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

Herdman, M. Trend, Sriboonvorakul, Natthida, Leopold, Stije J., Douthwaite, Sam, Mohanty, Sanjib, Hassan, M. Mahtab Uddin, Maude, Richard J., Kingston, Hugh W. F., Plewes, Katherine, Charunwatthana, Prakaykaew, Silamut, Kamolrat, Woodrow, Charles J., Chotinavich, Kesinee, Hossain, Md. Amir, Faiz, M. Abdul, Mishra, Saroj, Leepipatpiboon, Natchanun, White, Nicholas J., Day, Nicholas P. J., Tarning, Joel and Dondorp, Arjen M. (2015). The role of previously unmeasured organic acids in the pathogenesis of severe malaria. Critical Care,19(Article No. 317).

Document type: Journal Article
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IRMA ID 81144320xPUB101
Title The role of previously unmeasured organic acids in the pathogenesis of severe malaria
Author Herdman, M. Trend
Sriboonvorakul, Natthida
Leopold, Stije J.
Douthwaite, Sam
Mohanty, Sanjib
Hassan, M. Mahtab Uddin
Maude, Richard J.
Kingston, Hugh W. F.
Plewes, Katherine
Charunwatthana, Prakaykaew
Silamut, Kamolrat
Woodrow, Charles J.
Chotinavich, Kesinee
Hossain, Md. Amir
Faiz, M. Abdul
Mishra, Saroj
Leepipatpiboon, Natchanun
White, Nicholas J.
Day, Nicholas P. J.
Tarning, Joel
Dondorp, Arjen M.
Journal Name Critical Care
Publication Date 2015
Volume Number 19
Issue Number Article No. 317
ISSN 1364-8535   (check CDU catalogue  open catalogue search in new window)
Scopus ID 2-s2.0-84940862463
Total Pages 11
Place of Publication United Kingdom
Publisher BioMed Central Ltd.
HERDC Category C1 - Journal Article (DIISR)
Abstract 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.
DOI http://dx.doi.org/10.1186/s13054-015-1023-5   (check subscription with CDU E-Gateway service for CDU Staff and Students  check subscription with CDU E-Gateway in new window)
Additional Notes This is an Open Access article distributed under the terms of the Creative Commons Attribution License 4.0, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Description for Link Link to CC Attribution 4.0 License
URL https://creativecommons.org/licenses/by/4.0/au


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