The Global Landscape of Plasmodium falciparum Drug Resistance Markers, 2005-2025: A Systematic Review and...

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.