Data from: A randomized feasibility trial comparing four antimalarial drug regimens to induce Plasmodium falciparum gametocytemia in the controlled human malaria infection model

Background: Malaria elimination strategies require a thorough
understanding of parasite transmission from human to mosquito. A clinical
model to induce gametocytes to understand their dynamics and evaluate
transmission-blocking interventions (TBI) is currently unavailable. Here,
we explore the use of the well-established Controlled Human Malaria
Infection model (CHMI) to induce gametocyte carriage with different
antimalarial drug regimens. Methods: In a single centre, open-label
randomised trial, healthy malaria-naive participants (aged 18–35 years)
were infected with Plasmodium falciparum by bites of infected Anopheles
mosquitoes (ClinicalTrials.gov, NCT02836002). Participants were randomly
allocated to four different treatment arms (n = 4 per arm) comprising
low-dose (LD) piperaquine (PIP) or sulfadoxine-pyrimethamine (SP),
followed by a curative regimen upon recrudescence. Male and female
gametocyte densities were determined by molecular assays. Findings: Mature
gametocytes were observed in all participants (16/16, 100%). Gametocytes
appeared 8.5–12 days after the first detection of asexual parasites. Peak
gametocyte densities and gametocyte burden was highest in the LD-PIP/SP
arm, and associated with the preceding asexual parasite biomass (p=0.026).
Male gametocytes had a mean estimated circulation time of 2.7 days (95% CI
1.5–3.9) compared to 5.1 days (95% CI 4.1–6.1) for female gametocytes.
Exploratory mosquito feeding assays showed successful sporadic mosquito
infections. There were no serious adverse events or significant
differences in the occurrence and severity of adverse events between study
arms (p=0.49 and p=0.28). Conclusions: The early appearance of gametocytes
indicates gametocyte commitment during the first wave of asexual parasites
emerging from the liver. Treatment by LD-PIP followed by a curative SP
regimen, results in the highest gametocyte densities and the largest
number of gametocyte-positive days. This model can be used to evaluate the
effect of drugs and vaccines on gametocyte dynamics, and lays the
foundation for fulfilling the critical unmet need to evaluate
transmission-blocking interventions against falciparum malaria for
downstream selection and clinical development. Funding: PATH Malaria
Vaccine Initiative (MVI)