Journal article

Contribution of Functional Antimalarial Immunity to Measures of Parasite Clearance in Therapeutic Efficacy Studies of Artemisinin Derivatives

Katherine O'Flaherty, Ricardo Ataide, 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, Tinh Hien Tran, Ye Htut, Mayfong Mayxay, M Abul Faiz, James G Beeson, Francois Nosten Show all

The Journal of Infectious Diseases | OXFORD UNIV PRESS INC | Published : 2019

Abstract

BACKGROUND: Antibodies to the blood-stages of malaria enhance parasite-clearance and antimalarial efficacy. The antibody subclass and functions that contribute to parasite-clearance during anti-malarial treatment and their relationship with malaria transmission intensity have not been characterised. METHODS: IgG subclasses and C1q-fixation in response to P. falciparum merozoite antigens (EBA-175RIII-V, MSP-2 and MSP-142), and opsonic-phagocytosis of merozoites were measured in a multinational trial assessing the efficacy of artesunate across 11 South-East Asian sites. Regression analyses assessed the effects of antibody seropositivity on parasite-clearance half-life (hours)(PC½), PC½≥5 hours..

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Grants

Awarded by National Health and Medical Research Council of Australia


Awarded by Australian Centre for Research Excellence in Malaria Elimination


Awarded by Australian Research Council


Awarded by Ramaciotti Foundation


Funding Acknowledgements

This work was supported by the National Health and Medical Research Council of Australia (project grant 1060785 [to F. J. I. F., J. A. S., and F. N.], program grant APP637406 [to J. G. B.], training fellowship 637396 [to F. J. I. F.], and senior research fellowships APP1077636 [to J. G. B.] and 1104975 [to J. A. S.]); the Australian Centre for Research Excellence in Malaria Elimination (1134989); the Australian Research Council (Future Fellowships FT130101122 [to F. J. I. F.] and FT0992317 [to J. G. B.]); the Ramaciotti Foundation (Establishment Grant 3245/2011); the Ian Potter Foundation (grant to F. J. I. F.); the Australian Commonwealth Government (Australian Government Research Training Program Scholarship to K. O.); the Victorian State Government (Operational Infrastructure Support grant); the United Kingdom Department for International Development, with additional support from the Worldwide Antimalarial Resistance Network, and the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health; and the Wellcome Trust of Great Britain (support to the Wellcome Trust Mahidol Oxford Tropical Medicine Research Programme).