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Anti-Gametocyte Antigen Humoral Immunity and Gametocytemia During Treatment of Uncomplicated Falciparum Malaria: A Multi-National Study

INTRODUCTION: Understanding the human immune response to Plasmodium falciparum gametocytes and its association with gametocytemia is essential for understanding the transmission of malaria as well as progressing transmission blocking vaccine candidates. METHODS: In a multi-national clinical efficacy...

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Autores principales: O’Flaherty, Katherine, Chan, Jo-Anne, Cutts, Julia C., Zaloumis, Sophie G., Ashley, Elizabeth A., Phyo, Aung Pyae, Drew, Damien R., Dondorp, Arjen M., Day, Nicholas P., Dhorda, Mehul, Fairhurst, Rick M., Lim, Pharath, Amaratunga, Chanaki, Pukrittayakamee, Sasithon, Hien, Tran Tinh, Htut, Ye, Mayxay, Mayfong, Faiz, M. Abul, Mokuolu, Olugbenga A., Onyamboko, Marie A., Fanello, Caterina, Takashima, Eizo, Tsuboi, Takafumi, Theisen, Michael, Nosten, Francois, Beeson, James G., Simpson, Julie A., White, Nicholas J., Fowkes, Freya J. I.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9022117/
https://www.ncbi.nlm.nih.gov/pubmed/35463638
http://dx.doi.org/10.3389/fcimb.2022.804470
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author O’Flaherty, Katherine
Chan, Jo-Anne
Cutts, Julia C.
Zaloumis, Sophie G.
Ashley, Elizabeth A.
Phyo, Aung Pyae
Drew, Damien R.
Dondorp, Arjen M.
Day, Nicholas P.
Dhorda, Mehul
Fairhurst, Rick M.
Lim, Pharath
Amaratunga, Chanaki
Pukrittayakamee, Sasithon
Hien, Tran Tinh
Htut, Ye
Mayxay, Mayfong
Faiz, M. Abul
Mokuolu, Olugbenga A.
Onyamboko, Marie A.
Fanello, Caterina
Takashima, Eizo
Tsuboi, Takafumi
Theisen, Michael
Nosten, Francois
Beeson, James G.
Simpson, Julie A.
White, Nicholas J.
Fowkes, Freya J. I.
author_facet O’Flaherty, Katherine
Chan, Jo-Anne
Cutts, Julia C.
Zaloumis, Sophie G.
Ashley, Elizabeth A.
Phyo, Aung Pyae
Drew, Damien R.
Dondorp, Arjen M.
Day, Nicholas P.
Dhorda, Mehul
Fairhurst, Rick M.
Lim, Pharath
Amaratunga, Chanaki
Pukrittayakamee, Sasithon
Hien, Tran Tinh
Htut, Ye
Mayxay, Mayfong
Faiz, M. Abul
Mokuolu, Olugbenga A.
Onyamboko, Marie A.
Fanello, Caterina
Takashima, Eizo
Tsuboi, Takafumi
Theisen, Michael
Nosten, Francois
Beeson, James G.
Simpson, Julie A.
White, Nicholas J.
Fowkes, Freya J. I.
author_sort O’Flaherty, Katherine
collection PubMed
description INTRODUCTION: Understanding the human immune response to Plasmodium falciparum gametocytes and its association with gametocytemia is essential for understanding the transmission of malaria as well as progressing transmission blocking vaccine candidates. METHODS: In a multi-national clinical efficacy trial of artemisinin therapies (13 sites of varying transmission over South-East Asia and Africa), we measured Immunoglobulin G (IgG) responses to recombinant P. falciparum gametocyte antigens expressed on the gametocyte plasma membrane and leading transmission blocking vaccine candidates Pfs230 (Pfs230c and Pfs230D1M) and Pfs48/45 at enrolment in 1,114 participants with clinical falciparum malaria. Mixed effects linear and logistic regression were used to determine the association between gametocyte measures (gametocytemia and gametocyte density) and antibody outcomes at enrolment. RESULTS: Microscopy detectable gametocytemia was observed in 11% (127/1,114) of participants at enrolment, and an additional 9% (95/1,114) over the follow-up period (up to day 42) (total 20% of participants [222/1,114]). IgG levels in response to Pfs230c, Pfs48/45 and Pfs230D1M varied across study sites at enrolment (p < 0.001), as did IgG seroprevalence for anti-Pfs230c and D1M IgG (p < 0.001), but not for anti-Pfs48/45 IgG (p = 0.159). In adjusted analyses, microscopy detectable gametocytemia at enrolment was associated with an increase in the odds of IgG seropositivity to the three gametocyte antigens (Pfs230c OR [95% CI], p: 1.70 [1.10, 2.62], 0.017; Pfs48/45: 1.45 [0.85, 2.46], 0.174; Pfs230D1M: 1.70 [1.03, 2.80], 0.037), as was higher gametocyte density at enrolment (per two-fold change in gametocyte density Pfs230c OR [95% CI], p: 1.09 [1.02, 1.17], 0.008; Pfs48/45: 1.05 [0.98, 1.13], 0.185; Pfs230D1M: 1.07 [0.99, 1.14], 0.071). CONCLUSION: Pfs230 and Pfs48/45 antibodies are naturally immunogenic targets associated with patent gametocytemia and increasing gametocyte density across multiple malaria endemic settings, including regions with emerging artemisinin-resistant P. falciparum.
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spelling pubmed-90221172022-04-22 Anti-Gametocyte Antigen Humoral Immunity and Gametocytemia During Treatment of Uncomplicated Falciparum Malaria: A Multi-National Study O’Flaherty, Katherine Chan, Jo-Anne Cutts, Julia C. Zaloumis, Sophie G. Ashley, Elizabeth A. Phyo, Aung Pyae Drew, Damien R. Dondorp, Arjen M. Day, Nicholas P. Dhorda, Mehul Fairhurst, Rick M. Lim, Pharath Amaratunga, Chanaki Pukrittayakamee, Sasithon Hien, Tran Tinh Htut, Ye Mayxay, Mayfong Faiz, M. Abul Mokuolu, Olugbenga A. Onyamboko, Marie A. Fanello, Caterina Takashima, Eizo Tsuboi, Takafumi Theisen, Michael Nosten, Francois Beeson, James G. Simpson, Julie A. White, Nicholas J. Fowkes, Freya J. I. Front Cell Infect Microbiol Cellular and Infection Microbiology INTRODUCTION: Understanding the human immune response to Plasmodium falciparum gametocytes and its association with gametocytemia is essential for understanding the transmission of malaria as well as progressing transmission blocking vaccine candidates. METHODS: In a multi-national clinical efficacy trial of artemisinin therapies (13 sites of varying transmission over South-East Asia and Africa), we measured Immunoglobulin G (IgG) responses to recombinant P. falciparum gametocyte antigens expressed on the gametocyte plasma membrane and leading transmission blocking vaccine candidates Pfs230 (Pfs230c and Pfs230D1M) and Pfs48/45 at enrolment in 1,114 participants with clinical falciparum malaria. Mixed effects linear and logistic regression were used to determine the association between gametocyte measures (gametocytemia and gametocyte density) and antibody outcomes at enrolment. RESULTS: Microscopy detectable gametocytemia was observed in 11% (127/1,114) of participants at enrolment, and an additional 9% (95/1,114) over the follow-up period (up to day 42) (total 20% of participants [222/1,114]). IgG levels in response to Pfs230c, Pfs48/45 and Pfs230D1M varied across study sites at enrolment (p < 0.001), as did IgG seroprevalence for anti-Pfs230c and D1M IgG (p < 0.001), but not for anti-Pfs48/45 IgG (p = 0.159). In adjusted analyses, microscopy detectable gametocytemia at enrolment was associated with an increase in the odds of IgG seropositivity to the three gametocyte antigens (Pfs230c OR [95% CI], p: 1.70 [1.10, 2.62], 0.017; Pfs48/45: 1.45 [0.85, 2.46], 0.174; Pfs230D1M: 1.70 [1.03, 2.80], 0.037), as was higher gametocyte density at enrolment (per two-fold change in gametocyte density Pfs230c OR [95% CI], p: 1.09 [1.02, 1.17], 0.008; Pfs48/45: 1.05 [0.98, 1.13], 0.185; Pfs230D1M: 1.07 [0.99, 1.14], 0.071). CONCLUSION: Pfs230 and Pfs48/45 antibodies are naturally immunogenic targets associated with patent gametocytemia and increasing gametocyte density across multiple malaria endemic settings, including regions with emerging artemisinin-resistant P. falciparum. Frontiers Media S.A. 2022-04-07 /pmc/articles/PMC9022117/ /pubmed/35463638 http://dx.doi.org/10.3389/fcimb.2022.804470 Text en Copyright © 2022 O’Flaherty, Chan, Cutts, Zaloumis, Ashley, Phyo, Drew, Dondorp, Day, Dhorda, Fairhurst, Lim, Amaratunga, Pukrittayakamee, Hien, Htut, Mayxay, Faiz, Mokuolu, Onyamboko, Fanello, Takashima, Tsuboi, Theisen, Nosten, Beeson, Simpson, White and Fowkes https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cellular and Infection Microbiology
O’Flaherty, Katherine
Chan, Jo-Anne
Cutts, Julia C.
Zaloumis, Sophie G.
Ashley, Elizabeth A.
Phyo, Aung Pyae
Drew, Damien R.
Dondorp, Arjen M.
Day, Nicholas P.
Dhorda, Mehul
Fairhurst, Rick M.
Lim, Pharath
Amaratunga, Chanaki
Pukrittayakamee, Sasithon
Hien, Tran Tinh
Htut, Ye
Mayxay, Mayfong
Faiz, M. Abul
Mokuolu, Olugbenga A.
Onyamboko, Marie A.
Fanello, Caterina
Takashima, Eizo
Tsuboi, Takafumi
Theisen, Michael
Nosten, Francois
Beeson, James G.
Simpson, Julie A.
White, Nicholas J.
Fowkes, Freya J. I.
Anti-Gametocyte Antigen Humoral Immunity and Gametocytemia During Treatment of Uncomplicated Falciparum Malaria: A Multi-National Study
title Anti-Gametocyte Antigen Humoral Immunity and Gametocytemia During Treatment of Uncomplicated Falciparum Malaria: A Multi-National Study
title_full Anti-Gametocyte Antigen Humoral Immunity and Gametocytemia During Treatment of Uncomplicated Falciparum Malaria: A Multi-National Study
title_fullStr Anti-Gametocyte Antigen Humoral Immunity and Gametocytemia During Treatment of Uncomplicated Falciparum Malaria: A Multi-National Study
title_full_unstemmed Anti-Gametocyte Antigen Humoral Immunity and Gametocytemia During Treatment of Uncomplicated Falciparum Malaria: A Multi-National Study
title_short Anti-Gametocyte Antigen Humoral Immunity and Gametocytemia During Treatment of Uncomplicated Falciparum Malaria: A Multi-National Study
title_sort anti-gametocyte antigen humoral immunity and gametocytemia during treatment of uncomplicated falciparum malaria: a multi-national study
topic Cellular and Infection Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9022117/
https://www.ncbi.nlm.nih.gov/pubmed/35463638
http://dx.doi.org/10.3389/fcimb.2022.804470
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