Effectiveness and cost-effectiveness of reactive, targeted indoor residual spraying for malaria control in low-transmission settings: a cluster-randomised, non-inferiority trial in South Africa

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, Immo Kleinschmidt, 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, Immo Kleinschmidt

Abstract

Background: Increasing 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.

Methods: This 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.

Findings: Malaria 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.

Interpretation: Targeted 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.

Funding: Joint 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.

Figures

Figure 1
Figure 1
Study location (A) Location of trial provinces. (B) Location of clusters within trial provinces. (C) Allocation of clusters to study groups within Mpumalanga. (D) Allocation of clusters to study groups within Limpopo. IRS=indoor residual spraying.
Figure 2
Figure 2
Rate difference between targeted IRS and standard IRS for 2-year study period This figure shows the rate difference between annual cluster incidence, crude and adjusted for province, with large caps representing 95% CIs and smaller caps representing 90% CIs. The red dotted vertical line represents the non-inferiority margin (1 case per 1000 person-years increase in incidence). Non-inferiority p value is the probability of obtaining the rate difference by chance if the actual difference is more than 1. Margin of non-inferiority is breached if CIs encompass 1. IRS=indoor residual spraying.
Figure 3
Figure 3
Cost-effectiveness plane Economic cost savings (from a health service perspective) and DALYs incurred by switching from standard IRS to targeted IRS are shown for the 2-year trial period (A) and individual study years (B). Costs and DALYs shown in the figure are incremental with respect to standard IRS (which is shown at [0,0]) in each study year. The large dots show the mean incremental cost and mean incremental DALYs across the 10 000 model simulations. Individual model simulations are shown as smaller dots, for each year. DALY=disability-adjusted life-year. IRS=indoor residual spraying.
Figure 4
Figure 4
Deterministic sensitivity of ICERs to plausible variation in individual model parameters Where targeted IRS is the dominant strategy (ie, less costly and more effective than standard IRS), this has been stated in the cell. DALY=disability-adjusted life-year. ICER=incremental cost-effectiveness ratio. IRS=indoor residual spraying. NA=not applicable. *ICER estimates are based on best estimates for each parameter; therefore, they slightly differ from the ICER estimates presented in the main text, which are calculated as the mean incremental cost savings divided by the mean incremental DALYs from 10 000 model simulations. † Adjusted for province. ‡Contract sprayer-days is the number of contract sprayers employed each year multiplied by the number of days in the annual mass spraying season.

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