Plasmodium vivaxmalaria serological exposure markers: Assessing the degree and implications of cross-reactivity with P. knowlesi

Serological markers are a promising tool for surveillance and targeted interventions for Plasmodium vivaxmalaria. P. vivaxis closely related to the zoonotic parasite P. knowlesi, which also infects humans. P. vivaxand P. knowlesiare co-endemic across much of South East Asia, making it important to design serological markers that minimize cross-reactivity in this region. To determine the degree of IgG cross-reactivity against a panel of P. vivaxserological markers, we assayed samples from human patients with P. knowlesimalaria. IgG antibody reactivity is high against P. vivaxproteins with high sequence identity with their P. knowlesiortholog. IgG reactivity peaks at 7 days post-P. knowlesiinfection and is short-lived, with minimal responses 1 year post-infection. We designed a panel of eight P. vivaxproteins with low levels of cross-reactivity with P. knowlesi. This panel can accurately classify recent P. vivaxinfections while reducing misclassification of recent P. knowlesiinfections.