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Abstract
BackgroundThe 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.MethodsWe 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.ResultsBased 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.ConclusionsThis 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.
Highlights
The Lives Saved Tool (LiST) model was developed to estimate the impact of the scale-up of child survival interventions on child mortality
Treatment of uncomplicated malaria with effective antimalarials Among the 49 double-blind randomized placebo controlled equivalency trials identified from our review [15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63], the weighted mean case fatality ratios (CFR) among children with uncomplicated P. falciparum malaria treated promptly with an Artemisinin-based combination therapies (ACTs) was 0.068% (11 / 16,086); an additional 67 cases were reported as early treatment failures that received rescue therapy and went on to recovery
In the years immediately following the spread of chloroquine resistance, children who continued to be treated with chloroquine had approximately a three-fold higher CFR than children treated with an effective antimalarial [81]
Summary
The Lives Saved Tool (LiST) model was developed to estimate the impact of the scale-up of child survival interventions on child mortality. 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 being considered for inclusion in the LiST model. Among children with severe malaria, effective case management with parenteral or rectal artemisinin or quinine is recognized to be highly effective at preventing death [6,7,8]. The impact of prompt and effective treatment of uncomplicated malaria and case management of severe malaria on reducing child malaria deaths has not been quantified with placebo-randomized controlled trials for obvious ethical reasons
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