Longitudinal associations of plasma amino acid levels with recovery from malarial coma

Abstract

Background: Disordered amino acid metabolism is observed in cerebral malaria (CM). This study sought to determine whether abnormal amino acid concentrations were associated with level of consciousness in children recovering from coma. Twenty-one amino acids and coma scores were quantified longitudinally and the data were analysed for associations.

Methods: In a prospective observational study, 42 children with CM were enrolled. Amino acid levels were measured at entry and at frequent intervals thereafter and consciousness was assessed by Blantyre Coma Scores (BCS). Thirty-six healthy children served as controls for in-country normal amino acid ranges. Logistic regression was employed using a generalized linear mixed-effects model to assess associations between out-of-range amino acid levels and BCS.

Results: At entry 16/21 amino acid levels were out-of-range. Longitudinal analysis revealed 10/21 out-of-range amino acids were significantly associated with BCS. Elevated phenylalanine levels showed the highest association with low BCS. This finding held when out-of-normal-range data were analysed at each sampling time.

Conclusion: Longitudinal data is provided for associations between abnormal amino acid levels and recovery from CM. Of 10 amino acids significantly associated with BCS, elevated phenylalanine may be a surrogate for impaired clearance of ether lipid mediators of inflammation and may contribute to CM pathogenesis.

Keywords: Amino acids; Blantyre coma score; Cerebral malaria; Generalized linear mixed-effects model; Glyceryl lipid ethers; Tetrahydrobiopterin.

Fig. 1

Out-of-range amino acid levels significantly associated with Blantyre Coma Score at sampling time intervals. Plasma levels of each amino acid (circles, mean ± SEM) significantly associated with BCS (Table 4) are shown at sampling times. Blantyre Coma Score (triangles, mean ± SEM) at the same sampling times are reproduced for each amino acid panel

Fig. 2

Effect of sampling time on having an amino acid level outside of, or within, the normal range. Bar graphs for each amino acid show odds ratios (± 95% CI) at each sampling time. Odds ratios below 1.0 with Asterix denote significant association with levels outside normal ranges. Odds ratios above 1.0 with Asterix denote significant association with levels within normal ranges. Bars without Asterix are without significance. Box plot in the lower right hand panel shows median BCS with variance measures at sampling intervals. Boxes represent interquartile ranges (IQR). Dark lines within boxes are medians. Whiskers indicate minimum and maximum values within 1.5 times the IQR