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

  1. Harriet Adrama
  2. Erin J. Dela Cruz
  3. Nida Ozarslan
  4. Abel Kakuru
  5. Bakar Odongo
  6. Stephanie L. Gaw
  7. Jade Benjamin-Chung
  8. Jimmy Kizza
  9. Miriam Aguti
  10. John Ategeka
  11. Peter Olwoch
  12. Miriam Nakalembe
  13. Bishop Opira
  14. Tamara D. Clark
  15. Moses R. Kamya
  16. Philip J. Rosenthal
  17. Grant Dorsey
  18. Michelle E. Roh
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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.

Article activity feed

  1. Version published to 10.1101/2025.07.02.25330769 on medRxiv