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Towards improving point-of-care diagnosis of non-malaria febrile illness: a metabolomics approach

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dc.contributor.author Decuypere, S.
dc.contributor.author Maltha, J.
dc.contributor.author Deborggraeve, S.
dc.contributor.author Rattray, N. J.
dc.contributor.author Issa, G.
dc.contributor.author Bérenger, K.
dc.contributor.author Lompo, P.
dc.contributor.author Tahita, M. C.
dc.contributor.author Ruspasinghe, T.
dc.contributor.author McConville, M.
dc.contributor.author Goodacre, R.
dc.contributor.author Tinto, H.
dc.contributor.author Jacobs, J.
dc.contributor.author Carapetis, J. R.
dc.date.accessioned 2016-06-02T11:24:22Z
dc.date.available 2016-06-02T11:24:22Z
dc.date.issued 2016
dc.identifier.issn 1935-2727
dc.identifier.doi http://dx.doi.org/10.1371/journal.pntd.0004480
dc.identifier.other ITG-C2B
dc.identifier.other ITG-B3A
dc.identifier.other ITG-C13A
dc.identifier.other MULTI
dc.identifier.other DCS
dc.identifier.other U-TLM
dc.identifier.other DBM
dc.identifier.other U-DIABAC
dc.identifier.other JIF
dc.identifier.other DOI
dc.identifier.other FTA
dc.identifier.other OAJ
dc.identifier.other Abstract
dc.identifier.other UPD62
dc.identifier.uri http://hdl.handle.net/10390/8901
dc.description.abstract INTRODUCTION: Non-malaria febrile illnesses such as bacterial bloodstream infections (BSI) are a leading cause of disease and mortality in the tropics. However, there are no reliable, simple diagnostic tests for identifying BSI or other severe non-malaria febrile illnesses. We hypothesized that different infectious agents responsible for severe febrile illness would impact on the host metabololome in different ways, and investigated the potential of plasma metabolites for diagnosis of non-malaria febrile illness. METHODOLOGY: We conducted a comprehensive mass-spectrometry based metabolomics analysis of the plasma of 61 children with severe febrile illness from a malaria-endemic rural African setting. Metabolite features characteristic for non-malaria febrile illness, BSI, severe anemia and poor clinical outcome were identified by receiver operating curve analysis. PRINCIPAL FINDINGS: The plasma metabolome profile of malaria and non-malaria patients revealed fundamental differences in host response, including a differential activation of the hypothalamic-pituitary-adrenal axis. A simple corticosteroid signature was a good classifier of severe malaria and non-malaria febrile patients (AUC 0.82, 95% CI: 0.70-0.93). Patients with BSI were characterized by upregulated plasma bile metabolites; a signature of two bile metabolites was estimated to have a sensitivity of 98.1% (95% CI: 80.2-100) and a specificity of 82.9% (95% CI: 54.7-99.9) to detect BSI in children younger than 5 years. This BSI signature demonstrates that host metabolites can have a superior diagnostic sensitivity compared to pathogen-detecting tests to identify infections characterized by low pathogen load such as BSI. CONCLUSIONS: This study demonstrates the potential use of plasma metabolites to identify causality in children with severe febrile illness in malaria-endemic settings. en_US
dc.language English en_US
dc.subject Bacterial diseases en_US
dc.subject Bacterial bloodstream infection (bBSI) en_US
dc.subject Malaria en_US
dc.subject Febrile attacks en_US
dc.subject Diagnosis en_US
dc.subject Metabolomics en_US
dc.subject Plasma en_US
dc.subject Mass spectrometry en_US
dc.subject Children en_US
dc.subject Corticosteroids en_US
dc.subject Specificity en_US
dc.subject Sensitivity en_US
dc.subject Burkina Faso en_US
dc.subject Africa, West en_US
dc.title Towards improving point-of-care diagnosis of non-malaria febrile illness: a metabolomics approach en_US
dc.type Article-E en_US
dc.citation.issue 3 en_US
dc.citation.jtitle PLoS Neglected Tropical Diseases en_US
dc.citation.volume 10 en_US
dc.citation.pages e0004480 en_US
dc.identifier.pmid http://www.ncbi.nlm.nih.gov/pubmed/26943791
dc.citation.jabbreviation PLoS Negl Trop Dis en_US


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