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Plasmodium vivax  remains a global health problem and its ability to cause relapses and subpatent infections challenge control and elimination strategies. Even in low malaria transmission settings, such as the Amazon basin, where progress in malaria control has caused a remarkable reduction in case incidence, a recent increase in  P .  vivax  transmission demonstrates the continued vulnerability of  P . vivax -exposed populations. As part of a search for complementary approaches to  P . vivax  surveillance in areas in which adults are the majority of the exposed-population, here we evaluated the potential of serological markers covering a wide range of immunogenicity to estimate malaria transmission trends. For this, antibodies against leading  P .  vivax  blood-stage vaccine candidates were assessed during a 9 year follow-up study among adults exposed to unstable malaria transmission in the Amazon rainforest. Circulating antibody levels against immunogenic  P .  vivax  proteins, such as the Apical Membrane Antigen-1, were a sensitive measure of recent  P .  vivax  exposure, while antibodies against less immunogenic proteins were indicative of naturally-acquired immunity, including the novel engineered Duffy binding protein II immunogen (DEKnull-2). Our results suggest that the robustness of serology to estimate trends in  P . vivax  malaria transmission will depend on the immunological background of the study population, and that for adult populations exposed to unstable  P . vivax  malaria transmission, the local heterogeneity of antibody responses should be considered when considering use of serological surveillance.

Blood-stage Plasmodium vivax antibody dynamics in a low transmission setting: A nine year follow-up study in the Amazon region