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

Lopansri, Bert K., Anstey, Nicholas M., Stoddard, Gregory J., Mwaikambo, Esther D., Boutlis, Craig S., Tjitra, Emiliana, Maniboey, Helena, Hobbs, Maurine R., Levesque, Marc C., Weinberg, J. Brice and Granger, Donald L. (2006). Elevated plasma phenylalanine in sever malaria and implications for pathophysiology of neurological complications. Infection and Immunity,74(6):3355-3359.

Document type: Journal Article
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Title Elevated plasma phenylalanine in sever malaria and implications for pathophysiology of neurological complications
Author Lopansri, Bert K.
Anstey, Nicholas M.
Stoddard, Gregory J.
Mwaikambo, Esther D.
Boutlis, Craig S.
Tjitra, Emiliana
Maniboey, Helena
Hobbs, Maurine R.
Levesque, Marc C.
Weinberg, J. Brice
Granger, Donald L.
Journal Name Infection and Immunity
Publication Date 2006
Volume Number 74
Issue Number 6
ISSN 0019-9567   (check CDU catalogue open catalogue search in new window)
Start Page 3355
End Page 3359
Total Pages 5
Place of Publication Washington, United States
Publisher American Society for Microbiology
HERDC Category C1 - Journal Article (DEST)
Abstract 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 µM) and was markedly elevated in children with cerebral malaria (median [95% confidence interval], 163 [134 to 193] µM; P < 0.0001) and adults with all forms of severe malaria (median [95% confidence interval], 129 [111 to 155] µM; 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.
DOI http://dx.doi.org/10.1128/IAI.02106-05   (check subscription with CDU E-Gateway service for CDU Staff and Students  check subscription with CDU E-Gateway in new window)
Additional Notes Copyright by the American Society for Microbiology


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