Title: Plasmodium falciparum Genetic Diversity in Continental Equatorial Guinea before and after Introduction of Artemisinin-Based Combination Therapy
Authors: Guerra, Mónica 
Neres, Rita 
Salgueiro, Patrícia 
Mendes, Cristina 
Ndong-Mabale, Nicolas 
Berzosa, Pedro 
de Sousa, Bruno 
Arez, Ana Paula 
Keywords: Amodiaquine;Antigens, Protozoan;Antimalarials;Artemisinins;Chloroquine;DNA Copy Number Variations;Drug Combinations;Drug Resistance;Equatorial Guinea;Female;Genetic Loci;Genotype;Humans;Malaria, Falciparum;Male;Membrane Transport Proteins;Microsatellite Repeats;Plasmodium falciparum;Point Mutation;Protozoan Proteins;Pyrimethamine;Sulfadoxine;Tetrahydrofolate Dehydrogenase;Genetic Variation
Issue Date: 2017
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.
URI: http://hdl.handle.net/10316/46908
DOI: 10.1128/AAC.02556-15
Rights: openAccess
Appears in Collections:I&D CINEICC - Artigos em Revistas Internacionais

Files in This Item:
File Description SizeFormat 
2017_Guerra_et_al.pdf799.64 kBAdobe PDFView/Open
Show full item record
Google ScholarTM
Check
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.