背景:疟疾负担在撒哈拉以南非洲持续存在,青蒿素耐药性的出现给控制工作带来了复杂性。监测以青蒿素为基础的疟疾治疗的疗效对于应对这一挑战至关重要。这项研究评估了尼日利亚人群中蒿甲醚-本美曲碱(AL)的治疗效果和恶性疟原虫分离株的遗传多样性。
方法:在拉各斯卫生中心出现无并发症疟疾临床症状的参与者,尼日利亚,筛选恶性疟原虫。登记的参与者接受AL治疗,并通过计划的检查访问进行监测,临床和实验室检查28天。通过对裂殖子表面蛋白(msp1和msp2)的聚合酶链反应(PCR)分析评估了寄生虫的清除和遗传多样性。通过恶性疟原虫多药耐药基因1(mdr1)基因分型,然后通过恶性疟原虫泛素特异性蛋白酶1(ubp1)基因测序评估耐药突变的患病率。
结果:未校正的PCR治疗结果显示94.4%的临床和寄生虫学反应(ACPR)和5.6%的晚期寄生虫学衰竭(LPF)率。PCR校正后,未发现疑似LPF病例,所有个体均达到ACPR67/67(100%).此外,mdr1N86Y的野生型等位基因患病率很高(93.7%),和mdr1D1246Y(87.5%)被观察到。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%)。估计感染复数(MOI)为1.7,其中5-15岁年龄组的MOI最高。ubp1序列分析以低频率(1.6%)鉴定了一个非同义E1528D多态性。
结论:该研究证明了AL治疗无并发症的恶性疟原虫疟疾的持续疗效。遗传多样性分析揭示了各种等位基因类型,提示多克隆感染的发生。尽管如此,检测到显著的ubp1多态性可能对人群中抗疟疾药物耐药性的流行病学具有未来意义.
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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%).
CONCLUSIONS: 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.