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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...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2020
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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 |
format | Online Article Text |
id | pubmed-8514191 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
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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