Anti-Gametocyte Antigen Humoral Immunity and Gametocytemia During Treatment of Uncomplicated Falciparum Malaria: A Multi-National Study
Issued Date
2022-04-07
Resource Type
eISSN
22352988
Scopus ID
2-s2.0-85128699175
Pubmed ID
35463638
Journal Title
Frontiers in Cellular and Infection Microbiology
Volume
12
Rights Holder(s)
SCOPUS
Bibliographic Citation
Frontiers in Cellular and Infection Microbiology Vol.12 (2022)
Suggested Citation
O’Flaherty K., Chan J.A., Cutts J.C., Zaloumis S.G., Ashley E.A., Phyo A.P., Drew D.R., Dondorp A.M., Day N.P., Dhorda M., Fairhurst R.M., Lim P., Amaratunga C., Pukrittayakamee S., Hien T.T., Htut Y., Mayxay M., Faiz M.A., Mokuolu O.A., Onyamboko M.A., Fanello C., Takashima E., Tsuboi T., Theisen M., Nosten F., Beeson J.G., Simpson J.A., White N.J., Fowkes F.J.I. Anti-Gametocyte Antigen Humoral Immunity and Gametocytemia During Treatment of Uncomplicated Falciparum Malaria: A Multi-National Study. Frontiers in Cellular and Infection Microbiology Vol.12 (2022). doi:10.3389/fcimb.2022.804470 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/84996
Title
Anti-Gametocyte Antigen Humoral Immunity and Gametocytemia During Treatment of Uncomplicated Falciparum Malaria: A Multi-National Study
Author(s)
O’Flaherty K.
Chan J.A.
Cutts J.C.
Zaloumis S.G.
Ashley E.A.
Phyo A.P.
Drew D.R.
Dondorp A.M.
Day N.P.
Dhorda M.
Fairhurst R.M.
Lim P.
Amaratunga C.
Pukrittayakamee S.
Hien T.T.
Htut Y.
Mayxay M.
Faiz M.A.
Mokuolu O.A.
Onyamboko M.A.
Fanello C.
Takashima E.
Tsuboi T.
Theisen M.
Nosten F.
Beeson J.G.
Simpson J.A.
White N.J.
Fowkes F.J.I.
Chan J.A.
Cutts J.C.
Zaloumis S.G.
Ashley E.A.
Phyo A.P.
Drew D.R.
Dondorp A.M.
Day N.P.
Dhorda M.
Fairhurst R.M.
Lim P.
Amaratunga C.
Pukrittayakamee S.
Hien T.T.
Htut Y.
Mayxay M.
Faiz M.A.
Mokuolu O.A.
Onyamboko M.A.
Fanello C.
Takashima E.
Tsuboi T.
Theisen M.
Nosten F.
Beeson J.G.
Simpson J.A.
White N.J.
Fowkes F.J.I.
Author's Affiliation
WorldWide Antimalarial Resistance Network
Faculty of Tropical Medicine, Mahidol University
Oxford University Clinical Research Unit
Melbourne School of Population and Global Health
Ministry of Health Myanmar
Universite de Kinshasa
Københavns Universitet
University of Melbourne
Statens Serum Institut
Monash University
National Institute of Allergy and Infectious Diseases (NIAID)
Mahosot Hospital, Lao
Faculty of Medicine, Nursing and Health Sciences
University of Ilorin
Nuffield Department of Medicine
Burnet Institute
Ehime University
University of Health Sciences
Myanmar Oxford Clinical Research Unit
Dev Care Foundation
Faculty of Tropical Medicine, Mahidol University
Oxford University Clinical Research Unit
Melbourne School of Population and Global Health
Ministry of Health Myanmar
Universite de Kinshasa
Københavns Universitet
University of Melbourne
Statens Serum Institut
Monash University
National Institute of Allergy and Infectious Diseases (NIAID)
Mahosot Hospital, Lao
Faculty of Medicine, Nursing and Health Sciences
University of Ilorin
Nuffield Department of Medicine
Burnet Institute
Ehime University
University of Health Sciences
Myanmar Oxford Clinical Research Unit
Dev Care Foundation
Other Contributor(s)
Abstract
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.