BACKGROUND - Leprosy is a significant public health problem. Early detection, treatment, and prevention are crucial to reduce transmission and disabilities. The World Health Organization (WHO) recommends single-dose rifampicin post-exposure prophylaxis (SDR-PEP) for screened contacts of leprosy patients. The PEP4LEP 2.0 study builds upon the EDCTP2-PEP4LEP project to identify the most effective intervention to screen individuals for leprosy, other skin neglected infectious diseases (skinNIDs) and common skin diseases, and to provide SDR-PEP. The study takes place in leprosy high-endemic areas in Ethiopia, Tanzania and Mozambique. It determines which intervention has most effect on leprosy case finding and detection delay. However, the COVID-19 pandemic hampered the initial PEP4LEP study through delayed interventions and medication shortages, affecting the main outcome indicator: case detection delay. METHODS - PEP4LEP 2.0 is a two-arm, cluster-randomized implementation trial to compare two interventions: 1) a community-based skin camp intervention, screening 100 leprosy patient's community contacts for leprosy and other skin diseases, and administering SDR-PEP; and 2) a health centre-based screening intervention, inviting leprosy patients’ household contacts to health centres for screening and SDR-PEP. To ensure a scientific sound analysis, PEP4LEP 2.0 collects additional data, increasing the sample size by 25%, to understand the pandemic's effects and enable analysis with and without COVID-19 influences. Skin camp organization, skinNID distribution, health staff capacity and acceptability will also be studied. Results will be modelled to assess the long-term impact related to costs. IMPACT - PEP4LEP 2.0 results will reflect scientific, societal and economic impact towards reduced leprosy transmission. They will be disseminated to all stakeholders: scientists, policymakers, WHO, health staff, affected communities, NGOs and the general public in the EU and Africa.