Plasmodium vivax malaria serological exposure markers: assessing the degree and implications of cross-reactivity with P. knowlesi

Summary Serological exposure 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 P. vivax serological markers that minimise cross-reactivity in this region. Our objective was to determine the degree of IgG antibody cross-reactivity against a panel of P. vivax serological markers in samples from human participants with P. knowlesi malaria. We observed higher levels of IgG antibody reactivity against P. vivax proteins that had high levels of sequence identity with their P. knowlesi ortholog. IgG reactivity peaked at 7 days post P. knowlesi infection and was short-lived, with minimal responses detected at 1-year post-infection. Using these data, we designed a panel of 8 P. vivax proteins with low-levels of cross-reactivity with P. knowlesi . This panel was able to accurately classify recent P. vivax infections whilst reducing misclassification of recent P. knowlesi infections.