• David Bath, Jackie Cook, John Govere, Phillemon Mathebula, Natashia Morris, Khumbulani Hlongwana, Jaishree Raman, Ishen Seocharan, Alpheus Zitha, Matimba Zitha, Aaron Mabuza, Frans Mbokazi, Elliot Machaba, Erik Mabunda, Eunice Jamesboy, Joseph Biggs, Chris Drakeley, Devanand Moonasar, Rajendra Maharaj, Maureen Coetzee, Catherine Pitt, and Immo Kleinschmidt.
• Department of Global Health and Development, London School of Hygiene & Tropical Medicine, London, UK; Department of Health Services Research and Policy, London School of Hygiene & Tropical Medicine, London, UK. Electronic address: david.bath@lshtm.ac.uk.
• Lancet. 2021 Feb 27; 397 (10276): 816827816-827.

BackgroundIncreasing insecticide costs and constrained malaria budgets could make universal vector control strategies, such as indoor residual spraying (IRS), unsustainable in low-transmission settings. We investigated the effectiveness and cost-effectiveness of a reactive, targeted IRS strategy.MethodsThis cluster-randomised, open-label, non-inferiority trial compared reactive, targeted IRS with standard IRS practice in northeastern South Africa over two malaria seasons (2015-17). In standard IRS clusters, programme managers conducted annual mass spray campaigns prioritising areas using historical data, expert opinion, and other factors. In targeted IRS clusters, only houses of index cases (identified through passive surveillance) and their immediate neighbours were sprayed. The non-inferiority margin was 1 case per 1000 person-years. Health service costs of real-world implementation were modelled from primary and secondary data. Incremental costs per disability-adjusted life-year (DALY) were estimated and deterministic and probabilistic sensitivity analyses conducted. This study is registered with ClinicalTrials.gov, NCT02556242.FindingsMalaria incidence was 0·95 per 1000 person-years (95% CI 0·58 to 1·32) in the standard IRS group and 1·05 per 1000 person-years (0·72 to 1·38) in the targeted IRS group, corresponding to a rate difference of 0·10 per 1000 person-years (-0·38 to 0·59), demonstrating non-inferiority for targeted IRS (p<0·0001). Per additional DALY incurred, targeted IRS saved US$7845 (2902 to 64 907), giving a 94-98% probability that switching to targeted IRS would be cost-effective relative to plausible cost-effectiveness thresholds for South Africa ($2637 to $3557 per DALY averted). Depending on the threshold used, targeted IRS would remain cost-effective at incidences of less than 2·0-2·7 per 1000 person-years. Findings were robust to plausible variation in other parameters.InterpretationTargeted IRS was non-inferior, safe, less costly, and cost-effective compared with standard IRS in this very-low-transmission setting. Saved resources could be reallocated to other malaria control and elimination activities.FundingJoint Global Health Trials.Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.

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