Journal article

Development and validation of serological markers for detecting recent Plasmodium vivax infection

Rhea J Longley, Michael T White, Eizo Takashima, Jessica Brewster, Masayuki Morita, Matthias Harbers, Thomas Obadia, Leanne J Robinson, Fumie Matsuura, Zoe SJ Liu, Connie SN Li-Wai-Suen, Wai-Hong Tham, Julie Healer, Christele Huon, Chetan E Chitnis, Wang Nguitragool, Wuelton Monteiro, Carla Proietti, Denise L Doolan, Andre M Siqueira Show all

Nature Medicine | NATURE PUBLISHING GROUP | Published : 2020

Abstract

A major gap in the Plasmodium vivax elimination toolkit is the identification of individuals carrying clinically silent and undetectable liver-stage parasites, called hypnozoites. This study developed a panel of serological exposure markers capable of classifying individuals with recent P. vivax infections who have a high likelihood of harboring hypnozoites. We measured IgG antibody responses to 342 P. vivax proteins in longitudinal clinical cohorts conducted in Thailand and Brazil and identified candidate serological markers of exposure. Candidate markers were validated using samples from year-long observational cohorts conducted in Thailand, Brazil and the Solomon Islands and antibody resp..

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Grants

Awarded by Global Health Innovative Technology Fund


Awarded by National Institute of Allergy and Infectious Diseases (National Institutes of Health)


Awarded by National Health and Medical Research Council Australia


Awarded by NHMRC Senior Research Fellowship


Awarded by NHMRC Principal Research Fellowship


Awarded by Japan Society for the Promotion of Science


Awarded by Howard Hughes Medical Institute-Wellcome Trust


Funding Acknowledgements

We acknowledge the extensive field teams that contributed to sample collection and qPCR assays, including A. Kuehn, Y. W. Quah, P. Sripoorote and A. Waltmann. We thank all the individuals who participated in each of the studies and thank the Australian and Thai Red Cross and the RBB for donation of plasma samples. We thank the Volunteer Blood Donor Registry at WEHI for donation of plasma samples and L. Laskos and J. Harris for their collection and advice. We thank C. King (Case Western Reserve University) for provision of the Papua New Guinea control plasma pool. M. Bahlo (Walter and Eliza Hall Institute) is thanked for her advice on algorithm development. We acknowledge funding from the Global Health Innovative Technology Fund (T2015-142 to I.M.), the National Institute of Allergy and Infectious Diseases (National Institutes of Health grant 5R01 AI 104822 to J.S. and 5U19AI089686-06 to J.K.) and the National Health and Medical Research Council Australia (1092789 and 1134989 to I.M. and 1143187 to W.-H.T.). Cohort samples were derived from field studies originally funded by the TransEPI consortium (supported by the Bill and Melinda Gates Foundation). This work has been supported by FIND with funding from the Australian and British governments. We also acknowledge support from the National Research Council of Thailand. This work was made possible through Victorian State Government Operational Infrastructure Support and Australian Government National Health and Medical Research Council (NHMRC) Independent Research Institute Infrastructure Support Scheme. I.M. is supported by an NHMRC Senior Research Fellowship (1043345). D.L.D. is supported by an NHMRC Principal Research Fellowship (1023636). T.T. was supported in part by Japan Society for the Promotion of Science Grant-in-Aid for Scientific Research (KAKENHI, JP15H05276, JP16K15266). W.H.T. is a Howard Hughes Medical Institute-Wellcome Trust International Research Scholar (208693/Z/17/Z). R.J.L. received the Page Betheras Award from WEHI to provide funding for technical support for this project during parental leave. M. V.G.L. and W.M.M. are fellows of the Brazilian National Council for Scientific and Technological Development.