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Abstract
Objective STIs during pregnancy increase adverse pregnancy and birth outcomes and may increase HIV risk. STI syndromic management is standard of care in South Africa. Our study evaluated the prevalence and incidence of STIs in pregnant women and the associated risk factors.
Methods We combined data from two prospective observational studies of pregnant women enrolled while attending their first antenatal clinic (ANC) visit in Tshwane District and Cape Town. Women ≥18 years were tested at first ANC visit and at their first postpartum visit for Chlamydia trachomatis, Neisseria gonorrhoeae and Trichomonas vaginalis using Xpert assays (Cepheid, USA). We evaluated the prevalence and incidence of STI and the associated risk factors using multivariable regression models.
Results We enrolled 669 pregnant women, 64% (n=427) from Tshwane District and 36% (n=242) from Cape Town; 80% (n=534) were women living with HIV (WLHIV) and 20% (n=135) without HIV. At enrolment, 37% (n=250) were diagnosed with at least one STI, of which 76% (n=190) were asymptomatic. STI prevalence was 40% (n=213) in WLHIV and 27% (n=37) in women without HIV (p=0.01). Baseline STI infection was associated with younger age (OR=0.95 per year, 95% CI 0.92 to 0.98), higher gestational age (adjusted OR (aOR)=1.03 per week, 95% CI 1.00 to 1.05), single relationship status (aOR=1.53, 95% CI 1.09 to 2.15) and HIV status (aOR=1.86, 95% CI 1.17 to 2.95). Of 419 participants with no STI at baseline, 21 had an incident STI during follow-up, with a mean follow-up time of 140 days. The incidence rate of STI during pregnancy and early post partum was 15 infections per 100 women-years (95% CI 9 to 23). Younger age was associated with STI incidence.
Conclusion Our study shows high prevalence and incidence of STIs in pregnancy, especially in WLHIV, demonstrating the need for STI screening in ANC to prevent adverse pregnancy and birth outcomes. Most STI cases were asymptomatic and would have gone untreated with syndromic management. Aetiological STI screening is urgently needed to reduce the burden of STIs in pregnancy.
- Chlamydia trachomatis
- Neisseria gonorrhoeae
- Trichomonas
- HIV
- syndromic management
Data availability statement
Data are available upon reasonable request. Data may be obtained from a third party and are not publicly available. All data relevant to the study are included in the article or uploaded as supplementary information. Analyses were performed from data collected from women attending an antenatal care clinic. Data were maintained in a database using de-identified participant coding.
This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
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Introduction
STIs are among the most common health conditions in the world and remain a serious public health issue. Global estimates of the prevalence and incidence of curable STIs such as Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), Trichomonas vaginalis (TV) and syphilis remain high with approximately one million new infections each day.1 Global STI prevalence estimates have consistently remained high from 2012 (357 million) to 2016 (376 million).2 3 In Sub-Saharan Africa, data from studies of pregnant women using molecular, microbiological and culture methods showed high prevalence of curable STIs, ranging from 8% to 38%.4–7 STIs during pregnancy have been associated with several adverse pregnancy and birth outcomes, including stillbirth, prematurity, low birth weight and several secondary life-threatening conditions in surviving neonates.8–11 STIs can cause chronic abdominal pain, and when left untreated they can cause damage to reproductive organs, resulting in long-term complications such as tubal factor infertility.10 12
STIs have also been shown to increase the risk of HIV acquisition and transmission.13–15 Sub-Saharan Africa bears a heavy HIV burden, accounting for approximately 61% of all people living with HIV in 2018.16 South Africa has the largest number of people living with HIV globally, with 7.9 million people living with HIV in 2018.17 In 2017, the HIV prevalence among pregnant women attending antenatal care in South Africa was 30.8%.18 In pregnant women living with HIV (WLHIV), STI coinfection may increase the risk of vertical HIV transmission. However, successful scale-up of maternal antiretroviral treatment use in pregnancy has dramatically reduced infant HIV acquisition. Specifically, a recent study found that mothers with HIV and either CT and NG had a 3.5-fold increased risk of vertical HIV transmission.13 Recent studies conducted in South Africa have shown high prevalence of curable STIs among pregnant women, ranging from 32% to 40%.6 19 The dual burden of STIs and HIV remains a major threat to reproductive health in South Africa. Henceforth, the high prevalence of STIs in pregnant WLHIV justifies the need to introduce universal screening of STIs using definitive diagnostic tests in antenatal clinics (ANCs) and key populations.
Consistent with WHO guidelines, South Africa currently adheres to syndromic management and treatment of STIs.20–22 A major concern is that many asymptomatically infected individuals go without diagnosis and treatment.6 19 23 24 Moreover, vaginal discharge is common in pregnancy and will often occur even in the absence of an STI,25–27 leading to overtreatment. In addition, syndromic management approach is not appropriate for aetiological agent management since it offers treatment for a group of diseases.21 In this analysis, we evaluated the prevalence and incidence of STIs in pregnant women who received point-of-care STI screening during ANC visits and the percentage of pregnant women who had STI symptoms. We also evaluated the risk factors associated with having STI during pregnancy.
Methods
Study design and setting
We collated data from two observational prospective studies of pregnant women attending public sector ANCs in Tshwane District and Cape Town, South Africa. Study enrolment in Tshwane District occurred between June 2016 and October 2017, with the purpose of the study to determine the acceptability and feasibility of integrating point-of-care STI testing and same-day treatment into antenatal care services for pregnant WLHIV. The study setting, eligibility criteria, data collection, and specimen collection and testing have been described elsewhere.6 Study enrolment in Cape Town occurred between January 2018 and January 2019. The purpose of the study was to understand the prevalence and incidence of bacterial STIs among pregnant women. The study setting, eligibility criteria, data collection, and specimen collection and testing have been described elsewhere.23 Briefly, to be part of both studies, pregnant women had to be ≥18 years of age, attending their first ANC visit, with gestational age less than 35 weeks, confirmed HIV status and with intent to reside within the community for the duration of the pregnancy up to delivery. Women were screened, recruited and interviewed by trained study staff. Sociodemographic and clinical data were collected through interview-administered structured questionnaires and abstractions from clinical folders.
Specimen collection, testing and treatment
As previously described,6 23 women self-collected vulvovaginal swab specimens using Xpert CT/NG Vaginal/Endocervical Specimen Collection Kits (Cepheid, Sunnyvale, California). Specimens were tested for CT, NG and TV at first ANC visit and at the first visit within 1 month (4 weeks) post partum. Specimens were tested immediately, and women were given the results before leaving the clinic. Women with a positive STI test result were given treatment based on the Xpert result in accordance with South African national guidelines.21 CT infections were treated with 1 g azithromycin orally in front of a nurse, NG with an intramuscular injection of 250 mg ceftriaxone plus 1 g azithromycin orally (2 g azithromycin in case of significant penicillin allergy), and TV with 400 mg metronidazole orally every 12 hours for 7 days. As per the national STI guidelines, women were given counselling and were provided with condoms and partner notification/referral letter. The partner notification letter included the specific STI(s) that the participant was diagnosed with and a recommendation for partner treatment. At the following visit, participants were asked if they disclosed their STI status to partners and if partners took medications to treat the STI. In the Cape Town study, all pregnant women had a confirmed HIV test result at enrolment, and repeat HIV testing for women without HIV at every antenatal appointment and after delivery.
Data management
Study data were collected and managed using Research Electronic Data Capture (REDCap).28 All study data used a unique participant identifier allocated at study enrolment, and all electronic communications were done through password-protected, encrypted files.
Statistical analysis
Participant characteristics were compared using Wilcoxon test, χ2 test or Fisher’s exact test as appropriate. We evaluated the prevalence of STI at first ANC visit and factors associated using a logistic regression model. We estimated the incidence of any curable STI and factors associated with time to incident STI using Poisson regression model. For all models, exploratory analyses were performed using directed acyclic graphs for each analysis to consider a priori confounders to be included in multivariable models.29
All women participating in the two studies provided informed written consent for their own participation.
Results
We enrolled and followed 669 pregnant women at their first ANC visit: 427 (64%) women from Tshwane District (all WLHIV) and 242 (36%) from Cape Town (44% (n=107) WLHIV and 56% (n=135) women without HIV). The median age of participants was 30 years (IQR 25–34 years) and the median gestational age was 18 weeks (IQR 13–24 weeks) (table 1). Half of the women reported being married or cohabitating with partner and a third (34%) were formally employed. Almost all women (89%) reported having vaginal sex during pregnancy.
Baseline characteristics and prevalence of any STI and by STI type among pregnant women attending first antenatal visit in South Africa (2016–2019)
Prevalence of STI at first ANC visit
At baseline, 37% (n=250) of pregnant women in our study were diagnosed with at least one STI (95% CI, 33% to 41%; n=250) (table 1 and figure 1). The most common infection was CT (26%, n=175), followed by TV (18%, n=123) then NG (6%, n=38); 12% (n=79) of pregnant women had >1 STI infection. Women with curable STI coinfections were of younger age, with a median age of 27 years (IQR 23–33 years), compared with all women (median age 30 years, IQR 25–34 years), and more than 60% were not married or cohabitating with their partner. When stratified by HIV status, 40% (n=213) of WLHIV were diagnosed with at least one of CT, NG or TV vs 27% (n=37) in pregnant women living without HIV (p=0.01) (figure 1). CT monoinfection was the most common STI in both women living with HIV and living without HIV (15.3% vs 14.8%), followed by TV monoinfection higher in WLHIV (10.3% vs 5.9%) (figure 2). Coinfection of CT/NG occurred in 7.7% of WLHIV vs 4.4% in HIV-uninfected women; 3.2% of WLHIV had CT/NG coinfection vs 1.5% of HIV-uninfected women. Coinfection of NG and TV and infection with CT/NG/TV occurred only among WLHIV, with 1.3% and 1.1% of women, respectively (figure 2). Of the 175 women who had a positive CT infection at first ANC visit, 8.6% (n=15) were still infected with CT by follow-up visit. Of the 123 women who had a positive TV infection at first ANC visit, 10.5% (n=13) were still infected with TV by follow-up visit. Of the 38 women who had a positive NG infection at first ANC visit, 13.1% (n=5) were still infected with NG by follow-up visit (figure 1). A large proportion of participants (76%, n=190) had an asymptomatic infection (table 1). Among WLHIV, 76% (n=161) had asymptomatic STI infection compared with 70% (n=26) among women living without HIV. Asymptomatic STI infection did not vary by HIV status.
Prevalence and incidence of curable STIs in pregnant women screened at first antenatal clinic (ANC) visit in South Africa, 2016–2019 (n=669). Curable STIs include Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG) and Trichomonas vaginalis (TV).
STI prevalence by HIV status in pregnant women screened at first antenatal visit in South Africa, 2016–2019. Curable STIs include Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG) and Trichomonas vaginalis (TV).
Correlates of any STI infection at first antenatal visit
At baseline, STI infection was associated with younger age (OR=0.95 per year, 95% CI 0.92 to 0.98). In adjusted analyses, STI infection was associated with higher gestational age at first ANC visit (adjusted OR (aOR)=1.03 per week, 95% CI 1.00 to 1.05) and non-marital/cohabitating relationship (aOR=1.53, 95% CI 1.09 to 2.15). No relationship (aOR=2.64, 95% CI 1.18 to 5.87), HIV-positive status (aOR=1.86, 95% CI 1.1 to 2.95), reported concordant HIV-positive serostatus with partner (aOR=2.72, 95% CI 1.50 to 4.93) and unknown partner serostatus (aOR=1.67, 95% CI 1.00 to 2.82) were associated with STI infection at first ANC visit adjusting for other covariates (table 2). Reporting of symptoms at baseline was not associated with having STI.
Factors associated with STI prevalence at first ANC visit in pregnant women in South Africa (2016–2018)
Incidence of any STI from first ANC visit to the first postnatal visit
Of the 419 participants who were not infected with any STI at baseline, 21 women were diagnosed with an incident STI during a follow-up period of 1624 woman-months, with a median follow-up time of 140 days (IQR 98–168). The total incidence of any STI during pregnancy and early post partum was 15 infections per 100 women-years (95% CI 9 to 23). Of the 21 incident STIs, 81% were in WLHIV (n=17; 5% of WLHIV) and 19% in women without HIV (n=4; 4% of women without HIV) (figure 1). There was no difference in follow-up time among WLHIV, with a median follow-up time 140 days (IQR 98–175), from women without HIV, with a median follow-up time 140 days (IQR 98–168). The most common incident infection was CT (4%, n=17), followed by TV (1.2%, n=5) then NG (1%, n=2) (figure 3). TV and NG infections occurred only among WLHIV and 1% (n=3) of women had >1 STI infection during the follow-up period.
Monoinfection and multiple incident infections among 21 women with a positive STI during follow-up in South Africa, 2016–2017 (n=419).
Correlates of any incident STI from first ANC visit to the first postnatal visit
During the follow-up period, incident STI infection was associated with younger age (incidence rate ratio (IRR)=0.96, 95% CI 0.89 to 0.98) and having a once-off sexual partner (IRR 14.3, 95% CI 3.0 to 68.8) (table 3).
Factors associated with STI incidence in pregnant women in South Africa (2016–2018)
Discussion
Our study measured the prevalence and incidence of curable STIs (CT, NG and TV) in pregnant women living with and without HIV who were attending ANC care in community health centres in two health districts in South Africa. In this study, we identified high STI prevalence and incidence among WLHIV, but also relatively high prevalence among women living without HIV. Three-quarters of the women diagnosed with an STI were asymptomatic. The most common infection was CT, followed by TV; 12% of women were infected with more than one curable STI. Risk factors for having STI included younger age, increased gestational age when presenting at first ANC visit, HIV status and non-married/cohabitating relationship status.
The maternal STI prevalence of 37% in antenatal care is consistent with results found in several previous studies of pregnant women in Sub-Saharan Africa.4–6 19 23 30 When stratified by HIV status, 40% of WLHIV were diagnosed with at least one STI vs 27% in pregnant women living without HIV. This reflects either common risk behaviours that increase both HIV and STI acquisition risk, or increased risk of HIV acquisition due to genital tract infections.6 13–15 In light of adverse pregnancy, infant and HIV outcomes in women with STI,8 10 11 30 we advocate for the adoption of aetiological STI screening and treatment in antenatal care.6 23 25 Demonstrated and well documented in other studies, our findings re-emphasise that women of younger age and non-married/cohabitating relationship status had increased odds of an STI infection in pregnancy.6 13 19 23 We noted persistent STIs among 14.1% of WLHIV who had an STI at first ANC visit and 8.1% of women living without HIV who had an STI at first ANC. This could be attributable to treatment failure/poor adherence, risky sexual behaviours among the pregnant women or reinfection from sexual partners. Given that almost 90% of the pregnant women remained sexually active during their pregnancy, partner notification and partner treatment are critical to avoid reinfection. Although partner notification is an important component of STI management in the syndromic approach,22 future studies on different partner notification and partner treatment strategies are necessary to understand barriers to successful STI treatment during pregnancy.
The overall STI incidence was 15 infections per 100 women-years (95% CI 9 to 23), lower than the findings from a 2015 study in KwaZulu Natal of pregnant women living with and without HIV, with a high incidence rate of 43.8 per 100 person-years.19 The high STI incidence in KwaZulu Natal could be due to the study setting with a high-risk population. It could also be due to longer postpartum follow-up of 14 weeks postdelivery in the KwaZulu Natal study, where women had possibly resumed having unprotected sexual intercourse after delivery, vs 4 weeks in our study.19 However, both studies have findings of high proportions of STIs being asymptomatic consistent with other STI studies in South Africa.6 11 19 The current global STI control is hampered by a large proportion of asymptomatic infections, yet programmes in low-income and middle-income countries lack a feasible point-of-care diagnostic test for appropriate STI screening in STI and ANC health centres.6 11 20 23 Forthcoming studies need to investigate on the impact of STIs and STI treatment during pregnancy on adverse pregnancy and birth outcomes.
Our study had several strengths. We collated data from two sites to increase generalisability of our study findings. Although our study provides important evidence for the need to revise STI screening and treatment guidelines, it is not without limitations. Sexual behaviour data during pregnancy were self-reported, which may be biased by recall or social desirability bias, hence resulting in under-reporting of risky sexual behaviours. Lastly, our study had WLHIV over-represented relative to women without HIV; hence, our results should not be interpreted as being representative of pregnant women in general.
Conclusion
We found a high prevalence and incidence of CT, NG and TV in pregnant women followed up to the first postpartum visit. Prevalence was higher in pregnant WLHIV, demonstrating the need for appropriate STI screening and treatment to prevent mother to child vertical transmission of STIs and HIV. Risk factors for STIs during pregnancy included younger maternal age, increased gestational age, HIV status and being unmarried/not cohabitating. The majority of STI cases in our study were asymptomatic, providing compelling evidence to employ a rapid diagnostic test for STI screening during pregnancy in South Africa.
Key messages
Overall 37% of pregnant women at first antenatal clinic visit were diagnosed with Chlamydia trachomatis, Neisseria gonorrhoeae and/or Trichomonas vaginalis: 40% in HIV-positive women vs 27% in HIV-negative women.
The composite incidence during pregnancy and early post partum was 15 infections per 100 women-years.
Risk factors for STI diagnosis in pregnancy included younger age, higher gestational age at enrolment, single relationship and HIV status.
Three-quarters of women with STIs had no symptoms, providing compelling evidence for integrating aetiological STI screening into antenatal care in South Africa.
Supplemental material
Data availability statement
Data are available upon reasonable request. Data may be obtained from a third party and are not publicly available. All data relevant to the study are included in the article or uploaded as supplementary information. Analyses were performed from data collected from women attending an antenatal care clinic. Data were maintained in a database using de-identified participant coding.
Ethics statements
Ethics approval
Ethical approval was provided by the Institutional Review Boards at the University of Cape Town’s Faculty of Health Sciences Research Ethics Committee (UCT-HREC, reference number 454/2017), University of Pretoria’s Faculty of Health Sciences Research Ethics Committee (reference number 401/2015) and the University of California, Los Angeles (reference number 15-001351).
Acknowledgments
We would like to acknowledge the participants in our studies and the study staff in Tshwane and Gugulethu who worked on these studies.
References
Footnotes
Handling editor Katy M E Turner
Twitter @DorothyNyemba
Contributors DCN, DJD and LFJ collaborated in the writing of the manuscript. DJD, RP and AM-M designed and conducted the study and data collection. DCN performed the statistical analyses. DJD, LFJ, RP, AM-M, JK, LM and PN reviewed the manuscript before submission. DCN and DJD determined the hypotheses to be tested.
Funding The authors disclosed receipt of the following financial support for the research, authorship and/or publication of this article: The research has been supported by the Eunice Kennedy Shriver Institute of Child Health and Human Development (NICHD) of the National Institutes of Health (NIH) under award number R21HD084274-01A1 to AM-M and JK, and the President’s Emergency Plan for AIDS Relief (PEPFAR) through the US Agency for International Development under the terms of the Cooperative Agreement AID 674-A-12–00017 (AM-M and PN). DJD received funding from the National Institutes of Health and Fogarty International Center (K01TW011187). DJD and LM received funding from the National Institute of Mental Health (R01MH116771). The authors received a donation of STI Xpert assays from Cepheid (California, USA).
Competing interests The authors received a donation of STI Xpert assays from Cepheid (California, USA).
Provenance and peer review Not commissioned; externally peer reviewed.