Journal article
The role of previously unmeasured organic acids in the pathogenesis of severe malaria
- Abstract:
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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.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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- Publisher copy:
- 10.1186/s13054-015-1023-5
Authors
- Grant:
- Major Overseas Programme Core Grant number 089275/Z/09/Z
- Publisher:
- BioMed Central
- Journal:
- Critical Care More from this journal
- Volume:
- 19
- Issue:
- 1
- Article number:
- 317
- Publication date:
- 2015-12-01
- Acceptance date:
- 2015-08-11
- DOI:
- EISSN:
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1466-609X
- ISSN:
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1364-8535
- Language:
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English
- Pubs id:
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pubs:545500
- UUID:
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uuid:06192f30-b033-4226-80b6-2a40ddad3fed
- Local pid:
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pubs:545500
- Source identifiers:
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545500
- Deposit date:
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2016-03-31
- ARK identifier:
Terms of use
- Copyright holder:
- Herdman et al
- Copyright date:
- 2015
- Rights statement:
- Copyright © 2015 Herdman et al. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
- Notes:
- An erratum to this article was published on 01 December 2015 and is available at https://doi.org/10.1186/s13054-015-1116-1
- Licence:
- CC Attribution (CC BY)
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