{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T02:03:05Z","timestamp":1778637785811,"version":"3.51.4"},"reference-count":103,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2024,12,20]],"date-time":"2024-12-20T00:00:00Z","timestamp":1734652800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia (FCT)","award":["GHTMUID\/04413\/2020"],"award-info":[{"award-number":["GHTMUID\/04413\/2020"]}]},{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia (FCT)","award":["LA-REAL-LA\/P\/0117\/2020"],"award-info":[{"award-number":["LA-REAL-LA\/P\/0117\/2020"]}]},{"name":"Instituto CAM\u00d5ES BOLSAS CAM\u00d5ES, FUNDA\u00c7\u00c3O MILLENNIUM BCP","award":["GHTMUID\/04413\/2020"],"award-info":[{"award-number":["GHTMUID\/04413\/2020"]}]},{"name":"Instituto CAM\u00d5ES BOLSAS CAM\u00d5ES, FUNDA\u00c7\u00c3O MILLENNIUM BCP","award":["LA-REAL-LA\/P\/0117\/2020"],"award-info":[{"award-number":["LA-REAL-LA\/P\/0117\/2020"]}]},{"name":"Par\u00f3quia de S\u00e3o Nicolau\u2014Lisboa","award":["GHTMUID\/04413\/2020"],"award-info":[{"award-number":["GHTMUID\/04413\/2020"]}]},{"name":"Par\u00f3quia de S\u00e3o Nicolau\u2014Lisboa","award":["LA-REAL-LA\/P\/0117\/2020"],"award-info":[{"award-number":["LA-REAL-LA\/P\/0117\/2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Malaria continues to be a significant public health burden in many tropical and subtropical regions. Mozambique ranks among the top countries affected by malaria, where it is a leading cause of morbidity and mortality, accounting for 29% of all hospital deaths in the general population and 42% of deaths amongst children under five. This review presents a comparative analysis of data on five critical genes associated with antimalarial drug resistance: pfmdr1, pfcrt, pfk13, pfdhfr, and pfdhps, along with the copy number variation (CNV) in genes pfmdr1 and pfpm2\/3. These are genes associated with parasite response to antimalarials currently used to treat uncomplicated P. falciparum malaria in Mozambique. The review synthesizes data collected from published studies conducted in Mozambique after the introduction of artemisinin-based combination therapies (ACTs) (2006) up to June 2024, highlighting the presence or absence of mutations in these genes across Mozambique. We aimed at mapping the prevalence and distribution of these molecular markers across the country in order to contribute to the development of targeted interventions to sustain the efficacy of malaria treatments in Mozambique. Four databases were used to access the articles: PubMed, Science Direct, Scopus, and Google scholar. The search strategy identified 132 studies addressing malaria and antimalarial resistance. Of these, 112 were excluded for various reasons, leaving 20 studies to be included in this review. Children and pregnant women represent the majority of target groups in studies on all types of antimalarials. Most studies (87.5%) were conducted in the provinces of Maputo and Gaza. The primary alleles reported were pfcrt CVMNK, and in the most recent data, its wild-type form was found in the majority of patients. A low prevalence of mutations in the pfk13 gene was identified reflecting the effectiveness of ACTs. In pfk13, only mutation A578S was reported in Niassa and Tete. CNVs were observed in studies carried out in the south of Mozambique, with a frequency of 1.1\u20135.1% for pfmdr1 and a frequency of 1.1\u20133.4% for pfpm2. This review indicates that molecular markers linked to malaria resistance show considerable variation across provinces in Mozambique, with most up-to-date data accessible for Maputo and Gaza. In contrast, provinces such as Zambezia and Inhambane have limited data on several genes, while Nampula lacks data on all drug resistance markers.<\/jats:p>","DOI":"10.3390\/ijms252413645","type":"journal-article","created":{"date-parts":[[2024,12,20]],"date-time":"2024-12-20T06:44:33Z","timestamp":1734677073000},"page":"13645","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Mapping Antimalarial Drug Resistance in Mozambique: A Systematic Review of Plasmodium falciparum Genetic Markers Post-ACT Implementation"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-4953-3815","authenticated-orcid":false,"given":"Celso Raul Silambo","family":"Chaves","sequence":"first","affiliation":[{"name":"Global Health and Tropical Medicine (GHTM), Associate Laboratory in Translation and Innovation Towards Global Health (LA-REAL), Instituto de Higiene e Medicina Tropical (IHMT), Universidade NOVA de Lisboa (UNL), Rua da Junqueira 100, 1349-008 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2083-2579","authenticated-orcid":false,"given":"Clemente","family":"da Silva","sequence":"additional","affiliation":[{"name":"Global Health and Tropical Medicine (GHTM), Associate Laboratory in Translation and Innovation Towards Global Health (LA-REAL), Instituto de Higiene e Medicina Tropical (IHMT), Universidade NOVA de Lisboa (UNL), Rua da Junqueira 100, 1349-008 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0822-5549","authenticated-orcid":false,"given":"Ac\u00e1cio","family":"Salamandane","sequence":"additional","affiliation":[{"name":"Faculdade de Ci\u00eancias de Sa\u00fade, Universidade L\u00fario, Campus Universit\u00e1rio de Marrere, Nampula 4250, Mozambique"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0313-0778","authenticated-orcid":false,"given":"Fatima","family":"Nogueira","sequence":"additional","affiliation":[{"name":"Global Health and Tropical Medicine (GHTM), Associate Laboratory in Translation and Innovation Towards Global Health (LA-REAL), Instituto de Higiene e Medicina Tropical (IHMT), Universidade NOVA de Lisboa (UNL), Rua da Junqueira 100, 1349-008 Lisboa, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1007\/s40471-021-00266-5","article-title":"Antimalarial Drug Resistance and Implications for the WHO Global Technical Strategy","volume":"8","author":"Ippolito","year":"2021","journal-title":"Curr. Epidemiol. Rep."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"104366","DOI":"10.1016\/j.amsu.2022.104366","article-title":"Increasing Challenges of Malaria Control in Sub-Saharan Africa: Priorities for Public Health Research and Policymakers","volume":"81","author":"Oladipo","year":"2022","journal-title":"Ann. Med. Surg."},{"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":"(2024, August 06). WHO World Malaria Report. Available online: https:\/\/www.who.int\/teams\/global-malaria-programme\/reports\/world-malaria-report-2023."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e1002380","DOI":"10.1371\/journal.pbio.1002380","article-title":"Tools and Strategies for Malaria Control and Elimination: What Do We Need to Achieve a Grand Convergence in Malaria?","volume":"14","author":"Hemingway","year":"2016","journal-title":"PLoS Biol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1186\/s12936-022-04115-8","article-title":"Malaria Chemoprevention and Drug Resistance: A Review of the Literature and Policy Implications","volume":"21","author":"Plowe","year":"2022","journal-title":"Malar. J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1080\/14787210.2021.1962291","article-title":"Current and Emerging Strategies to Combat Antimalarial Resistance","volume":"20","author":"Rasmussen","year":"2022","journal-title":"Expert. Rev. Anti Infect. Ther."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2569","DOI":"10.1111\/febs.14127","article-title":"Combating Multidrug-resistant Plasmodium Falciparum Malaria","volume":"284","author":"Thu","year":"2017","journal-title":"FEBS J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/S1473-3099(02)00239-6","article-title":"Epidemiology of Drug-Resistant Malaria","volume":"2","author":"Wongsrichanalai","year":"2002","journal-title":"Lancet Infect. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e25992","DOI":"10.1371\/journal.pone.0025992","article-title":"Five Years of Antimalarial Resistance Marker Surveillance in Gaza Province, Mozambique, Following Artemisinin-Based Combination Therapy Roll Out","volume":"6","author":"Raman","year":"2011","journal-title":"PLoS ONE"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1016\/j.pt.2012.08.002","article-title":"PfCRT and Its Role in Antimalarial Drug Resistance","volume":"28","author":"Ecker","year":"2012","journal-title":"Trends Parasitol."},{"key":"ref_12","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_13","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1186\/s12936-020-03281-x","article-title":"Prevalence of Mutations in the Plasmodium Falciparum Chloroquine Resistance Transporter, PfCRT, and Association with Ex Vivo Susceptibility to Common Anti-Malarial Drugs against African Plasmodium Falciparum Isolates","volume":"19","author":"Foguim","year":"2020","journal-title":"Malar. J."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"536","DOI":"10.4269\/ajtmh.12-0525","article-title":"Rapid Selection of Plasmodium Falciparum Chloroquine Resistance Transporter Gene and Multidrug Resistance Gene-1 Haplotypes Associated with Past Chloroquine and Present Artemether-Lumefantrine Use in Inhambane District, Southern Mozambique","volume":"88","author":"Bygbjerg","year":"2013","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"12689","DOI":"10.1073\/pnas.221440898","article-title":"Evolution of a Unique Plasmodium Falciparum Chloroquine-Resistance Phenotype in Association with Pfcrt Polymorphism in Papua New Guinea and South America","volume":"98","author":"Mehlotra","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1038\/nature00813","article-title":"Genetic Diversity and Chloroquine Selective Sweeps in Plasmodium Falciparum","volume":"418","author":"Wootton","year":"2002","journal-title":"Nature"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1186\/1475-2875-13-284","article-title":"Declining efficacy of artesunate plus sulphadoxine-pyrimethamine in northeastern India","volume":"13","author":"Mishra","year":"2014","journal-title":"Malar. J."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e1002319","DOI":"10.1371\/journal.pmed.1002319","article-title":"The US President\u2019s Malaria Initiative and under-5 child mortality in sub-Saharan Africa: A difference-in-differences analysis","volume":"14","author":"Jakubowski","year":"2017","journal-title":"PLoS Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1007\/s00436-018-5754-5","article-title":"Prevalence of the Pfdhfr and Pfdhps Mutations among Asymptomatic Pregnant Women in Southeast Nigeria","volume":"117","author":"Esu","year":"2018","journal-title":"Parasitol. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/j.pt.2013.08.002","article-title":"Mapping \u2018Partially Resistant\u2019, \u2018Fully Resistant\u2019, and \u2018Super Resistant\u2019 Malaria","volume":"29","author":"Naidoo","year":"2013","journal-title":"Trends Parasitol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1186\/s12936-021-03922-9","article-title":"In Vivo Efficacy and Safety of Artemether\u2013Lumefantrine and Amodiaquine\u2013Artesunate for Uncomplicated Plasmodium Falciparum Malaria in Mozambique, 2018","volume":"20","author":"Nhama","year":"2021","journal-title":"Malar. J."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Nsanzabana, C. (2019). Resistance to Artemisinin Combination Therapies (ACTs): Do Not Forget the Partner Drug!. Trop. Med. Infect. Dis., 4.","DOI":"10.3390\/tropicalmed4010026"},{"key":"ref_23","unstructured":"Li, G., Li, Y., Li, Z., and Zeng, M. (2018). Artemisinin and Derivatives Pharmacodynamics, Toxicology, Pharmacokinetics, Mechanism of Action, Resistance, and Immune Regulation. Artemisinin-Based and Other Antimalarials, Elsevier. Chapter 5."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1097\/QCO.0000000000000766","article-title":"Artemisinin and Multidrug-Resistant Plasmodium Falciparum\u2014A Threat for Malaria Control and Elimination","volume":"34","author":"Dhorda","year":"2021","journal-title":"Curr. Opin. Infect. Dis."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1146\/annurev-micro-020518-115546","article-title":"Molecular Mechanisms of Drug Resistance in Plasmodium Falciparum Malaria","volume":"74","author":"Wicht","year":"2020","journal-title":"Annu. Rev. Microbiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1093\/cid\/ciw388","article-title":"Declining Efficacy of Artemisinin Combination Therapy Against P. falciparum Malaria on the Thai\u2013Myanmar Border (2003\u20132013): The Role of Parasite Genetic Factors","volume":"63","author":"Phyo","year":"2016","journal-title":"Clin. Infect. Dis."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1016\/S0140-6736(04)16767-6","article-title":"Mefloquine Resistance in Plasmodium Falciparum and Increased Pfmdr1 Gene Copy Number","volume":"364","author":"Price","year":"2004","journal-title":"Lancet"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e64299","DOI":"10.1371\/journal.pone.0064299","article-title":"The Role of Pfmdr1 and Pfcrt in Changing Chloroquine, Amodiaquine, Mefloquine and Lumefantrine Susceptibility in Western-Kenya P. falciparum Samples during 2008\u20132011","volume":"8","author":"Eyase","year":"2013","journal-title":"PLoS ONE"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"4858","DOI":"10.1128\/AAC.01748-10","article-title":"Genomewide Scan Reveals Amplification of Mdr1 as a Common Denominator of Resistance to Mefloquine, Lumefantrine, and Artemisinin in Plasmodium Chabaudi Malaria Parasites","volume":"55","author":"Borges","year":"2011","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1509","DOI":"10.1128\/AAC.00241-08","article-title":"Plasmodium Falciparum Pfmdr1 Amplification, Mefloquine Resistance, and Parasite Fitness","volume":"53","author":"Preechapornkul","year":"2009","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1111\/j.1365-2958.2005.04729.x","article-title":"Pfmdr1 Mutations Contribute to Quinine Resistance and Enhance Mefloquine and Artemisinin Sensitivity in Plasmodium Falciparum","volume":"57","author":"Sidhu","year":"2005","journal-title":"Mol. Microbiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1006\/expr.1998.4195","article-title":"Pfmdr1Asn1042AspandAsp1246TyrPolymorphisms, Thought to Be Associated with Chloroquine Resistance, Are Present in Chloroquine-Resistant and -Sensitive Brazilian Field Isolates OfPlasmodium Falciparum","volume":"88","author":"Adagu","year":"1998","journal-title":"Exp. Parasitol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1038\/345255a0","article-title":"Several Alleles of the Multidrug-Resistance Gene Are Closely Linked to Chloroquine Resistance in Plasmodium Falciparum","volume":"345","author":"Foote","year":"1990","journal-title":"Nature"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1016\/j.meegid.2011.01.003","article-title":"Increased Prevalence of the Plasmodium Falciparum Pfmdr1 86N Genotype among Field Isolates from Franceville, Gabon after Replacement of Chloroquine by Artemether\u2013Lumefantrine and Artesunate\u2013Mefloquine","volume":"11","author":"Boutamba","year":"2011","journal-title":"Infect. Genet. Evol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/1475-2875-1-12","article-title":"Molecular Characterisation of Drug-Resistant Plasmodium Falciparum from Thailand","volume":"1","author":"Lopes","year":"2002","journal-title":"Malar. J."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"7032","DOI":"10.1128\/AAC.03494-14","article-title":"Role of Pfmdr1 in In Vitro Plasmodium Falciparum Susceptibility to Chloroquine, Quinine, Monodesethylamodiaquine, Mefloquine, Lumefantrine, and Dihydroartemisinin","volume":"58","author":"Wurtz","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1893","DOI":"10.1128\/AAC.50.5.1893-1895.2006","article-title":"Selection of Plasmodium Falciparum Pfmdr1 Alleles Following Therapy with Artemether-Lumefantrine in an Area of Uganda Where Malaria Is Highly Endemic","volume":"50","author":"Dokomajilar","year":"2006","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1016\/S1473-3099(15)70049-6","article-title":"Dihydroartemisinin-Piperaquine Failure Associated with a Triple Mutant Including Kelch13 C580Y in Cambodia: An Observational Cohort Study","volume":"15","author":"Spring","year":"2015","journal-title":"Lancet Infect. Dis."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"715","DOI":"10.3201\/eid2304.161872","article-title":"Treatment Failure of Dihydroartemisinin\/ Piperaquine for Plasmodium Falciparum Malaria, Vietnam","volume":"23","author":"Phuc","year":"2017","journal-title":"Emerg. Infect. Dis."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.ijid.2023.11.026","article-title":"Identification of the PfK13 Mutations R561H and P441L in the Democratic Republic of Congo","volume":"139","author":"Kahunu","year":"2024","journal-title":"Int. J. Infect. Dis."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1902","DOI":"10.3201\/eid2707.203230","article-title":"Plasmodium Falciparum Kelch 13 Mutations, 9 Countries in Africa, 2014\u20132018","volume":"27","author":"Schmedes","year":"2021","journal-title":"Emerg. Infect. Dis."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e66277","DOI":"10.7554\/eLife.66277","article-title":"Plasmodium Falciparum K13 Mutations in Africa and Asia Impact Artemisinin Resistance and Parasite Fitness","volume":"10","author":"Stokes","year":"2021","journal-title":"Elife"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"g7647","DOI":"10.1136\/bmj.g7647","article-title":"Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) 2015: Elaboration and Explanation","volume":"349","author":"Shamseer","year":"2015","journal-title":"BMJ"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1186\/s13643-021-01626-4","article-title":"The PRISMA 2020 Statement: An Updated Guideline for Reporting Systematic Reviews","volume":"10","author":"Page","year":"2021","journal-title":"Syst. Rev."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1186\/1475-2875-8-141","article-title":"Efficacy of Sulphadoxine-Pyrimethamine with or without Artesunate for the Treatment of Uncomplicated Plasmodium Falciparum Malaria in Southern Mozambique: A Randomized Controlled Trial","volume":"8","author":"Allen","year":"2009","journal-title":"Malar. J."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1186\/1475-2875-6-35","article-title":"Analysis of Sulphadoxine\/Pyrimethamine Resistance-Conferring Mutations of Plasmodium Falciparum from Mozambique Reveals the Absence of the Dihydrofolate Reductase 164L Mutant","volume":"6","author":"Fernandes","year":"2007","journal-title":"Malar. J."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1186\/s12936-023-04589-0","article-title":"Anti-Malarial Resistance in Mozambique: Absence of Plasmodium Falciparum Kelch 13 (K13) Propeller Domain Polymorphisms Associated with Resistance to Artemisinins","volume":"22","author":"Matias","year":"2023","journal-title":"Malar. J."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e0119215","DOI":"10.1371\/journal.pone.0119215","article-title":"Polymorphisms in Plasmodium Falciparum K13-Propeller in Angola and Mozambique after the Introduction of the ACTs","volume":"10","author":"Escobar","year":"2015","journal-title":"PLoS ONE"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"e1002815","DOI":"10.1371\/journal.pmed.1002815","article-title":"Malaria Morbidity and Mortality Following Introduction of a Universal Policy of Artemisinin-Based Treatment for Malaria in Papua, Indonesia: A Longitudinal Surveillance Study","volume":"16","author":"Kenangalem","year":"2019","journal-title":"PLoS Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1356","DOI":"10.1038\/s41598-017-01365-4","article-title":"In-Vivo Efficacy of Chloroquine to Clear Asymptomatic Infections in Mozambican Adults: A Randomized, Placebo-Controlled Trial with Implications for Elimination Strategies","volume":"7","author":"Galatas","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"256","DOI":"10.4269\/ajtmh.2008.78.256","article-title":"Differential Effect of Regional Drug Pressure on Dihydrofolate Reductase and Dihydropteroate Synthetase Mutations in Southern Mozambique","volume":"78","author":"Raman","year":"2008","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e0240174","DOI":"10.1371\/journal.pone.0240174","article-title":"Effect of Mass Dihydroartemisinin\u2013Piperaquine Administration in Southern Mozambique on the Carriage of Molecular Markers of Antimalarial Resistance","volume":"15","author":"Gupta","year":"2020","journal-title":"PLoS One"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"40","DOI":"10.3201\/eid2401.170864","article-title":"Drug-Resistant Polymorphisms and Copy Numbers in Plasmodium Falciparum, Mozambique, 2015","volume":"24","author":"Gupta","year":"2018","journal-title":"Emerg. Infect. Dis."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1186\/s12936-021-03930-9","article-title":"Molecular Surveillance for Polymorphisms Associated with Artemisinin-Based Combination Therapy Resistance in Plasmodium Falciparum Isolates Collected in Mozambique, 2018","volume":"20","author":"Chidimatembue","year":"2021","journal-title":"Malar. J."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1737","DOI":"10.1086\/588144","article-title":"Molecular Markers of Resistance to Sulfadoxine-Pyrimethamine during Intermittent Preventive Treatment for Malaria in Mozambican Infants","volume":"197","author":"Mayor","year":"2008","journal-title":"J. Infect. Dis."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"102684","DOI":"10.1016\/j.tmaid.2023.102684","article-title":"Artemisinin Resistance-Associated Gene Mutations in Plasmodium Falciparum: A Case Study of Severe Malaria from Mozambique","volume":"57","author":"Casanova","year":"2024","journal-title":"Travel Med. Infect. Dis."},{"key":"ref_57","first-page":"293","article-title":"Counter-Selection of Antimalarial Resistance Polymorphisms by Intermittent Preventive Treatment in Pregnancy","volume":"221","author":"Huijben","year":"2020","journal-title":"J. Infect. Dis."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"788","DOI":"10.4269\/ajtmh.2010.09-0401","article-title":"Five Years of Large-Scale Dhfr and Dhps Mutation Surveillance Following the Phased Implementation of Artesunate Plus Sulfadoxine-Pyrimethamine in Maputo Province, Southern Mozambique","volume":"82","author":"Raman","year":"2010","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1186\/1475-2875-7-115","article-title":"Rapid Increase of Plasmodium Falciparum Dhfr\/Dhps Resistant Haplotypes, after the Adoption of Sulphadoxine-Pyrimethamine as First Line Treatment in 2002, in Southern Mozambique","volume":"7","author":"Enosse","year":"2008","journal-title":"Malar. J."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"e1765","DOI":"10.1016\/S2214-109X(23)00414-X","article-title":"Prevalence of Molecular Markers of Resistance to Sulfadoxine\u2013Pyrimethamine before and after Community Delivery of Intermittent Preventive Treatment of Malaria in Pregnancy in Sub-Saharan Africa: A Multi-Country Evaluation","volume":"11","author":"Bissombolo","year":"2023","journal-title":"Lancet Glob. Health"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2402","DOI":"10.1038\/s41467-024-46535-x","article-title":"Genomic Malaria Surveillance of Antenatal Care Users Detects Reduced Transmission Following Elimination Interventions in Mozambique","volume":"15","author":"Brokhattingen","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"106144","DOI":"10.1016\/j.jinf.2024.106144","article-title":"Sustained Clinical Benefit of Malaria Chemoprevention with Sulfadoxine-Pyrimethamine (SP) in Pregnant Women in a Region with High SP Resistance Markers","volume":"88","author":"Matambisso","year":"2024","journal-title":"J. Infect."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1186\/1475-2875-13-300","article-title":"Prevalence of Pfmdr1 Alleles Associated with Artemether-Lumefantrine Tolerance\/Resistance in Maputo before and after the Implementation of Artemisinin-Based Combination Therapy","volume":"13","author":"Lobo","year":"2014","journal-title":"Malar. J."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"e0034624","DOI":"10.1128\/aac.00346-24","article-title":"Antimalarial Resistance Risk in Mozambique Detected by a Novel Quadruplex Droplet Digital PCR Assay","volume":"68","author":"Brown","year":"2024","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_65","first-page":"216","article-title":"A country-wide malaria survey in Mozambique. I","volume":"7","author":"Mabunda","year":"2008","journal-title":"Plasmodium falciparum infection in children in different epidemiological settings. Malar. J."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1186\/s12936-019-2716-z","article-title":"Persistence of Chloroquine Resistance Alleles in Malaria Endemic Countries: A Systematic Review of Burden and Risk Factors","volume":"18","author":"Ocan","year":"2019","journal-title":"Malar. J."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.actatropica.2012.05.007","article-title":"Changes in Genotypes of Plasmodium Falciparum Human Malaria Parasite Following Withdrawal of Chloroquine in Tiwi, Kenya","volume":"123","author":"Mbai","year":"2012","journal-title":"Acta Trop."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1186\/s12936-016-1637-3","article-title":"The Return of Chloroquine-Susceptible Plasmodium Falciparum Malaria in Zambia","volume":"15","author":"Mwanza","year":"2016","journal-title":"Malar. J."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1086\/655659","article-title":"Return of Chloroquine-Susceptible Falciparum Malaria in Malawi Was a Reexpansion of Diverse Susceptible Parasites","volume":"202","author":"Laufer","year":"2010","journal-title":"J. Infect. Dis."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Bwire, G.M., Ngasala, B., Mikomangwa, W.P., Kilonzi, M., and Kamuhabwa, A.A.R. (2020). Detection of Mutations Associated with Artemisinin Resistance at K13-Propeller Gene and a near Complete Return of Chloroquine Susceptible Falciparum Malaria in Southeast of Tanzania. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-60549-7"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"3314","DOI":"10.1038\/s41467-018-05652-0","article-title":"Emerging Southeast Asian PfCRT Mutations Confer Plasmodium Falciparum Resistance to the First-Line Antimalarial Piperaquine","volume":"9","author":"Ross","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_72","unstructured":"Orlando, P. (2019). Evaluation of Intermittent Preventive Treatment during Pregnancy (IPTp) in Ch\u00f3kw\u00e8 District, Southern Mozambique: Coverage and Effect on Pregnancy and Parasitological Outcomes, University of Antwerp."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1186\/s12936-018-2255-z","article-title":"Uptake of Intermittent Preventive Treatment and Pregnancy Outcomes: Health Facilities and Community Surveys in Ch\u00f3kw\u00e8 District, Southern Mozambique","volume":"17","author":"Arnaldo","year":"2018","journal-title":"Malar. J."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1038\/s41598-020-80017-6","article-title":"Polymorphisms in Plasmodium Falciparum Dihydropteroate Synthetase and Dihydrofolate Reductase Genes in Nigerian Children with Uncomplicated Malaria Using High-Resolution Melting Technique","volume":"11","author":"Kayode","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"996","DOI":"10.4269\/ajtmh.2012.12-0202","article-title":"Surveillance of Molecular Markers of Plasmodium Falciparum Resistance to Sulphadoxine-Pyrimethamine 5 Years after the Change of Malaria Treatment Policy in Ghana","volume":"87","author":"Duah","year":"2012","journal-title":"Am. Soc. Trop. Med. Hyg."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1186\/1475-2875-12-377","article-title":"Increased Pfmdr1 Gene Copy Number and the Decline in Pfcrt and Pfmdr1 Resistance Alleles in Ghanaian Plasmodium Falciparum Isolates after the Change of Anti-Malarial Drug Treatment Policy","volume":"12","author":"Duah","year":"2013","journal-title":"Malar. J."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1016\/j.jiph.2022.03.015","article-title":"Molecular Surveillance of Chloroquine-Resistant Plasmodium Falciparum in Sub-Saharan African Countries after Withdrawal of Chloroquine for Treatment of Uncomplicated Malaria: A Systematic Review","volume":"15","author":"Njiro","year":"2022","journal-title":"J. Infect. Public Health"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/s12936-020-03543-8","article-title":"Drug Resistance Markers within an Evolving Efficacy of Anti-Malarial Drugs in Cameroon: A Systematic Review and Meta-Analysis (1998\u20132020)","volume":"20","author":"Niba","year":"2021","journal-title":"Malar. J."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"e000999","DOI":"10.1136\/bmjgh-2018-000999","article-title":"Emerging Implications of Policies on Malaria Treatment: Genetic Changes in the Pfmdr-1 Gene Affecting Susceptibility to Artemether\u2013Lumefantrine and Artesunate\u2013Amodiaquine in Africa","volume":"3","author":"Okell","year":"2018","journal-title":"BMJ Glob. Health"},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Groger, M., Veletzky, L., Lalremruata, A., Cattaneo, C., Mischlinger, J., Zoleko-Manego, R., Endamne, L., Klicpera, A., Kim, J., and Nguyen, T. (2018). Prospective Clinical Trial Assessing Species-Specific Efficacy of Artemether-Lumefantrine for the Treatment of Plasmodium Malariae, Plasmodium Ovale, and Mixed Plasmodium Malaria in Gabon. Antimicrob. Agents Chemother., 62.","DOI":"10.1128\/AAC.01758-17"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1186\/s12936-020-03193-w","article-title":"Amplicon Deep Sequencing of Kelch13 in Plasmodium Falciparum Isolates from Senegal","volume":"19","author":"Gaye","year":"2020","journal-title":"Malar. J."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1186\/s12936-023-04812-y","article-title":"Molecular Surveillance of Kelch 13 Polymorphisms in Plasmodium Falciparum Isolates from Kenya and Ethiopia","volume":"23","author":"Jeang","year":"2024","journal-title":"Malar. J."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1038\/s42003-023-04997-7","article-title":"Targeted and Whole-Genome Sequencing Reveal a North-South Divide in P. falciparum Drug Resistance Markers and Genetic Structure in Mozambique","volume":"6","author":"Boene","year":"2023","journal-title":"Commun. Biol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1186\/s12936-019-2756-4","article-title":"African Isolates Show a High Proportion of Multiple Copies of the Plasmodium Falciparum Plasmepsin-2 Gene, a Piperaquine Resistance Marker","volume":"18","author":"Leroy","year":"2019","journal-title":"Malar. J."},{"key":"ref_85","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_86","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1093\/infdis\/jiaa687","article-title":"Changing Prevalence of Potential Mediators of Aminoquinoline, Antifolate, and Artemisinin Resistance Across Uganda","volume":"223","author":"Asua","year":"2021","journal-title":"J. Infect. Dis."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1056\/NEJMoa2211803","article-title":"Evolution of Partial Resistance to Artemisinins in Malaria Parasites in Uganda","volume":"389","author":"Conrad","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1162","DOI":"10.1056\/NEJMp2309142","article-title":"Artemisinin-Resistant and HRP-Negative Malaria Parasites in Africa","volume":"389","author":"Greenwood","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref_89","unstructured":"World Health Organization (2023). WHO Guidelines for Malaria\u201414 March 2023, World Health Organization."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.ijpddr.2021.06.001","article-title":"A Review of the Frequencies of Plasmodium Falciparum Kelch 13 Artemisinin Resistance Mutations in Africa","volume":"16","author":"Ndwiga","year":"2021","journal-title":"Int. J. Parasitol. Drugs Drug Resist."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"107102","DOI":"10.1016\/j.ijid.2024.107102","article-title":"Lack of Selection of Antimalarial Drug Resistance Markers after Intermittent Preventive Treatment of Schoolchildren (IPTsc) against Malaria in Northeastern Tanzania","volume":"146","author":"Makenga","year":"2024","journal-title":"Int. J. Infect. Dis."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/S2221-1691(15)30008-3","article-title":"Identification of Chloroquine Resistance Pfcrt-K76T and Determination of Pfmdr1-N86Y Copy Number by SYBR Green I QPCR","volume":"5","author":"Tajebe","year":"2015","journal-title":"Asian Pac. J. Trop. Biomed."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"8308","DOI":"10.1038\/srep08308","article-title":"Analysis of Major Genome Loci Underlying Artemisinin Resistance and Pfmdr1 Copy Number in Pre- and Post-ACTs in Western Kenya","volume":"5","author":"Ngalah","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1186\/s12936-023-04602-6","article-title":"Clinical Isolates of Uncomplicated Falciparum Malaria from High and Low Malaria Transmission Areas Show Distinct Pfcrt and Pfmdr1 Polymorphisms in Western Ethiopia","volume":"22","author":"Tadele","year":"2023","journal-title":"Malar. J."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"105042","DOI":"10.1016\/j.meegid.2021.105042","article-title":"Mutations in Pfcrt and Pfmdr1 Genes of Plasmodium Falciparum Isolates from Two Sites in Northcentral and Southwest Nigeria","volume":"95","author":"Agomo","year":"2021","journal-title":"Infect. Genet. Evol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1186\/s12936-021-03636-y","article-title":"Assessment of Plasmodium Falciparum Anti-Malarial Drug Resistance Markers in Pfk13-Propeller, Pfcrt and Pfmdr1 Genes in Isolates from Treatment Failure Patients in Democratic Republic of Congo, 2018\u20132019","volume":"20","author":"Yobi","year":"2021","journal-title":"Malar. J."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"e0041322","DOI":"10.1128\/spectrum.00413-22","article-title":"Molecular Surveillance of Artemisinin-Based Combination Therapies Resistance in Plasmodium Falciparum Parasites from Bioko Island, Equatorial Guinea","volume":"10","author":"Liu","year":"2022","journal-title":"Microbiol. Spectr."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1186\/s12936-021-04021-5","article-title":"Efficacy and Safety of Artemether-Lumefantrine and Dihydroartemisinin-Piperaquine for the Treatment of Uncomplicated Plasmodium Falciparum Malaria and Prevalence of Molecular Markers Associated with Artemisinin and Partner Drug Resistance in Uganda","volume":"20","author":"Ebong","year":"2021","journal-title":"Malar. J."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1186\/s12936-022-04140-7","article-title":"Artesunate\u2013Amodiaquine and Artemether\u2013Lumefantrine for the Treatment of Uncomplicated Falciparum Malaria in Liberia: In Vivo Efficacy and Frequency of Molecular Markers","volume":"21","author":"Koko","year":"2022","journal-title":"Malar. J."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/S1473-3099(15)00487-9","article-title":"Dihydroartemisinin\u2013Piperaquine Resistance in Plasmodium Falciparum Malaria in Cambodia: A Multisite Prospective Cohort Study","volume":"16","author":"Amaratunga","year":"2016","journal-title":"Lancet Infect. Dis."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/S1473-3099(16)30409-1","article-title":"Genetic Markers Associated with Dihydroartemisinin\u2013Piperaquine Failure in Plasmodium Falciparum Malaria in Cambodia: A Genotype\u2013Phenotype Association Study","volume":"17","author":"Amato","year":"2017","journal-title":"Lancet Infect. Dis."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/S1473-3099(16)30415-7","article-title":"A Surrogate Marker of Piperaquine-Resistant Plasmodium Falciparum Malaria: A Phenotype\u2013Genotype Association Study","volume":"17","author":"Witkowski","year":"2017","journal-title":"Lancet Infect. Dis."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1590\/S1518-8787.2016050006105","article-title":"Increase in Cases of Malaria in Mozambique, 2014: Epidemic or New Endemic Pattern?","volume":"50","author":"Arroz","year":"2016","journal-title":"Rev. Saude Publica"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/24\/13645\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:56:22Z","timestamp":1760115382000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/24\/13645"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,20]]},"references-count":103,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["ijms252413645"],"URL":"https:\/\/doi.org\/10.3390\/ijms252413645","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,20]]}}}