An optimised serological machine learning model enabling targeted test-and-treat for <i>Plasmodium vivax</i> malaria

<jats:label>1</jats:label> <jats:title>Summary</jats:title> <jats:p> The persistence of <jats:italic>Plasmodium vivax</jats:italic> is driven by the hidden reservoirs of infection, presenting a key obstacle to elimination. Antibodies persist after asexual infections are cleared from peripheral blood and therefore can indicate current and recent past infections. Here, we present a machine learning algorithm that classifies recent <jats:italic>P. vivax</jats:italic> infections using serological markers to identify likely hypnozoite carriers. Using serological measurements from year-long observational cohort studies conducted in three low-transmission settings (including negative controls, <jats:italic>N</jats:italic> =2,635), we selected optimal subsets of markers by balancing sero-diagnostic performance against assay complexity and scalability. We initially trained a random forest classifier and then subsequently we compared several machine learning classifiers. Tree-based methods consistently performed best, although differences were marginal. An online R Shiny application (PvSeroApp) was developed to automate data processing, quality control, and serostatus classification. This algorithm underpins the <jats:italic>P. vivax</jats:italic> serological testing and treatment (PvSeroTAT) strategy, enabling targeted anti-hypnozoite therapy and strengthening elimination efforts. </jats:p>