{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T22:03:10Z","timestamp":1790632990936,"version":"4.1.0"},"reference-count":51,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,3,29]],"date-time":"2025-03-29T00:00:00Z","timestamp":1743206400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Jouf University","award":["Fast Track"],"award-info":[{"award-number":["Fast Track"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["TropicalMed"],"abstract":"<jats:p>Malaria has been and remains a significant challenge in Africa and other endemic settings. Roughly, 95% of global morbidity and mortality due to malaria occurs within African populations and affects millions of individuals, especially those living in sub-Saharan countries, predominantly due to disease complications. Cultural factors such as unawareness of and disinterest in using recommended preventive tools and combating the primary host (i.e., the female Anopheles mosquito) play a significant role. This host transmits the malaria-causing Plasmodium parasite by biting an infected individual and spreading it to humans. The current overview focuses on the molecular markers associated with antimalarial drug resistance in Plasmodium falciparum (P. falciparum) in Rwanda, considered an exemplar of sub-Saharan countries where malaria is prevalent and effective policies on the development of malaria treatment, approved recently by WHO in 2025, have been adopted. The prevalence of mutations in key resistance genes, including pfcrt, pfmdr1, and pfdhfr\/pfdhps, are linked to resistance against common antimalarial drugs such as chloroquine and sulfadoxine-pyrimethamine (SP). In addition, the Plasmodium falciparum kelch13 (pfk13) gene is linked to resistance against artemisinin, as its mutations can cause delayed parasite clearance and treatment failure. Despite changes in therapeutic use policies owing to high prevalence of variant alleles, which reduce the drug\u2019s efficacy resistance to SP, the gene persists in Rwanda. Malaria parasites are becoming more resistant to chloroquine, leading to diminished effectiveness and slower recovery or treatment failure. Surveillance data reported from several studies provide crucial insights into the evolving trends of resistance markers and are vital for guiding treatment protocols and informing therapeutic use policy decisions. It is important that we continue to maintain and develop the effectiveness of malaria prevention strategies and treatments, due to the multiple types of resistance found in the population.<\/jats:p>","DOI":"10.3390\/tropicalmed10040089","type":"journal-article","created":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T04:21:01Z","timestamp":1743481261000},"page":"89","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["A Narrative Review on the Prevalence of Plasmodium falciparum Resistance Mutations to Antimalarial Drugs in Rwanda"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-7858-8288","authenticated-orcid":false,"given":"Muharib","family":"Alruwaili","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Sakaka 72388, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6219-5312","authenticated-orcid":false,"given":"Abozer","family":"Elderdery","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Sakaka 72388, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emad","family":"Manni","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Sakaka 72388, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1719-9047","authenticated-orcid":false,"given":"Jeremy","family":"Mills","sequence":"additional","affiliation":[{"name":"School of Medicine, Pharmacy and Biomedical Sciences, University of Portsmouth, Portsmouth PO1 2DT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Venkatesan, P. (2025). WHO world malaria report 2024. Lancet Microbe, 101073.","DOI":"10.1016\/j.lanmic.2025.101073"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1016\/j.cell.2016.07.055","article-title":"Malaria: Biology and Disease","volume":"167","author":"Cowman","year":"2016","journal-title":"Cell"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1016\/S1097-2765(05)00077-8","article-title":"Mutations in the P. falciparum digestive vacuole transmembrane protein PfCRT and evidence for their role in chloroquine resistance","volume":"6","author":"Fidock","year":"2000","journal-title":"Mol. Cell"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"9109","DOI":"10.1073\/pnas.85.23.9109","article-title":"Amino acid changes linked to pyrimethamine resistance in the dihydrofolate reductase-thymidylate synthase gene of Plasmodium falciparum","volume":"85","author":"Cowman","year":"1988","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1054\/drup.1998.0060","article-title":"The mechanism of resistance to sulfa drugs in Plasmodium falciparum","volume":"2","author":"Triglia","year":"1999","journal-title":"Drug Resist. Updates"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Pulcini, S., Staines, H.M., Lee, A.H., Shafik, S.H., Bouyer, G., Moore, C.M., Daley, D.A., Hoke, M.J., Altenhofen, L.M., and Painter, H.J. (2015). Mutations in the Plasmodium falciparum chloroquine resistance transporter, PfCRT, enlarge the parasite\u2019s food vacuole and alter drug sensitivities. Sci. Rep., 5.","DOI":"10.1038\/srep14552"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"4935","DOI":"10.1111\/febs.16378","article-title":"Plasmodium falciparum Kelch13 and its artemisinin-resistant mutants assemble as hexamers in solution: A SAXS data-driven modelling study","volume":"289","author":"Goel","year":"2022","journal-title":"FEBS J."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.actatropica.2011.07.003","article-title":"Molecular analysis of pfatp6 and pfmdr1 polymorphisms and their association with in vitro sensitivity in Plasmodium falciparum isolates from the Thai-Myanmar border","volume":"120","author":"Phompradit","year":"2011","journal-title":"Acta Trop."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1186\/s12936-019-2947-z","article-title":"Rare mutations in Pfmdr1 gene of Plasmodium falciparum detected in clinical isolates from patients treated with anti-malarial drug in Nigeria","volume":"18","author":"Idowu","year":"2019","journal-title":"Malar. J."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Eyase, F.L., Akala, H.M., Ingasia, L., Cheruiyot, A., Omondi, A., Okudo, C., Juma, D., Yeda, R., Andagalu, B., and Wanja, E. (2013). The role of Pfmdr1 and Pfcrt in changing chloroquine, amodiaquine, mefloquine and lumefantrine susceptibility in western-Kenya P. falciparum samples during 2008\u20132011. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0064299"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/S0166-6851(00)00201-2","article-title":"The tyrosine-86 allele of the pfmdr1 gene of Plasmodium falciparum is associated with increased sensitivity to the anti-malarials mefloquine and artemisinin","volume":"108","author":"Duraisingh","year":"2000","journal-title":"Mol. Biochem. Parasitol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1126\/science.1074045","article-title":"Chloroquine resistance in Plasmodium falciparum malaria parasites conferred by pfcrt mutations","volume":"298","author":"Sidhu","year":"2002","journal-title":"Science"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1186\/s12936-016-1287-5","article-title":"Malaria case clinical profiles and Plasmodium falciparum parasite genetic diversity: A cross sectional survey at two sites of different malaria transmission intensities in Rwanda","volume":"15","author":"Kateera","year":"2016","journal-title":"Malar. J."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.actatropica.2016.09.008","article-title":"Molecular surveillance of Plasmodium falciparum drug resistance markers reveals partial recovery of chloroquine susceptibility but sustained sulfadoxine-pyrimethamine resistance at two sites of different malaria transmission intensities in Rwanda","volume":"164","author":"Kateera","year":"2016","journal-title":"Acta Trop."},{"key":"ref_15","unstructured":"Republic of Rwanda, Ministry of Health, Rwanda Biomedical Centre (2025, March 22). Rwanda Malaria Strategic Plan 2020\u20132024. Available online: https:\/\/mesamalaria.org\/wp-content\/uploads\/2024\/07\/RWANDA-MALARIA-STRATEGIC-PLAN_2020-2024.pdf."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1056\/NEJMoa1314981","article-title":"Spread of artemisinin resistance in Plasmodium falciparum malaria","volume":"371","author":"Ashley","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.3201\/eid2107.150213","article-title":"Slow Clearance of Plasmodium falciparum in Severe Pediatric Malaria, Uganda, 2011\u20132013","volume":"21","author":"Hawkes","year":"2015","journal-title":"Emerg. Infect. Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1056\/NEJMoa0808859","article-title":"Artemisinin resistance in Plasmodium falciparum malaria","volume":"361","author":"Dondorp","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"ref_19","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_20","doi-asserted-by":"crossref","first-page":"e08714","DOI":"10.7554\/eLife.08714","article-title":"Genomic epidemiology of artemisinin resistant malaria","volume":"5","author":"Malaria","year":"2016","journal-title":"eLife"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"294","DOI":"10.3201\/eid2701.203527","article-title":"Increase in Kelch 13 Polymorphisms in Plasmodium falciparum, Southern Rwanda","volume":"27","author":"Bergmann","year":"2021","journal-title":"Emerg. Infect. Dis."},{"key":"ref_22","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_23","doi-asserted-by":"crossref","first-page":"1411","DOI":"10.1093\/infdis\/jiab352","article-title":"High Prevalence of Plasmodium falciparum K13 Mutations in Rwanda Is Associated With Slow Parasite Clearance After Treatment With Artemether-Lumefantrine","volume":"225","author":"Straimer","year":"2022","journal-title":"J. Infect. Dis."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1056\/NEJMoa2101746","article-title":"Evidence of Artemisinin-Resistant Malaria in Africa","volume":"385","author":"Balikagala","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1602","DOI":"10.1038\/s41591-020-1005-2","article-title":"Emergence and clonal expansion of in vitro artemisinin-resistant Plasmodium falciparum kelch13 R561H mutant parasites in Rwanda","volume":"26","author":"Uwimana","year":"2020","journal-title":"Nat. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"6353","DOI":"10.1038\/s41467-022-33873-x","article-title":"Decreased susceptibility of Plasmodium falciparum to both dihydroartemisinin and lumefantrine in northern Uganda","volume":"13","author":"Tumwebaze","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1870","DOI":"10.1086\/375419","article-title":"Reemergence of chloroquine-sensitive Plasmodium falciparum malaria after cessation of chloroquine use in Malawi","volume":"187","author":"Kublin","year":"2003","journal-title":"J. Infect. Dis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1959","DOI":"10.1056\/NEJMoa062032","article-title":"Return of chloroquine antimalarial efficacy in Malawi","volume":"355","author":"Laufer","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1186\/1475-2875-6-121","article-title":"World Antimalarial Resistance Network (WARN) III: Molecular markers for drug resistant malaria","volume":"6","author":"Plowe","year":"2007","journal-title":"Malar. J."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"eaav1636","DOI":"10.1126\/scitranslmed.aav1636","article-title":"In vitro selection predicts malaria parasite resistance to dihydroorotate dehydrogenase inhibitors in a mouse infection model","volume":"11","author":"Mandt","year":"2019","journal-title":"Sci. Transl. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1186\/s12936-020-03407-1","article-title":"History of malaria control in Rwanda: Implications for future elimination in Rwanda and other malaria-endemic countries","volume":"19","author":"Karema","year":"2020","journal-title":"Malar. J."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.actatropica.2011.09.009","article-title":"Molecular markers of Plasmodium falciparum drug resistance in southern highland Rwanda","volume":"121","author":"Zeile","year":"2012","journal-title":"Acta Trop."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1128\/AAC.00498-09","article-title":"Molecular correlates of high-level antifolate resistance in Rwandan children with Plasmodium falciparum malaria","volume":"54","author":"Karema","year":"2010","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Fanello, C.I., Karema, C., Avellino, P., Bancone, G., Uwimana, A., Lee, S.J., d\u2019Alessandro, U., and Modiano, D. (2008). High risk of severe anaemia after chlorproguanil-dapsone+artesunate antimalarial treatment in patients with G6PD (A-) deficiency. PLoS ONE, 3.","DOI":"10.1371\/journal.pone.0004031"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.4269\/ajtmh.23-0225","article-title":"Peripheral and Placental Prevalence of Sulfadoxine-Pyrimethamine Resistance Markers in Plasmodium falciparum among Pregnant Women in Southern Province, Rwanda","volume":"109","author":"Alruwaili","year":"2023","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_36","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_37","doi-asserted-by":"crossref","first-page":"833","DOI":"10.4269\/ajtmh.14-0031","article-title":"Polymorphisms in Plasmodium falciparum chloroquine resistance transporter and multidrug resistance 1 genes: Parasite risk factors that affect treatment outcomes for P. falciparum malaria after artemether-lumefantrine and artesunate-amodiaquine","volume":"91","author":"Venkatesan","year":"2014","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.4269\/ajtmh.16-0483","article-title":"Artemisinin Resistance-Associated K13 Polymorphisms of Plasmodium falciparum in Southern Rwanda, 2010-2015","volume":"95","author":"Tacoli","year":"2016","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Okell, L.C., Griffin, J.T., and Roper, C. (2017). Mapping sulphadoxine-pyrimethamine-resistant Plasmodium falciparum malaria in infected humans and in parasite populations in Africa. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-06708-9"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Deutsch-Feldman, M., Aydemir, O., Carrel, M., Brazeau, N.F., Bhatt, S., Bailey, J.A., Kashamuka, M., Tshefu, A.K., Taylor, S.M., and Juliano, J.J. (2019). The changing landscape of Plasmodium falciparum drug resistance in the Democratic Republic of Congo. BMC Infect. Dis., 19.","DOI":"10.1186\/s12879-019-4523-0"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"54","DOI":"10.4269\/ajtmh.13-0647","article-title":"Temporal changes in prevalence of molecular markers mediating antimalarial drug resistance in a high malaria transmission setting in Uganda","volume":"91","author":"Mbogo","year":"2014","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1186\/1475-2875-13-152","article-title":"High levels of sulphadoxine-pyrimethamine resistance Pfdhfr-Pfdhps quintuple mutations: A cross sectional survey of six regions in Tanzania","volume":"13","author":"Matondo","year":"2014","journal-title":"Malar. J."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1016\/j.actatropica.2013.09.010","article-title":"Prevalence of sulfadoxine-pyrimethamine resistance-associated mutations in dhfr and dhps genes of Plasmodium falciparum three years after SP withdrawal in Bahir Dar, Northwest Ethiopia","volume":"128","author":"Hailemeskel","year":"2013","journal-title":"Acta Trop."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1016\/S0140-6736(01)06201-8","article-title":"Plasmodium falciparum cross-resistance between trimethoprim and pyrimethamine","volume":"358","author":"Iyer","year":"2001","journal-title":"Lancet"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.actatropica.2005.04.008","article-title":"Contribution of the pfmdr1 gene to antimalarial drug-resistance","volume":"94","author":"Duraisingh","year":"2005","journal-title":"Acta Trop."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1186\/1475-2875-12-415","article-title":"Trends in chloroquine resistance marker, Pfcrt-K76T mutation ten years after chloroquine withdrawal in Tanzania","volume":"12","author":"Mohammed","year":"2013","journal-title":"Malar. J."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1186\/1475-2875-12-103","article-title":"Temporal trends of molecular markers associated with artemether-lumefantrine tolerance\/resistance in Bagamoyo district, Tanzania","volume":"12","author":"Malmberg","year":"2013","journal-title":"Malar. J."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1086\/596738","article-title":"In vivo selection of Plasmodium falciparum parasites carrying the chloroquine-susceptible pfcrt K76 allele after treatment with artemether-lumefantrine in Africa","volume":"199","author":"Sisowath","year":"2009","journal-title":"J. Infect. Dis."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.ijpddr.2014.07.003","article-title":"Temporal trends in prevalence of Plasmodium falciparum drug resistance alleles over two decades of changing antimalarial policy in coastal Kenya","volume":"4","author":"Okombo","year":"2014","journal-title":"Int. J. Parasitol. Drugs Drug Resist."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2001","DOI":"10.1093\/infdis\/jiu358","article-title":"Directional selection at the pfmdr1, pfcrt, pfubp1, and pfap2mu loci of Plasmodium falciparum in Kenyan children treated with ACT","volume":"210","author":"Henriques","year":"2014","journal-title":"J. Infect. Dis."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"5069","DOI":"10.1128\/AAC.00638-09","article-title":"In vitro activities of piperaquine, lumefantrine, and dihydroartemisinin in Kenyan Plasmodium falciparum isolates and polymorphisms in pfcrt and pfmdr1","volume":"53","author":"Mwai","year":"2009","journal-title":"Antimicrob. Agents Chemother."}],"container-title":["Tropical Medicine and Infectious Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2414-6366\/10\/4\/89\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:05:37Z","timestamp":1760029537000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2414-6366\/10\/4\/89"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,29]]},"references-count":51,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2025,4]]}},"alternative-id":["tropicalmed10040089"],"URL":"https:\/\/doi.org\/10.3390\/tropicalmed10040089","relation":{},"ISSN":["2414-6366"],"issn-type":[{"value":"2414-6366","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,29]]}}}