Quantifying Reductions in Plasmodium falciparum Infectivity to Mosquitos: A Sample Size Calculator to Inform Clinical Trials on Transmission-Reducing Interventions

Abstract

Malaria transmission depends on the presence of mature Plasmodium transmission stages (gametocytes) that may render blood-feeding Anopheles 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.

Understanding and maximising the community impact of seasonal malaria chemoprevention in Burkina Faso (INDIE-SMC): study protocol for a cluster randomised evaluation trial

“…While the number of feeding assays will be informed by feasibility (eg, mosquito husbandry), we provide an indication of study power. When recruiting 100 children who received SPAQ (arm 3) and 100 children who did not (arms 1 and 2) and dissecting 40 mosquitoes per experiment, simulations show we would have >90% power to detect a 70% reduction in infectivity 37…”

“…When recruiting 100 children who received SPAQ (arm 3) and 100 children who did not (arms 1 and 2) and dissecting 40 mosquitoes per experiment, simulations show we would have >90% power to detect a 70% reduction in infectivity. 37 …”

“…who not (arms 1 and 2) and dissecting 40 mosquitoes per experiment, simulations show we would have >90% power to detect a 70% reduction in infectivity. 37 Outside study area survey To give a broad indication of the potential influence the presence of the study team may have on the operational delivery of SMC in arm 1, we will perform a single crosssectional survey outside the study area. The survey is not part of any main comparisons, and an exact sample size justification is complicated.…”

A Pfs48/45-based vaccine to block Plasmodium falciparum transmission: phase 1, open-label, clinical trial

“…Two-sided p -values < 0.05 were considered significant; Bonferroni correction for multiple testing was used where appropriate and as indicated. Individual level TRA of affinity purified R0.6C-specific IgGs was estimated using a mixed effects negative binomial regression model available as online data analysis tool [ 25 ].…”