Table_2_Low Complexity of Infection Is Associated With Molecular Persistence of Plasmodium falciparum in Kenya and Tanzania.XLSX

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.

疟原虫恶性疟（Plasmodium falciparum）对基于青蒿素联合疗法（artemisinin-based combination therapies, ACTs）的抗药性构成了疟疾根除的威胁。亚洲地区ACT抗药性的出现引起了非洲地区抗药性可能出现的担忧。尽管大多数数据表明非洲地区ACT方案的疗效较高，但仍有一些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。研究方法：在肯尼亚和坦桑尼亚，纳入了300名年龄在2至10岁之间的无并发症P. falciparum感染儿童，并在接受阿莫地喹-卢氟沙星治疗后的0小时、24小时、48小时和72小时以及之后的每周，直至治疗28天后采集血液样本。本研究评估了寄生虫和宿主遗传学、临床、行为和环境特征，以及宿主对疟疾血清学反应。研究结果：在两个研究地点，寄生虫清除率存在广泛差异，但在治疗72小时后，肯尼亚和坦桑尼亚的样本中分别有85%和96%为qPCR阳性但显微镜检查阴性。感染复杂性（COI）与72小时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可检测到的寄生虫血症呈边际相关（每1,000个寄生虫/μl的变化，OR：1.02，95% CI：1.01–1.03）。人口统计学、血清学和宿主基因分型特征与72小时可检测到的寄生虫血症无关联。针对寄生虫单倍型特异性的清除斜率围绕平均值分组，未发现特定单倍型与较慢的清除率之间存在关联。研究结论：识别如COI等导致P. falciparum感染清除缓慢的风险因素，对于持续监测肯尼亚、坦桑尼亚以及更广泛的撒哈拉以南非洲地区的ACT治疗失败至关重要。