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Indoor residual spray (IRS) of insecticides and insecticide-treated bednets (ITNs) are the two most important malaria vector control tools in the tropical world. Application of both tools in the same locations is being implemented for malaria control in endemic and epidemic Africa. The two tools are assumed to have synergistic benefits in reducing malaria transmission because they both act at multiple stages of the transmission cycle. However, this assumption has not been rigorously examined, empirically or theoretically. Using mathematical modelling, we obtained the conditions for which a combination strategy can be expected to improve upon single control tools. Specifically, spraying of dichlorodiphenyltrichloroethane (DDT) in all houses where residents are not using ITNs can reduce transmission of malaria (R₀) by up to 10 times more than the reduction achieved through ITNs alone. Importantly, however, we also …