{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T17:01:54Z","timestamp":1793638914868,"version":"4.5.1"},"reference-count":40,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2023,3,23]],"date-time":"2023-03-23T00:00:00Z","timestamp":1679529600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Medical Research Council UK","award":["G0600718"],"award-info":[{"award-number":["G0600718"]}]},{"name":"Medical Research Council UK","award":["098051"],"award-info":[{"award-number":["098051"]}]},{"name":"Wellcome Trust","award":["G0600718"],"award-info":[{"award-number":["G0600718"]}]},{"name":"Wellcome Trust","award":["098051"],"award-info":[{"award-number":["098051"]}]},{"name":"Plasmodium Diversity Network African (PDNA)","award":["G0600718"],"award-info":[{"award-number":["G0600718"]}]},{"name":"Plasmodium Diversity Network African (PDNA)","award":["098051"],"award-info":[{"award-number":["098051"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["TropicalMed"],"abstract":"<jats:p>The objective of this study was to analyze the relationship between the frequency of artemisinin-based combination (ACT) drug resistance molecular markers and clinical forms of P. falciparum malaria and parasitemia. A cross-sectional study was carried out between January and April 2014 at the Operational Clinical Research Unit of Melen in febrile children aged 12 to 240 months with a Plasmodium sp. infection. A total of 3 mL of peripheral blood collected from an EDTA tube was used for leukocyte depletion. DNA mutation detection was performed by next generation sequencing (NGS). A total of 1075 patients were screened for malaria. Among them, 384 had a Plasmodium infection. P. falciparum mono-infection was found in 98.9% of the patients. Pfcrt-326T mutation was found in all isolates, while 37.9% had Pfmdr2-484I mutant allele. The highest median parasite densities were found in patients infected by parasites carrying the CVIET haplotype of the Pfcrt gene. The different genetic profiles found here, and their variations according to clinical and biological signs of severe malaria, are additional arguments for the surveillance of P. falciparum strains.<\/jats:p>","DOI":"10.3390\/tropicalmed8040184","type":"journal-article","created":{"date-parts":[[2023,3,23]],"date-time":"2023-03-23T02:35:26Z","timestamp":1679538926000},"page":"184","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Drug Resistance Molecular Markers of Plasmodium falciparum and Severity of Malaria in Febrile Children in the Sentinel Site for Malaria Surveillance of Melen in Gabon: Additional Data from the Plasmodium Diversity Network African Network"],"prefix":"10.3390","volume":"8","author":[{"given":"Jacques Mari","family":"Ndong Ngomo","sequence":"first","affiliation":[{"name":"Faculty of Medicine, Department of Parasitology and Mycology, Universit\u00e9 des Sciences de la Sant\u00e9, Libreville BP 4009, Gabon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denise Patricia","family":"Mawili-Mboumba","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Department of Parasitology and Mycology, Universit\u00e9 des Sciences de la Sant\u00e9, Libreville BP 4009, Gabon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4994-3355","authenticated-orcid":false,"given":"No\u00e9 Patrick","family":"M\u2019Bondoukw\u00e9","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Department of Parasitology and Mycology, Universit\u00e9 des Sciences de la Sant\u00e9, Libreville BP 4009, Gabon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bridy Moutombi","family":"Ditombi","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Department of Parasitology and Mycology, Universit\u00e9 des Sciences de la Sant\u00e9, Libreville BP 4009, Gabon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeanne Vanessa","family":"Koumba Lengongo","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Department of Parasitology and Mycology, Universit\u00e9 des Sciences de la Sant\u00e9, Libreville BP 4009, Gabon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fanny Bertrande","family":"Batchy Ognagosso","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Department of Parasitology and Mycology, Universit\u00e9 des Sciences de la Sant\u00e9, Libreville BP 4009, Gabon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7992-4630","authenticated-orcid":false,"given":"Marielle Karine","family":"Bouyou-Akotet","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Department of Parasitology and Mycology, Universit\u00e9 des Sciences de la Sant\u00e9, Libreville BP 4009, Gabon"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,23]]},"reference":[{"key":"ref_1","unstructured":"WHO (2022). World Malaria Report 2022."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1016\/j.jinf.2016.02.001","article-title":"UK Malaria Treatment Guidelines 2016","volume":"72","author":"Lalloo","year":"2016","journal-title":"J. Infect."},{"key":"ref_3","unstructured":"WHO (2021). Word Malaria Report 2021."},{"key":"ref_4","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_5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1128\/microbiolspec.EI10-0013-2016","article-title":"Artemisinin-Resistant Plasmodium falciparum Malaria","volume":"4","author":"Fairhurst","year":"2016","journal-title":"Microbiol. Spectr."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Duru, V., Khim, N., Leang, R., Kim, S., Domergue, A., Kloeung, N., Ke, S., Chy, S., Eam, R., and Khean, C. (2015). Plasmodium Falciparum Dihydroartemisinin-Piperaquine Failures in Cambodia Are Associated with Mutant K13 Parasites Presenting High Survival Rates in Novel Piperaquine in Vitro Assays: Retrospective and Prospective Investigations. BMC Med., 13.","DOI":"10.1186\/s12916-015-0539-5"},{"key":"ref_7","unstructured":"Plasmodium, M. Genomic Epidemiology of Artemisinin Resistant Malaria. Epidemiol. Glob. Health Microbiol. Infect. Dis., 2016."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1126\/science.1260867","article-title":"K13-Propeller Mutations Confer Artemisinin Resistance in Plasmodium Falciparum Clinical Isolates","volume":"347","author":"Straimer","year":"2015","journal-title":"Science"},{"key":"ref_9","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":"2016","journal-title":"Nature"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1038\/ng.3189","article-title":"Genetic architecture of artemisinin-resistant Plasmodium falciparum","volume":"47","author":"Miotto","year":"2015","journal-title":"Nat. Genet."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1186\/s12936-017-1753-8","article-title":"Molecular Surveillance of Artemisinin Resistance Falciparum Malaria among Migrant Goldmine Workers in Myanmar","volume":"16","author":"Nyunt","year":"2017","journal-title":"Malar. J."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1186\/s12936-017-1983-9","article-title":"Clinical and Molecular Surveillance of Artemisinin Resistant Falciparum Malaria in Myanmar (2009\u20132013)","volume":"16","author":"Nyunt","year":"2017","journal-title":"Malar. J."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/s12936-019-2645-x","article-title":"An Online Mapping Database of Molecular Markers of Drug Resistance in Plasmodium Falciparum: The ACT Partner Drug Molecular Surveyor","volume":"18","author":"Otienoburu","year":"2019","journal-title":"Malar. J."},{"key":"ref_14","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_15","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1016\/j.pt.2007.04.013","article-title":"Is PfCRT a Channel or a Carrier? Two Competing Models Explaining Chloroquine Resistance in Plasmodium Falciparum","volume":"23","author":"Sanchez","year":"2007","journal-title":"Trends Parasitol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/S1473-3099(16)30409-1","article-title":"Europe PMC Funders Group Genetic Markers Associated with Dihydroartemisinin\u2014Piperaquine Failure in Plasmodium Falciparum Malaria in Cambodia: A Genotype-Phenotype Association Study","volume":"17","author":"Amato","year":"2017","journal-title":"Lancet Infect. Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1186\/s12936-016-1503-3","article-title":"Selection of Plasmodium Falciparum Pfcrt and Pfmdr1 Polymorphisms after Treatment with Artesunate\u2014Amodiaquine Fixed Dose Combination or Artemether\u2014Lumefantrine in Liberia","volume":"15","author":"Otienoburu","year":"2016","journal-title":"Malar. J."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1186\/1475-2875-10-304","article-title":"A Thirteen-Year Analysis of Plasmodium Falciparum Populations Reveals High Conservation of the Mutant Pfcrt Haplotype despite the Withdrawal of Chloroquine from National Treatment Guidelines in Gabon","volume":"10","author":"Frank","year":"2011","journal-title":"Malar. J."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1186\/s12936-016-1469-1","article-title":"Malaria in Urban, Semi-Urban and Rural Areas of Southern of Gabon: Comparison of the Pfmdr 1 and Pfcrt Genotypes from Symptomatic Children","volume":"15","author":"Nzondo","year":"2016","journal-title":"Malar. J."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/1475-2875-12-3","article-title":"Increase in Malaria Prevalence and Age of at Risk Population in Different Areas of Gabon","volume":"12","author":"Akotet","year":"2013","journal-title":"Malar. J."},{"key":"ref_21","unstructured":"Ndong Ngomo, M.J., Abang Ekouaghe, P.L., M\u2019boundoukowe, N.P., Koumba Lengongo, J.V., Mawili-Mboumba, D.P., and Bouyou-Akotet, M.K. (2016). Profil Clinico-Biologique Du Paludisme Grave Dans Un Contexte de Transition \u00c9pid\u00e9miologique, Congress of the Ivorian Society of Parasitology and Mycology, Universit\u00e9 F\u00e9lix Houphouet-Boigny. [2nd ed.]."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1186\/1475-2875-9-321","article-title":"Malaria Transmission and Insecticide Resistance of Anopheles Gambiae in Libreville and Port-Gentil, Gabon","volume":"9","author":"Mourou","year":"2010","journal-title":"Malar. J."},{"key":"ref_23","unstructured":"(2023, January 16). WHO World Malaria Report 2005 (WHO\/HTM\/MAL\/2005.1102). Available online: https:\/\/www.rbm.who.int\/wmr2005\/html\/1----2.htm."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"599","DOI":"10.4269\/ajtmh.2001.65.599","article-title":"Comparison of Methods for the Rapid Laboratory Assessment of Children with Malaria","volume":"65","author":"Planche","year":"2001","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1128\/AAC.02655-16","article-title":"Molecular Profile of Malaria Drug Resistance Markers of Plasmodium Falciparum in Suriname","volume":"61","author":"Chenet","year":"2017","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2943","DOI":"10.1128\/AAC.43.12.2943","article-title":"The Pfmdr1 Gene Is Associated with a Multidrug-Resistant Phenotype in Plasmodium Falciparum from the Western Border of Thailand","volume":"43","author":"Price","year":"1999","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"11553","DOI":"10.1038\/ncomms11553","article-title":"Globally Prevalent PfMDR1 Mutations Modulate Plasmodium falciparum susceptibility to artemisinin-based combination therapies","volume":"7","author":"Veiga","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_28","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_29","first-page":"1352","article-title":"K13-Propeller Polymorphisms in Plasmodium Falciparum Parasites from Sub-Saharan Africa","volume":"211","author":"Kamau","year":"2015","journal-title":"J. Infect. Dis."},{"key":"ref_30","unstructured":"Wellems, T.E., and Plowe, C. (1990). V Chloroquine-Resistant Malaria, Nature Publishing Group."},{"key":"ref_31","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_32","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1093\/infdis\/jis747","article-title":"Plasmodium Falciparum Drug Resistance Phenotype as Assessed by Patient Antimalarial Drug Levels and Its Association with Pfmdr1 Polymorphisms","volume":"207","author":"Malmberg","year":"2013","journal-title":"J. Infect. Dis."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1","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_34","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1093\/trstmh\/tru147","article-title":"Pfcrt 76T and Pfmdr1 86Y Allele Frequency in Plasmodium Falciparum Isolates and Use of Self-Medication in a Rural Area of Gabon","volume":"108","author":"Ngomo","year":"2014","journal-title":"Trans. R. Soc. Trop. Med. Hyg."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1186\/s12936-016-1306-6","article-title":"Molecular Mutation Profile of Pfcrt in Plasmodium Falciparum Isolates Imported from Africa in Henan Province","volume":"15","author":"Zhou","year":"2016","journal-title":"Malar. J."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1186\/s12936-019-2730-1","article-title":"Efficacy and Safety of Artemether-Lumefantrine for the Treatment of Uncomplicated Malaria and Prevalence of Pfk13 and Pfmdr1 Polymorphisms after a Decade of Using Artemisinin\u2014Based Combination Therapy in Mainland Tanzania","volume":"18","author":"Ishengoma","year":"2019","journal-title":"Malar. J."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.2147\/IDR.S160164","article-title":"Prevalence of Plasmodium Falciparum Antimalarial Drug Resistance Genes in Southeastern Gabon from 2011 to 2014","volume":"11","author":"Kouna","year":"2018","journal-title":"Infect. Drug Resist."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1186\/s12936-017-1816-x","article-title":"Molecular Surveillance of Plasmodium Falciparum Drug Resistance in the Republic of Congo: Four and Nine Years after the Introduction of Artemisinin - Based Combination Therapy","volume":"16","author":"Koussounda","year":"2017","journal-title":"Malar. J."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1186\/s12936-016-1490-4","article-title":"Selection of N86F184D1246 Haplotype of Pfmrd1 Gene by Artemether\u2014Lumefantrine Drug Pressure on Plasmodium Falciparum Populations in Senegal","volume":"15","author":"Mbaye","year":"2016","journal-title":"Malar. J."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1186\/s12936-017-1868-y","article-title":"Molecular Markers of Anti-Malarial Drug Resistance in Central, West and East African Children with Severe Malaria","volume":"16","author":"Nguetse","year":"2017","journal-title":"Malar. J."}],"container-title":["Tropical Medicine and Infectious Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2414-6366\/8\/4\/184\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:01:08Z","timestamp":1760122868000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2414-6366\/8\/4\/184"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,23]]},"references-count":40,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2023,4]]}},"alternative-id":["tropicalmed8040184"],"URL":"https:\/\/doi.org\/10.3390\/tropicalmed8040184","relation":{},"ISSN":["2414-6366"],"issn-type":[{"value":"2414-6366","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,23]]}}}