Author:
Herdman M. Trent,Sriboonvorakul Natthida,Leopold Stije J.,Douthwaite Sam,Mohanty Sanjib,Hassan M. Mahtab Uddin,Maude Richard J.,Kingston Hugh WF,Plewes Katherine,Charunwatthana Prakaykaew,Silamut Kamolrat,Woodrow Charles J.,Chotinavich Kesinee,Hossain Md. Amir,Faiz M. Abul,Mishra Saroj,Leepipatpiboon Natchanun,White Nicholas J.,Day Nicholas PJ,Tarning Joel,Dondorp Arjen M.
Abstract
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.
Publisher
Springer Science and Business Media LLC
Subject
Critical Care and Intensive Care Medicine
Cited by
16 articles.
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