Measuring the blockade of malaria transmission - An analysis of the Standard Membrane Feeding Assay
Measuring the blockade of malaria transmission - An analysis of the Standard Membrane Feeding Assay
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DOI：
10.1016/j.ijpara.2012.09.002
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发表时间：
2012-10-01
影响因子：
4
通讯作者：
Sinden, Robert E.
中科院分区：
文献类型：
--
作者：
Churcher, Thomas S.;Blagborough, Andrew M.;Sinden, Robert E.
目前，标准膜喂养试验（SMFA）被认为是评估疟疾传播阻断干预措施（TBI）在体内有效性的“金标准”。SMFA的操作和分析在实验室之间有所不同：现场科学家通常将TBI疗效作为受感染蚊子流行率的降低来衡量，而实验室科学家更可能将疗效引用为蚊子内卵囊数量的变化。这些指标给出的输出差异很大，因此需要更好地理解SMFA如何为TBI评估提供信息。使用数据从536个不同的测定（进行恶性疟原虫和伯氏疟原虫，在冈比亚按蚊或斯氏按蚊），它表明，这些指标之间的关系是复杂的，但可预测的。结果表明，蚊子之间的卵囊分布是高度聚集的，使效力估计的基础上减少强度高度不确定。对同一TBI进行的30个SMFA的分析证实，观察到的患病率降低取决于寄生虫暴露（通过对照组中的卵囊强度测量），暴露较低的测定似乎更有效。相比之下，如果将疗效估计为卵囊强度的降低，则该候选药物显示出恒定的疗效，与暴露水平无关。为了准确地报告传播阻断效果，SMFA的结果应该给出对照组和干预组中卵囊的患病率和强度。应根据一系列寄生虫接触情况对候选人进行评估，以便将实验室结果外推到不同的实地情况。目前，许多评估TBI的研究动力不足，疗效估计的不确定性很少报道。解释卵囊过度分散的统计技术可以减少需要解剖的蚊子数量，并允许准确比较来自不同实验室的TBI候选人。(C)2012年澳大利亚寄生虫学会由爱思唯尔有限公司出版。保留所有权利。
The standard membrane feeding assay (SMFA) is currently considered to be the 'gold standard' for assessing the effectiveness of malaria transmission blocking interventions (TBIs) in vivo. The operation and analysis of SMFAs has varied between laboratories: field scientists often measure TBI efficacy as a reduction in the prevalence of infected mosquitoes whilst laboratory scientists are more likely to quote efficacy as a change in the number of oocysts within the mosquito. These metrics give outputs that differ widely, resulting in a need for greater understanding of how the SMFA informs TBI assessment. Using data from 536 different assays (conducted on Plasmodium falciparum and Plasmodium berghei, in either Anopheles gambiae or Anopheles stephensi) it is shown that the relationship between these metrics is complex, yet predictable. Results demonstrate that the distribution of oocysts between mosquitoes is highly aggregated, making efficacy estimates based on reductions in intensity highly uncertain. Analysis of 30 SMFAs carried out on the same TBI confirms that the observed reduction in prevalence depends upon the parasite exposure (as measured by oocyst intensity in the control group), with assays which have lower exposure appearing more effective. By contrast, if efficacy is estimated as a reduction in oocyst intensity, then this candidate demonstrated constant efficacy, irrespective of the exposure level. To report transmission-blockade efficacy accurately, the results of SMFAs should give both the prevalence and intensity of oocysts in both the control and intervention group. Candidates should be assessed against a range of parasite exposures to allow laboratory results to be extrapolated to different field situations. Currently, many studies assessing TBIs are underpowered and uncertainties in efficacy estimates rarely reported. Statistical techniques that account for oocyst over-dispersion can reduce the number of mosquitoes that need to be dissected and allow TBI candidates from different laboratories to be accurately compared. (C) 2012 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.