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菲律宾巴拉望岛疟原虫和间日疟原虫抗疟药物耐药相关突变的流行率和时间变化。

Prevalence and temporal changes of mutations linked to antimalarial drug resistance in Plasmodium falciparum and Plasmodium vivax in Palawan, Philippines.

机构信息

Department of Parasitology and National Reference Centre for Malaria and Other Parasites, Research Institute for Tropical Medicine, Department of Health, Muntinlupa City, Philippines.

Department of Infection Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom.

出版信息

Int J Infect Dis. 2022 Mar;116:174-181. doi: 10.1016/j.ijid.2021.12.318. Epub 2021 Dec 7.

Abstract

OBJECTIVE

This study provides 2016 data on the prevalence of key single nucleotide polymorphisms (SNPs) associated with antimalarial drug resistance in Palawan, Philippines. Findings were combined with historical data to model temporal changes in the prevalence of these SNPs in Plasmodium isolates.

METHODS

Plasmodium isolates were genotyped using drug resistance markers pfmdr1, pfcrt, pfdhfr, pfdhps, kelch-13, pvmdr1, pvdhfr, and pvdhps. Temporal trends in the probability of mutations were estimated as a function of time using a binomial generalised linear model.

RESULTS

All samples sequenced for Plasmodium falciparum chloroquine markers pfmdr1 and pfcrt had wild-type alleles. Varying mutation patterns were observed for the sulphadoxine/pyrimethamine markers pfdhps and pfdhfr; complete quintuplet mutations were not found. No SNPs were observed for the artemisinin marker kelch-13. For Plasmodium vivax, differing patterns were detected for pvmdr1, pvdhfr, and pvdhps.

CONCLUSIONS

The study findings suggest that the current drugs remain effective and that there is limited importation and establishment of resistant parasites in the area. Clear temporal trends were recognised, with prominent decreases in the proportions of pfcrt and pfmdr mutations detected within the past 15 years, consistent with a change in antimalarial drug policy. Continuous surveillance of antimalarial drug resistance is important to support malaria elimination efforts.

摘要

目的

本研究提供了 2016 年菲律宾巴拉望岛与抗疟药物耐药性相关的关键单核苷酸多态性(SNP)流行率数据。研究结果与历史数据相结合,建立了这些 SNP 在疟原虫分离株中流行率的时间变化模型。

方法

使用耐药性标记物 pfmdr1、pfcrt、pfdhfr、pfdhps、kelch-13、pvmdr1、pvdhfr 和 pvdhps 对疟原虫分离株进行基因分型。使用二项广义线性模型,根据时间估计突变概率的时间趋势。

结果

所有测序的恶性疟原虫氯喹标记物 pfmdr1 和 pfcrt 均具有野生型等位基因。磺胺多辛/乙胺嘧啶标记物 pfdhps 和 pfdhfr 的突变模式各不相同;未发现完全五联突变。kelch-13 没有观察到抗青蒿素标记物的 SNP。对于间日疟原虫,pvmdr1、pvdhfr 和 pvdhps 检测到不同的模式。

结论

研究结果表明,目前的药物仍然有效,该地区耐药寄生虫的输入和建立有限。明确的时间趋势被识别出来,过去 15 年来,pfcrt 和 pfmdr 突变的比例显著下降,这与抗疟药物政策的改变一致。对抗疟药物耐药性的持续监测对于支持疟疾消除工作非常重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a66/8866131/e28965ddfb5f/gr1.jpg

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