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-tochild
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. Costeffectiveness
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 NCT04 446611. Registered on 25 June 2020.
