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

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.

Incidence and admission rates for severe malaria and their impact on mortality in Africa

“…This is especially the case for which is close to linearly related to . If is much greater than the OpenMalaria value of (and therefore also higher than the core estimates, as in Thwing et al [4]) then the primary estimates substantially understate the variation between countries in the incidence of severe malaria cases that are not admitted.…”

“…Hospital case fatality rates for well-defined severe malaria are relatively well established [2, 3]. However these do not translate directly into estimates of the impact of effective management of severe disease on malaria mortality rates, for which only estimates based on expert opinion are available [4] and, to date, there are no good estimates of how these translate into numbers of malaria deaths averted.…”

Efficacy of artemisinin combination therapy for the treatment of uncomplicated falciparum malaria in Nigerian children

“…Clinical trials of ACTs in different parts of Nigeria since its introduction have shown good efficacy and tolerability of ACTs in the treatment of uncomplicated malaria in children [7,8]. The high cure rates of ACTs have also been confirmed in different studies across sub-Saharan Africa [9].…”

Comparing the Impact of Artemisinin-Based Combination Therapies on Malaria Transmission in Sub-Saharan Africa

“…7,8 As a result of the ability of the artemisinin component to rapidly reduce para sitemia, early treatment of uncomplicated malaria with ACTs may prevent progression to severe disease, thereby reducing the number of severe cases and the malaria mortality rate. 9 The ACTs may also reduce overall malaria transmission by decreasing human infectivity to mosquitoes 10,11 and by extending the prophylactic period after treatment. 8 A variety of ACTs exists, such as artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DP), which vary in their efficacy profile against uncomplicated malaria, tolerability, and their ability to reduce infectivity to mosquitoes.…”