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Reference: Philip Bejon, James A. Berkley, Tabitha Mwangi et al., (2007). Defining childhood severe falciparum malaria for intervention studies. PLoS Medicine, 4 (8), Article: e251.Citable link to this page:


Defining childhood severe falciparum malaria for intervention studies

Abstract: Background: Clinical trials of interventions designed to prevent severe falciparum malaria in children require a clear endpoint. The internationally accepted definition of severe malaria is sensitive, and appropriate for clinical purposes. However, this definition includes individuals with severe nonmalarial disease and coincident parasitaemia, so may lack specificity in vaccine trials. Although there is no ‘‘gold standard’’ individual test for severe malaria, malaria-attributable fractions (MAFs) can be estimated among groups of children using a logistic model, which we use to test the suitability of various case definitions as trial endpoints.Methods and Findings: A total of 4,583 blood samples were taken from well children in cross-sectional surveys and from 1,361 children admitted to a Kenyan District hospital with severe disease. Among children under 2 y old with severe disease and over 2,500 parasites per microliter of blood, the MAFs were above 85% in moderate- and low-transmission areas, but only 61% in a high-transmission area. HIV and malnutrition were not associated with reduced MAFs, but gastroenteritis with severe dehydration (defined by reduced skin turgor), lower respiratory tract infection (clinician’sfinal diagnosis), meningitis (on cerebrospinal fluid [CSF] examination), and bacteraemia were associated with reduced MAFs. The overall MAF was 85% (95% confidence interval [CI] 83.8%–86.1%) without excluding these conditions, 89% (95% CI 88.4%–90.2%) after exclusions, and 95% (95% CI 94.0%–95.5%) when a threshold of 2,500 parasites/ll was also applied. Applying a threshold and exclusion criteria reduced sensitivity to 80% (95% CI 77%–83%).Conclusions: The specificity of a case definition for severe malaria is improved by applying a parasite density threshold and by excluding children with meningitis, lower respiratory tract infection (clinician’s diagnosis), bacteraemia, and gastroenteritis with severe dehydration, but not by excluding children with HIV or malnutrition.

Publication status:PublishedPeer Review status:Peer reviewedVersion:Publisher's version Funder: KEMRI   Funder: Wellcome Trust   Notes:Citation: Bejon, P. et al. (2007). 'Defining childhood severe falciparum malaria for intervention studies', PLoS Medicine, 4(8), e251. [Available at]. © 2007 Bejon et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Bibliographic Details

Publisher: Public Library of Science

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Host: PLoS Medicinesee more from them

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Issue Date: 2007-August

Copyright Date: 2007

pages:Article: e251Identifiers


Issn: 1549-1277

Eissn: 1549-1676

Urn: uuid:faf352fe-bef7-443a-90af-a84f0bb83cec Item Description

Type: Article: post-print;

Language: en

Version: Publisher's versionSubjects: Medical Sciences Malaria Paediatrics Tropical medicine Tiny URL: ora:3075


Author: Philip Bejon - institutionKenya Medical Research Institute KEMRI–Wellcome Trust Collaborative Research Programme, Centre for Ge



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