Hsiang MS, Ntshalintshali N, Dufour MSK, et al. - The widely practiced malaria elimination intervention is reactive case detection (RACD) whereby malaria testing is performed in close contacts of index cases to inform treatment and other interventions, researchers here sought for the optimal diagnostic and operational approaches for this resource-intensive strategy. A 3-year prospective national evaluation of RACD was performed in Eswatini, a malaria elimination setting. Comparison was performed of loop-mediated isothermal amplification (LAMP) with traditional rapid diagnostic testing (RDT) for the improved identification of infections and for hotspots (RACD events yielding ≥ 1 additional infection). This work is identified to be the first large-scale national evaluation of optimal RACD approaches from a malaria elimination setting. Among 377 RACD events, screening was done in 10,890 participants residing within 500 m of index cases. Compared with RDT, LAMP presented a 3-fold and 2.3-fold higher yield to identify infections (1.7% vs 0.6%) and hotspots (29.7% vs 12.7%), respectively. A dose-dependent increased infection risk was observed in correlation with proximity to the index case (up to 4-fold). Consideration was provided to individual-, index case–, and other RACD-level factors but the simple approach of restricting RACD to a 200-m radius increased the yield and efficiency to greatest. They recommend utilizing more sensitive diagnostics and clear context-specific operational parameters to inform delivery of antimalarial drugs or other interventions, RACD .