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Plasmodium falciparum Genetic Diversity in Continental Equatorial Guinea before and after Introduction of Artemisinin-Based Combination Therapy

Identifieur interne : 001230 ( Main/Curation ); précédent : 001229; suivant : 001231

Plasmodium falciparum Genetic Diversity in Continental Equatorial Guinea before and after Introduction of Artemisinin-Based Combination Therapy

Auteurs : M Nica Guerra [Portugal] ; Rita Neres [Portugal] ; Patrícia Salgueiro [Portugal] ; Cristina Mendes [Portugal] ; Nicolas Ndong-Mabale [Guinée équatoriale] ; Pedro Berzosa [Espagne] ; Bruno De Sousa [Portugal] ; Ana Paula Arez [Portugal]

Source :

Antimicrobial Agents and Chemotherapy [ 0066-4804 ] ; 2016.

RBID : PMC:5192141

Abstract

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.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5192141

DOI: 10.1128/AAC.02556-15
PubMed: 27795385
PubMed Central: 5192141

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PMC:5192141

Le document en format XML

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 Genetic Diversity in Continental Equatorial Guinea before and after Introduction of Artemisinin-Based Combination Therapy</title>
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 Genetic Diversity in Continental Equatorial Guinea before and after Introduction of Artemisinin-Based Combination Therapy</title>
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<series><title level="j">Antimicrobial Agents and Chemotherapy</title>
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<front><div type="abstract" xml:lang="en"><title>ABSTRACT</title>
<p>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 <named-content content-type="genus-species">Plasmodium falciparum</named-content>
 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 <named-content content-type="genus-species">P. falciparum</named-content>
 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 <italic>Pfmsp2</italic>
 gene and neutral microsatellite loci. <italic>Pfdhps</italic>
 and <italic>Pfdhfr</italic>
 alleles associated with sulfadoxine-pyrimethamine (SP) resistance and flanking microsatellite loci were investigated, and the prevalences of drug resistance-associated point mutations of the <italic>Pfcrt</italic>
, <italic>Pfmdr1</italic>
, <italic>Pfdhfr</italic>
, and <italic>Pfdhps</italic>
 genes were estimated. Further, to monitor the use of ACT, we provide the baseline prevalences of K13 propeller mutations and <italic>Pfmdr1</italic>
 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.</p>
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Plasmodium falciparum Genetic Diversity in Continental Equatorial Guinea before and after Introduction of Artemisinin-Based Combination Therapy

Plasmodium falciparum Genetic Diversity in Continental Equatorial Guinea before and after Introduction of Artemisinin-Based Combination Therapy

Source :

Abstract

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