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Title: Contribution of Functional Antimalarial Immunity to Measures of Parasite Clearance in Therapeutic Efficacy Studies of Artemisinin Derivatives
Authors: Katherine O'Flaherty
Ricardo Ataíde
Sophie G. Zaloumis
Elizabeth A. Ashley
Rosanna Powell
Gaoqian Feng
Linda Reiling
Arjen M. Dondorp
Nicholas P. Day
Mehul Dhorda
Rick M. Fairhurst
Pharath Lim
Chanaki Amaratunga
Sasithon Pukrittayakamee
Tran Tinh Hien
Ye Htut
Mayfong Mayxay
M. Abul Faiz
James G. Beeson
Francois Nosten
Julie A. Simpson
Nicholas J. White
Freya J.I. Fowkes
Melbourne School of Population and Global Health
Shoklo Malaria Research Unit
University of Oxford
University of Melbourne
Monash University
National Institute of Allergy and Infectious Diseases
University of Maryland School of Medicine
Mahidol University
Howard Hughes Medical Institute
Burnet Institute
Mahosot Hospital
Dev Care Foundation
Malaria Research Group
University of Health Sciences
Keywords: Medicine
Issue Date: 30-Aug-2019
Citation: Journal of Infectious Diseases. Vol.220, No.7 (2019), 1178-1187
Abstract: © 2019 The Author(s). Published by Oxford University Press for the Infectious Diseases Society of America. Background: Antibodies to the blood stages of malaria parasites enhance parasite clearance and antimalarial efficacy. The antibody subclass and functions that contribute to parasite clearance during antimalarial treatment and their relationship to malaria transmission intensity have not been characterized. Methods: Levels of immunoglobulin G (IgG) subclasses and C1q fixation in response to Plasmodium falciparum merozoite antigens (erythrocyte-binding antigen [EBA] 175RIII-V, merozoite surface protein 2 [MSP-2], and MSP-142) and opsonic phagocytosis of merozoites were measured in a multinational trial assessing the efficacy of artesunate therapy across 11 Southeast Asian sites. Regression analyses assessed the effects of antibody seropositivity on the parasite clearance half-life (PC), having a PC of ≥5 hours, and having parasitemia 3 days after treatment. Results: IgG3, followed by IgG1, was the predominant IgG subclass detected (seroprevalence range, 5%-35% for IgG1 and 27%-41% for IgG3), varied across study sites, and was lowest in study sites with the lowest transmission intensity and slowest mean PC. IgG3, C1q fixation, and opsonic-phagocytosis seropositivity were associated with a faster PC (range of the mean reduction in PC, 0.47-1.16 hours; P range,. 001-.03) and a reduced odds of having a PC of ≥5 hours and having parasitemia 3 days after treatment. Conclusions: The prevalence of IgG3, complement-fixing antibodies, and merozoite phagocytosis vary according to transmission intensity, are associated with faster parasite clearance, and may be sensitive surrogates of an augmented clearance capacity of infected erythrocytes. Determining the functional immune mechanisms associated with parasite clearance will improve characterization of artemisinin resistance.
ISSN: 15376613
Appears in Collections:Scopus 2019

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