Maternal and newborn seroprevalence of Hepatitis E virus at Medani Hospital, Sudan

Introduction

Hepatitis E virus (HEV) is a single-stranded RNA virus and an emerging infectious agent where it can cause acute viral hepatitis worldwide with estimated 20 million cases of HEV infection occur globally and 70 000 deaths (Aggarwal & Gandhi, 2010; Rein et al., 2012). Due to hormonal and immunological changes, pregnant women are more prone to have severe form of HEV infections where there is increasing evidence that HEV is an important contributor to maternal and perinatal morbidity and mortality, especially in the developing countries (Ahmed et al., 2008; Bose et al., 2011; Bose et al., 2014; Kumar et al., 2001; Navaneethan et al., 2008; Ornoy & Tenebaum, 2006; Rayis et al., 2013). In previous studies, Stoszek et al. (2006) and Patra et al. (2007) reported prevalence rates of 84.3% and 60% of anti-HEV antibodies among pregnant women in Egypt and India, respectively.

In Sudan, a high mortality rate was reported among pregnant women in an outbreak of HEV in Darfur and in eastern Sudan (Boccia et al., 2006; Rayis et al., 2013). In spite of this there are no published data on the seroprevalence of anti-HEV IgG in Sudan and screening of HEV is not part of the antenatal care programme. Research on the seroprevalence of HEV is of paramount importance for health policy makers as well as for the practicing clinicians and it will yield data necessary for developing preventive measures. This study was conducted to determine the seroprevalence of anti-HEV IgG among a population of pregnant women and their newborns in Medani, Sudan.

Materials and methods

A cross-sectional study was conducted at the delivery ward of Medani Maternity Hospital, Sudan during the period of March 2013. Medani Hospital is a tertiary care hospital in central Sudan, located in Al Gezira state which is the second largest state in Sudan. Women with a singleton pregnancy were approached to be enrolled to the study. Mothers who experienced stillbirths and those who had been diagnosed with diabetes or hypertension were excluded from the current study. After signing an informed consent form, socio-demographic, medical and obstetric characteristics were gathered using a questionnaire that was applied in the local language (Arabic; see Supplementary file 1 for sample questionnaire). A convenience sampling method was used where consecutive eligible women were recruited every day until the total desired sample size was achieved (206). The sample size of 206 women was calculated based on a 2-sided hypothesis test using Epiinfo software (Centre for Disease Control, USA; version 6) that yielded 80% power and a confidence interval of 95% with 10% of women expected to have incomplete data or samples.

Body mass index (BMI) was calculated by maternal weight and height that were measured. Five millilitres of blood was collected from each woman along with the corresponding infants’ umbilical cord. The umbilical cords were stored in plain tubes and all samples were labelled and kept at room temperature for 30 minutes, centrifuged at 2000 rpm for 10 minutes to separate blood components. Serum was stored at -20 degrees until analyzed for anti-HEV IgG using specific antibody profiles using HEV IgG-specific ELISA (Euroimmun, Lübeck, Germany).

Statistics

Data were entered in computer using SPSS software (IBM, UK; version 16) for Windows. Statistics were described as mean (SD) for continuous data and as frequency and percentages (%) for categorized data. T-test and X² were used to compare continuous and categorized data, respectively between women who were seropositive for HEV IgG antibodies and women with a negative result for HEV antibodies. Binary logistic regression was conducted where seropositivity for HEV IgG antibodies was the dependent variable and socio-demographic, clinical characteristics were the independent variable. Odds ratio and 95% confidence interval were calculated, and P values of < 0.05 were considered statistically significant.

Ethics

Ethical approval was obtained from the Ethical committee of University of Khartoum.

Results

Two hundred and nine women were enrolled in the study. The mean (SD) of their ages, parities and gestational ages were 27.5 (5.5) years, 2.2 (1.5) and 38.8 (1.8) weeks, respectively. Out of these 209, 25 (12.5%) women had a positive result for anti-HEV IgG and two (1.0%) newborns whose mothers also had a positive anti-HEV IgG showed a positive result for anti-HEV IgG.

There was no significant difference in the age, parity, education, gestational age, BMI or history of miscarriage between seropositive and seronegative anti-HEV IgG women (Table 1). Likewise, in logistic regression none of these investigated factors were associated with anti-HEV IgG seropositivity (Table 2).

Discussion and conclusions

The main findings of the current study were: the high prevalence (12.1%) of HEV IgG antibodies among pregnant women regardless of their age, parity, residence and educational levels. Recently Caron & Kazanji (2008) found that 14.1% of 840 pregnant women in Gabon had anti-HEV IgG and the prevalence was significantly higher in the urban areas than in the rural ones (13.5 vs. 6.4%). Yet a much higher (28.66%) HEV IgG seroprevalence was observed among Ghanaian pregnant women, especially pregnant women who were 21–25 years of age and women in their third trimester (Adjei et al., 2009). Furthermore, a high prevalence of HEV infection among pregnant women was reported in their neighboring countries, Egypt (84.3%) (Stoszek et al., 2006), Ethiopia (59%) (Tsega et al., 1993) and during an epidemic in Darfur, Sudan (31.1%; Boccia et al., 2006). Interestingly a low (3.6%) prevalence of anti-HEV IgG was reported in Iran and can be explained by the good hygiene and water supply in the investigated area (Rostamzadeh et al., 2013) and in Mexico (5.7%), where pregnant women of advancing age were more likely to be seropositive for HEV IgG (Alvarado-Esquivel et al., 2014).

In the current study, two of the newborns showed a positive result for anti-HEV IgG. Recently, Mesquita et al. (2013) observed that four pairs (mother and newborn) of participants of the 12 pairs tested were seropositive for anti-HEV IgG. In Egypt, anti-HEV IgG was detected in 31% of 29 neonates with clinical suspicion of congenital infections (El Sayed Zaki et al., 2013). It is worth mentioning that although vertical HEV infection is common and can lead to a high neonatal mortality, HEV is a self-limiting infection in survivors with short-lasting viremia (Khuroo et al., 2009).

Previously (2001), Kumar and colleagues reported 100% transmission of anti-HEV IgG from the mother to the infant and suggested transplacental transmission of IgG. It has been recently demonstrated for the first time that HEV replication occurs in human placenta and that placenta is a proposed site of extrahepatic replication of HEV in humans (Bose et al., 2014). HEV is mainly transmitted by the fecal-oral route, zoonotic transmission from animal reservoirs (including donkeys) to humans, blood borne, human to human, and vertical transmission from mother to child have been reported (Mirazo et al., 2014).

The high seroprevalence of HEV amongst pregnant women in central Sudan may suggest that HEV may be widespread among pregnant women in the country as well as in the general population. Furthermore, because the virus is transmitted mainly through the fecal-oral route, sanitary and hygiene conditions should be in optimum conditions to reduce the risk of infection. Perhaps the policy of not screening for HEV antibodies in pregnant women in Sudan is based on the assumed low prevalence; screening for HEV should be employed based on the results of the current study. Moreover, antenatal screening of pregnant women would ensure that treating clinicians could take further precautions to protect against perinatal HEV transmission, minimizing the risk. One of the limitations of the current study is the failure to investigate the HEV genotyping which should be considered in the future study.

In summary, the current study revealed a high seroprevalence of HEV among pregnant women in central Sudan regardless of their age, parity and gestational age. Optimal preventive measures against HEV infection should be employed.

Data availability

F1000Research: Dataset 1. Raw dataset for Eltayeb et al., 2015 ‘Maternal and newborn seroprevalence of Hepatitis E virus at Medani Hospital, Sudan’, 10.5256/f1000research.7041.d101652