Pyrimethamine 7.5mg/5ml oral suspension

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.

Abstract licence: Public domain

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.

Abstract licence: CC BY

This study aimed to evaluate the efficacy of DHP as an alternative to SP for the prevention of malaria and malaria-related complications during pregnancy. A systematic review and meta-analysis were conducted using pooled effect sizes extracted from published studies. Compared to SP, DHP significantly reduced maternal malaria infection by 78% (RR 0.22, 95% CI: 0.09-0.55), placental malaria infection by 73% (RR 0.27, 95% CI: 0.08-0.98), and maternal anaemia by 16% (RR = 0.84, 95% CI: 0.79-0.89). Women randomized to the DHP arm had a 28% lower risk of foetal loss (RR 0.72, 95% CI: 0.40-1.31), a 4% lower risk of low birth weight (RR 0.96, 95% CI: 0.69-1.32), and a 17% lower risk of preterm births compared with those receiving SP (RR 0.83, 95% CI: 0.61-1.13), though the reduction was not statistically significant. Therefore, DHP appears to be more effective than SP as IPTp therapy for reducing maternal malaria infection, placental malaria infection, and maternal anaemia. However, this study does not significant advantage of DHP over SP in reducing adverse birth outcomes.

Abstract licence: CC BY-NC-ND