To inform global efforts to eliminate malaria in resource-limited settings, an active area of research evaluates whether targeted interventions delivered to malaria cases recently seen at local clinics and their neighbors can halt transmission in low endemic settings. This study will use novel statistical methods to measure whether these reactive, focal interventions (presumptive treatment with antimalarials and indoor residual spraying) in Namibia, Swaziland, and Zambia can reduce transmission of *Plasmodium falciparum* from intervention recipients to non-recipients in nearby areas – i.e., whether interventions produce spillover effects, evidence of which would indicate that these interventions hold promise for malaria elimination. Information about the magnitude of spillover effects and the distribution of spillover effects over space, time, and intervention coverage level will inform whether reactive, focal interventions hold promise for malaria elimination when scaled up or whether interventions require modification; the methods developed in this study will form a template that can be used in other trials of focal interventions for malaria or other infectious diseases. This research is funded by NIAID (K01AI141616).