Chinese pregnant women in their third trimester are more susceptible to HEV infection Academic research paper on "Health sciences"

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Letter to the Editor

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Chinese pregnant women in their third trimester are more susceptible to HEV infection

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 (40-20IU/L) was higher than that in general population

(<20IU/L). Results suggested that pregnant women in their third trimester of pregnancy were more susceptible to HEV infection and caused more severe liver lesions, which may partly explain the extremely high mortality rate in the third trimester.

Among the serum samples, 8.76% (24/274) of pregnant women and 10.53% (12/114) of the general population were positive to HEV IgG antibody, which was similar to the rate found in 2011 in this city (30/293,10.24%, p > 0.05). The positiv-ity 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 1 - Seroprevalence of HEV in pregnant women in Kunming city.

Stage Pregnant women Non-pregnant general population

First Second Third IgM IgG

IgM IgG IgM IgG IgM IgG

2015 90 90 92 92 92 92 114 114

0 8 1 11 9 5 5 12

0 8.89% 1.09% 11.96% 9.78% 5.43% 4.39% 10.53%

2011 80 30 78 185 135 78

0 2 2 19 2 9

0 6.67% 2.56% 10.27% 1.48% 11.54%

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 Infect Dis. 2015. http://dx.doi.org/10.10167j.bjid.2015.08.009

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300 250 200 150 100 50 0

2015 2011 First trimester

2015 2011 Second trimester

2015 2011 Third trimester

■ Number for IgG test IgG positive Number for IgM test IgM positive

I— GU1 1 J

99 JNi

JQ740781/Human/Nanjing/2009 GU188851/Human/Wuhan/2009 GU119961/Swine/Xinjiang/2009

JN613156/Swine/Yunnan/2011 KJ155502/Swine/Yunnan/2010 ▲ KR872415/Human/Yunnan/2015

A 8/Human/Yunnan/2015 A KR872417/Human/Yunnan/2015 KF703731/Swine/Yunnan/2011 99 JN542514//Sus scrofa/Yunnan/2011 HQ828104/Yunnan/2011 AB082545/Human/Japan/2009

DQ431471/Swine/Changchun/2006 KC692453/Swine/Shandong/2011 AF117275/Human/Taiwan/2000 AJ344171/Human/Beijing/2001

GU119960/Swine/Xinjiang/2009 AB108537/Human/Changchun/2000 GU119960/Swine/Xinjiang/2009 JF915746/Swine/Shanghai/2013

EF570133/Swine/Shanghai/2007

-AB124818/Swine/France/2009

99 p AJ344186/Human/Beijing/2001 A

AJ344192/Human/Beijing/2001 — DQ279091/Swine/Heilongjiang/2007 JN613152/Swine/Yunnan/2011 GU560156/Yunnan/2011

JX855794/Swine/Guangdong/2014 -JX855794/Swine/Guangdong/2011

- GU206559/Swine/Beijing/2008 -AY596308/Swine/Xinjiang/2004

- AJ344181/Human/Beijing/2001

- KJ534657/Swine/Hebei/2013 -KM024042/Swine/Hebei/2014

- KM024042/Swine/Hebei/2013

JN906975/Swine/France/2010

-AB089824/Human/Japan/2009

-M74506/Huamn/Mexican/1993 ' Genotype 2

Genotype 3

NC001434/Human/Xinjiang/1991 M80581/Human/Burma/1992

Genotype 1

Fig. 1 - 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 5' UTR and 3' 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 4 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 8 was deposited into GenBank database and is still being processed.

Genotype 4

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 76

study. This study was supported by National Natural Science 77

Foundation of China (31360619), Natural Science Foundation 78

of Yunnan province in China (Grant 2011FZ068, 2013FB032 79

and 2013FZ142), and China Postdoctoral Science Foundation 80

(2014M562672 and 2015T81138). 81

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 Infect Dis. 2015. http://dx.doi.org/10.10167j.bjid.2015.08.009

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references

84 1. Jia Z, Yi Y, Liu J, et al. Epidemiology of hepatitis E virus in

85 China: results from the Third National Viral Hepatitis

86 Prevalence Survey, 2005-2006. PLOS ONE. 2014;9:e110837.

87 2. Huang F, Ma T, Li L, Zeng W, Jing S. Low seroprevalence of

88 hepatitis E virus infection in pregnant women in Yunnan,

89 China. Braz J Infect Dis. 2013;17:716-7.

90 3. Cong W, Sui JC, Zhang XY, Qian AD, Chen J, Zhu XQ.

91 Seroprevalence of hepatitis E virus among pregnant women

92 and control subjects in China. J Med Virol. 2015;87:446-50.

93 4. Yu WMT, Zhao X, He Z, Yang C, Bi Y, Huang F. Complete

94 genome sequence of Swine hepatitis e virus prevalent in

95 Southwest China. Genome Announc. 2014;2, e00090-00014.

96 5. Li W, Shu X, Pu Y, Bi J, Yang G, Yin G. Seroprevalence and

97 molecular detection of hepatitis E virus in Yunnan Province,

98 China. Arch Virol. 2011;156:1989-95.

Fen Huangab*, Jue Wangb, Chenchen Yangb, Feiyan Longb, Q1 Yunlong Lib, Li Lic, Shenrong Jingb, Huixuan Wanga 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 99 of Science and Technology, Yunnan, China. 100

E-mail address: huangfen6789@163.com (F. Huang). 101

Received 31 July 2015 102

Accepted 12 August 2015 103

1413-8670/© 2015 Elsevier Editora Ltda. All rights reserved. 104

http://dx.doi.org/10.10167j.bjid.2015.08.009 105

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 Infect Dis. 2015. ittp://dx.doi.org/10.1016/j.bjid.2015.08.009