Swihart Bruce J, Fay Michael P, Miura Kazutoyo
Biostatistics Research Branch, NIAID, NIH, Rockville, MD.
National Institute of Allergy and Infectious Diseases, Laboratory of Malaria and Vector Research, National Institutes of Health, Rockville, MD.
J Am Stat Assoc. 2018;113(522):534-545. doi: 10.1080/01621459.2017.1356313. Epub 2018 Jun 12.
Transmission blocking vaccines for malaria are not designed to directly protect vaccinated people from malaria disease, but to reduce the probability of infecting other people by interfering with the growth of the malaria parasite in mosquitoes. Standard membrane-feeding assays compare the growth of parasites in mosquitoes from a test sample (using antibodies from a vaccinated person) compared to a control sample. There is debate about whether to estimate the transmission reducing activity (TRA) which compares the mean number of parasites between test and control samples, or transmission blocking activity (TBA) which compares the proportion of infected mosquitoes. TBA appears biologically more important since each mosquito with any parasites is potentially infective; however, TBA is less reproducible and may be an overly strict criterion for screening vaccine candidates. Through a statistical model, we show that the TBA estimand depends on , the mean number of parasites in the control mosquitoes, a parameter not easily experimentally controlled. We develop a standardized TBA estimator based on the model and a given target value for which has better mean squared error than alternative methods. We discuss types of statistical inference needed for using these assays for vaccine development.
疟疾传播阻断疫苗并非旨在直接保护接种疫苗的人免受疟疾疾病侵害，而是通过干扰疟原虫在蚊子体内的生长来降低感染他人的可能性。标准膜饲试验将测试样本（使用来自接种疫苗者的抗体）中蚊子体内寄生虫的生长情况与对照样本进行比较。关于是估计比较测试样本和对照样本之间寄生虫平均数量的传播减少活性（TRA），还是比较受感染蚊子比例的传播阻断活性（TBA），存在争议。TBA在生物学上似乎更重要，因为每只带有任何寄生虫的蚊子都有潜在传染性；然而，TBA的可重复性较差，可能是筛选候选疫苗的过于严格标准。通过一个统计模型，我们表明TBA估计量取决于对照蚊子体内寄生虫的平均数量 ，这是一个不易通过实验控制的参数。我们基于该模型和给定的 目标值开发了一种标准化的TBA估计器，其均方误差比其他方法更好。我们讨论了将这些试验用于疫苗研发所需的统计推断类型。
