Centre for Genomic Research in Biomedicine, Mountain Top University, Ibafo, Nigeria.
Nigerian Institute of Medical Research, Lagos, Nigeria.
Malar J. 2024 Aug 29;23(1):261. doi: 10.1186/s12936-024-05088-6.
The burden of malaria persists in sub-Saharan Africa and the emergence of artemisinin resistance has introduced complexity to control efforts. Monitoring the efficacy of artemisinin-based treatment for malaria is crucial to address this challenge. This study assessed treatment efficacy of artemether-lumefantrine (AL) and genetic diversity of Plasmodium falciparum isolates in a Nigerian population.
Participants presenting with clinical symptoms of uncomplicated malaria at a health centre in Lagos, Nigeria, were screened for P. falciparum. Enrolled participants were treated with AL and monitored through scheduled check-up visits, clinical and laboratory examinations for 28 days. Parasite clearance and genetic diversity were assessed through polymerase chain reaction (PCR) analysis of merozoite surface proteins (msp1 and msp2). The prevalence of drug resistance mutations was assessed by P. falciparum multidrug resistance gene 1 (mdr1) genotyping followed by P. falciparum ubiquitin-specific protease 1 (ubp1) gene sequencing.
The PCR-uncorrected treatment outcome revealed 94.4% adequate clinical and parasitological response (ACPR) and 5.6% late parasitological failure (LPF) rates. After PCR correction, no suspected LPF case was detected and ACPR 67/67 (100%) was achieved in all the individuals. Moreover, a high prevalence of wild-type alleles for mdr1 N86Y (93.7%), and mdr1 D1246Y (87.5%) was observed. Genetic diversity analysis revealed predominant K1 allelic family for msp1 (90.2%) and FC27 for msp2 (64.4%). Estimated multiplicity of infection (MOI) was 1.7, with the highest MOI observed in the 5-15 years age group. ubp1 sequence analysis identified one nonsynonymous E1528D polymorphism at a low frequency (1.6%).
The study demonstrated sustained efficacy of AL for treating uncomplicated P. falciparum malaria. Genetic diversity analysis revealed various allelic types, suggesting occurrences of polyclonal infections. Nonetheless, the detection of a significant ubp1 polymorphism could have future implications for the epidemiology of anti-malarial drug resistance in the population.
疟疾在撒哈拉以南非洲仍然存在，并且青蒿素耐药性的出现给控制工作带来了复杂性。监测青蒿素为基础的疟疾治疗效果对于应对这一挑战至关重要。本研究评估了尼日利亚人群中青蒿琥酯-咯萘啶（AL）的治疗效果和恶性疟原虫分离株的遗传多样性。
在尼日利亚拉各斯的一个医疗中心，对出现无并发症疟疾临床症状的参与者进行恶性疟原虫筛查。入组的参与者接受 AL 治疗，并通过定期随访、临床和实验室检查监测 28 天。通过聚合酶链反应（PCR）分析裂殖子表面蛋白（msp1 和 msp2）评估寄生虫清除率和遗传多样性。通过恶性疟原虫多药耐药基因 1（mdr1）基因分型评估耐药突变的流行率，然后对恶性疟原虫泛素特异性蛋白酶 1（ubp1）基因进行测序。
未经 PCR 校正的治疗结果显示，充分的临床和寄生虫学反应（ACPR）为 94.4%，迟发性寄生虫学失败（LPF）率为 5.6%。经 PCR 校正后，未发现疑似 LPF 病例，所有个体的 ACPR 为 67/67（100%）。此外，mdr1 N86Y（93.7%）和 mdr1 D1246Y（87.5%）野生型等位基因的高流行率。遗传多样性分析显示 msp1 的主要 K1 等位基因家族（90.2%）和 msp2 的 FC27（64.4%）。估计感染量（MOI）为 1.7，最高 MOI 见于 5-15 岁年龄组。ubp1 序列分析发现一个低频的非同义 E1528D 多态性（1.6%）。
本研究表明，AL 对治疗无并发症恶性疟原虫疟疾的疗效持续。遗传多样性分析显示存在各种等位基因类型，表明存在多克隆感染。尽管 ubp1 多态性的检测可能对该人群抗疟药物耐药性的流行病学有重要意义。
