{"doi":"10.1101/2025.07.02.25330769","title":"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","abstract":"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.","journal":"medRxiv","year":2025,"id":569692,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9531,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1475184,"name":"Elio Cruz","orcid":null,"position":1,"is_corresponding":false},{"id":305910,"name":"Nida Özarslan","orcid":"0000-0003-3235-1238","position":2,"is_corresponding":false},{"id":367278,"name":"Abel Kakuru","orcid":"0000-0001-9941-1309","position":3,"is_corresponding":false},{"id":1475185,"name":"Bakar Odongo","orcid":null,"position":4,"is_corresponding":false},{"id":273919,"name":"Stephanie L. Gaw","orcid":"0000-0003-0891-6964","position":5,"is_corresponding":false},{"id":328647,"name":"Jade Benjamin‐Chung","orcid":"0000-0003-3631-3132","position":6,"is_corresponding":false},{"id":1087437,"name":"Jimmy Kizza","orcid":"0000-0003-0224-4044","position":7,"is_corresponding":false},{"id":1278815,"name":"Miriam Aguti","orcid":"0009-0005-8885-6931","position":8,"is_corresponding":false},{"id":455323,"name":"John Ategeka","orcid":"0000-0002-6604-2532","position":9,"is_corresponding":false},{"id":621664,"name":"Peter Olwoch","orcid":"0000-0002-7396-3348","position":10,"is_corresponding":false},{"id":455380,"name":"Miriam Nakalembe","orcid":"0000-0001-7569-8173","position":11,"is_corresponding":false},{"id":455961,"name":"Bishop Opira","orcid":null,"position":12,"is_corresponding":false},{"id":255292,"name":"Tamara D. Clark","orcid":"0000-0003-1109-6039","position":13,"is_corresponding":false},{"id":242453,"name":"Moses R. Kamya","orcid":"0000-0001-9106-4234","position":14,"is_corresponding":false},{"id":242457,"name":"Philip J. Rosenthal","orcid":"0000-0002-7953-7622","position":15,"is_corresponding":false},{"id":242454,"name":"Grant Dorsey","orcid":"0000-0003-0740-0317","position":16,"is_corresponding":false},{"id":729900,"name":"Michelle E. Roh","orcid":"0000-0002-6268-0801","position":17,"is_corresponding":false},{"id":1004134,"name":"Harriet Adrama","orcid":null,"position":0,"is_corresponding":true}],"reference_count":35,"raw_metadata":null,"created_at":"2026-07-19T02:57:03.510013Z","pmid":"40630588","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}