title: Plasmodium falciparum Genetic Diversity in Continental Equatorial Guinea before and after Introduction of Artemisinin-Based Combination Therapy.
abstract: Efforts to control malaria may affect malaria parasite genetic variability and drug resistance, the latter of which is associated with genetic events that promote mechanisms to escape drug action. The worldwide spread of drug resistance has been a major obstacle to controlling Plasmodium falciparum malaria, and thus the study of the origin and spread of associated mutations may provide some insights into the prevention of its emergence. This study reports an analysis of P. falciparum genetic diversity, focusing on antimalarial resistance-associated molecular markers in two socioeconomically different villages in mainland Equatorial Guinea. The present study took place 8 years after a previous one, allowing the analysis of results before and after the introduction of an artemisinin-based combination therapy (ACT), i.e., artesunate plus amodiaquine. Genetic diversity was assessed by analysis of the Pfmsp2 gene and neutral microsatellite loci. Pfdhps and Pfdhfr alleles associated with sulfadoxine-pyrimethamine (SP) resistance and flanking microsatellite loci were investigated, and the prevalences of drug resistance-associated point mutations of the Pfcrt, Pfmdr1, Pfdhfr, and Pfdhps genes were estimated. Further, to monitor the use of ACT, we provide the baseline prevalences of K13 propeller mutations and Pfmdr1 copy numbers. After 8 years, noticeable differences occurred in the distribution of genotypes conferring resistance to chloroquine and SP, and the spread of mutated genotypes differed according to the setting. Regarding artemisinin resistance, although mutations reported as being linked to artemisinin resistance were not present at the time, several single nucleotide polymorphisms (SNPs) were observed in the K13 gene, suggesting that closer monitoring should be maintained to prevent the possible spread of artemisinin resistance in Africa.
authors: Global Health and Tropical Medicine (GHTM), Instituto de Higiene e Medicina Tropical (IHMT), Universidade Nova de Lisboa (UNL), Lisbon, Portugal.
authors: Mónica
authors: M
authors: Guerra
authors: Global Health and Tropical Medicine (GHTM), Instituto de Higiene e Medicina Tropical (IHMT), Universidade Nova de Lisboa (UNL), Lisbon, Portugal.
authors: Rita
authors: R
authors: Neres
authors: Global Health and Tropical Medicine (GHTM), Instituto de Higiene e Medicina Tropical (IHMT), Universidade Nova de Lisboa (UNL), Lisbon, Portugal.
authors: Patrícia
authors: P
authors: Salgueiro
authors: Global Health and Tropical Medicine (GHTM), Instituto de Higiene e Medicina Tropical (IHMT), Universidade Nova de Lisboa (UNL), Lisbon, Portugal.
authors: Cristina
authors: C
authors: Mendes
authors: Centro de Referencia para el Control de Endemias, Instituto de Salud Carlos III, Bata, Equatorial Guinea.
authors: Nicolas
authors: N
authors: Ndong-Mabale
authors: Centro Nacional de Medicina Tropical, Instituto de Salud Carlos III, Madrid, Spain.
authors: Pedro
authors: P
authors: Berzosa
authors: Faculdade de Psicologia e de Ciências da Educação, Universidade de Coimbra, Coimbra, Portugal.
authors: Bruno
authors: B
authors: de Sousa
authors: Global Health and Tropical Medicine (GHTM), Instituto de Higiene e Medicina Tropical (IHMT), Universidade Nova de Lisboa (UNL), Lisbon, Portugal aparez@ihmt.unl.pt.
authors: Ana Paula
authors: 0000-0002-0497-6532
authors: AP
authors: Arez
mesh_terms: D000655:Amodiaquine / Q000627:therapeutic use*; D000953:Antigens, Protozoan / Q000235:genetics / Q000378:metabolism; D000962:Antimalarials / Q000627:therapeutic use*; D037621:Artemisinins / Q000627:therapeutic use*; D000077332:Artesunate; D002738:Chloroquine / Q000627:therapeutic use; D056915:DNA Copy Number Variations; D004338:Drug Combinations; D004351:Drug Resistance / Q000235:genetics*; D016703:Equatorial Guinea; D005260:Female; D056426:Genetic Loci; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000469:parasitology; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D018895:Microsatellite Repeats; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development; D017354:Point Mutation; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism; D011739:Pyrimethamine / Q000627:therapeutic use; D013413:Sulfadoxine / Q000627:therapeutic use; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics / Q000378:metabolism
chemical_list: D000953:Antigens, Protozoan; D000962:Antimalarials; D037621:Artemisinins; D004338:Drug Combinations; D026901:Membrane Transport Proteins; C416369:PfCRT protein, Plasmodium falciparum; D015800:Protozoan Proteins; C065974:merozoite surface protein 2, Plasmodium; D000655:Amodiaquine; C001205:fanasil, pyrimethamine drug combination; D000077332:Artesunate; D013413:Sulfadoxine; D002738:Chloroquine; D013762:Tetrahydrofolate Dehydrogenase; D011739:Pyrimethamine
keywords: ACT introduction; Equatorial Guinea; Kelch propeller protein K13 polymorphisms; Pfcrt; Pfdhfr; Pfdhps; Pfmdr1; Plasmodium falciparum; drug resistance molecular markers; genetic diversity; malaria; neutral and flanking microsatellites