Skip to main content

Free Content Age-dependent effect of plasma nitric oxide on parasite density in Ghanaian children with severe malaria

Download Article:

You have access to the full text article on a website external to Ingenta Connect.

Please click here to view this article on Wiley Online Library.

You may be required to register and activate access on Wiley Online Library before you can obtain the full text. If you have any queries please visit Wiley Online Library



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.

Keywords: Plasmodium falciparum; iNOS promoter polymorphisms; nitric oxide; severe malaria

Document Type: Research Article


Affiliations: 1: Institute of Tropical Medicine Berlin, Charité– University Medicine Berlin, Germany 2: Department of Surgery, Charité– University Medicine Berlin, Germany 3: Bernhard-Nocht-Institute for Tropical Medicine, Hamburg, Germany 4: School of Medicine and Health Sciences, University for Development Studies, Tamale, Ghana 5: Northern Region Malaria Project, NORMAP, Tamale, Ghana 6: Division for International Health, Charité– University Medicine Berlin, Germany 7: Bernsteinklinik Binz, Binz auf Rügen, Germany

Publication date: 2005-07-01

  • Access Key
  • Free content
  • Partial Free content
  • New content
  • Open access content
  • Partial Open access content
  • Subscribed content
  • Partial Subscribed content
  • Free trial content
Cookie Policy
Cookie Policy
Ingenta Connect website makes use of cookies so as to keep track of data that you have filled in. I am Happy with this Find out more