Tracking Plasmodium falciparum antimalarial resistance markers during a malaria pre-elimination period in the Pacific coast of South America

在南美洲太平洋沿岸疟疾消除前期,追踪恶性疟原虫抗疟药耐药性标记物

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Abstract

Antimalarial resistance in Plasmodium falciparum is a public health problem in the fight against malaria in Ecuador. Characterizing the molecular epidemiology of drug resistance genes helps to understand the emergence and spread of resistant parasites. In this study, the effects of drug pressure and human migration on antimalarial resistance in P. falciparum were evaluated. Sixty-seven samples from northwestern Ecuador from the 2019-2021 period were analyzed. SNPs in Pfcrt, Pfdhps, Pfdhfr, Pfmdr-1, Pfk13 and Pfaat1 were identified by Sanger sequencing and whole-genome sequencing. A comparison of the frequencies of the haplotypes was made with data from the 2013-2015 period. Also, nucleotide and haplotype diversity were calculated. The frequencies of the mutant haplotypes, CVMET in Pfcrt and CICNI in Pfdhfr increased and became dominant (100% of infections) in Esmeraldas. NEDFSDFY in Pfmdr-1 was detected for the first time, while two wild-type haplotypes, SAKAA in Pfdhps and MYRIC in Pfk13, remained in 100% of samples. Interestingly, the A16V mutation in Pfdhfr that gives resistance to proguanil is reported in Ecuador for the first time. In conclusion, parasites resistant to chloroquine (Pfcrt) and pyrimethamine (Pfdhfr) increased in recent years, while parasites sensitive to sulfadoxine (Pfdhps) and artemisinin (Pfk13) prevail in Ecuador. These results suggest that the current first-line treatment (artemether-lumefantrine + primaquine) is still useful against P. falciparum.

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