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chinese pregnant women in their third trimester are more susceptible to hev infection

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ARTICLE IN PRESS BJID 506 1–3 b r a z j i n f e c t d i s 5;x x x(x x):xxx–xxx The Brazilian Journal of INFECTIOUS DISEASES www.elsevier.com/locate/bjid Letter to the Editor Chinese pregnant women in their third trimester are more susceptible to HEV infection 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 To the Editor, HEV is one of the most important causes of acute clinical hepatitis in adults with particularly high mortality in pregnant women in developing countries, such as China.1 Although low seroprevalence of HEV infection in pregnant women was reported in Kunming City, Yunnan Province, China in 2011,2 an outbreak of HEV occurred in the city in 2015 affecting both pregnant women and general population In the present study, the prevalence of HEV was investigated in Kunming city by ELISA and RT-PCR methods Results indicated that HEV infection epidemic in Kunming city was associated with swine HEV, and pregnant women in their third trimester were more susceptible to HEV infection Serum samples of asymptomatic pregnant women (n = 274, 90 samples in the first, 92 samples in the second, and 92 samples in the third trimesters of pregnancy) and general population (n = 114) were collected for HEV antibodies and HEV RNA detection from January to April 2015 IgM antibody was detected during the acute stage of HEV infection Among samples of the pregnant women, 10 sera (10/274, 3.65%) were positive to HEV IgM, which was similar to the general population in 2015 (5/114, 4.39%), but higher than that in 2011 in the same city (4/293, 1.37%),2 and Shandong Province, China in 2011–2013 (2.6%).3 Surprisingly, 90% of pregnant women positive for HEV IgM antibody (9/10) were in their third trimester of pregnancy, which was significantly higher than in other stages of pregnancy (Table 1) Furthermore, the activity of AST in HEV IgM positive pregnant women (40–20 IU/L) was higher than that in general population ( 0.05) The positivity rates of anti-HEV IgG antibody in the first, second, and third trimesters of pregnancy were 8.89% (8/90), 11.96% (11/92), and 5.43% (5/92), respectively (Fig 1A) The highest rate of positive anti-HEV IgG antibody (11/24, 45.83%) was also in the second trimester of pregnancy, similar to that investigated in 2011 in the same city (Fig 1A) One third of IgM positive people (5/15) were also positive to HEV RNA The complete sequences of HEV, two strains isolated from pregnant women, and one strain from non-pregnant people of the general population were obtained by RT-nPCR according to our previous study.4 Sequences were submitted to the GenBank database (KR872417 and KR872415 isolated from pregnant women) Phylogenetic analysis indicated that the three human HEV strains belong to HEV genotype 4, sharing 99.3–99.8% homology with each other and 96.8–99.4% similarity to swine HEV strains isolated from 2009 to 2011 in this city (Fig 1B) This result indicates that the source of HEV infection in Kunming city in 2015 may originate from the same strain, probably a swine strain The high prevalence of HEV infection in Yunnan province may be associated with the traditional raw pork meat Table – Seroprevalence of HEV in pregnant women in Kunming city Stage Pregnant women First 2015 2011 Non-pregnant general population Second IgM IgG IgM 90 0 80 0 90 8.89% 30 6.67% 92 1.09% 78 2.56% Third IgG 92 11 11.96% 185 19 10.27% IgM 92 9.78% 135 1.48% IgG IgM IgG 92 5.43% 78 11.54% 114 4.39% 114 12 10.53% Please cite this article in press as: Huang F, et al Chinese pregnant women in their third trimester are more susceptible to HEV infection Braz J BJID 506 1–3 Infect Dis 2015 http://dx.doi.org/10.1016/j.bjid.2015.08.009 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 ARTICLE IN PRESS BJID 506 1–3 b r a z j i n f e c t d i s 5;x x x(x x):xxx–xxx A B JQ740781/Human/Nanjing/2009 72 GU188851/Human/Wuhan/2009 300 250 200 150 100 78 92 90 19 11 90 2015 30 2011 First trimester 92 8/Human/Yunnan/2015 83 90 135 99 KR872417/Human/Yunnan/2015 KF703731/Swine/Yunnan/2011 92 78 99 JN542514//Sus scrofa/Yunnan/2011 87 HQ828104/Yunnan/2011 AB082545/Human/Japan/2009 2015 2011 Second trimester 2015 DQ431471/Swine/Changchun/2006 2011 59 Third trimester KC692453/Swine/Shandong/2011 99 AF117275/Human/Taiwan/2000 88 Number for IgG test KR872415/Human/Yunnan/2015 31 99 80 50 JN613156/Swine/Yunnan/2011 KJ155502/Swine/Yunnan/2010 92 185 GU119961/Swine/Xinjiang/2009 18 52 IgG positive Number for IgM test IgM positive AJ344171/Human/Beijing/2001 84 49 GU119960/Swine/Xinjiang/2009 AB108537/Human/Changchun/2000 Genotype GU119960/Swine/Xinjiang/2009 69 JF915746/Swine/Shanghai/2013 99 59 EF570133/Swine/Shanghai/2007 AB124818/Swine/France/2009 82 99 95 47 AJ344186/Human/Beijing/2001 AJ344192/Human/Beijing/2001 DQ279091/Swine/Heilongjiang/2007 87 JN613152/Swine/Yunnan/2011 GU560156/Yunnan/2011 95 55 90 JX855794/Swine/Guangdong/2014 JX855794/Swine/Guangdong/2011 GU206559/Swine/Beijing/2008 90 99 AY596308/Swine/Xinjiang/2004 AJ344181/Human/Beijing/2001 66 KJ534657/Swine/Hebei/2013 32 KM024042/Swine/Hebei/2014 98 KM024042/Swine/Hebei/2013 JN906975/Swine/France/2010 Genotype AB089824/Human/Japan/2009 99 M74506/Huamn/Mexican/1993 Genotype NC001434/Human/Xinjiang/1991 94 Genotype 99 M80581/Human/Burma/1992 0.05 Fig – Prevalence of HEV infection in Kunming city and phylogenetic analysis (A) Seroprevalence of HEV in pregnant women in Kunming city in 2011 and 2015 (B) Phylogenetic analysis based on nearly full-length (7067 bp, exclude UTR and poly (A)) nucleotide sequence of isolates in this study and other 37 references of four genotypes of HEV, using the neighbor-joining method The tree was evaluated using the interior branch test method with Mega software The scale bar represents nucleotide substitutions per base GenBank accession number, origin, and host are indicated The isolates identified in this study are marked with a triangle Strains isolated from Yunnan province are marked with red color Isolate was deposited into GenBank database and is still being processed 62 63 64 65 66 67 68 69 70 71 72 73 74 consumption and swine-breeder liver in the same house The third national viral hepatitis prevalence survey of China during 2005–2006 revealed that Yunnan had one of the highest seroprevalence of HEV in China.1 Consuming raw pig livers or raw pork meat have a high potential risk of HEV infection; about 78.9% of the swine in Kunming City tested positive to HEV IgG antibody5 and raw pork meat is consumed frequently as a traditional food during the Spring Festival Therefore, Hepatitis E should be considered in the differential diagnosis during pregnancy in order to prevent the loss of mother or baby Infection was highly associated with the prevalence of swine HEV infection in this region, underscoring the zoonotic transmission of HEV Conflict of interest All authors declare to have no conflict of interest 75 Acknowledgements We thank all the patients who actively participated in this study This study was supported by National Natural Science Foundation of China (31360619), Natural Science Foundation of Yunnan province in China (Grant 2011FZ068, 2013FB032 and 2013FZ142), and China Postdoctoral Science Foundation (2014M562672 and 2015T81138) Please cite this article in press as: Huang F, et al Chinese pregnant women in their third trimester are more susceptible to HEV infection Braz J BJID 506 1–3 Infect Dis 2015 http://dx.doi.org/10.1016/j.bjid.2015.08.009 76 77 78 79 80 81 BJID 506 1–3 ARTICLE IN PRESS b r a z j i n f e c t d i s 5;x x x(x x):xxx–xxx 82 references 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 Jia Z, Yi Y, Liu J, et al Epidemiology of hepatitis E virus in China: results from the Third National Viral Hepatitis Prevalence Survey, 2005–2006 PLOS ONE 2014;9:e110837 Huang F, Ma T, Li L, Zeng W, Jing S Low seroprevalence of hepatitis E virus infection in pregnant women in Yunnan, China Braz J Infect Dis 2013;17:716–7 Cong W, Sui JC, Zhang XY, Qian AD, Chen J, Zhu XQ Seroprevalence of hepatitis E virus among pregnant women and control subjects in China J Med Virol 2015;87:446–50 Yu WMT, Zhao X, He Z, Yang C, Bi Y, Huang F Complete genome sequence of Swine hepatitis e virus prevalent in Southwest China Genome Announc 2014;2, e00090–00014 Li W, Shu X, Pu Y, Bi J, Yang G, Yin G Seroprevalence and molecular detection of hepatitis E virus in Yunnan Province, China Arch Virol 2011;156:1989–95 Fen Huang a,b,∗ , Jue Wang b , Chenchen Yang b , Feiyan Long b , Q1 Yunlong Li b , Li Li c , Shenrong Jing b , Huixuan Wang a a Kunming General Hospital of Chengdu Military Region, Kunming, PR China b Medical Faculty, Kunming University of Science and Technology, Kunming, PR China c Kunming Maternal and Child Health Hospital, Kunming, PR China ∗ Corresponding author at: Medical Faculty, Kunming University of Science and Technology, Yunnan, China E-mail address: huangfen6789@163.com (F Huang) Received 31 July 2015 Accepted 12 August 2015 1413-8670/© 2015 Elsevier Editora Ltda All rights reserved http://dx.doi.org/10.1016/j.bjid.2015.08.009 Please cite this article in press as: Huang F, et al Chinese pregnant women in their third trimester are more susceptible to HEV infection Braz J BJID 506 1–3 Infect Dis 2015 http://dx.doi.org/10.1016/j.bjid.2015.08.009 99 100 101 102 103 104 105

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