Elevated plasma phenylalanine in severe malaria and implications for pathophysiology of neurological complications.

Update item information
Publication Type Journal Article
School or College School of Medicine
Department Internal Medicine; Orthopaedics; Human Genetics
Program Institute of Human Genetics; Howard Hughes Medical Institute (HHMI)
Creator Lopansri, Bert; Stoddard, Gregory J.; Hobbs, Maurine R.; Granger, Donald Lee
Other Author Anstey, Nicholas M.; Mwaikambo, Esther D.; Tjitra, Emiliana; Maniboey, Helena; Levesque, Marc C.; Weinberg, J. Brice
Title Elevated plasma phenylalanine in severe malaria and implications for pathophysiology of neurological complications.
Date 2006-06-01
Description Cerebral malaria is associated with decreased production of nitric oxide and decreased levels of its precursor, l-arginine. Abnormal amino acid metabolism may thus be an important factor in malaria pathogenesis. We sought to determine if other amino acid abnormalities are associated with disease severity in falciparum malaria. Subjects were enrolled in Dar es Salaam, Tanzania (children) (n = 126), and Papua, Indonesia (adults) (n = 156), in two separate studies. Plasma samples were collected from subjects with WHO-defined cerebral malaria (children), all forms of severe malaria (adults), and uncomplicated malaria (children and adults). Healthy children and adults without fever or illness served as controls. Plasma amino acids were measured using reverse-phase high-performance liquid chromatography with fluorescence detection. Several plasma amino acids were significantly lower in the clinical malaria groups than in healthy controls. Despite the differences, phenylalanine was the only amino acid with mean levels outside the normal range (40 to 84 microM) and was markedly elevated in children with cerebral malaria (median [95% confidence interval], 163 [134 to 193] microM; P < 0.0001) and adults with all forms of severe malaria (median [95% confidence interval], 129 [111 to 155] microM; P < 0.0001). In adults who survived severe malaria, phenylalanine levels returned to normal, with clinical improvement (P = 0.0002). Maintenance of plasma phenylalanine homeostasis is disrupted in severe malaria, leading to significant hyperphenylalaninemia. This is likely a result of an acquired abnormality in the function of the liver enzyme phenylalanine hydroxylase. Determination of the mechanism of this abnormality may contribute to the understanding of neurological complications in malaria.
Type Text
Publisher American Society for Microbiology
Volume 74
Issue 6
First Page 3355
Last Page 3359
Subject Dystonia; Phenylalanine Hydroxylase; Tyrosine
Subject MESH Malaria; Malaria, Cerebral; Phenylalanine
Language eng
Bibliographic Citation Infect Immun. 2006 Jun;74(6):3355-9. Lopansri BK, Anstey NM, Stoddard GJ, Mwaikambo ED, Boutlis CS, Tjitra E, Maniboey H, Hobbs MR, Levesque MC, Weinberg JB, Granger DL. Elevated plasma phenylalanine in severe malaria and implications for pathophysiology of neurological complications. Retrieved April 10, 2007 http://iai.asm.org/cgi/content/full/74/6/3355?view=long&pmid=16714564.
Rights Management Copyright © 2006 American Society for Microbiology. All rights reserved.
Format Medium application/pdf
Identifier undthes,929
ARK ark:/87278/s66w9v6s
Setname ir_uspace
Date Created 2012-06-13
Date Modified 2012-06-13
ID 702938
Reference URL https://collections.lib.utah.edu/ark:/87278/s66w9v6s