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2012-2022 年期间西非地区疟原虫分离株中磺胺多辛-乙胺嘧啶耐药相关分子标志物的流行情况。

Prevalence of molecular markers of sulfadoxine-pyrimethamine resistance in Plasmodium falciparum isolates from West Africa during 2012-2022.

机构信息

Department of Parasite Disease Control and Prevention, Henan Provincial Key Laboratory of Pathogenic Microbiology, Henan Provincial Medical Key Laboratory of Parasitic Diseases and Vector, Henan Province Center for Disease Control and Prevention, Zhengzhou, People's Republic of China.

College of Public Health, Zhengzhou University, Zhengzhou, People's Republic of China.

出版信息

Sci Rep. 2024 Nov 4;14(1):26567. doi: 10.1038/s41598-024-75828-w.

Abstract

Sulfadoxine-pyrimethamine (SP) is a key drug recommended by the World Health Organization for the chemoprevention of malaria. However, the strategy is affected by the parasite resistance to SP. This study evaluated Plasmodium falciparum dihydrofolate reductase (Pfdhfr) and dihydropteroate synthase (Pfdhps) genes, associated with SP resistance, from 508 P. falciparum isolates imported from West African countries to Henan Province, China, during 2012-2022. High mutant prevalence of the genes Pfdhfr (94.7%) and Pfdhps (96.8%) was observed. The mutants Pfdhfr N51I, C59R, S108N, and Pfdhps A437G were at high frequency in all countries analyzed. The overall prevalence of the mutant Pfdhps K540E was low (3.4%), but with a high frequency in Liberia (24.3%). The frequency of mutants Pfdhps I431V, A581G, and A613S was 11.7%, 9.8%, and 16.2%, respectively, all of which had the highest mutant prevalence in Nigeria. The mutant Pfdhps A581G and A613S were identified in the absence of K540E. The partially resistant haplotype (IRN - G) was the most common (72.6%), and the fully resistant haplotype (IRN - GE) had a low prevalence of 3.4% and mainly occurred in Liberia. No super resistant haplotype was identified. The mutant Pfdhps I431V and the octuple mutant haplotype IRN - VAGGS deserve more attention. In areas of high SP resistance, the intervention still reduces low birthweight and maternal anaemia. SP should continue to be used in areas of high SP resistance until more effective alternatives for malaria chemoprevention are found. It is important to continuously monitor the molecular markers associated with SP resistance to better implement intermittent preventive treatment policies in pregnancy (IPTp) and infants (IPTi).

摘要

磺胺多辛-乙胺嘧啶(SP)是世界卫生组织推荐的用于疟疾化学预防的关键药物。然而,该策略受到寄生虫对 SP 耐药性的影响。本研究评估了 2012 年至 2022 年期间从西非国家输入中国河南省的 508 株恶性疟原虫二氢叶酸还原酶(Pfdhfr)和二氢蝶酸合成酶(Pfdhps)基因与 SP 耐药性相关的基因。观察到这些基因 Pfdhfr(94.7%)和 Pfdhps(96.8%)的突变体高流行率。所有分析国家均高度流行 Pfdhfr N51I、C59R、S108N 和 Pfdhps A437G 突变体。突变体 Pfdhps K540E 的总体流行率较低(3.4%),但在利比里亚的流行率较高(24.3%)。突变体 Pfdhps I431V、A581G 和 A613S 的流行率分别为 11.7%、9.8%和 16.2%,均在尼日利亚的流行率最高。突变体 Pfdhps A581G 和 A613S 的出现与 K540E 无关。部分耐药单倍型(IRN-G)最常见(72.6%),完全耐药单倍型(IRN-GE)的流行率较低(3.4%),主要发生在利比里亚。未鉴定出超级耐药单倍型。突变体 Pfdhps I431V 和八倍突变体单倍型 IRN-VAGGS 值得更多关注。在 SP 耐药性高的地区,干预仍可降低低出生体重和产妇贫血。在找到更有效的疟疾化学预防替代方法之前,SP 应继续在 SP 耐药性高的地区使用。重要的是要不断监测与 SP 耐药性相关的分子标志物,以更好地实施妊娠间歇性预防治疗(IPTp)和婴儿间歇性预防治疗(IPTi)政策。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60a1/11535326/7689834d9dc4/41598_2024_75828_Fig1_HTML.jpg

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