Introduction

Globally an estimated 1.36 million pregnant women had active syphilis in 2008 [1]. In that year, maternal syphilis resulted in more than 520,000 adverse outcomes, including stillbirths, early fetal losses, neonatal deaths, preterm or low birthweight infants, and infants born with congenital syphilis (CS) [1]. Many of these women seek prenatal care in rural regions of low- and middle-income nations that do not have the capacity to implement traditional syphilis screening [1]–[4]. In turn, pregnant women in these contexts either receive testing during the third trimester after their babies have been affected or never receive testing [1]–[3].

This lack of syphilis testing in rural regions leads to uncertainty about the extent of the syphilis epidemic among rural pregnant women. However, developments in point-of-care (POC) technology now allow accurate syphilis screening using immunochromatographic strips [5]. These tests, which have demonstrated sensitivity and specificity comparable to laboratory-based methods, can provide a rapid result within 30 minutes of testing. This development enables routine syphilis testing in low-level rural health facilities that serve large numbers of pregnant women [6].

Responding to the need for improved syphilis screening across our province in China, we launched a rural syphilis project to examine the prevalence and correlates of infection.

Methods

Results

A total of 27,150 pregnant women in rural Guangdong received POC syphilis screening. They were recruited from 55 hygiene stations, 12 general hospitals, and 4 women and children's hospitals. Demographic characteristics of pregnant women who received screening are presented in Table 1. Women included in this study were primarily married (96.9%), middle school educated (73.8%), and between the ages of 21 and 30 years (72.6%). A large proportion of women in the study (43.8%) had no previous children. At the time of syphilis screening, only 17.3% of women were in their first trimester; most women (53.6%) were in their third trimester or later. Among the pregnant women screened, 106 (0.39%) were diagnosed with syphilis infection. Of these 106 cases, 78 (73.6%) received treatment for syphilis.

Download:

• PPT
  PowerPoint slide
• PNG
  larger image
• TIFF
  original image

Table 1. Demographic characteristics of pregnant women screened for syphilis (N = 27,150).

https://doi.org/10.1371/journal.pone.0072149.t001

Univariate analysis revealed a higher proportion of syphilis infection among older women, unmarried women, women with a history of adverse pregnancy outcome, and women whose partners spent between 1 week and 3 months outside the home (Table 2). Compared to women 20 years or younger, women ages 31 to 35 and women ages 31 to 35 were significantly more likely to be infected with syphilis (odds ratio [OR] 3.19, 95% confidence interval [CI] 1.19–8.56; OR 7.29, 95% CI 2.73–19.46, respectively). Unmarried women were 2.55 times more likely to be infected (95% CI 1.24–5.26) compared to married women. A history of adverse pregnancy was associated with 3.81 times greater odds of syphilis infection (95% CI 2.50–5.81). And compared to women whose partners spent less than 1 week outside the home, those whose partners spent 1 week to 3 months outside the home were more likely to be infected (OR 3.03, 95% CI 1.45–6.32).

Download:

• PPT
  PowerPoint slide
• PNG
  larger image
• TIFF
  original image

Table 2. Univariate and multivariate analysis of demographic and socioeconomic factors associated with positive syphilis test among pregnant women.

https://doi.org/10.1371/journal.pone.0072149.t002

In the multivariate analysis, older age and history of adverse pregnancy outcome remained significantly associated with syphilis infection (Table 2). Compared to women less than 21 years old, women 31–35 years of age were 2.70 times more likely to be infected with syphilis (95% CI 0.99–7.32), and women older than 35 years were 5.90 times more likely to be infected (95% CI 2.13–16.34). Women with a history of adverse pregnancy outcomes were 3.64 times more likely to have syphilis (95% CI 2.30–5.76) compared to those without a history of adverse outcomes.

Discussion

Syphilis remains a major cause of preventable death and disability among neonates and young children [3], [11], [12]. Although an estimated 80% of pregnant women with active syphilis attend antenatal care, many of these women are not tested for syphilis [1]. Approximately 60% of the more than 520,000 adverse outcomes caused by maternal syphilis occur among women who attend ANC but are not tested or treated for syphilis [1]. To our knowledge, this is the first comprehensive syphilis study conducted among pregnant women in rural China. China has experienced a resurgence of syphilis during the past 20 years [13]. One population-representative survey [14] and case report data suggest [7] that urban Chinese have more sexual risk behaviors and a greater burden of STIs [13]. However, syphilis diagnostic capacity in rural health facilities is limited [6], and there have been few studies of syphilis outside of urban areas [13], [15]. Thus, the burden of syphilis in rural areas is poorly understood. Additionally, in 2003–2004 the Chinese government phased out the compulsory premarital health check that included syphilis screening [13], and there have been few comprehensive studies of the syphilis burden in non-core groups since then. This study sought to address these gaps by examining the prevalence of syphilis among pregnant women accessing care at health facilities in rural Guangdong province.

Our study found a high burden of syphilis among rural pregnant women in Guangdong Province. The overall syphilis prevalence (0.39%) among pregnant women in this study is comparable to the prevalence reported among pregnant women in urban Fuzhou (0.2%), Shanghai (0.3%), and Shenzhen (0.5%) [16]–[18]. The burden of syphilis among this population of pregnant women in rural South China is also similar to what has been reported in studies conducted at regional blood donation centers that cover urban and rural areas throughout China (0.30–0.63%) [19]–[21]. Compared to other countries, the prevalence reported here is lower than among pregnant women in rural low-income settings in sub-Saharan Africa and Haiti [22]–[30] but higher than among women in rural areas in high-income countries like the U.S. [31] The syphilis epidemic among pregnant women in rural Guangdong province might be partially explained by female migrants or their husbands returning to their rural origins from the cities with untreated syphilis and persistently risky sexual behavior [32]. Studies have found that migrants in some Chinese cities have high-risk sexual behavior [33] and a higher prevalence of syphilis compared to local residents [16], [17], but few studies have examined the sexual risk of returning migrants.

We found that older age was associated with syphilis infection among pregnant women in rural Guangdong province. National STI surveillance data show that men over 50 years of age represent a substantial and increasing proportion of notified syphilis cases in China [34]. However, it is not clear whether these patterns reflect an increased sexual risk in this population or an increased likelihood of being routinely screened as part of a hospital admission. A national population-based study also demonstrated that chlamydia infection was associated with older age among women [14]. These results are consistent findings from sub-Saharan Africa, Australia, and the U.S. that also reveal a sizable burden of STIs among older persons [35]. Additionally, a study of STI patients in Guangxi showed high rates of purchasing commercial sex and low rates of condom use in individuals 50 years and older [34], [36]. Our finding that older women were more likely to be infected with syphilis suggests the need to integrate syphilis screening with routine health services for older women, such as screening for breast, cervical, and other cancers. Taking advantage of these opportunities to establish periodic syphilis screening is an important way of reaching women who are no longer having pregnancies and thus not accessing screening offered during antenatal care.

Women with a history of adverse pregnancy outcomes were also more likely to be infected with syphilis in this study. This finding is consistent with the observation that approximately 60% of pregnancies in women with untreated syphilis will result in some adverse outcome [11]. About 40% of such pregnancies will end in miscarriage, stillbirth, or perinatal death, and surviving newborns are at risk for congenital malformations [11], [37]–[39]. The higher prevalence of syphilis among women with a history of adverse pregnancy outcomes also points to an opportunity for integrating syphilis control and reproductive health services beyond antenatal care. Few studies of STIs in China have examined women seeking termination of pregnancy, but this population may be in particular need of STI screening because unsafe sexual behavior is a risk factor for both unwanted pregnancy and STIs [40]. Integrating syphilis screening with family planning services, such as intrauterine device insertions, also represents another way of reaching older women. HIV testing has been successfully integrated with post-abortion and other family planning services in settings in Kenya [41], Ethiopia [42], Tanzania [43], and the U.S. [44]

This study revealed a high burden of syphilis in rural South China among a non-core group believed to be at low risk. These findings suggest that syphilis may be moving toward a generalized epidemic in China. Making syphilis testing universally available in rural health facilities is fundamental in order to respond this challenge. The 10-year National Syphilis Prevention and Control Plan, announced by the Ministry of Health in 2010, is a promising step forward with its emphasis on expanding syphilis testing coverage among pregnant women in urban and rural areas [45]. However, the screening and treatment coverage targets are too low to meet the goal of reducing congenital syphilis by 2020 [46]. A key element missing from the national plan is an emphasis on earlier antenatal screening. Mother-to-child transmission of syphilis is preventable if the mother receives adequate treatment early during the pregnancy, ideally during the first trimester. In our study, more than half of the pregnant women had their first syphilis screening in the third trimester or around the time of delivery, some even after labor. This is consistent with a study in a neighboring province in South China that found that 57.7% pregnant women in rural areas had not yet made their first antenatal visit by the last month before labor [47]. Thus, improving antenatal care coverage is key for effective syphilis control.

This study has a number of limitations. We cannot confirm whether adverse pregnancy outcomes reported by women with syphilis infection were syphilis-related. Some of these adverse outcomes may have predated the syphilis infection detected in this study. Additionally, our data on linkage to care may underestimate the proportion of syphilis cases that received treatment if patients sought treatment in locations other than the local referral center, such as private health care facilities. Despite these limitations, this study offers valuable data on the prevalence of syphilis among a large population of pregnant women throughout rural areas of Guangdong province.

To achieve the goals of the National Syphilis Prevention and Control Plan, the capacity for diagnosing syphilis in rural health facilities in China needs to be strengthened. Rapid POC syphilis testing, which has been used in remote communities in Brazil [48] and other settings [5], is an excellent option, especially in rural areas with limited laboratory facilities. In our project, syphilis screening by POC syphilis testing with referral of positive cases to local STD centers was well accepted by rural pregnant women and local health facilities. Improving antenatal care coverage, promoting retention in care, and integrating syphilis screening with other routine health services are also key for effective syphilis control in rural China.