Revisiting the circulation time of Plasmodium falciparum gametocytes: molecular detection methods to estimate the duration of gametocyte carriage and the effect of gametocytocidal drugs
Revisiting the circulation time of Plasmodium falciparum gametocytes: molecular detection methods to estimate the duration of gametocyte carriage and the effect of gametocytocidal drugs
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DOI：
10.1186/1475-2875-9-136
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发表时间：
2010-05-24
期刊：
影响因子：
3
通讯作者：
Drakeley, Chris
中科院分区：
文献类型：
--
作者：
Bousema, Teun;Okell, Lucy;Drakeley, Chris
背景：人们重新认识到，以配子体为靶点对疟疾控制和消除工作至关重要。简单的数学模型拟合从临床试验的数据，以确定平均配子体循环时间和配子体携带治疗malaria patients.Methods的持续时间：数据来自东非的临床试验。第一项试验比较了非青蒿素联合疗法（非ACT：磺胺嘧啶-乙胺嘧啶（SP）加阿莫地喹）和青蒿素联合疗法（ACT：SP加青蒿琥酯（AS）或蒿甲醚-苯芴醇）。第二项试验比较了ACT（SP+AS）与ACT联合单剂量伯氨喹（ACT-PQ：SP+AS+PQ）。通过基于核酸序列的扩增定量外周血样品中的成熟配子母细胞。一个简单的确定性房室模型拟合配子体密度，以估计每个配子体的循环时间;一个类似的模型拟合配子体患病率，以估计有效treatment.Results后配子体运输的持续时间：配子体的平均循环时间为4.6-6.5天。在非ACT治疗后，估计患者平均携带配子母细胞55天（95% CI 28.7 - 107.7）。ACT使配子体携带持续时间缩短4倍至13.4天（95% CI 10.2-17.5）。此外，PQ ACT导致配子体carrier.Conclusions的持续时间进一步减少了四倍：这些研究结果证实了以前的估计配子体的循环时间，但表明一个更长的持续时间（低密度）配子体carrier. After显然成功清除无性寄生虫。ACT大大缩短了配子体运输期，与PQ结合时对成熟配子体的影响最明显。
Background: There is renewed acknowledgement that targeting gametocytes is essential for malaria control and elimination efforts. Simple mathematical models were fitted to data from clinical trials in order to determine the mean gametocyte circulation time and duration of gametocyte carriage in treated malaria patients.Methods: Data were used from clinical trials from East Africa. The first trial compared non-artemisinin combination therapy (non-ACT: sulphadoxine-pyrimethamine (SP) plus amodiaquine) and artemisinin-based combination therapy (ACT: SP plus artesunate (AS) or artemether-lumefantrine). The second trial compared ACT (SP+AS) with ACT in combination with a single dose of primaquine (ACT-PQ: SP+AS+PQ). Mature gametocytes were quantified in peripheral blood samples by nucleic acid sequence based amplification. A simple deterministic compartmental model was fitted to gametocyte densities to estimate the circulation time per gametocyte; a similar model was fitted to gametocyte prevalences to estimate the duration of gametocyte carriage after efficacious treatment.Results: The mean circulation time of gametocytes was 4.6-6.5 days. After non-ACT treatment, patients were estimated to carry gametocytes for an average of 55 days (95% CI 28.7 - 107.7). ACT reduced the duration of gametocyte carriage fourfold to 13.4 days (95% CI 10.2-17.5). Addition of PQ to ACT resulted in a further fourfold reduction of the duration of gametocyte carriage.Conclusions: These findings confirm previous estimates of the circulation time of gametocytes, but indicate a much longer duration of (low density) gametocyte carriage after apparently successful clearance of asexual parasites. ACT shortened the period of gametocyte carriage considerably, and had the most pronounced effect on mature gametocytes when combined with PQ.