Protective efficacy of malaria case management for preventing malaria mortality in children: a systematic review for the Lives Saved Tool

Background: The Lives Saved Tool (LiST) model was developed to estimate the impact of the scale-up of child survival interventions on child mortality. New advances in antimalarials have improved their efficacy of treating uncomplicated and severe malaria. Artemisinin-based combination therapies (ACTs) for uncomplicated Plasmodium falciparum malaria and parenteral or rectal artemisinin or quinine for severe malaria syndromes have been shown to be very effective for the treatment of malaria in children. These interventions are now being considered for inclusion in the LiST model. However, for obvious ethical reasons, their protective efficacy (PE) compared to placebo is unknown and their impact on reducing malaria-attributable mortality has not been quantified. Methods: We performed systematic literature reviews of published studies in P. falciparum endemic settings to determine the protective efficacy (PE) of ACT treatment against malaria deaths among children with uncomplicated malaria, as well as the PE of effective case management including parenteral quinine against malaria deaths among all hospitalized children. As no randomized placebo-controlled trials of malaria treatment have been conducted, we used multiple data sources to ascertain estimates of PE, including a previously performed Delphi estimate for treatment of uncomplicated malaria. Results: Based on multiple data sources, we estimate the PE of ACT treatment of uncomplicated P. falciparum malaria on reducing malaria mortality in children 1-23 months to be 99% (range: 94-100%), and in children 24-59 months to be 97% (range: 86-99%). We estimate the PE of treatment of severe P. falciparum malaria with effective case management including intravenous quinine on reducing malaria mortality in children 1-59 months to be 82% (range: 63-94%) compared to no treatment. Conclusions: This systematic review quantifies the PE of ACT used for treating uncomplicated malaria and effective case management including parenteral quinine for treating severe P. falciparum malaria for preventing malaria mortality in children <5. These data will be used in the Lives Saved Tool (LiST) model for estimating the impact of scaling-up these interventions against malaria. However, in order to estimate the reduction in child mortality due to scale-up of these interventions, it is imperative to develop standardized indicators to measure population coverage of these interventions.