With significant declines in malaria, infections are increasingly clustered in households, or groups of households where malaria transmission is higher than in surrounding household/villages. To decrease transmission in such cases, reactive interventions target household members of clinical malaria cases, with the intervention unit (e.g., the "household/s") derived from an epidemiological and operational perspective. A lack of unanimity regarding the spatial range of the intervention unit calls for greater importance to be placed on social context in conceptualizing the appropriate unit. A novel malaria elimination strategy based on reactive treatment was recently evaluated by a cluster randomized trial in a low transmission setting in The Gambia. Transdisciplinary research was used to assess and improve the effectiveness of the intervention which consisted, among others, of reflecting on whether the household was the most adequate unit of analysis. The intervention was piloted on the smallest treatment unit possible and was further adapted following a better understanding of the social and epidemiological context. Intervention units defined according to (i) shared sleeping spaces and (ii) household membership, showed substantial limitations as it was not possible to define them clearly and they were extremely variable within the study setting. Incorporating local definitions and community preference in the trial design led to the appropriate intervention unit-the compound-defined as an enclosed space containing one or several households belonging to the same extended patrilineal family. Our study demonstrates the appropriateness of using transdisciplinary research for investigating alternative intervention units that are better tailored to reactive treatment approaches.