Data_Sheet_2_Low Complexity of Infection Is Associated With Molecular Persistence of Plasmodium falciparum in Kenya and Tanzania.PDF

BackgroundPlasmodium falciparum resistance to artemisinin-based combination therapies (ACTs) is a threat to malaria elimination. ACT-resistance in Asia raises concerns for emergence of resistance in Africa. While most data show high efficacy of ACT regimens in Africa, there have been reports describing declining efficacy, as measured by both clinical failure and prolonged parasite clearance times.MethodsThree hundred children aged 2–10 years with uncomplicated P. falciparum infection were enrolled in Kenya and Tanzania after receiving treatment with artemether-lumefantrine. Blood samples were taken at 0, 24, 48, and 72 h, and weekly thereafter until 28 days post-treatment. Parasite and host genetics were assessed, as well as clinical, behavioral, and environmental characteristics, and host anti-malarial serologic response.ResultsWhile there was a broad range of clearance rates at both sites, 85% and 96% of Kenyan and Tanzanian samples, respectively, were qPCR-positive but microscopy-negative at 72 h post-treatment. A greater complexity of infection (COI) was negatively associated with qPCR-detectable parasitemia at 72 h (OR: 0.70, 95% CI: 0.53–0.94), and a greater baseline parasitemia was marginally associated with qPCR-detectable parasitemia (1,000 parasites/uL change, OR: 1.02, 95% CI: 1.01–1.03). Demographic, serological, and host genotyping characteristics showed no association with qPCR-detectable parasitemia at 72 h. Parasite haplotype-specific clearance slopes were grouped around the mean with no association detected between specific haplotypes and slower clearance rates.ConclusionsIdentifying risk factors for slow clearing P. falciparum infections, such as COI, are essential for ongoing surveillance of ACT treatment failure in Kenya, Tanzania, and more broadly in sub-Saharan Africa.

背景：恶性疟原虫对基于青蒿素联合疗法（ACTs）的耐药性构成了疟疾根除的威胁。亚洲地区ACTs的耐药性问题引发了非洲地区出现耐药性的担忧。尽管多数数据显示非洲地区ACTs治疗方案具有高疗效，但已有报道指出其疗效呈现下降趋势，这一趋势可通过临床治疗失败和寄生虫清除时间延长来衡量。方法：在肯尼亚和坦桑尼亚，对300名2至10岁的无并发症恶性疟原虫感染儿童进行了治疗，治疗药物为双氢青蒿素-乙胺嘧啶。分别在治疗前的0小时、24小时、48小时、72小时以及治疗后的每周进行血液样本采集，直至28天。对寄生虫和宿主遗传学进行了评估，同时分析了临床、行为和环境特征，以及宿主对疟疾的血清学反应。结果：在两个研究地点均观察到广泛的清除率，但72小时后，85%的肯尼亚样本和96%的坦桑尼亚样本在qPCR检测中呈阳性，但在显微镜下呈阴性。感染复杂性（COI）与72小时内的qPCR可检测到的寄生虫血症呈负相关（OR：0.70，95%CI：0.53–0.94），而基线寄生虫血症与qPCR可检测到的寄生虫血症呈边际相关（每微升1,000个寄生虫的变化，OR：1.02，95%CI：1.01–1.03）。人口统计学、血清学以及宿主基因分型特征与72小时内的qPCR可检测到的寄生虫血症无相关性。寄生虫单倍型特异性清除斜率围绕平均值分组，未检测到特定单倍型与清除速率减慢之间的关联。结论：识别如COI等导致恶性疟原虫感染清除缓慢的风险因素对于肯尼亚、坦桑尼亚及撒哈拉以南非洲地区持续监测ACTs治疗失败至关重要。