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Novel interventions are needed to accelerate malaria elimination, especially in areas where asymptomatic parasitemia is common, and where transmission generally occurs outside of village-based settings. Testing of community members linked to a person with clinical illness (reactive case detection, RACD) has not shown effectiveness in prior studies due to the limited sensitivity of current point-of-care tests. This study aims to assess the effectiveness of active case finding in village-based and forested-based settings using novel high-sensitivity rapid diagnostic tests in Lao People’s Democratic Republic (Lao PDR).    Methods and analysis:  This study is a cluster-randomized split-plot design trial. The interventions include village-based mass test and treat (MTAT), focal test and treat in high-risk populations (FTAT), and the combination of these approaches, using high-sensitivity rapid diagnostic tests (HS-RDTs) to asses  P. falciparum  infection status. Within four districts in Champasak province, Lao PDR fourteen health center-catchment areas will be randomized to either FTAT or control; and within these HCCAs, 56 villages will be randomized to either MTAT or control. In intervention areas, FTAT will be conducted by community-based peer navigators on a routine basis, and three separate rounds of MTAT are planned. The primary study outcome will be PCR-based  Plasmodium falciparum  prevalence after one year of implementation. Secondary outcomes include malaria incidence; interventional coverage; operational feasibility and acceptability; and cost and cost- effectiveness.    Ethics and dissemination:  Findings will be reported on clinicaltrials.gov, in peer-reviewed publications and through stakeholder meetings with Ministry of Health and community leaders in Lao PDR and throughout the Greater Mekong Subregion.    Trial registration:  clinicaltrials.gov  NCT03783299  (21/12/2018)

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Study protocol for a cluster-randomized split-plot design trial to assess the effectiveness of targeted active malaria case detection among high-risk populations in Southern Lao PDR (the AcME-Lao study)