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评估 2018-2021 年洪都拉斯和尼加拉瓜分离株中 pfcrt 和 pfmdr1 基因的恶性疟原虫抗疟药耐药标志物。

Assessment of Plasmodium falciparum anti-malarial drug resistance markers in pfcrt and pfmdr1 genes in isolates from Honduras and Nicaragua, 2018-2021.

机构信息

Microbiology Research Institute, National Autonomous University of Honduras, Tegucigalpa, Honduras.

National Malaria Laboratory, National Department of Surveillance, Ministry of Health of Honduras, Tegucigalpa, Honduras.

出版信息

Malar J. 2021 Dec 14;20(1):465. doi: 10.1186/s12936-021-03977-8.

Abstract

BACKGROUND

Central America and the island of Hispaniola have set out to eliminate malaria by 2030. However, since 2014 a notable upturn in the number of cases has been reported in the Mosquitia region shared by Nicaragua and Honduras. In addition, the proportion of Plasmodium falciparum malaria cases has increased significantly relative to vivax malaria. Chloroquine continues to be the first-line drug to treat uncomplicated malaria in the region. The objective of this study was to evaluate the emergence of chloroquine resistant strains of P. falciparum using a genetic approach. Plasmodium vivax populations are not analysed in this study.

METHODS

205 blood samples from patients infected with P. falciparum between 2018 and 2021 were analysed. The pfcrt gene fragment encompassing codons 72-76 was analysed. Likewise, three fragments of the pfmdr1 gene were analysed in 51 samples by nested PCR and sequencing.

RESULTS

All samples revealed the CVMNK wild phenotype for the pfcrt gene and the N86, Y184F, S1034C, N1042D, D1246 phenotype for the pfmdr1 gene.

CONCLUSIONS

The increase in falciparum malaria cases in Nicaragua and Honduras cannot be attributed to the emergence of chloroquine-resistant mutants. Other possibilities should be investigated further. This is the first study to report the genotype of pfmdr1 for five loci of interest in Central America.

摘要

背景

中美洲和伊斯帕尼奥拉岛已设定目标,将于 2030 年前消灭疟疾。然而,自 2014 年以来,尼加拉瓜和洪都拉斯共有莫斯基蒂亚地区报告疟疾病例显著增加。此外,与间日疟原虫相比,恶性疟原虫疟疾病例的比例显著增加。氯喹仍然是该地区治疗无并发症疟疾的一线药物。本研究的目的是采用遗传方法评估恶性疟原虫对氯喹耐药株的出现。本研究不分析间日疟原虫种群。

方法

分析了 2018 年至 2021 年间感染恶性疟原虫的 205 例患者的血液样本。分析了包含密码子 72-76 的 pfcrt 基因片段。同样,通过巢式 PCR 和测序分析了 51 个样本中的 pfmdr1 基因的三个片段。

结果

所有样本均显示 pfcrt 基因的 CVMNK 野生表型和 pfmdr1 基因的 N86、Y184F、S1034C、N1042D、D1246 表型。

结论

尼加拉瓜和洪都拉斯恶性疟病例的增加不能归因于氯喹耐药突变体的出现。应进一步调查其他可能性。这是首次在中美洲报告 pfmdr1 基因五个感兴趣的基因座的基因型的研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4332/8670165/9bc875f9b9a1/12936_2021_3977_Fig1_HTML.jpg

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