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A Randomized Clinical Trial to Compare Plasmodium falciparum Gametocytemia and Infectivity After Blood-Stage or Mosquito Bite–Induced Controlled Malaria Infection

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 Plasmo...

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Autores principales: Alkema, Manon, Reuling, Isaie J, de Jong, Gerdie M, Lanke, Kjerstin, Coffeng, Luc E, van Gemert, Geert-Jan, van de Vegte-Bolmer, Marga, de Mast, Quirijn, van Crevel, Reinout, Ivinson, Karen, Ockenhouse, Christian F, McCarthy, James S, Sauerwein, Robert, Collins, Katharine A, Bousema, Teun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8514191/
https://www.ncbi.nlm.nih.gov/pubmed/32239171
http://dx.doi.org/10.1093/infdis/jiaa157
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author Alkema, Manon
Reuling, Isaie J
de Jong, Gerdie M
Lanke, Kjerstin
Coffeng, Luc E
van Gemert, Geert-Jan
van de Vegte-Bolmer, Marga
de Mast, Quirijn
van Crevel, Reinout
Ivinson, Karen
Ockenhouse, Christian F
McCarthy, James S
Sauerwein, Robert
Collins, Katharine A
Bousema, Teun
author_facet Alkema, Manon
Reuling, Isaie J
de Jong, Gerdie M
Lanke, Kjerstin
Coffeng, Luc E
van Gemert, Geert-Jan
van de Vegte-Bolmer, Marga
de Mast, Quirijn
van Crevel, Reinout
Ivinson, Karen
Ockenhouse, Christian F
McCarthy, James S
Sauerwein, Robert
Collins, Katharine A
Bousema, Teun
author_sort Alkema, Manon
collection PubMed
description 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
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spelling pubmed-85141912021-10-14 A Randomized Clinical Trial to Compare Plasmodium falciparum Gametocytemia and Infectivity After Blood-Stage or Mosquito Bite–Induced Controlled Malaria Infection Alkema, Manon Reuling, Isaie J de Jong, Gerdie M Lanke, Kjerstin Coffeng, Luc E van Gemert, Geert-Jan van de Vegte-Bolmer, Marga de Mast, Quirijn van Crevel, Reinout Ivinson, Karen Ockenhouse, Christian F McCarthy, James S Sauerwein, Robert Collins, Katharine A Bousema, Teun J Infect Dis Major Articles and Brief Reports 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 Oxford University Press 2020-04-02 /pmc/articles/PMC8514191/ /pubmed/32239171 http://dx.doi.org/10.1093/infdis/jiaa157 Text en © The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Major Articles and Brief Reports
Alkema, Manon
Reuling, Isaie J
de Jong, Gerdie M
Lanke, Kjerstin
Coffeng, Luc E
van Gemert, Geert-Jan
van de Vegte-Bolmer, Marga
de Mast, Quirijn
van Crevel, Reinout
Ivinson, Karen
Ockenhouse, Christian F
McCarthy, James S
Sauerwein, Robert
Collins, Katharine A
Bousema, Teun
A Randomized Clinical Trial to Compare Plasmodium falciparum Gametocytemia and Infectivity After Blood-Stage or Mosquito Bite–Induced Controlled Malaria Infection
title A Randomized Clinical Trial to Compare Plasmodium falciparum Gametocytemia and Infectivity After Blood-Stage or Mosquito Bite–Induced Controlled Malaria Infection
title_full A Randomized Clinical Trial to Compare Plasmodium falciparum Gametocytemia and Infectivity After Blood-Stage or Mosquito Bite–Induced Controlled Malaria Infection
title_fullStr A Randomized Clinical Trial to Compare Plasmodium falciparum Gametocytemia and Infectivity After Blood-Stage or Mosquito Bite–Induced Controlled Malaria Infection
title_full_unstemmed A Randomized Clinical Trial to Compare Plasmodium falciparum Gametocytemia and Infectivity After Blood-Stage or Mosquito Bite–Induced Controlled Malaria Infection
title_short A Randomized Clinical Trial to Compare Plasmodium falciparum Gametocytemia and Infectivity After Blood-Stage or Mosquito Bite–Induced Controlled Malaria Infection
title_sort randomized clinical trial to compare plasmodium falciparum gametocytemia and infectivity after blood-stage or mosquito bite–induced controlled malaria infection
topic Major Articles and Brief Reports
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8514191/
https://www.ncbi.nlm.nih.gov/pubmed/32239171
http://dx.doi.org/10.1093/infdis/jiaa157
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