A Randomized Clinical Trial to Compare Plasmodium falciparum Gametocytemia and Infectivity After Blood-Stage or Mosquito Bite-Induced Controlled Malaria Infection
Manon Alkema, Isaie J Reuling, Gerdie M de Jong, Kjerstin Lanke, Luc E Coffeng, Geert-Jan van Gemert, Marga van de Vegte-Bolmer, Quirijn de Mast, Reinout van Crevel, Karen Ivinson, Christian F Ockenhouse, James S McCarthy, Robert Sauerwein, Katharine A Collins, Teun Bousema, Manon Alkema, Isaie J Reuling, Gerdie M de Jong, Kjerstin Lanke, Luc E Coffeng, Geert-Jan van Gemert, Marga van de Vegte-Bolmer, Quirijn de Mast, Reinout van Crevel, Karen Ivinson, Christian F Ockenhouse, James S McCarthy, Robert Sauerwein, Katharine A Collins, Teun Bousema
Abstract
Background: For malaria elimination efforts, it is important to better understand parasite transmission to mosquitoes and develop models for early-clinical evaluation of transmission-blocking interventions.
Methods: In a randomized open-label trial, 24 participants were infected by bites from Plasmodium falciparum 3D7-infected mosquitoes (mosquito bite [MB]; n = 12) or by induced blood-stage malaria (IBSM) with the same parasite line (n = 12). After subcurative piperaquine treatment, asexual parasite and gametocytes kinetics were assessed, and mosquito feeding experiments were performed.
Results: Study procedures were well tolerated. The median peak gametocyte density was 1304/mL (interquartile range, 308-1607/mL) after IBSM, compared with 14/mL (10-64/mL) after MB inoculation (P < .001), despite similar peak asexual parasite densities (P = .48). Peak gametocyte density was correlated with preceding pfap2-g transcripts, indicative of gametocyte commitment (ρ = 0.62; P = .002). Direct feeding assays resulted in mosquito infections from 9 of 12 participants after IBSM versus 0 of 12 after MB inoculation (P < .001).
Conclusions: We observed a striking effect of inoculation method on gametocyte production, suggesting higher gametocyte commitment after IBSM. Our direct comparison of MB and IBSM establishes the controlled human malaria infection transmission model, using intravenous administration of P. falciparum-infected erythrocytes as a model for early-clinical evaluation of interventions that aim to interrupt malaria transmission.
Clinical trial registration: NCT03454048.
Keywords: Plasmodium falciparum; anopheles; controlled infection; gametocyte.
© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.
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References
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Source: PubMed