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鉴定刚果民主共和国 PfK13 突变株 R561H 和 P441L。

Identification of the PfK13 mutations R561H and P441L in the Democratic Republic of Congo.

机构信息

Department of Pharmacology and Therapeutics, University of Kinshasa, Kinshasa, Democratic Republic of the Congo.

Center for Medical Parasitology, Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark; Department of Infectious Diseases, Copenhagen University Hospital, Copenhagen, Denmark.

出版信息

Int J Infect Dis. 2024 Feb;139:41-49. doi: 10.1016/j.ijid.2023.11.026. Epub 2023 Nov 26.

Abstract

OBJECTIVES

Partial artemisinin resistance, mediated by Plasmodium falciparum K13 (PfK13) mutations, has been confirmed in certain areas of East Africa that are historically associated with high-level antimalarial resistance. The Democratic Republic of Congo (DRC) borders these areas in the East. This study aimed to determine the prevalence of resistance markers in six National Malaria Control Program surveillance sites; Boende, Kabondo, Kapolowe, Kimpese, Mikalayi, and Rutshuru.

METHODS

The single nucleotide polymorphisms (SNPs) in P. falciparum genes PfK13, Pfdhfr, Pfdhps, Pfmdr1, and Pfcrt were assessed using targeted next-generation sequencing of isolates collected at enrollment in therapeutic efficacy studies.

RESULTS

PfK13 SNPs were detected in two samples: in Kabondo (R561H) and in Rutshuru (P441L), both areas near Uganda and Rwanda. The Pfdhps ISGEGA haplotype, associated with reduced sulfadoxine-pyrimethamine chemoprevention efficacy, ranged from 0.8% in Mikalayi (central DRC) to 42.2% in Rutshuru (East DRC).

CONCLUSIONS

R561H and P441L observed in eastern DRC are a concern, as they are associated with delayed artemisinin-based combination therapies-clearance and candidate marker of resistance, respectively. This is consistent with previous observations of shared drug resistance profiles in parasites of that region with bordering areas of Rwanda and Uganda. The likely circulation of parasites has important implications for the ongoing surveillance of partial artemisinin-resistant P. falciparum and for future efforts to mitigate its dispersal.

摘要

目的

由恶性疟原虫 K13(PfK13)突变介导的青蒿素部分耐药性已在东非某些历史上与高水平抗疟药耐药性相关的地区得到证实。刚果民主共和国(DRC)与这些地区接壤。本研究旨在确定六个国家疟疾控制规划监测点(Boende、Kabondo、Kapolowe、Kimpese、Mikalayi 和 Rutshuru)中耐药标记物的流行率。

方法

采用靶向性下一代测序技术对招募参加疗效研究的分离株进行 PfK13、Pfdhfr、Pfdhps、Pfmdr1 和 Pfcrt 等基因的单核苷酸多态性(SNPs)检测。

结果

在 Kabondo(R561H)和 Rutshuru(P441L)两个靠近乌干达和卢旺达的地区检测到 PfK13 SNPs。与磺胺多辛-乙胺嘧啶化学预防效果降低相关的 Pfdhps ISGEGA 单倍型,从位于刚果民主共和国中部的 Mikalayi(0.8%)到位于刚果民主共和国东部的 Rutshuru(42.2%)不等。

结论

在刚果民主共和国东部观察到的 R561H 和 P441L 令人担忧,因为它们分别与青蒿素为基础的联合治疗清除延迟和耐药候选标记物相关。这与该地区与卢旺达和乌干达接壤地区寄生虫耐药谱的共享相一致。寄生虫的可能传播对正在进行的青蒿素部分耐药性恶性疟原虫的监测以及未来减轻其传播的努力具有重要意义。

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