Plasmodium vivax malaria serological exposure markers: Assessing the degree and implications of cross-reactivity with P. knowlesi
Rhea J. Longley, Matthew J. Grigg, Kael L. Schoffer, Thomas Obadia, Stephanie R. Hyslop, Kim A. Piera, Narimane Nekkab, Ramin Mazhari, Eizo Takashima, Takafumi Tsuboi, Matthias Harbers, Kevin K. A. Tetteh, Chris Drakeley, Chetan E. Chitnis, Julie Healer, Wai‐Hong Tham, Jetsumon Sattabongkot, Michael White, Daniel J Cooper, Giri Shan Rajahram, Bridget E. Barber, Timothy William, Nicholas M. Anstey, Ivo Müeller
Abstract
Serological markers are a promising tool for surveillance and targeted interventions for Plasmodium vivax malaria. P. vivax is closely related to the zoonotic parasite P. knowlesi, which also infects humans. P. vivax and P. knowlesi are 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. vivax serological markers, we assayed samples from human patients with P. knowlesi malaria. IgG antibody reactivity is high against P. vivax proteins with high sequence identity with their P. knowlesi ortholog. IgG reactivity peaks at 7 days post-P. knowlesi infection and is short-lived, with minimal responses 1 year post-infection. We designed a panel of eight P. vivax proteins with low levels of cross-reactivity with P. knowlesi. This panel can accurately classify recent P. vivax infections while reducing misclassification of recent P. knowlesi infections.