Sexually transmitted infection screening to prevent adverse birth and newborn outcomes: study protocol for a randomized-controlled hybrid-effectiveness trial

Andrew Medina-Marino, Susan Cleary, Christina A Muzny, Christopher Taylor, Ashutosh Tamhane, Phuti Ngwepe, Charl Bezuidenhout, Shelley N Facente, Koleka Mlisana, Remco P H Peters, Jeffrey D Klausner, Andrew Medina-Marino, Susan Cleary, Christina A Muzny, Christopher Taylor, Ashutosh Tamhane, Phuti Ngwepe, Charl Bezuidenhout, Shelley N Facente, Koleka Mlisana, Remco P H Peters, Jeffrey D Klausner

Abstract

Background: Sexually transmitted infections (STIs) during pregnancy are associated with adverse birth outcomes, including preterm birth, low birth weight, perinatal death, and congenital infections such as increased mother-to-child HIV transmission. Prevalence of STIs among pregnant women in South Africa remains high, with most women being asymptomatic for their infection(s). Unfortunately, most STIs remain undetected and untreated due to standard practice syndromic management in accordance with World Health Organization (WHO) guidelines. Although lab-based and point-of-care molecular tests are available, optimal screening strategies during pregnancy, their health impact, and cost-effectiveness are unknown.

Methods: We will implement a 3-arm (1:1:1) type-1 hybrid effectiveness-implementation randomized-controlled trial (RCT). We will enroll 2500 pregnant women attending their first antenatal care (ANC) visit for their current pregnancy at participating health facilities in Buffalo City Metro District, Eastern Cape Province, South Africa. Participants allocated to arms 1 and 2 (intervention) will receive GeneXpert® point-of-care diagnostic testing for Neisseria gonorrhoeae, Chlamydia trachomatis, and Trichomonas vaginalis, with same-day treatment for detected infection(s). Arm 1 will additionally receive a test-of-cure 3 weeks post-treatment, while Arm 2 will receive a repeat test at 30-34 weeks' gestation. Those allocated to Arm 3 will receive syndromic management (standard-of-care). The RE-AIM framework will be used to guide collection of implementation indicators to inform potential future scale up. Primary outcome measures include (1) frequency of adverse birth outcomes among study arms, defined by a composite measure of low birth weight and pre-term delivery, and (2) change in STI prevalence between baseline and birth outcome among intervention arms and compared to standard-of-care. Estimates and comparative costs of the different screening strategies relative to standard-of-care and the costs of managing adverse birth outcomes will be calculated. Cost-effectiveness will be assessed per STI and disability-adjusted life year averted.

Discussion: This trial is the first RCT designed to identify optimal, cost-effective screening strategies that decrease the burden of STIs during pregnancy and reduce adverse birth outcomes. Demonstrating the impact of diagnostic screening and treatment, compared to syndromic management, on birth outcomes will provide critical evidence to inform changes to WHO guidelines for syndromic management of STIs during pregnancy.

Trial registration: ClinicalTrials.gov NCT04446611 . Registered on 25 June 2020.

Keywords: Antenatal care; Cost-effectiveness; Low birth weight; Preterm birth; STI screening; STIs; Pregnancy; Sexually transmitted infections; Syndromic management.

Conflict of interest statement

Co-author CAM is part of the Cepheid speakers’ bureau for topics regarding vaginal infections and sexually transmitted infections. She is also a consultant for the Centers for Diseases Control and Prevention, Lupin Pharmaceuticals, Abbott Molecular, BioMed Diagnostics, Cepheid, and PhagoMed. She has received research funding support from Lupin Pharmaceuticals, Gilead, and Abbott Molecular and speaker honoraria from Abbott Molecular, Cepheid, Roche Diagnostics, and Becton Dickinson. Co-author JDK has, in the past 12 months, received consulting fees from Abbott, Cepheid, Curative, Danaher, Roche, Talis Bio, and Visby Medical. The other authors declare no competing interests.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Participant recruitment and enrollment flow
Fig. 2
Fig. 2
Birth outcomes
Fig. 3
Fig. 3
Specimen collection and tests performed at each study time point. *Post-delivery vaginal and NP swabs will be batch tested using Xpert® CT/NG and Xpert® TV assays at the end of the study

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