A study protocol for an Observational Feasibility Study on Mass Drug Administration and Serology Integrated with Reactive Case Detection for Vivax Malaria Elimination in Cambodia

Abstract Background Plasmodium vivax (P. vivax) has emerged as the primary cause of malaria in Cambodia. Achieving malaria elimination and securing malaria-free certification requires a focused effort on addressing P. vivax malaria. This is essential because the elimination of P. vivax often lags behind that of Plasmodium falciparum , making it a critical component in the overall strategy. This study assesses the feasibility of the Mass Drug Administration (MDA) and P. vivax Serological Testing and Treatment (PvSeroTAT) integrated with Reactive Case Detection (RACD) in two of the highest malaria burden operational districts of Cambodia and examines the potential for integrating these two approaches with existing malaria elimination efforts. Methods This study employs an observational, prospective cohort design. MDA with chloroquine (CQ) will be conducted in Stung Treng through four monthly rounds, while RACD with PvSeroTAT will be implemented in Sen Monorom, targeting households near confirmed P. vivax cases. Data on coverage, compliance, cost, and stakeholder perceptions will be collected through surveys, interviews, and malaria case monitoring. A Composite Feasibility Index will integrate quantitative and qualitative indicators. Cost and budget impact analyses will assess scalability for malaria-endemic districts. Discussion Innovative and targeted public health approaches and tools are necessary to ensure the elimination of the malaria parasite reservoir, including the hidden hypnozoites. While MDA with CQ clears active blood-stage infections leading to immediate reductions in malaria prevalence, PvSeroTAT can detect past exposure to P. vivax by using serological markers allowing for targeted treatment of individuals at risk of developing relapsing infections with an 8-aminoquinoline. This helps reduce the parasite reservoir more efficiently. This study will provide insight into operational feasibility, implementation costs, community acceptance, and long-term sustainability. The findings will guide Cambodia’s malaria elimination efforts through improved surveillance and targeted interventions. Trial Registration OSF Preregistration: https://doi.org/10.17605/OSF.IO/5KZH7 , retrospectively registered 15 October 2025.