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尼日利亚西南部接受磺胺多辛-乙胺嘧啶间歇性预防治疗的无症状孕妇中恶性疟原虫抗原生物标志物的基因分析

Genetic profiling of Plasmodium falciparum antigenic biomarkers among asymptomatic pregnant women on intermittent preventive treatment with sulfadoxine-pyrimethamine from southwest Nigeria.

作者信息

Funwei R I, Olaleye A, Uyaiabasi G N, Hammed W, Obadimeji M M, Elikwu C J, Adepoju A, Okangba C, Akinyede A, Ojurongbe O, Falade C, Walker O

机构信息

Department of Pharmacology, Babcock University, Ilishan-Remo, Ogun, Nigeria; Centre for Advanced Medical Research and Biotechnology, Babcock University, Ilishan-Remo, Ogun, Nigeria.

Two Hills Medical Clinic, Two Hills, Alberta, Canada; Centre for Advanced Medical Research and Biotechnology, Babcock University, Ilishan-Remo, Ogun, Nigeria.

出版信息

Placenta. 2025 Jan;159:161-169. doi: 10.1016/j.placenta.2024.12.016. Epub 2024 Dec 22.

Abstract

INTRODUCTION

The genetic complexity of Plasmodium falciparum is contributory to the emergence of drug resistant-parasites. Intermittent preventive treatment of malaria in pregnancy with sulfadoxine-pyrimethamine (IPTp-SP) in malaria endemic settings is recommended by WHO. This study evaluated the prevalence of Plasmodium falciparum multidrug resistance-1 gene (Pfmdr-1), genetic diversity of merozoite surface proteins (msp-1, msp-2) and glutamate-rich protein (glurp) among pregnant women with sub-patent parasitaemia from southwest Nigeria.

METHODS

One hundred PCR-confirmed Plasmodium falciparum isolates, collected at first visit-V-1 (n = 52), delivery (n = 31) and cord blood (n = 17), were selected for analysis. The Pfmdr-1 alleles was evaluated using restriction fragment length polymorphism (RLFP), while msp-1, msp-2 and glurp genes were genotyped. Allelic frequency distribution and multiplicity of infection were calculated at p-value ≤0.05.

RESULTS

The Pfmdr-1 (N86/N86Y) combination was detected in 11.8 %, 61.3 % and 58.8 % (p ≤ 0.05) in V-1, Delivery and Cord isolates respectively. The N86Y haplotype was detected only in cord (5.9 %). The allelic frequency distribution for msp-1 was 244 (K1 = 81, MAD20 = 84 and RO33 = 79), and msp-2; 110 alleles, representing 43.6 % (FC27) and 56.4 % (3D7). While glurp expressed 25 alleles, 84 % (V-1), 12 % (delivery) and 4 % (cord), respectively (p ≤ 0.05). The msp-1 and msp-2 recorded higher MOIs than glurp.

DISCUSSION

Genetically diverse P. falciparum strains with Pfmdr-1 mutant alleles were detected in pregnant women with sub-patent parasitaemia in southwest Nigeria, which may reduce IPTp-SP effectiveness. Thus, continuous molecular surveillance of resistant-parasites to sulphadoxine-pyrimethamine and ACTs is essential.

摘要

引言

恶性疟原虫的遗传复杂性促使耐药寄生虫的出现。世界卫生组织建议在疟疾流行地区对孕妇进行磺胺多辛-乙胺嘧啶间歇性预防治疗(IPTp-SP)。本研究评估了尼日利亚西南部亚临床疟原虫血症孕妇中恶性疟原虫多药耐药-1基因(Pfmdr-1)的流行情况、裂殖子表面蛋白(msp-1、msp-2)和富含谷氨酸蛋白(glurp)的遗传多样性。

方法

选取100株经聚合酶链反应(PCR)确诊的恶性疟原虫分离株进行分析,这些分离株分别在首次就诊-V-1(n = 52)、分娩时(n = 31)和脐血(n = 17)采集。使用限制性片段长度多态性(RLFP)评估Pfmdr-1等位基因,同时对msp-1、msp-2和glurp基因进行基因分型。在p值≤0.05时计算等位基因频率分布和感染复数。

结果

Pfmdr-1(N86/N86Y)组合在V-1、分娩和脐血分离株中的检出率分别为11.8%、61.3%和58.8%(p≤0.05)。N86Y单倍型仅在脐血中检出(5.9%)。msp-1的等位基因频率分布为244(K1 = 81、MAD20 = 84和RO33 = 79),msp-2为110个等位基因,分别代表43.6%(FC27)和56.4%(3D7)。而glurp表达25个等位基因,分别为84%(V-1)、12%(分娩时)和4%(脐血)(p≤0.05)。msp-1和msp-2的感染复数高于glurp。

讨论

在尼日利亚西南部亚临床疟原虫血症孕妇中检测到具有Pfmdr-1突变等位基因的基因多样化恶性疟原虫菌株,这可能会降低IPTp-SP的有效性。因此,持续对磺胺多辛-乙胺嘧啶和青蒿素类联合疗法耐药寄生虫进行分子监测至关重要。

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