Increased plasma levels of histidine and histamine in falciparum malaria : relevance to severity of infection

Severe falciparum malaria, with its associated hyperpyrexia, distorts plasma levels of large neutral amino acids (NAA) and consequently, brain uptake of individual NAA. Since brain levels of NAA determine cerebral synthesis of monoamines (serotonin, histamine, catecholamines), we measured plasma con...

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Published in:	Journal of Neural Transmission Vol. 107; no. 11; pp. 1273 - 1287
Main Authors:	ENWONWU, C. O, AFOLABI, B. M, SALAKO, L. O, IDIGBE, E. O, BASHIRELAHI, N
Format:	Journal Article
Language:	English
Published:	Wien Springer 01-01-2000 New York, NY
Subjects:	Amino Acids - blood Amino Acids - metabolism Antimalarials - therapeutic use Biological and medical sciences Blood-Brain Barrier Brain - metabolism Child Child, Preschool Chloroquine - therapeutic use Female Histamine - blood Histidine - blood Human protozoal diseases Humans Infant Infectious diseases Kinetics Malaria Malaria, Falciparum - blood Malaria, Falciparum - drug therapy Malaria, Falciparum - physiopathology Male Medical sciences Parasitic diseases Phenylalanine - blood Prospective Studies Protozoal diseases Reference Values Severity of Illness Index Tropical medicine Human Protozoa Apicomplexa Protozoal disease Malaria Chloroquine Parasitosis Blood plasma Infection Histamine Plasmodium falciparum Chemotherapy Histidine Treatment
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Summary:	Severe falciparum malaria, with its associated hyperpyrexia, distorts plasma levels of large neutral amino acids (NAA) and consequently, brain uptake of individual NAA. Since brain levels of NAA determine cerebral synthesis of monoamines (serotonin, histamine, catecholamines), we measured plasma concentrations of NAA, and also plasma histamine (Hm) in children with falciparum malaria and in uninfected controls. Malaria elicited a marked (P < 0.025) increase in plasma histidine (His) with a 5-fold significant (P < 0.001) elevation in histamine, as well as a 2.5-fold increase (P < 0.005) in plasma phenylalanine (Phe), with no changes in the other NAA. Using kinetic parameters of NAA transport at human blood-brain barrier (BBB), we showed that malaria significantly altered calculated brain uptake of His (+30%), Phe (+96%), Trp (-30%) and Ile (-27%), with no change in the other NAA, compared with controls. Our data suggested enhanced cerebral synthesis of Hm with impaired production of serotonin and the catecholamines in the patients, and therefore, the need to evaluate the encephalopathy in severe malaria within the context of abnormalities in metabolism of Hm and other monoamines resulting from imbalance in plasma levels of the large neutral amino acids. Of clinical relevance also is the impaired inactivation of increased brain Hm by antimalarials such as the widely used aminoisoquinolines leading to elevated brain levels of imidazole-4-acetic acid (IAA), a potent inducer of a sleep-like state often accompanied by seizures, analgesia, decreased blood pressure and other effects.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0300-9564 1435-1463
DOI:	10.1007/s007020070017