The role of previously unmeasured organic acids in the pathogenesis of severe malariaReportar como inadecuado

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Critical Care

, 19:317

First Online: 07 September 2015Received: 30 May 2015Accepted: 11 August 2015


IntroductionSevere 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.

MethodsIn 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.

ResultsPatients 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.

ConclusionsNewly 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.

AbbreviationsANOVAanalysis of variance

AUROCCarea under the receiver operating characteristic curve

CIconfidence interval

CrClcreatinine clearance EDTA, ethylenediaminetetraacetic acid

EMAethylmalonic acid

GCSGlasgow Coma Scale



HPLAhydroxyphenyllactic acid


IQRinterquartile range

LAlactic acid

LC-MSliquid chromatography-mass spectrometry

MAmalonic acid

MMAmethylmalonic acid

ORodds ratio

pCO2partial pressure of carbon dioxide

PfHRP2Plasmodium falciparum histidine-rich protein 2

SBDstandard base deficit

SBPsystolic blood pressure

SDstandard deviation

SIDstrong ion difference

SIGstrong ion gap


WHOWorld Health Organisation

α-HBAα-hydroxybutyric acid

α-KGAα-ketoglutaric acid

β-HBAβ-hydroxybutyric acid

Electronic supplementary materialThe online version of this article doi:10.1186-s13054-015-1023-5 contains supplementary material, which is available to authorized users.

An erratum to this article can be found at

An erratum to this article is available at

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Autor: M. Trent Herdman - Natthida Sriboonvorakul - Stije J. Leopold - Sam Douthwaite - Sanjib Mohanty - M. Mahtab Uddin Hassan


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