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CHERG - Child Epidemiology Reference Group

Malaria Treatment with ACT (uncomplicated) or
Effective Case Management (complicated)

Thwing J, Eisele TP, Steketee RW.  Protective efficacy of malaria case management for preventing malaria mortality in children: a systematic review for the Lives Saved Tool.  BMC Public Health 2011, 11 (Suppl 3): S14.


  • WHO estimates that 243 million malaria cases and 863,000 malaria deaths occurred globally in 2009 (over 90% of which were in sub-Saharan Africa). (1)
  • Artemisinin combination therapies (ACT) are highly effective for preventing an uncomplicated P. falciparum malaria fever from progressing to severe disease (2,3)
  • Effective case management with parenteral or rectal artemisinin or quinine is highly effective at preventing death in children with severe malaria. (4-6)

Intervention Effects

ACT treatment among children with uncomplicated malaria on malaria mortality

  • Weighted mean CFR among children with uncomplicated P. falciparum malaria treated promptly with ACT was 0.068% (95 ci: .024-.112) – 49 double-blind randomized placebo controlled equivalency trials – High Quality Data
  • Utilized Delphi estimates of mortality generated by expert opinion (7)- Low Quality Data:
    • Mortality in untreated children < 2 years with uncomplicated P. falciparum malaria = 5%
    • Mortality in untreated 2-5 year olds with uncomplicated P. falciparum malaria = 2%
  • 99% (range: 94-100%) reduction in malaria mortality in children 1-23 months that have received ACT treatment for uncomplicated P. falciparum malaria.

Case management (including parenteral quinine among all hospitalized children) on malaria mortality 

  • Weighted mean CFR of 3.4% (95% ci: 1.6-5.2) when all malaria is included and weighted mean CFR of 13.6% (95% ci: 8.4-18.8) when restricted to severe disease – Moderate Quality Data
  • Proxy for mortality of untreated hospitalized malaria was used, resulting in an estimated CFR of untreated hospitalized malaria ranging from 13-21% – Low Quality Data
  • 82% (range: 63-94%) reduction in malaria mortality in children 1-59 months old treated for severe P. falciparum malaria with effective case management including intravenous quinine.
  • Mortality of children hospitalized with malaria in a setting of chloroquine failure was used as the proxy for the natural history of mortality of children eligible for hospitalization with malaria.  This may underestimate the natural history of mortality in children who went untreated for malaria requiring hospitalization, which would result in an underestimation of the protective efficacy of effective case management of severe malaria.

References from Thwing Paper Cited Here

  1. WHO: World Malaria Report 2008. Geneva: World Health Organization; WHO 2008.
  2. Sinclair D, Zani B, Donegan S, Olliaro P, Garner P: Artemisinin-based combination therapy for treating uncomplicated malaria. Cochrane database of systematic reviews (Online) 2009, (3):CD007483.
  3. Adjuik M, Babiker A, Garner P, Olliaro P, Taylor W, White N: Artesunate combinations for treatment of malaria: meta-analysis.  Lancet 2004, 363(9402):9-17.
  4. McIntosh HM, Olliaro P: Artemisinin derivatives for treating severe malaria.  Cochrane database of systematic reviews (Online) 2000, (2):CD000527.
  5. Day N, Dondorp AM: The management of patients with severe malaria. The American journal of tropical medicine and hygiene 2007, 77(6 Suppl):29-35.
  6. Karunajeewa HA, Manning L, Mueller I, Ilett KF, Davis TM: Rectal administration of artemisinin derivatives for the treatment of malaria. JAMA 2007, 297(21):2381-2390.
  7. Sudre P, Breman JG, Koplan JP: Delphi survey of malaria mortality and drug resistance in Africa. Lancet 1990, 335(8691):722.

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