Document Detail

Age-dependent effect of plasma nitric oxide on parasite density in Ghanaian children with severe malaria.
MedLine Citation:
PMID:  15960706     Owner:  NLM     Status:  MEDLINE    
Nitric oxide (NO) has toxic properties against Plasmodium falciparum. While high blood levels have been associated with protection against severe malarial disease, they may also contribute to the pathophysiology of cerebral malaria and severe anaemia. Promoter variants in the inducible nitric oxide synthase (iNOS) gene have been shown to influence NO concentrations and disease manifestation. However, findings are conflicting. We examined associations of plasma NO metabolites (NOx) with symptoms of severe malaria, particularly malarial anaemia and cerebral malaria, and with iNOS promoter variants. In 210 Ghanaian children with severe malaria, we measured plasma nitrite, nitrate, and S-nitrosothiol, and genotyped the iNOS promoter variants -954G-->C, -1173C-->T, and the -2.5 kb (CCTTT)(n) microsatellite. NOx levels decreased with age. In young children (<24 months), high NOx was associated with reduced parasite density. This was not seen in patients of 24-48 months of age and reversed in older children. Subgroup analysis revealed that in children with severe anaemia but without cerebral involvement (prostration, impaired consciousness, convulsions), high NOx levels correlated with low parasitaemia (P = 0.02). In these children, elevated NOx levels were also associated with the iNOS-954C-->T/(CCTTT)(8) haplotype (P = 0.03). No association between NOx or iNOS genotypes and cerebral malaria was observed. Our findings suggest that in young children with severe malaria NOx reduces parasitaemia. This effect wanes at higher ages and may reflect a predominance of unspecific immune responses to infection in early childhood. This finding may have importance for the understanding of associations between iNOS variants and severe malaria in regions of differing disease manifestation.
Jakob P Cramer; Andreas K Nüssler; Stephan Ehrhardt; Jana Burkhardt; Rowland N Otchwemah; Philipp Zanger; Ekkehart Dietz; Sabine Gellert; Ulrich Bienzle; Frank P Mockenhaupt
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Tropical medicine & international health : TM & IH     Volume:  10     ISSN:  1360-2276     ISO Abbreviation:  Trop. Med. Int. Health     Publication Date:  2005 Jul 
Date Detail:
Created Date:  2005-06-17     Completed Date:  2005-07-19     Revised Date:  2011-10-27    
Medline Journal Info:
Nlm Unique ID:  9610576     Medline TA:  Trop Med Int Health     Country:  England    
Other Details:
Languages:  eng     Pagination:  672-80     Citation Subset:  IM    
Institute of Tropical Medicine Berlin, Charité- University Medicine Berlin, Germany.
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MeSH Terms
Age Factors
Anemia / blood,  parasitology
Child, Preschool
Ghana / epidemiology
Malaria, Cerebral / blood,  parasitology
Malaria, Falciparum / blood,  epidemiology,  parasitology*
Nitrates / blood
Nitric Oxide / blood*
Nitric Oxide Synthase / blood
Nitric Oxide Synthase Type II
Nitrites / blood
Parasite Egg Count
Plasmodium falciparum / isolation & purification
Polymorphism, Genetic / genetics
Promoter Regions, Genetic / genetics
S-Nitrosothiols / blood
Reg. No./Substance:
0/Nitrates; 0/Nitrites; 0/S-Nitrosothiols; 10102-43-9/Nitric Oxide; EC protein, human; EC Oxide Synthase; EC Oxide Synthase Type II

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