Radboud Institute for Molecular Life Sciences, Department of Medical Microbiology, Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, Netherlands.
Department for Health Evidence, Biostatistics Research Group, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, Netherlands.
Front Immunol. 2022 Jun 3;13:899615. doi: 10.3389/fimmu.2022.899615. eCollection 2022.
Malaria transmission depends on the presence of mature transmission stages (gametocytes) that may render blood-feeding mosquitos infectious. Transmission-blocking antimalarial drugs and vaccines can prevent transmission by reducing gametocyte densities or infectivity to mosquitos. Mosquito infection outcomes are thereby informative biological endpoints of clinical trials with transmission blocking interventions. Nevertheless, trials are often primarily designed to determine intervention safety; transmission blocking efficacy is difficult to incorporate in sample size considerations due to variation in infection outcomes and considerable inter-study variation. Here, we use clinical trial data from studies in malaria naive and naturally exposed study participants to present an online sample size calculator tool. This sample size calculator allows studies to be powered to detect reductions in the proportion of infected mosquitos or infection burden (oocyst density) in mosquitos. The utility of this online tool is illustrated using trial data with transmission blocking malaria drugs.
疟疾传播取决于成熟的传播阶段（配子体）的存在，这些阶段可能使吸血蚊子具有传染性。阻断疟疾传播的抗疟药物和疫苗可以通过降低配子体密度或对蚊子的感染力来预防传播。因此，蚊子感染的结果是具有阻断疟疾传播的干预措施临床试验的有意义的生物学终点。然而，临床试验通常主要设计用于确定干预措施的安全性；由于感染结果的变化和研究之间的巨大差异，很难将阻断疟疾传播的疗效纳入样本量考虑因素中。在这里，我们使用来自无疟疾和自然暴露研究参与者的临床试验数据，提出了一个在线样本量计算器工具。这个样本量计算器允许研究具有检测感染蚊子的比例或蚊子感染负担（卵囊密度）降低的能力。使用具有阻断疟疾传播的药物的临床试验数据说明了这个在线工具的实用性。
