10.5061/DRYAD.60H41
Reuling, Isaie J.
Department of Medical Microbiology, Radboud university medical center,
Nijmegen, Netherlands
van de Schans, Lisanne A
Department of Medical Microbiology, Radboud university medical center,
Nijmegen, Netherlands
Coffeng, Luc E
Erasmus University Medical Center
Lanke, Kjerstin
Department of Medical Microbiology, Radboud university medical center,
Nijmegen, Netherlands
Meerstein-Kessel, Lisette
Department of Medical Microbiology, Radboud university medical center,
Nijmegen, Netherlands
Graumans, Wouter
Department of Medical Microbiology, Radboud university medical center,
Nijmegen, Netherlands
van Gemert, Geert-Jan
Department of Medical Microbiology, Radboud university medical center,
Nijmegen, Netherlands
Teelen, Karina
London School of Hygiene & Tropical Medicine
Siebelink-Stoter, Rianne
Department of Medical Microbiology, Radboud university medical center,
Nijmegen, Netherlands
van de Vegte-Bolmer, Marga
Radboud University Nijmegen
de Mast, Quirijn
Radboud University Nijmegen
van der Ven, André J
Radboud University Nijmegen
Ivinson, Karen
Program for Appropriate Technology in Health
Hermsen, Cornelus C
Department of Medical Microbiology, Radboud university medical center,
Nijmegen, Netherlands
de Vlas, Sake
Erasmus University Medical Center
Bradley, John
London School of Hygiene & Tropical Medicine
Collins, Katharine A
QIMR Berghofer Medical Research Institute
Ockenhouse, Christian F
Program for Appropriate Technology in Health
McCarthy, James
QIMR Berghofer Medical Research Institute
Sauerwein, Robert W.
Department of Medical Microbiology, Radboud university medical center,
Nijmegen, Netherlands
Bousema, Teun
Department of Medical Microbiology, Radboud university medical center,
Nijmegen, Netherlands
Data from: A randomized feasibility trial comparing four antimalarial drug
regimens to induce Plasmodium falciparum gametocytemia in the controlled
human malaria infection model
Dryad
dataset
2018
Plasmodium falciparum
Malaria
transmission
Gametocytes
2018-02-28T20:26:08Z
2018-02-28T20:26:08Z
en
https://doi.org/10.7554/eLife.31549
192699 bytes
1
CC0 1.0 Universal (CC0 1.0) Public Domain Dedication
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)
2017-06-14 Results PCR - CHMI-trans1 - coffeng - FINAL FOR DRYADAll qPCR
and qRT-PCR datasets of asexual and sexual parasites of individual
participants generated and analysed in the current study.