@article {Vilakatie005021, author = {Sibonakaliso Vilakati and Nontokozo Mngadi and Jade Benjamin-Chung and Nomcebo Dlamini and Mi-Suk Kang Dufour and Brooke Whittemore and Khayelihle Bhangu and Lisa M Prach and Kimberly Baltzell and Nomcebo Nhlabathi and Calisile Malambe and Bongani Dlamini and Danica Helb and Bryan Greenhouse and Gugu Maphalala and Deepa Pindolia and Muhindo Kalungero and Getahun Tesfa and Roly Gosling and Nyasatu Ntshalintshali and Simon Kunene and Michelle S Hsiang}, title = {Effectiveness and safety of reactive focal mass drug administration (rfMDA) using dihydroartemisinin{\textendash}piperaquine to reduce malaria transmission in the very low-endemic setting of Eswatini: a pragmatic cluster randomised controlled trial}, volume = {6}, number = {6}, elocation-id = {e005021}, year = {2021}, doi = {10.1136/bmjgh-2021-005021}, publisher = {BMJ Specialist Journals}, abstract = {Introduction To reduce malaria transmission in very low-endemic settings, screening and treatment near index cases (reactive case detection (RACD)), is widely practised, but the rapid diagnostic tests (RDTs) used miss low-density infections. Reactive focal mass drug administration (rfMDA) may be safe and more effective.Methods We conducted a pragmatic cluster randomised controlled trial in Eswatini, a very low-endemic setting. 77 clusters were randomised to rfMDA using dihydroartemisin{\textendash}piperaquine (DP) or RACD involving RDTs and artemether{\textendash}lumefantrine. Interventions were delivered by the local programme. An intention-to-treat analysis was used to compare cluster-level cumulative confirmed malaria incidence among clusters with cases. Secondary outcomes included safety and adherence.Results From September 2015 to August 2017, 222 index cases from 47 clusters triggered 46 RACD events and 64 rfMDA events. RACD and rfMDA were delivered to 1455 and 1776 individuals, respectively. Index case coverage was 69.5\% and 62.4\% for RACD and rfMDA, respectively. Adherence to DP was 98.7\%. No serious adverse events occurred. For rfMDA versus RACD, cumulative incidences (per 1000 person-years) of all malaria were 2.11 (95\% CI 1.73 to 2.59) and 1.97 (95\% CI 1.57 to 2.47), respectively; and of locally acquired malaria, they were 1.29 (95\% CI 1.00 to 1.67) and 0.97 (95\% CI 0.71 to 1.34), respectively. Adjusting for imbalance in baseline incidence, incidence rate ratio for rfMDA versus RACD was 0.93 (95\% CI 0.54 to 1.62) for all malaria and 0.84 (95\% CI 0.42 to 1.66) for locally acquired malaria. Similar results were obtained in a per-protocol analysis that excluded clusters with \<80\% index case coverage.Conclusion In a very low-endemic, real-world setting, rfMDA using DP was safe, but did not lower incidence compared with RACD, potentially due to insufficient coverage and/or power. To assess impact of interventions in very low-endemic settings, improved coverage, complementary interventions and adaptive ring trial designs may be needed.Trial registration number NCT02315690.The data that support the findings of this study are not publicly available. Data are available from the authors on reasonable request and with permission of Eswatini Ministry of Health.}, URL = {https://gh.bmj.com/content/6/6/e005021}, eprint = {https://gh.bmj.com/content/6/6/e005021.full.pdf}, journal = {BMJ Global Health} }