Pyrimethamine 25mg / Sulfadoxine 500mg tablets

BackgroundResistance of Plasmodium falciparum to sulfadoxine-pyrimethamine threatens the antimalarial effectiveness of intermittent preventive treatment during pregnancy (IPTp) with sulfadoxine-pyrimethamine (ITPp-SP) in sub-Saharan Africa. We updated an aggregated-data meta-analysis to assess the associations between sulfadoxine-pyrimethamine resistance and the effectiveness of IPTp-SP to inform policy.MethodsWe searched databases (Jan 1, 1990, to June 8, 2024) for observational studies or trials reporting data on malaria, low birthweight (FindingsOverall, 122 studies involving 148 693 participants were included. For west and central Africa (69 studies comprising 63 745 participants), very low resistance was categorised as a prevalence of the dihydropteroate synthase (dhps) Lys540Glu mutation in the parasite population of less than 4%, and low resistance as a prevalence of Lys540Glu of 4% or higher. In east and southern Africa (53 studies comprising 84 948 participants), moderate resistance was categorised as a prevalence of the Lys540Glu mutation of less than 60% combined with a prevalence of the Ala581Gly mutation of less than 5%, high resistance as a prevalence of Lys540Glu of 60% or higher combined with a prevalence of Ala581Gly of less than 5%, and very high resistance as a prevalence of the Lys540Glu mutation of 60% or higher combined with a prevalence of Ala581Gly of 5% or higher. There was a marked trend towards lower efficacy of IPTp-SP on reducing malaria infection with increasing resistance levels. In west and central Africa, when comparing three versus two doses, the aRR was 0·71 (95% CI 0·65-0·78) in areas with very low resistance and 0·83 (0·72-0·95) in areas with low resistance (p=0·0144 for the difference between dose-response curves in very low vs low resistance). For east and southern Africa, the same trend was observed: the aRR was 0·63 (95% CI 0·57-0·69) in areas with moderate resistance, 0·89 (0·82-0·96) in areas with high resistance, and 0·93 (0·85-1·01) in areas with very high resistance (pInterpretationIPTp-SP antimalarial efficacy is greatly reduced in very high resistance areas. However, it remains effective at reducing low birthweight in these areas, possibly through non-malaria effects on fetal growth. While IPTp-SP use should continue in high SP-resistance areas, alternative malaria preventive strategies are urgently needed in these areas.FundingWHO and WorldWide-Antimalarial-Resistance-Network.

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Malaria remains a global health threat, with Plasmodium falciparum causing most deaths, especially in sub-Saharan Africa. Although artemisinin-based therapies reduce the burden, drug-resistant parasites threaten control efforts. Mapping the distribution and evolution of molecular resistance markers is vital for evidence-based strategies. This systematic review mapped the global distribution, pooled prevalence, and temporal trends of key P. falciparum antimalarial resistance markers. Following the PRISMA methodology (PROSPERO: CRD4202511098991), databases (PubMed, Web of Science, Scopus, and Google Scholar) and gray sources were searched (July 2005-July 2025). Data were extracted in Rayyan, assessed via the JBI prevalence tool, and analyzed using Python v3.13 for WHO regional distribution, temporal trends, and treatment outcome trends. Of the 1972 records, 261 studies from 64 countries qualified for inclusion in this review. The pooled prevalence was highest for pfdhfr (85.7%), followed by pfcrt (78.0%), pfdhps (73.7%), pfmdr1 (60.5%), and pfk13 (45.0%). High heterogeneity (I2 > 95%) and rising pfk13 since 2012 highlight emerging artemisinin resistance, while persistent pfdhfr/pfdhps mutations show that ongoing sulfadoxine-pyrimethamine (SP) pressure on P. falciparum drug resistance, decreased parasite clearance, and treatment failure remain widespread and evolving in Africa. Integrating molecular surveillance into national malaria programs is essential to guide treatment modalities and support progress toward malaria elimination.

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Summary Each year, over 50 million children receive preventive malaria treatment. However, to date there has been no consensus on the most effective antimalarial drugs to use, especially given geographic differences in drug resistance. Here, we conduct a systematic review comparing the effectiveness of the most commonly used antimalarial chemopreventive regimen, sulfadoxine-pyrimethamine plus amodiaquine (SP+AQ), with other antimalarial drugs in preventing new infections. We searched MEDLINE, Embase, Global Health, PubMed and WWARN clinical trial databases until 06 December 2025 for studies satisfying the inclusion criteria. Studies were included if they were peer-reviewed, randomised-controlled studies in Africa, measuring incidence of infection or clinical episodes of Plasmodium falciparum malaria for at least 28 days post-treatment. We also compiled data on the prevalence of markers of resistance in the parasite dhfr, dhps and mdr1 genes in the study areas. We conducted meta-analyses of incidence rates, with subgroup analyses by drug resistance levels. This review is registered on PROSPERO (CRD42024577149). We identified 27 studies representing 38,252 participants in 32 sites across 13 countries. In pooled analysis, SP+AQ reduced incidence of malaria by 54.6% (95% CI: 33.8–68.8%) compared to SP alone, including significantly outperforming SP even in areas with low SP resistance. These findings suggest that countries currently using SP alone for chemoprevention should consider switching to SP+AQ. Where AQ resistance remains low, available evidence suggests SP+AQ remains efficacious for malaria chemoprevention. SP+AQ was comparable to the artemisinin-based treatment, dihydroartemisinin-piperaquine across all studies (incidence rate ratio 0.93; 95% CI 0.78- 1.11). By resistance levels, SP+AQ had slightly higher efficacy in areas with low SP and AQ resistance but had comparable or slightly lower efficacy in areas with higher resistance. Using artemisinin-based treatments for chemoprevention must be balanced against the risk of worsening artemisinin resistance in Eastern and Southern Africa. This study was funded by the UK Royal Society.

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BackgroundTo mitigate adverse consequences of malaria in pregnancy, the World Health Organization recommends intermittent preventive treatment of malaria in pregnancy (IPTp) with sulfadoxine-pyrimethamine. However, the effectiveness of IPTp with sulfadoxine-pyrimethamine has been threatened by widespread Plasmodium falciparum resistance, especially in East and Southern Africa. For IPTp, dihydroartemisinin-piperaquine has shown superior antimalarial effects compared to sulfadoxine-pyrimethamine, but sulfadoxine-pyrimethamine has been associated with improved birth outcomes compared to dihydroartemisinin-piperaquine. We hypothesized that a combination of both dihydroartemisinin-piperaquine and sulfadoxine-pyrimethamine would provide superior birth outcomes compared to either drug alone.Methods and findingsWe conducted a double-blinded, randomized, controlled trial of 2,757 pregnant women in Uganda, where resistance of malaria parasites to sulfadoxine-pyrimethamine is widespread. Women were randomly assigned (1:1:1) to monthly IPTp with sulfadoxine-pyrimethamine, dihydroartemisinin-piperaquine, or dihydroartemisinin-piperaquine plus sulfadoxine-pyrimethamine. The primary outcome was the risk of a composite adverse birth outcome defined as any of the following: spontaneous abortion, stillbirth, low birthweight (LBW, ConclusionsDespite the superior antimalarial activity of dihydroartemisinin-piperaquine, sulfadoxine-pyrimethamine alone was associated with improved birth outcomes. Combining dihydroartemisinin-piperaquine plus sulfadoxine-pyrimethamine for IPTp did not improve birth outcomes compared to either sulfadoxine-pyrimethamine or dihydroartemisinin-piperaquine alone.Trial registrationClinicalTrials.gov (NCT04336189; https://clinicaltrials.gov/study/NCT04336189).

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BackgroundIn 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 the intermittent preventive treatment of malaria in pregnancy (IPTp), may reduce the STI/RTI burden due to its antimicrobial activity. We assessed the impact of IPTp regimens on STI/RTI prevalence and evaluated associations between STIs/RTIs and adverse birth outcomes.MethodsWe 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) by using GeneXpert; bacterial vaginosis was assessed by using Nugent scoring. Log-binomial regression was used to compare STI/RTI prevalence between IPTp arms; IPTp-DP served 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.ResultsAmong the 2265 participants assessed, the IPTp-SP arm had an 80% [95% confidence interval (CI): 67%-88%] lower prevalence of C. trachomatis (2.5% vs 12.4%) and a 35% (95% CI: 1%-57%) lower prevalence of GBS (7.7% vs 11.7%) at delivery compared with the IPTp-DP arm. Chlamydia trachomatis was associated with increased preterm delivery [prevalence ratio (PR) = 1.86, 95% CI: 1.07-3.25] and GBS was associated with increased term LBW (PR = 2.08, 95% CI: 1.06-4.08).ConclusionMonthly IPTp-SP may reduce the risk of adverse birth outcomes through its activity against C. trachomatis and GBS, highlighting its potential non-malarial benefits.

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ABSTRACT Background To mitigate adverse consequences of malaria in pregnancy, the World Health Organization recommends intermittent preventive treatment (IPTp) with sulfadoxine-pyrimethamine. However, the effectiveness of IPTp with sulfadoxine-pyrimethamine has been threatened by widespread P. falciparum resistance, especially in East and southern Africa. For IPTp, dihydroartemisinin-piperaquine has shown superior antimalarial effects compared to sulfadoxine-pyrimethamine, but sulfadoxine-pyrimethamine has been associated with improved birth outcomes. We hypothesized that a combination of both dihydroartemisinin-piperaquine and sulfadoxine-pyrimethamine would provide superior birth outcomes compared to either drug alone. Methods and Findings We conducted a double-blinded, randomized, controlled trial of 2757 pregnant women in Uganda, where resistance of malaria parasites to sulfadoxine-pyrimethamine is widespread. Women were randomly assigned (1:1:1) to monthly IPTp with sulfadoxine-pyrimethamine, dihydroartemisinin- piperaquine, or dihydroartemisinin-piperaquine plus sulfadoxine-pyrimethamine. The primary outcome was the risk of a composite adverse birth outcome defined as any of the following: spontaneous abortion, stillbirth, low birthweight (LBW, Conclusions Despite the superior antimalarial activity of dihydroartemisinin-piperaquine, sulfadoxine-pyrimethamine was associated with improved birth outcomes. Combining dihydroartemisinin- piperaquine plus sulfadoxine-pyrimethamine for IPTp did not improve birth outcomes compared to either sulfadoxine-pyrimethamine or dihydroartemisinin-piperaquine alone. Funding National Institute of Allergy and Infectious Diseases, National Institutes of Health (U01AI141308). Trial registration ClinicalTrials.gov ( NCT04336189 )

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