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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物耐药性标志物

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

作者信息

Ñacata Isaac, Early Angela M, Boboy Janeth, Neafsey Daniel E, Sáenz Fabián E

机构信息

Centro de Investigación para la Salud en América Latina, Facultad de Ciencias Exactas y Naturales, Pontificia Universidad Católica del Ecuador, Quito, Ecuador.

Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA.

出版信息

Sci Rep. 2025 Jul 14;15(1):25376. doi: 10.1038/s41598-025-10500-5.

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.

摘要

恶性疟原虫的抗疟药耐药性是厄瓜多尔抗击疟疾过程中的一个公共卫生问题。对耐药基因的分子流行病学特征进行表征有助于了解耐药寄生虫的出现和传播情况。在本研究中,评估了药物压力和人类迁移对恶性疟原虫抗疟药耐药性的影响。分析了2019年至2021年期间来自厄瓜多尔西北部的67个样本。通过桑格测序和全基因组测序鉴定了Pfcrt、Pfdhps、Pfdhfr、Pfmdr-1、Pfk13和Pfaat1中的单核苷酸多态性。将单倍型频率与2013年至2015年期间的数据进行了比较。此外,还计算了核苷酸和单倍型多样性。在埃斯梅拉达斯,Pfcrt中的突变单倍型CVMET和Pfdhfr中的CICNI的频率增加并成为主导(100%的感染)。首次检测到Pfmdr-1中的NEDFSDFY,而Pfdhps中的SAKAA和Pfk13中的MYRIC这两种野生型单倍型在100%的样本中仍然存在。有趣的是,在厄瓜多尔首次报道了赋予对氯胍耐药性的Pfdhfr中的A16V突变。总之,近年来对氯喹(Pfcrt)和乙胺嘧啶(Pfdhfr)耐药的寄生虫有所增加,而对磺胺多辛(Pfdhps)和青蒿素(Pfk13)敏感的寄生虫在厄瓜多尔占主导地位。这些结果表明,目前的一线治疗方案(蒿甲醚-本芴醇+伯氨喹)对恶性疟原虫仍然有效。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7585/12259837/18c72a4b87de/41598_2025_10500_Fig1_HTML.jpg

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