Abstract
Background
Curable sexually transmitted infections (STIs) contribute to adverse maternal and neonatal outcomes. Syndromic management is standard care in South Africa. We evaluated prevalence, symptomology, and correlates of curable STIs, among pregnant women in Eastern Cape, South Africa.
Methods
We conducted a cross-sectional analysis using baseline data from a randomized controlled trial of pregnant women attending their first antenatal care visit at public clinics in Buffalo City Municipality (2021–2024). Participants were tested for Chlamydia (C.) trachomatis, Neisseria (N.) gonorrhoeae, Trichomonas (T.) vaginalis using GeneXpert point-of-care tests and for syphilis using Alere Determine TP rapid test. Symptoms were self-reported and clinically-observed. Adjusted prevalence ratios were estimated using Poisson regression models with robust standard errors.
Results
Among 1491 participants (median age: 28 years (IQR: 24–33); gestational age: 13 weeks (IQR: 8–18); HIV prevalence: 30%), STI prevalence was 27.6% (95% CI: 25.3–29.9): C. trachomatis 14.7%, N. gonorrhea 5%, T. vaginalis 10.2%, syphilis 3.4%. Women with HIV had higher STI prevalence (32.8% vs 25.3%, p = .003), particularly for T. vaginalis (17% vs 7.3%, p < .001); 20.1% of women with C. trachomatis, N. gonorrhea, and/or T. vaginalis were symptomatic, and 63% of symptomatic women tested STI-negative. Younger age, lower education, multiple sex partners and unknown HIV-serostatus of partners were associated with increased STI prevalence.
Conclusion
We observed a high prevalence of STIs, particularly among women with HIV, with many asymptomatic cases; emphasizing the need for integrated point-of-care testing to ensure timely treatment, reduce antibiotic overuse, and improve maternal and neonatal outcomes.
Introduction
Globally, an estimated 374 million new cases of curable sexually transmitted infections (STIs), including Neisseria (N.) gonorrhoeae, Chlamydia (C.) trachomatis, Trichomonas (T.) vaginalis, and syphilis occurred in 2020, with the World Health Organization (WHO) African Region bearing a disproportionate burden of disease. 1 Women of reproductive age are particularly vulnerable to STIs and their sequelae. 2 STIs are associated with severe maternal and neonatal complications, including stillbirth, low-birth weight, preterm birth, conjunctivitis, and pneumonia.3–7 The presence of STIs also increase the risk of HIV acquisition and transmission.8,9
Prevalence of STIs among pregnant women, especially among women with HIV, is high in South Africa, with 50–76% of cases reported to be asymptomatic.10–14 Syndromic management, recommended by the WHO 15 and South African STI Management Guidelines, 16 is linked to both undertreatment and overtreatment. 17 While syphilis screening is routine in antenatal care in South Africa, 18 screening for C. trachomatis, N. gonorrhoeae, and T. vaginalis infections is not, despite their high burden and potential to cause adverse pregnancy outcomes.
Most epidemiological data on STIs in South Africa come from the Western Cape (Cape Town),10,11 Gauteng (Johannesburg and Pretoria),10,13,14 and Kwa-Zulu Natal (Durban) 12 provinces, leaving a research gap in the Eastern Cape, a historically disadvantaged region. 19 This limits our understanding of the STI burden and hinders the development of targeted interventions for pregnant women in the province.
This study aims to describe the prevalence, symptomology, and correlates of curable STIs among pregnant women with and without HIV in the Eastern Cape, providing insights to support the integration of routine diagnostic STI screening in antenatal care to reduce unnecessary antibiotic use and improve maternal and neonatal outcomes.
Methods
Study design and setting
We conducted a cross-sectional analysis of baseline data from a three-arm randomized controlled trial among pregnant women attending their first antenatal care visit at government clinics in Eastern Cape, South Africa. 20 The trial aimed to assess the impact of STI screening strategies on adverse birth outcomes and STI prevalence at delivery, as well as evaluate cost-effectiveness per STI and disability-adjusted life-year (DALY) averted. 20
The trial was conducted at four antenatal care clinics in Buffalo City Municipality from March 2021 to May 2024. Eligibility criteria included pregnant women aged ≥18, <27 weeks’ gestation confirmed by ultrasound, and planning delivery at hospital within Buffalo City Municipality. Exclusion criteria included planned relocation or participation in another antenatal study. Eligible women provided informed consent in their preferred language (isiXhosa or English) before randomization. This cross-sectional analysis included all 1491 women enrolled in the intervention cohort for diagnostic STI screening at their first antenatal visit. Ethical approval was granted by the University of Cape Town’s Faculty of Health Sciences Research Ethics Committee (UCT-HREC, reference number 676/2019). This analysis adhered to the STROBE reporting guidelines for cross-sectional studies. 21
Data collection and management
Study data were collected and managed using Research Electronic Data Capture (REDCap). 22 Participants were interviewed by study staff using a standardized questionnaire that gathered socio-demographic and clinical information (sexual health and obstetric history, participant self-report of abnormal vaginal discharge, co-morbidities, HIV treatment details). Research nurses performed pelvic exams on all participants to detect abnormal vaginal discharge. Each participant was assigned a unique identifier upon enrolment, and all electronic communications were securely handled through password-protected and encrypted files.
Specimen collection, testing, and treatment
At the first antenatal care visit, trained research nurses collected vaginal swab specimens using GeneXpert CT/NG Vaginal/Endocervical Specimen Collection Kits (Cepheid, Sunnyvale, California) for point-of-care testing of C. trachomatis, N. gonorrhoeae, and T. vaginalis. Participants received same-day results and immediate treatment per South African guidelines, 16 including oral Azithromycin (two 500 mg tablets) single dose for C. trachomatis, Ceftriaxone 500 mg intramuscular (IM) single dose for N. gonorrhoeae, and Metronidazole 400 mg twice a day for 7 days for T. vaginalis. Those unable to wait were telephonically contacted and requested to return for results and treatment following the same regimen as those treated same-day. Women testing positive were counselled on safe partner disclosure, including intimate partner violence risks, and provided notification slips for partner treatment. Participants received routine services per National Basic Antenatal Care Plus, 23 including testing for HIV and syphilis. 18 Syphilis testing was conducted using rapid treponemal tests performed onsite. Syphilis test type data were available for 802 participants, most of whom (n = 796) were tested with Alere Determine TP test (Abbott Laboratories, Inc., U.S.A). Six participants were tested with SD Bioline HIV/Syphilis Duo test (Standard Diagnostics, Inc., Gyeonggi-do, South Korea). Laboratory-based rapid plasma reagin (RPR) testing was used for confirmation of positive results. Treatment for syphilis followed the National Guidelines for Prevention of Vertical Transmission, 18 including 2.4 million units (MU) of benzathine penicillin IM x three doses, at weekly intervals, with the first dose administered immediately upon a positive rapid test result. HIV testing was conducted by clinic staff in line with the National HIV Testing Algorithm. 24 One Step Rapid HIV 1/2 (Guangzhou Wondfo Biotech Co., Ltd, Guangzhou, China) rapid tests were used for initial screening with reactive results followed by confirmatory testing with Colloidal Gold test kits (Kehua Bio-engineering Co., Ltd, Shanghai, China). All pregnant women who test positive for HIV are immediately started on lifelong antiretroviral therapy (ART), in line with national guidelines on the prevention of vertical transmission. 18
Outcome measures
Any curable STI
A composite variable for prevalence of any curable STI was calculated as the proportion of women with a positive diagnostic test result for C. trachomatis, N. gonorrhoeae, T. vaginalis, or syphilis out of all women tested.
C. trachomatis/N. gonorrhoeae/T. vaginalis infection
Prevalence for each organism was calculated as the proportion of women with a positive test result for the respective organism out of all women tested.
Syphilis infection
Prevalence was calculated as the proportion of women with a positive rapid treponemal test result out of all women tested, regardless of RPR titre. Due to limited clinical history data, we could not differentiate between active and past infection.
Symptomatic infection
A symptomatic STI case was defined as a positive diagnostic test for C. trachomatis, N. gonorrhoeae, or T. vaginalis with self-reported or clinically-observed abnormal vaginal discharge. Vaginal discharge is not aetiologically linked to syphilis, and thus women with syphilis monoinfection were not included in vaginal discharge symptom assessment. Variables on syphilis-associated symptoms (e.g., chancre, maculopapular rash, condylomata lata) were not tracked as a part of the parent trial. As this is a secondary analysis of baseline data, we were unable to assess symptomology among syphilis cases. Thus symptom assessment is limited to C. trachomatis, N. gonorrhoeae, and T. vaginalis. Pregnant women with reported or clinically-observed abnormal vaginal discharge who had negative test results for C. trachomatis, N. gonorrhoeae, and T. vaginalis were included in assessment of the overall prevalence of vaginal discharge syndrome, however, were excluded from the analysis of symptomatic infection.
Statistical analysis
Statistical analysis was performed using R Studio version 4.3.0 (2023–04-21). Participant characteristics were analyzed using Chi-squared, Fisher’s exact, or Kruskal-Wallis tests, as appropriate. STI prevalence and 95% confidence intervals (CI) were calculated for any curable STI and each organism, stratified by HIV serostatus. Prevalence ratios (PR) and adjusted prevalence ratios (aPR) with 95% CI were estimated using Poisson regression models with robust standard errors. Covariates with significant differences (p < .05) and a priori confounders identified through literature review and directed acyclic graphs 25 were included in adjusted models. Models were conducted overall and stratified by HIV serostatus and STI organism.
Results
Participant characteristics
Characteristics of pregnant women who underwent STI screening at first antenatal Visit, Buffalo City municipality, South Africa, 2021–2024.
aMedian (IQR); n (column %).
b“Missing” row indicates the number of participants without available data for each variable.
cBased on an exchange rate of USD18 to R1.
*Denominator adjusted due to missing data. Percentages are calculated based on available data.
§Data only obtained from participants who reported being in a casual relationship, steady relationship, or married.
± Data only obtained from participants who reported being married or in a steady partnership.
†Only includes data from participants who reported their partner to be living with HIV.
‡Only includes data from participants living with HIV.
ANC, antenatal care; ART, antiretroviral therapy; HIV, Human Immunodeficiency Virus; STI, sexually transmitted infection; ZAR, South African Rand.
STI prevalence
The prevalence of any curable STI was 27.6% (n = 411, 95% CI: 25.4 30). Prevalence of C. trachomatis was 14.7% (n = 219, 95% CI: 12.9–16.6), N. gonorrhoeae was 5% (n = 73, 95% CI: 4–6.1), T. vaginalis was 10.2% (n = 152, 95% CI: 8.7–11.8), and syphilis was 3.4% (n = 51, 95% CI: 2.6–4.5). (Figure 1 and Table 2). Among the women with a positive syphilis test, 20% (n = 10) had RPR titres <1:1, 32% (n = 15) between 1:1–1:4, 32% (n = 16) between 1:4–1:16, and 18% (n = 9) had values >1:16. One participant with a positive syphilis rapid test result did not have an RPR titre value available. Coinfection with two or more curable organisms (C. trachomatis, N. gonorrhoeae, T. vaginalis, and/or syphilis) was found in 5.1% of all women (n = 76)). No women were infected with all four organisms. (Table 2). Of the 379 women with C. trachomatis, N. gonorrhoeae, or T. vaginalis, 94.5% (n = 358) received treatment, 50.6% (n = 181) of whom received treatment on the same day. All 51 (100%) women with a positive syphilis rapid test result received same-day treatment of a first dose of benzathine penicillin G 2.4 MU and were requested to return for subsequent doses. Prevalence of curable sexually transmitted infection among pregnant women seeking antenatal care services, Buffalo City Municipality, South Africa, 2021–2024, stratified by organism, stratified by HIV status. CT, Chlamydia trachomatis; NG, Neisseria gonorrhoeae; TV, Trichomonas vaginalis. Prevalence Estimates, overall and HIV stratified among pregnant women seeking antenatal care services, Buffalo City Municipality, South Africa, 2021–2024. an (%) (95% Confidence Interval). bChi-square test. cDenominator is the total number of women infected with two or more organisms. CT, Chlamydia trachomatis; HIV, Human Immunodeficiency Virus; NG, Neisseria gonorrhoeae; STI, sexually transmitted infection; TV, Trichomonas vaginalis. p-values in bold indicate < 0.05.
In analysis stratified by HIV status, prevalence of any curable STI was 32.8% (n = 147, 95% CI: 28.5–37.4) among women with HIV and 25.3% (n = 264, 95% CI: 22.7–28.1) among women without HIV (p =.003). T. vaginalis prevalence was higher among women with HIV (16.9% vs 7.3%, p < .001) as was coinfection with two or more STIs (7.1% vs 4.2%, p = .025), while C. trachomatis, N. gonorrhoeae, and syphilis prevalence did not differ significantly by HIV status. (Table 2; Figure 1).
Symptomology
Factors associated with curable sexually transmitted infections among pregnant women undergoing STI screening, stratified by HIV Status, Buffalo City municipality, South Africa, 2021–2024.
Confidence intervals in bold had sufficient evidence to conclude that the groups were statistically significantly different.
† model adjusted for age, education, employment, married/cohabitating, HIV status, research site (HIV stratified models were not adjusted for HIV status).
± model adjusted for age education, married/cohabitating, HIV status, research site(HIV stratified models were not adjusted for HIV status).
‡ model adjusted for age, education, employment, research site (age excluded from adjusted model for gavidity due to collinearity).
* model adjusted for age, HIV status, research site(HIV stratified models were not adjusted for HIV status).
ANC, antenatal care; ART, antiretroviral therapy; aPR, adjusted prevalence ratio; PR, prevalence ratio.
aIncludes those who reported being self-employed.
bout of those who reported being married or in a steady partnership.
cout of women living with HIV.
dOnly includes participants with CT, NG, or TV as per South African STI Screening Algorithm.
Factors Associated with curable sexually transmitted Infections Among Pregnant Women Undergoing STI Screening, Stratified by Sexually Transmitted Organism, Buffalo City Municipality, South Africa, 2021–2024.
Confidence intervals in bold had sufficient evidence to conclude that the groups were statistically significantly different.
† model adjusted for age, education, employment, married/cohabitating, HIV status, research site.
± model adjusted for age education, married/cohabitating, HIV status, research site.
‡ model adjusted for age, education, employment, research site (age excluded from adjusted model for gravidity due to collinearity).
* model adjusted for age, HIV status, research site.
ANC, antenatal care; ART, antiretroviral therapy; CT, Chlamydia trachomatis; NG, Neisseria gonorrhoeae; TV, Trichomonas vaginalis; aPR, adjusted prevalence ratio; PR, prevalence ratio.
aIncludes those who reported being self-employed.
bout of those who reported being married or in a steady partnership.
cout of women living with HIV.
dOnly includes participants with CT, NG, or TV as per South African STI Screening Algorithm.
Correlates of curable STIs
Correlates of any curable STI, overall and by HIV serostatus, are shown in Table 3. In multivariate analysis, lower education (aPR: 1.42, 95% CI: 1.15–1.76), being married/cohabitating with partner (aPR: 1.43, 95% CI: 1.15–1.78), unknown HIV serostatus of partner(s) (aPR: 1.32, 95% CI: 1.06–1.65), reporting multiple sex partners (aPR: 1.5, 95% CI: 1.2–1.9), and HIV serostatus (aPR: 1.43, 95% CI: 1.15–1.77) were independently associated with increased prevalence of any curable STI. Older maternal age (aPR: 0.95, 95% CI: 0.93-0.96) and multigravidity (aPR: 0.78, 95% CI: 0.62-0.96) were associated with lower prevalence. Associations strengthened or attenuated when stratified by HIV serostatus.
Correlates of individual STIs are detailed in Table 4. Multivariable analysis showed strong associations between lower education and T. vaginalis (aPR: 1.74, 95% CI: 1.24–2.45) and syphilis (aPR: 1.79, 95% CI: 1.01–3.22). Reporting multiple sex partners was strongly associated with syphilis (aPR: 2.23, 95% CI: 1.18–4.03), N. gonorrhoeae (aPR: 1.83, 95% CI: 1.05–3.06), and T. vaginalis (aPR: 1.57, 95% CI: 1.03–2.33). Not being married or cohabitating with partner was also strongly associated with syphilis (aPR: 2.04, 95% CI: 1.05–4.27) and N. gonorrhoeae (aPR: 1.75, 95% CI: 1.01–3.18). Suspecting partner of having other partner(s) was also associated with syphilis (aPR: 1.98, 95% CI: 1.05–3.81) and N. gonorrhoeae (aPR: 1.76, 95% CI: 1.04–2.98). HIV serostatus was strongly associated with T. vaginalis, showing a 125% higher prevalence in women with HIV (aPR: 2.25, 95% CI: 1.6–3.2). Geographical variation was also observed, with a 149% higher prevalence of syphilis at research site 3 (aPR: 2.49, 95% CI: 1.18–5.24).
Discussion
Our study identified a high prevalence of curable STIs among pregnant women in Eastern Cape, South Africa, which was elevated among women with HIV. Most women with STIs were asymptomatic, while women without STIs were more likely to report symptoms. Although treatment rates were high, same-day treatment following point-of-care tests for C. trachomatis, N. gonorrhoeae, and T. vaginalis was moderate compared to syphilis rapid tests. We observed strong associations between curable STIs and several individual, behavioural, geographical, and partner characteristics. Our findings highlight the need to strengthen STI care for pregnant women and their partners, ensuring timely detection, treatment, and comprehensive care to improve maternal and neonatal health outcomes.
The prevalence of any curable STI in our study was slightly lower than in other South African regions,10,11 but higher than reports from Botswana,26,27 Kenya, 28 and Ethiopia. 29 Syphilis prevalence was lower than a recent South African study, 30 but higher than earlier reports from the country31–33 and exceeds rates reported in Tanzania 34 and Zimbabwe. 35 Heterogeneity of syphilis prevalence between studies may reflect differences in case definitions and diagnostic methods. In our study, half of women with a positive syphilis rapid test had low titres (≤1:4), but due to lack of clinical history, we could not distinguish between those with past-treated infections and those with active infection.
Women living with HIV had a 40% higher prevalence of curable STIs compared to those without HIV, consistent with findings from both high- and low-income countries.36,37 STIs increase HIV risk by disrupting mucosal barriers and promoting inflammation, 8 and women with HIV are more susceptible to other STIs. 38 Furthermore, overlapping demographic, socioeconomic, behavioural, and structural risk factors for HIV and other STIs have been reported in both high-and low-income countries.39–42 We observed a 125% higher prevalence of T. vaginalis among women with HIV, contributing to the elevated STI burden. Limited studies have reported associations between HIV infection and T. vaginalis among pregnant women in Brazil 43 and Uganda 39 and non-pregnant women in the United States 44 and Kenya. 45 A 2022 meta-analysis by Jarolimova et al. found a higher relative risk of T. vaginalis in women with HIV in sub-Saharan Africa, especially in antenatal care settings, with increasing risk over time. 36 Further research is needed to understand the epidemiological and clinical implications of HIV and T. vaginalis co-infection on reproductive and maternal-neonatal health.
We observed a high proportion (80%) of asymptomatic C. trachomatis, N. gonorrhoeae, and/or T. vaginalis cases, higher than previous reports from South Africa,10–13 Botswana, 27 and Kenya. 28 Variability in symptomatic case definitions and methods used for symptom screening between studies may explain observed differences in rates of asymptomatic cases. 46 Clinically-observed abnormal vaginal discharge was independently associated with higher prevalence of these STIs, but reported abnormal vaginal discharge was not, highlighting the importance of combining verbal report and provider-initiated screening. Additionally, most women who reported or had clinical signs of abnormal vaginal discharge were not diagnosed with an STI, underscoring the need for more accurate diagnostic approaches. Studies in South Africa, 47 Botswana, 48 and Papua New Guinea 49 have found point-of-care testing for curable STIs in antenatal care to be highly feasible and acceptable. Epidemiological research on the impact of diagnostic testing and treatment for curable STIs on adverse birth outcomes combined with cost-effectiveness and implementation science studies are needed to inform adoption, implementation, and maintenance of point-of-care testing within resource-constrained settings. The primary and secondary outcomes from the parent trial of this cross-sectional study will address these gaps. Data on syphilis-associated symptoms (i.e., chancre, maculopapular rash, condylomata lata) were not available for our study, which limited our ability to assess symptomology; however, standard care for antenatal syphilis screening in South Africa relies on diagnostic testing rather than symptom-based screening. 18
Nearly all women diagnosed with C. trachomatis, N. gonorrhoeae, or T. vaginalis received treatment, however only half were treated on the day of diagnosis, compared to 100% same-day treatment for syphilis. Similar moderate same-day treatment rates following point-of-care testing for STIs in antenatal care have been reported in South Africa. 50 These findings suggest that the 60–90-min turnaround time of current molecular tests presents barriers to timely treatment. Further implementation research is needed to identify these barriers and to inform test-and-treat strategies.
Younger age, lower education, unknown partner HIV serostatus, and multiple recent sex partners were strongly associated with STI diagnosis at the first antenatal care visit, consistent with previous studies.10,12,27,29,35 Variations in risk profiles by sexually transmitted organism suggest social determinants and behavioural factors may impact STI risk differently. However, these differences should be interpreted with caution. Small sample sizes when stratified by organism may have impacted our ability to detect meaningful associations. STI prevalence also varied by research site, with a 149% higher prevalence of syphilis at site 3, which is based in a rural settlement. This site also experienced a 39% higher prevalence of C. trachomatis and a 56% higher prevalence of T. vaginalis, although not statistically significant. These findings support the influence of hyperlocal epidemiological factors, such as household and neighbourhood characteristics and social networks, on STI transmission dynamics.51,52 Smaller communities, with a limited pool of sex partners and frequent sexual mixing, may experience increased STI risk. 53 HIV prevalence at site 3 (41%) was higher than the other sites, which also may contribute to elevated STI burden within this catchment population. Research from KwaZulu-Natal identified spatial clustering of high-risk sexual behaviours and overlapping HIV/STI prevalence in areas with shared risk factors. 54 These results highlight the need for comprehensive STI and HIV care that integrates individual and structural interventions and robust surveillance to tailor prevention strategies to community-specific needs.
Limitations
There are a few limitations to note. The cross-sectional design of our study restricts our ability to draw causal inferences between the identified risk factors and the prevalence of STIs. Further, the use of self-reported data for most participant characteristics and clinical history may have introduced recall or reporting bias. As previously discussed, we were unable to assess symptomology among syphilis cases due to lack of symptom-specific data captured in the parent study. Finally, our study was conducted in a specific geographic region within South Africa and only included women who were at least 18 years of age, less than 27 weeks’ gestation at their initial antenatal care visit, and who consented to participate in a clinical trial, which may limit the generalizability of the findings to other populations and settings with differing healthcare systems and demographics.
Conclusion
To our knowledge, this is the first study to report C. trachomatis, N. gonorrhoeae, T. vaginalis, and syphilis prevalence among pregnant women with and without HIV in the Eastern Cape, South Africa. STI prevalence was higher in women with HIV, emphasizing the need for integrated HIV and STI interventions, robust surveillance, and enhanced antenatal care. The high rate of asymptomatic infections and abnormal vaginal discharge in women without STIs highlight gaps in care. While point-of-care testing prevented most STI cases from going undetected and untreated, moderate same-day treatment rates suggest implementation challenges with turnaround times of current molecular tests. We recommend incorporating diagnostic tests, with optimized turnaround times, at point-of-care to enable timely, accurate treatment and reduce unnecessary antibiotic use. Further research on cost-effective and optimal implementation strategies for delivering timely results and treatment are critical, ultimately reducing transmission and improving maternal and neonatal outcomes.
Footnotes
Author note
A study of pregnant women in the Eastern Cape, South Africa found a high prevalence of curable STIs. Prevalence was higher among women living with HIV and most cases were asymptomatic.
Acknowledgements
We would like to acknowledge and thank the participants in our study and the Foundation for Professional Development staff in East London who worked on this study.
Declaration of conflicting interests
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
This study is funded by the U.S. National Institutes of Health (R01AI149339) to JDK and AMM. The funders had no role in study design; collection, management, analysis, and interpretation of data; writing of the report; nor the decision to submit the report for publication, and will not have ultimate authority over any of these activities.
Ethical statement
Data Availability Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.
