Asymptomatic Plasmodium vivax infections induce robust IgG responses to multiple blood-stage proteins in a low-transmission region of western Thailand

Rhea J Longley,Anjali Yadava,Wang Nguitragool,Chalermpon Kumpitak,Wai-Hong Tham,Julian C Rayner,Camila T França,Jetsumon Sattabongkot,Jakub Gruszczyk,Christopher L King,Ivo Mueller,Patiwat Sa-Angchai,Jessica B Hostetler,Michael T White,Rick M Fairhurst

doi:10.1186/s12936-017-1826-8

Abstract

BackgroundThailand is aiming to eliminate malaria by the year 2024. Plasmodium vivax has now become the dominant species causing malaria within the country, and a high proportion of infections are asymptomatic. A better understanding of antibody dynamics to P. vivax antigens in a low-transmission setting, where acquired immune responses are poorly characterized, will be pivotal for developing new strategies for elimination, such as improved surveillance methods and vaccines. The objective of this study was to characterize total IgG antibody levels to 11 key P. vivax proteins in a village of western Thailand.MethodsPlasma samples from 546 volunteers enrolled in a cross-sectional survey conducted in 2012 in Kanchanaburi Province were utilized. Total IgG levels to 11 different proteins known or predicted to be involved in reticulocyte binding or invasion (ARP, GAMA, P41, P12, PVX_081550, and five members of the PvRBP family), as well as the leading pre-erythrocytic vaccine candidate (CSP) were measured using a multiplexed bead-based assay. Associations between IgG levels and infection status, age, and spatial location were explored.ResultsIndividuals from a low-transmission region of western Thailand reacted to all 11 P. vivax recombinant proteins. Significantly greater IgG levels were observed in the presence of a current P. vivax infection, despite all infected individuals being asymptomatic. IgG levels were also higher in adults (18 years and older) than in children. For most of the proteins, higher IgG levels were observed in individuals living closer to the Myanmar border and further away from local health services.ConclusionsRobust IgG responses were observed to most proteins and IgG levels correlated with surrogates of exposure, suggesting these antigens may serve as potential biomarkers of exposure, immunity, or both.

Highlights

Thailand is aiming to eliminate malaria by the year 2024
Multiple Plasmodium vivax proteins are immunogenic in western Thailand IgG levels to the 11 P. vivax proteins were first analysed in all 546 samples collected in Bongti moo 3
Whilst the antibody levels cannot be directly compared between the different proteins, a higher proportion of volunteers reached the equivalent of a 1/100 dilution of the positive control plasma against the reticulocyte binding protein (RBP) and circumsporozoite protein (CSP) (3.5–5.7%), compared to the other four blood-stage proteins (0–0.6%)

Summary

Introduction

Thailand is aiming to eliminate malaria by the year 2024. Plasmodium vivax has become the dominant species causing malaria within the country, and a high proportion of infections are asymptomatic. The country is currently within the ‘control’ phase per the World Health Organization, and the National Malaria Strategy proposes to eliminate malaria by the year 2024 (Department of Disease Control, Ministry of Public Health, Thailand). This is part of a wider goal of a malaria-free Asia–Pacific by the year 2030, declared at the 9th East Asia Summit in 2014 by the Asia–Pacific Leaders Malaria Alliance. A greater understanding of the antibody dynamics to P. vivax in this lowtransmission region will be essential for developing and implementing key elimination tools, such as vaccines and improved surveillance methods [7]

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