恶性疟原虫在坦桑尼亚患有急性无并发症疟疾的儿童接受抗疟药物治疗早期阶段的种群动态。

Plasmodium falciparum population dynamics during the early phase of anti-malarial drug treatment in Tanzanian children with acute uncomplicated malaria.

机构信息

Infectious Diseases Unit, Department of Medicine Solna, Karolinska University Hospital, Karolinska Institutet, Retzius väg 10, S-171 77 Stockholm, Sweden.

出版信息

Malar J. 2011 Dec 20;10:380. doi: 10.1186/1475-2875-10-380.

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.

背景

本研究旨在探索在非洲高传播地区，采用青蒿素为基础的联合疗法治疗儿童临床疟疾时，抗疟药物治疗早期疟原虫种群动态。

方法

坦桑尼亚巴加莫约区共纳入 50 名年龄在 1-10 岁的急性无并发症恶性疟原虫感染儿童。参与者被收入院，根据体重接受 6 剂青蒿琥酯-咯萘啶监督下标准治疗，3 天内完成。共采集血样 11 次，即在诊断时（-2 h）和治疗开始后 0、2、4、8、16、24、36、48、60 和 72 h 时。采用巢式聚合酶链反应（PCR）-裂殖子表面蛋白（msp）1 和 2 基因分型来评估寄生虫种群动态。

结果

治疗开始后 9 次连续血样的 PCR 分析在 15/50（30%）和 14/50（28%）儿童的 msp1 和 msp2 中发现了 20 和 21 种额外基因型，在治疗前样本（-2 和 0 h 合并）中不可检测。这些基因型中的 15/20（75%）和 14/21（67%）在 24 小时内被识别，而 msp1 和 msp2 分别为 17/20（85%）和 19/21（90%）。基因型谱多样，在患者内和患者间、分子标记及其各自家族中，随时间变化较大。

结论

在早期治疗阶段采集的多个血样的 PCR 分析显示出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，并表明目前在抗疟药物试验中使用配对血样进行 PCR 调整可能高估了在非洲高传播地区的药物疗效评估。本研究在 http://www.clinicaltrials.gov 注册，注册号为 NCT00336375。