1016/S0140-6736(03)14025-1. [DOI] [PubMed] [Google Scholar]
- 13.Arankalle VA, Chobe LP. Hepatitis E virus: Can it be transmitted parenterally? J Viral Hep. 1999;6:161–164. doi: 10.1046/j.1365-2893.1999.00141.x. [DOI] [PubMed] [Google Scholar]
- 14.Arankalle VA, Chobe LP. Retrospective analysis of blood transfusion recipients: Evidence for post-transfusion hepatitis E. Vox Sang. 2000;79:72–74. doi: 10.1159/000031215. [DOI] [PubMed] [Google Scholar]
- 15.Taremi M, Gachkar L, MahmoudArabi S, Kheradpezhouh M, Khoshbaten M. Prevalence of antibodies to hepatitis E virus among male blood donors in Tabriz, Islamic Republic of Iran. East Mediterr Health J. 2007;13:98–102. [PubMed] [Google Scholar]
- 16.Taremi M, Khoshbaten M, Gachkar L, Ehsani Ardakani M, Zali M. Hepatitis E virus infection in hemodialysis patients: a seroepidemiological survey in Iran. BMC Infect Dis. 2005;5:36. doi: 10.1186/1471-2334-5-36. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Taremi M, Mohammad Alizadeh AH, Ardalan A, Ansari S, Zali MR. Seroprevalence of hepatitis E in Nahavand, Islamic Republic of Iran: a population-based study. East Mediterr Health J. 2008;14:157–1562. [PubMed] [Google Scholar]
- 18.Boxall E, Herborn A, Kochethu G, Pratt G, Adams D, Ijaz S, et al. Transfusion-transmitted hepatitis E in a ‘nonhyperendemic’ country. Transfus Med. 2006;16:79–83. doi: 10.1111/j.1365-3148.2006.00652.x. [DOI] [PubMed] [Google Scholar]
- 19.Tamura A, Shimizu YK, Tanaka T, Kuroda K, Arakawa Y, Takahashi K, et al. Persistent infection of hepatitis E virus transmitted by blood transfusion in a patient with T-cell lymphoma. Hepatol Res. 2007;37:113–120. doi: 10.1111/j.1872-034X.2007.00024.x. [DOI] [PubMed] [Google Scholar]
- 20.Matsubayashi K, Kang JH, Sakata H, Takahashi K, Shindo M, Kato M, et al. A case of transfusion-transmitted hepatitis E caused by blood from a donor infected with hepatitis E virus zoonotic food-borne route. Transfusion. 2008;48:1368–1375. doi: 10.1111/j.1537-2995.2008.01722.x. [DOI] [PubMed] [Google Scholar]
- 21.Assarehzadegan MA, Shakerinejad G, Amini A, Rezaee SA. Seroprevalence of hepatitis E virus in blood donors in Khuzestan Province, southwest Iran. Int J Infect Dis. 2008;12:387–90. doi: 10.1016/j.ijid.2007.09.015. [DOI] [PubMed] [Google Scholar]
- 22.Aminafshar S, Alimagham M, Gachkar L, Yousefi F, Attarchi Z. Anti-hepatitis E virus seropositivity in a group of blood donors. Iran J Public Health. 2004;33:53–6. [Google Scholar]
- 23.Meng XJ. Novel strains of hepatitis E virus identified from humans and other animal species: Is hepatitis E a zoonosis? J Hepatol. 2000;33:842–845. doi: 10.1016/s0168-8278(00)80319-0. [DOI] [PubMed] [Google Scholar]
- 24.Emerson SU, Purcell RH. Hepatitis E virus. Rev Med Virol. 2003;13:145–154. doi: 10.1002/rmv.384. [DOI] [PubMed] [Google Scholar]
- 25.Okamoto H, Takahashi M, Nishizawa T. Features of hepatitis E virus infection in Japan. Intern Med. 2003;42:1065–1071. doi: 10.2169/internalmedicine.42.1065. [DOI] [PubMed] [Google Scholar]
- 26.Alavian SM. Hepatitis E Virus Infection: A Neglected Problem in Our Region. Hepat Mon. 2007;7:119–121. [Google Scholar]
- 27.Safar MJ, Khalilian A, Farhadi R, Babamohmoodi F. Seroepidemiology of HEV infection in 2-25 years of saravi in 2004. J Mazandaran Univ Med Sci. 2005;75:82–85. [Google Scholar]
- 28.Ghadir M, Jafari E, Rezvan H, Amini Kafiabad S, Vahezjavadi M, Pourshams A. Hepatitis A and E in the east of Golestan province. J Med Council IRI. 2007;25:34–38. [Google Scholar]
- 29.Mohebbi SR, Rostami Nejad M, Tahaei SM, Pourhoseingholi MA, Habibi M, Azimzadeh P, et al. Seroepidemiology of hepatitis A and E virus infections in Tehran, Iran: a population based study. Trans R Soc Trop Med Hyg. 2012;106:528–531. doi: 10.1016/j.trstmh.2012.05.013. [DOI] [PubMed] [Google Scholar]
- 30.Rezazadeh M, Hahiloui M, Ghachkar L, Iadegari D, Kashani KM, Naghdi M. Study of antibody prevalence against Hepatitis E in blood donors in Hamedan. Infect Trop Dis. 2005;11:13–18. [Google Scholar]
- 31.Gachkar L, Taremi M, Mahmoodarabi S, Kheradpajooh M, Dehkhoda R, Torabi SE. Frequency of antibodies to hepatitis E virus among male blood donors in Tabriz. Blood. 2005;2:157–162. [Google Scholar]
- 32.Zanetti AR, Dawson GJ. Hepatitis type E in Italy: a seroepidemiological survey. Study Group of Hepatitis E. J Med Virol. 1994;42:318–320. doi: 10.1002/jmv.1890420321. [DOI] [PubMed] [Google Scholar]
- 33.Christensen PB, Engle RE, Hjort C, Homburg KM, Vach W, Georgsen J, et al. Time trend of the prevalence of hepatitis E antibodies among farmers and blood donors: a potential zoonosis in Denmark. Clin Infect Dis. 2008;47:1026–1031. doi: 10.1086/591970. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 34.Bortoliero AL, Bonametti AM, Morimoto HK, Matsuo T, Reiche EM. Seroprevalence for hepatitis E virus (HEV) infection among volunteer blood donors of the Regional Blood Bank of Londrina, State of Paraná, Brazil. Rev Inst Med Trop Sao Paulo. 2006;48:87–92. doi: 10.1590/s0036-46652006000200006. [DOI] [PubMed] [Google Scholar]
- 35.Guo QS, Yan Q, Xiong JH, Ge SX, Shih JW, Ng MH, et al. Prevalence of hepatitis E virus in Chinese blood donors. J Clin Microbiol. 2010;48(1):317–8. doi: 10.1128/JCM.01466-09. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 36.Irani Hakime N, Feghali Haibeh R. Hepatitis E virus: detection of antibodies in blood donors in Lebanon. J Med Liban. 1998;46:60–62. [PubMed] [Google Scholar]
- 37.Abdel Hady SI, El-Din MS, El-Din ME. A high hepatitis E virus (HEV) seroprevalence among unpaid blood donors and haemodialysis patients in Egypt. J Egypt Public Health Assoc. 1998;73(3-4):165–179. [PubMed] [Google Scholar]