The role of previously unmeasured organic acids in the pathogenesis of severe malaria

Introduction: Severe falciparum malaria is commonly complicated by metabolic acidosis. Together with lactic acid (LA), other previously unmeasured acids have been implicated in the pathogenesis of falciparum malaria. Methods: In this prospective study, we characterised organic acids in adults with...

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Main Authors: Herdman, M. Trent, Natthida Sriboonvorakul, Leopold, Stije J., Sam Douthwaite, Sanjib Mohanty, M. Mahtab Uddin Hassan, Maude, Richard J., Kingston, Hugh WF, Katherine Plewes, Prakaykaew Charunwatthana, Kamolrat Silamut, Woodrow, Charles J., Kesinee Chotinavich, Hossain, Md. Amir, Faiz, M. Abul, Saroj Mishra, Natchanun Leepipatpiboon, White, Nicholas J., Day, Nicholas PJ, Joel Tarning, Dondorp, Arjen M.
Other Authors: Mahidol University. Faculty of Tropical Medicine. Mahidol-Oxford Tropical Medicine Research Unit
Format: Article
Language:English
Published: 2017
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Online Access:https://repository.li.mahidol.ac.th/handle/123456789/3089
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spelling th-mahidol.30892023-03-31T06:03:25Z The role of previously unmeasured organic acids in the pathogenesis of severe malaria Herdman, M. Trent Natthida Sriboonvorakul Leopold, Stije J. Sam Douthwaite Sanjib Mohanty M. Mahtab Uddin Hassan Maude, Richard J. Kingston, Hugh WF Katherine Plewes Prakaykaew Charunwatthana Kamolrat Silamut Woodrow, Charles J. Kesinee Chotinavich Hossain, Md. Amir Faiz, M. Abul Saroj Mishra Natchanun Leepipatpiboon White, Nicholas J. Day, Nicholas PJ Joel Tarning Dondorp, Arjen M. Mahidol University. Faculty of Tropical Medicine. Mahidol-Oxford Tropical Medicine Research Unit Open Access article organic acids Malaria Introduction: Severe falciparum malaria is commonly complicated by metabolic acidosis. Together with lactic acid (LA), other previously unmeasured acids have been implicated in the pathogenesis of falciparum malaria. Methods: In this prospective study, we characterised organic acids in adults with severe falciparum malaria in India and Bangladesh. Liquid chromatography-mass spectrometry was used to measure organic acids in plasma and urine. Patients were followed until recovery or death. Results: Patients with severe malaria (n=138), uncomplicated malaria (n=102), sepsis (n=32) and febrile encephalopathy (n=35) were included. Strong ion gap (mean±SD) was elevated in severe malaria (8.2 mEq/L±4.5) and severe sepsis (8.6 mEq/L±7.7) compared with uncomplicated malaria (6.0 mEq/L±5.1) and encephalopathy (6.6 mEq/L±4.7). Compared with uncomplicated malaria, severe malaria was characterised by elevated plasma LA, hydroxyphenyllactic acid (HPLA), α-hydroxybutyric acid and β-hydroxybutyric acid (all P<0.05). In urine, concentrations of methylmalonic, ethylmalonic and α-ketoglutaric acids were also elevated. Multivariate logistic regression showed that plasma HPLA was a strong independent predictor of death (odds ratio [OR] 3.5, 95 % confidence interval [CI] 1.6–7.5, P=0.001), comparable to LA (OR 3.5, 95 % CI 1.5–7.8, P=0.003) (combined area under the receiver operating characteristic curve 0.81). Conclusions: Newly identified acids, in addition to LA, are elevated in patients with severe malaria and are highly predictive of fatal outcome. Further characterisation of their sources and metabolic pathways is now needed. 2017-11-09T03:39:13Z 2017-11-09T03:39:13Z 2017-11-09 2015 Research Article Critical Care. Vol.19, (2015), 317 10.1186/s13054-015-1023-5 https://repository.li.mahidol.ac.th/handle/123456789/3089 eng Mahidol University BioMed Central application/pdf
institution Mahidol University
building Mahidol University Library
continent Asia
country Thailand
Thailand
content_provider Mahidol University Library
collection Mahidol University Institutional Repository
language English
topic Open Access article
organic acids
Malaria
spellingShingle Open Access article
organic acids
Malaria
Herdman, M. Trent
Natthida Sriboonvorakul
Leopold, Stije J.
Sam Douthwaite
Sanjib Mohanty
M. Mahtab Uddin Hassan
Maude, Richard J.
Kingston, Hugh WF
Katherine Plewes
Prakaykaew Charunwatthana
Kamolrat Silamut
Woodrow, Charles J.
Kesinee Chotinavich
Hossain, Md. Amir
Faiz, M. Abul
Saroj Mishra
Natchanun Leepipatpiboon
White, Nicholas J.
Day, Nicholas PJ
Joel Tarning
Dondorp, Arjen M.
The role of previously unmeasured organic acids in the pathogenesis of severe malaria
description Introduction: Severe falciparum malaria is commonly complicated by metabolic acidosis. Together with lactic acid (LA), other previously unmeasured acids have been implicated in the pathogenesis of falciparum malaria. Methods: In this prospective study, we characterised organic acids in adults with severe falciparum malaria in India and Bangladesh. Liquid chromatography-mass spectrometry was used to measure organic acids in plasma and urine. Patients were followed until recovery or death. Results: Patients with severe malaria (n=138), uncomplicated malaria (n=102), sepsis (n=32) and febrile encephalopathy (n=35) were included. Strong ion gap (mean±SD) was elevated in severe malaria (8.2 mEq/L±4.5) and severe sepsis (8.6 mEq/L±7.7) compared with uncomplicated malaria (6.0 mEq/L±5.1) and encephalopathy (6.6 mEq/L±4.7). Compared with uncomplicated malaria, severe malaria was characterised by elevated plasma LA, hydroxyphenyllactic acid (HPLA), α-hydroxybutyric acid and β-hydroxybutyric acid (all P<0.05). In urine, concentrations of methylmalonic, ethylmalonic and α-ketoglutaric acids were also elevated. Multivariate logistic regression showed that plasma HPLA was a strong independent predictor of death (odds ratio [OR] 3.5, 95 % confidence interval [CI] 1.6–7.5, P=0.001), comparable to LA (OR 3.5, 95 % CI 1.5–7.8, P=0.003) (combined area under the receiver operating characteristic curve 0.81). Conclusions: Newly identified acids, in addition to LA, are elevated in patients with severe malaria and are highly predictive of fatal outcome. Further characterisation of their sources and metabolic pathways is now needed.
author2 Mahidol University. Faculty of Tropical Medicine. Mahidol-Oxford Tropical Medicine Research Unit
author_facet Mahidol University. Faculty of Tropical Medicine. Mahidol-Oxford Tropical Medicine Research Unit
Herdman, M. Trent
Natthida Sriboonvorakul
Leopold, Stije J.
Sam Douthwaite
Sanjib Mohanty
M. Mahtab Uddin Hassan
Maude, Richard J.
Kingston, Hugh WF
Katherine Plewes
Prakaykaew Charunwatthana
Kamolrat Silamut
Woodrow, Charles J.
Kesinee Chotinavich
Hossain, Md. Amir
Faiz, M. Abul
Saroj Mishra
Natchanun Leepipatpiboon
White, Nicholas J.
Day, Nicholas PJ
Joel Tarning
Dondorp, Arjen M.
format Article
author Herdman, M. Trent
Natthida Sriboonvorakul
Leopold, Stije J.
Sam Douthwaite
Sanjib Mohanty
M. Mahtab Uddin Hassan
Maude, Richard J.
Kingston, Hugh WF
Katherine Plewes
Prakaykaew Charunwatthana
Kamolrat Silamut
Woodrow, Charles J.
Kesinee Chotinavich
Hossain, Md. Amir
Faiz, M. Abul
Saroj Mishra
Natchanun Leepipatpiboon
White, Nicholas J.
Day, Nicholas PJ
Joel Tarning
Dondorp, Arjen M.
author_sort Herdman, M. Trent
title The role of previously unmeasured organic acids in the pathogenesis of severe malaria
title_short The role of previously unmeasured organic acids in the pathogenesis of severe malaria
title_full The role of previously unmeasured organic acids in the pathogenesis of severe malaria
title_fullStr The role of previously unmeasured organic acids in the pathogenesis of severe malaria
title_full_unstemmed The role of previously unmeasured organic acids in the pathogenesis of severe malaria
title_sort role of previously unmeasured organic acids in the pathogenesis of severe malaria
publishDate 2017
url https://repository.li.mahidol.ac.th/handle/123456789/3089
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