Plasmodium falciparum population dynamics during the early phase of anti-malarial drug treatment in Tanzanian children with acute uncomplicated malaria
Plasmodium falciparum population dynamics during the early phase of anti-malarial drug treatment in Tanzanian children with acute uncomplicated malaria
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DOI：
10.1186/1475-2875-10-380
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发表时间：
2011-12-20
期刊：
影响因子：
3
通讯作者：
Martensson, Andreas
中科院分区：
文献类型：
--
作者：
Carlsson, Anja M.;Ngasala, Billy E.;Martensson, Andreas
背景：本研究旨在探讨非洲高传播地区临床疟疾儿童接受以青蒿素为基础的联合治疗的抗疟药物治疗早期恶性疟种群动态。方法：纳入坦桑尼亚巴加莫约区 50 名 1-10 岁急性无并发症恶性疟儿童。参与者住院并根据体重接受监督标准治疗，三天内分六剂服用蒿甲醚-本芴醇。采集血样 11 次，即诊断时（-2 小时）以及治疗开始后 0、2、4、8、16、24、36、48、60 和 72 小时。使用巢式聚合酶链反应 (PCR) 对裂殖子表面蛋白 (msp) 1 和 2 进行基因分型来评估寄生虫种群动态。结果：对开始治疗后收集的 9 个连续血液样本进行 PCR 分析，分别在 15/50 (30%) 和 14/50 (28%) 患有 msp1 和 msp2 的儿童中识别出 20 和 21 个额外基因型，在治疗前样本中未检测到 (-2和 0 小时合计）。这些基因型中约 15/20 (75%) 和 14/21 (67%) 在 24 小时内被鉴定，而 msp1 和 msp2 在 48 小时内分别鉴定出 17/20 (85%) 和 19/21 (90%)。基因型谱多种多样，并且随着时间的推移，患者内部和患者之间、分子标记及其各自的家族之间都有很大差异。结论：对早期治疗阶段收集的多个血液样本进行 PCR 分析揭示了寄生虫亚群的复杂情况。这强调了谨慎解释 PCR 结果的重要性，并表明目前在抗疟疾药物试验中使用配对血液样本进行 PCR 调整可能高估了非洲高传播地区药物疗效的评估。该研究已在 http://www.clinicaltrials.gov 注册，标识符为 NCT00336375。
Background: This study aimed to explore Plasmodium falciparum population dynamics during the early phase of anti-malarial drug treatment with artemisinin-based combination therapy in children with clinical malaria in a high transmission area in Africa.Methods: A total of 50 children aged 1-10 years with acute uncomplicated P. falciparum malaria in Bagamoyo District, Tanzania, were enrolled. Participants were hospitalized and received supervised standard treatment with artemether-lumefantrine according to body weight in six doses over 3 days. Blood samples were collected 11 times, i.e. at time of diagnosis (-2 h) and 0, 2, 4, 8, 16, 24, 36, 48, 60 and 72 h after initiation of treatment. Parasite population dynamics were assessed using nested polymerase chain reaction (PCR)-genotyping of merozoite surface protein (msp) 1 and 2.Results: PCR-analyses from nine sequential blood samples collected after initiation of treatment identified 20 and 21 additional genotypes in 15/50 (30%) and 14/50 (28%) children with msp1 and msp2, respectively, non-detectable in the pre-treatment samples (-2 and 0 h combined). Some 15/20 (75%) and 14/21 (67%) of these genotypes were identified within 24 h, whereas 17/20 (85%) and 19/21 (90%) within 48 h for msp1 and msp2, respectively. The genotype profile was diverse, and varied considerably over time both within and between patients, molecular markers and their respective families.Conclusion: PCR analyses from multiple blood samples collected during the early treatment phase revealed a complex picture of parasite sub-populations. This underlines the importance of interpreting PCR-outcomes with caution and suggests that the present use of PCR-adjustment from paired blood samples in anti-malarial drug trials may overestimate assessment of drug efficacy in high transmission areas in Africa. The study is registered at http://www.clinicaltrials.gov with identifier NCT00336375.