{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T21:47:11Z","timestamp":1793742431708,"version":"4.6.1"},"reference-count":29,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T00:00:00Z","timestamp":1770336000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Rwanda, European Union-Team Europe Initiative-MAV+, and Access to Quality Vaccines, Medicines and Health Technologies","award":["RWA2100111"],"award-info":[{"award-number":["RWA2100111"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>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\u2013July 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 &gt; 95%) and rising pfk13 since 2012 highlight emerging artemisinin resistance, while persistent pfdhfr\/pfdhps mutations show that ongoing sulfadoxine\u2013pyrimethamine (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.<\/jats:p>","DOI":"10.3390\/pathogens15020179","type":"journal-article","created":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T11:10:38Z","timestamp":1770376238000},"page":"179","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["The Global Landscape of Plasmodium falciparum Drug Resistance Markers, 2005\u20132025: A Systematic Review and Meta-Analysis"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-4664-4408","authenticated-orcid":false,"given":"Felix","family":"Habarugira","sequence":"first","affiliation":[{"name":"Department of Biomedical Laboratory Sciences, School of Health Sciences, College of Medicine and Health Sciences, University of Rwanda, Kigali P.O. Box 3286, Rwanda"},{"name":"Pathology Department, Research Directorate, University Teaching Hospital of Butare, Huye P.O. Box 254, Rwanda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeanne","family":"Batamuriza","sequence":"additional","affiliation":[{"name":"Department of Biomedical Laboratory Sciences, School of Health Sciences, College of Medicine and Health Sciences, University of Rwanda, Kigali P.O. Box 3286, Rwanda"},{"name":"Pathology Department, Research Directorate, University Teaching Hospital of Butare, Huye P.O. Box 254, Rwanda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-0066-1826","authenticated-orcid":false,"given":"Raphael","family":"Ndahimana","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Parasitology, School of Medicine and Pharmacy, College of Medicine and Health Sciences, University of Rwanda, Huye P.O. Box 3286, Rwanda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1705-2099","authenticated-orcid":false,"given":"Jules Ndoli","family":"Minega","sequence":"additional","affiliation":[{"name":"Pathology Department, Research Directorate, University Teaching Hospital of Butare, Huye P.O. Box 254, Rwanda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3573-6697","authenticated-orcid":false,"given":"Mame Massar","family":"Dieng","sequence":"additional","affiliation":[{"name":"Program in Biology, Division of Sciences and Mathematics, New York University Abu Dhabi, Abu Dhabi P.O. Box 129188, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0868-1173","authenticated-orcid":false,"given":"Masceline Jenipher","family":"Mutsaka-Makuvaza","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Parasitology, School of Medicine and Pharmacy, College of Medicine and Health Sciences, University of Rwanda, Huye P.O. Box 3286, Rwanda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2520-8233","authenticated-orcid":false,"given":"Tolessa Muleta","family":"Daba","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Molecular Biology and Genetics, School of Medicine and Pharmacy, College of Medicine and Health Sciences, University of Rwanda, Huye P.O. Box 3286, Rwanda"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2768-9376","authenticated-orcid":false,"given":"Youssef","family":"Idaghdour","sequence":"additional","affiliation":[{"name":"Program in Biology, Division of Sciences and Mathematics, New York University Abu Dhabi, Abu Dhabi P.O. Box 129188, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5308-3706","authenticated-orcid":false,"given":"Leon","family":"Mutesa","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Molecular Biology and Genetics, School of Medicine and Pharmacy, College of Medicine and Health Sciences, University of Rwanda, Huye P.O. Box 3286, Rwanda"},{"name":"Centre for Human Genetics, University of Rwanda, Kigali P.O. Box 4285, Rwanda"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,6]]},"reference":[{"key":"ref_1","unstructured":"(2025, October 17). World Malaria Report 2024. Available online: https:\/\/www.who.int\/teams\/global-malaria-programme\/reports\/world-malaria-report-2024."},{"key":"ref_2","unstructured":"(2026, January 29). Malaria Caused by Plasmodium Falciparum|StatPearls|Treatment & Management. Available online: https:\/\/www.statpearls.com\/point-of-care\/search?q=Malaria+caused+by+Plasmodium+falciparum."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1007\/s44197-024-00228-2","article-title":"Current Status of Malaria Control and Elimination in Africa: Epidemiology, Diagnosis, Treatment, Progress and Challenges","volume":"14","author":"Li","year":"2024","journal-title":"J. Epidemiol. Glob. Health"},{"key":"ref_4","unstructured":"(2025, October 17). CDC Drug Resistance in the Malaria-Endemic World, Available online: https:\/\/www.cdc.gov\/malaria\/php\/public-health-strategy\/drug-resistance.html."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"a025619","DOI":"10.1101\/cshperspect.a025619","article-title":"Antimalarial Drug Resistance: A Threat to Malaria Elimination","volume":"7","author":"Menard","year":"2017","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1016\/S1473-3099(19)30392-5","article-title":"Evolution and Expansion of Multidrug-Resistant Malaria in Southeast Asia: A Genomic Epidemiology Study","volume":"19","author":"Hamilton","year":"2019","journal-title":"Lancet Infect. Dis."},{"key":"ref_7","unstructured":"(2026, January 29). Sequence and Gene Expression of Chloroquine Resistance Transporter (Pfcrt) in the Association of In Vitro Drugs Resistance of Plasmodium Falciparum\u2014PMC, Available online: https:\/\/pmc.ncbi.nlm.nih.gov\/articles\/PMC3055224\/."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1186\/s12936-025-05423-5","article-title":"Prevalence of Plasmodium Falciparum Plasmepsin2\/3 Gene Duplication in Africa and Asia: A Systematic Review and Meta-Analysis","volume":"24","author":"Marwa","year":"2025","journal-title":"Malar. J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.ijpddr.2020.10.009","article-title":"Evidence for Linkage of Pfmdr1, Pfcrt, and Pfk13 Polymorphisms to Lumefantrine and Mefloquine Susceptibilities in a Plasmodium Falciparum Cross","volume":"14","author":"Windle","year":"2020","journal-title":"Int. J. Parasitol. Drugs Drug Resist."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e209","DOI":"10.1016\/S2666-5247(20)30094-X","article-title":"Molecular Surveillance of Antimalarial Partner Drug Resistance in Sub-Saharan Africa: A Spatial-Temporal Evidence Mapping Study","volume":"1","author":"Ehrlich","year":"2020","journal-title":"Lancet Microbe"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1111\/nyas.12766","article-title":"Antimalarial Drug Resistance in Africa: Key Lessons for the Future","volume":"1342","author":"Laufer","year":"2015","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e0129923","DOI":"10.1128\/aac.01299-23","article-title":"Escalating Plasmodium falciparum K13 Marker Prevalence Indicative of Artemisinin Resistance in Southern Rwanda","volume":"68","author":"Schallenberg","year":"2024","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_13","unstructured":"(2025, October 17). The Emergence of Artemisinin Partial Resistance in Africa: How Do We Respond?\u2014The Lancet Infectious Diseases. Available online: https:\/\/www.thelancet.com\/journals\/laninf\/article\/PIIS1473-3099(24)00141-5\/fulltext."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1120","DOI":"10.1016\/S1473-3099(21)00142-0","article-title":"Association of Plasmodium Falciparum Kelch13 R561H Genotypes with Delayed Parasite Clearance in Rwanda: An Open-Label, Single-Arm, Multicentre, Therapeutic Efficacy Study","volume":"21","author":"Uwimana","year":"2021","journal-title":"Lancet Infect. Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 Statement: An Updated Guideline for Reporting Systematic Reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"(2025, August 10). Publish or Perish. Available online: https:\/\/jadpro.com\/issues\/volume-12-number-5-july-2021\/publish-or-perish\/.","DOI":"10.6004\/jadpro.2021.12.5.1"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"204","DOI":"10.4103\/sja.sja_632_21","article-title":"Publish or Perish, Information Overload, and Journal Impact Factors\u2014A Conflicting Tripod of Forces","volume":"16","author":"Grech","year":"2022","journal-title":"Saudi J. Anaesth."},{"key":"ref_18","unstructured":"(2025, November 03). How Do I Bulk Export the First 200 Results from Google Scholar?\u2014McGill Library FAQs. Available online: https:\/\/mcgill.libanswers.com\/citation\/faq\/212263."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1186\/s13643-016-0384-4","article-title":"Rayyan\u2014A Web and Mobile App for Systematic Reviews","volume":"5","author":"Ouzzani","year":"2016","journal-title":"Syst. Rev."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"20","DOI":"10.4103\/picr.PICR_55_21","article-title":"Evaluation of Medical Adherence, Adverse Drug Reactions, and Quality of Life in Post Tubercular Obstructive Airway Disease","volume":"14","author":"Awasthi","year":"2023","journal-title":"Perspect. Clin. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1186\/1475-2875-10-116","article-title":"Patterns of Chloroquine Use and Resistance in Sub-Saharan Africa: A Systematic Review of Household Survey and Molecular Data","volume":"10","author":"Frosch","year":"2011","journal-title":"Malar. J."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"25376","DOI":"10.1038\/s41598-025-10500-5","article-title":"Tracking Plasmodium Falciparum Antimalarial Resistance Markers during a Malaria Pre-Elimination Period in the Pacific Coast of South America","volume":"15","author":"Early","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Fankem, S.N., Mbonimpa, J.-B., Kalimba, E.M., Diallo, M.T., Teke, M.E., and Souopgui, J. (2025). Genomic Surveillance of Plasmodium Falciparum Drug Resistance Markers Between October 2021 and June 2023 in Kigali, Rwanda. Pathogens, 14.","DOI":"10.3390\/pathogens14111092"},{"key":"ref_24","unstructured":"(2025, November 04). Prevalence of Molecular Markers of Sulfadoxine-Pyrimethamine Resistance in Plasmodium Falciparum Isolates from West Africa During 2012\u20132022|Scientific Reports. Available online: https:\/\/www.nature.com\/articles\/s41598-024-75828-w."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1186\/s12936-020-03454-8","article-title":"Changes in the Frequencies of Plasmodium Falciparum Dhps and Dhfr Drug-Resistant Mutations in Children from Western Kenya from 2005 to 2018: The Rise of Pfdhps S436H","volume":"19","author":"Pacheco","year":"2020","journal-title":"Malar. J."},{"key":"ref_26","unstructured":"(2025, November 04). World Malaria Report 2022. Available online: https:\/\/www.who.int\/teams\/global-malaria-programme\/reports\/world-malaria-report-2022."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"11672","DOI":"10.1073\/pnas.1507142112","article-title":"Adaptive Evolution of Malaria Parasites in French Guiana: Reversal of Chloroquine Resistance by Acquisition of a Mutation in Pfcrt","volume":"112","author":"Pelleau","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1038\/nature12876","article-title":"A Molecular Marker of Artemisinin-Resistant Plasmodium Falciparum Malaria","volume":"505","author":"Ariey","year":"2014","journal-title":"Nature"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1186\/s12936-024-05024-8","article-title":"Two Decades of Molecular Surveillance in Senegal Reveal Rapid Changes in Known Drug Resistance Mutations over Time","volume":"23","author":"Ndiaye","year":"2024","journal-title":"Malar. J."}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/15\/2\/179\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T11:32:27Z","timestamp":1770377547000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/15\/2\/179"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,6]]},"references-count":29,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,2]]}},"alternative-id":["pathogens15020179"],"URL":"https:\/\/doi.org\/10.3390\/pathogens15020179","relation":{},"ISSN":["2076-0817"],"issn-type":[{"value":"2076-0817","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,6]]}}}