Impact of intermittent preventive treatment of malaria in pregnancy with sulfadoxine-pyrimethamine on sexually transmitted and reproductive tract infections: results from a randomised trial in Uganda

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Abstract Background In sub-Saharan Africa, sexually transmitted and reproductive tract infections (STIs/RTIs) are important, but underdiagnosed risk factors for adverse pregnancy outcomes. Sulfadoxine-pyrimethamine (SP), used for intermittent preventive treatment of malaria in pregnancy (IPTp), may reduce STI/RTI burden due to its antibacterial activity. We assessed the impact of IPTp regimens on STI/RTI prevalence at delivery and associations between these infections and adverse birth outcomes. Methods We conducted a secondary analysis of a randomized controlled trial comparing monthly IPTp with SP, dihydroartemisinin-piperaquine (DP), or DP+SP among pregnant women in Uganda. Vaginal swabs collected at or near delivery were tested for Chlamydia trachomatis , Neisseria gonorrhoeae , Trichomonas vaginalis , and Group B Streptococcus (GBS) using GeneXpert; bacterial vaginosis was assessed using Nugent scoring. Log-binomial regression was used to compare STI/RTI prevalence by IPTp arm, using IPTp-DP as the reference arm. Multivariable Poisson regression with robust standard errors was used to evaluate associations between infections and preterm delivery, term low birthweight (LBW), overall LBW, and small-for-gestational age. Results Among the 2265 participants assessed, IPTp-SP reduced prevalence of C. trachomatis by 80% (2.5% vs. 12.4%; RR=0.20, 95% CI: 0.12-0.33) and of GBS by 35% (7.7% vs 11.7%; RR=0.65, 95% CI: 0.43-0.99) compared to IPTp-DP. C. trachomatis was associated with increased preterm delivery risk (RR=1.86, 95% CI: 1.07-3.25) and GBS was associated with increased term LBW risk (RR=2.08, 95% CI: 1.06-4.08). Conclusions Monthly IPTp-SP reduced the prevalence of C. trachomatis and GBS. These infections were associated with adverse birth outcomes, highlighting the potential non-malarial benefits of IPTp-SP. Key Messages In sub-Saharan Africa, management of sexually transmitted and reproductive tract infections (STIs/RTIs) relies on syndromic management, despite its high prevalence and potential risks associated with asymptomatic infections. Prior studies suggest that sulfadoxine-pyrimethamine (SP), the standard-of-care drug used for intermittent preventive treatment of malaria in pregnancy (IPTp), may exhibit activity certain STI/RTI pathogens, likely stemming from the sulfonamide component of the drug. Using data from a randomized trial comparing monthly IPTp regimens, we found IPTp-SP was associated with an 80% [95% CI: 67%-88%] reduction in Chlamydia trachomatis (2.5% versus 12.4%) and a 35% [95% CI: 1%-57%] reduction in Group B Streptococcus (7.7% vs. 11.7%) compared to IPTp-DP, an antimalarial with no known antibiotic activity. C. trachomatis was associated with an increased risk of preterm delivery (RR=1.86 [95% CI: 1.07-3.25]); Group B Streptococcus colonization was associated with an increased risk of term low birthweight (RR=2.08 [95% CI: 1.06-4.08]). IPTp-SP appears to offer benefits independent of malaria prevention through its effects on certain STI/RTIs pathogens, potentially contributing to a decrease in adverse birth outcomes. These findings are relevant as replacements to SP for IPTp are being considered.

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