Towards Improving Point-of-Care Diagnosis of Non-malaria Febrile Illness: A Metabolomics Approach.
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 diffe...
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doaj-045a23a9805645fca2b9be2d3ca3c52f2020-11-24T20:42:58ZengPublic Library of Science (PLoS)PLoS Neglected Tropical Diseases1935-27271935-27352016-03-01103e000448010.1371/journal.pntd.0004480Towards Improving Point-of-Care Diagnosis of Non-malaria Febrile Illness: A Metabolomics Approach.Saskia DecuypereJessica MalthaStijn DeborggraeveNicholas J W RattrayGuiraud IssaKaboré BérengerPalpouguini LompoMarc C TahitaThusitha RuspasingheMalcolm McConvilleRoyston GoodacreHalidou TintoJan JacobsJonathan R CarapetisINTRODUCTION: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 metabolome 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.http://europepmc.org/articles/PMC4778767?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Saskia Decuypere Jessica Maltha Stijn Deborggraeve Nicholas J W Rattray Guiraud Issa Kaboré Bérenger Palpouguini Lompo Marc C Tahita Thusitha Ruspasinghe Malcolm McConville Royston Goodacre Halidou Tinto Jan Jacobs Jonathan R Carapetis |
spellingShingle |
Saskia Decuypere Jessica Maltha Stijn Deborggraeve Nicholas J W Rattray Guiraud Issa Kaboré Bérenger Palpouguini Lompo Marc C Tahita Thusitha Ruspasinghe Malcolm McConville Royston Goodacre Halidou Tinto Jan Jacobs Jonathan R Carapetis Towards Improving Point-of-Care Diagnosis of Non-malaria Febrile Illness: A Metabolomics Approach. PLoS Neglected Tropical Diseases |
author_facet |
Saskia Decuypere Jessica Maltha Stijn Deborggraeve Nicholas J W Rattray Guiraud Issa Kaboré Bérenger Palpouguini Lompo Marc C Tahita Thusitha Ruspasinghe Malcolm McConville Royston Goodacre Halidou Tinto Jan Jacobs Jonathan R Carapetis |
author_sort |
Saskia Decuypere |
title |
Towards Improving Point-of-Care Diagnosis of Non-malaria Febrile Illness: A Metabolomics Approach. |
title_short |
Towards Improving Point-of-Care Diagnosis of Non-malaria Febrile Illness: A Metabolomics Approach. |
title_full |
Towards Improving Point-of-Care Diagnosis of Non-malaria Febrile Illness: A Metabolomics Approach. |
title_fullStr |
Towards Improving Point-of-Care Diagnosis of Non-malaria Febrile Illness: A Metabolomics Approach. |
title_full_unstemmed |
Towards Improving Point-of-Care Diagnosis of Non-malaria Febrile Illness: A Metabolomics Approach. |
title_sort |
towards improving point-of-care diagnosis of non-malaria febrile illness: a metabolomics approach. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS Neglected Tropical Diseases |
issn |
1935-2727 1935-2735 |
publishDate |
2016-03-01 |
description |
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 metabolome 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. |
url |
http://europepmc.org/articles/PMC4778767?pdf=render |
work_keys_str_mv |
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