Age-dependent effect of plasma nitric oxide on parasite density in Ghanaian children with severe malaria.
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Age-dependent effect of plasma nitric oxide on parasite density in Ghanaian children with severe malaria. / Cramer, Jakob; Nüssler, Andreas K; Ehrhardt, Stephan; Burkhardt, Jana; Otchwemah, Rowland N; Zanger, Philipp; Dietz, Ekkehart; Gellert, Sabine; Bienzle, Ulrich; Mockenhaupt, Frank P.
in: TROP MED INT HEALTH, Jahrgang 10, Nr. 7, 7, 2005, S. 672-680.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - Age-dependent effect of plasma nitric oxide on parasite density in Ghanaian children with severe malaria.
AU - Cramer, Jakob
AU - Nüssler, Andreas K
AU - Ehrhardt, Stephan
AU - Burkhardt, Jana
AU - Otchwemah, Rowland N
AU - Zanger, Philipp
AU - Dietz, Ekkehart
AU - Gellert, Sabine
AU - Bienzle, Ulrich
AU - Mockenhaupt, Frank P
PY - 2005
Y1 - 2005
N2 - 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 (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.
AB - 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 (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.
M3 - SCORING: Zeitschriftenaufsatz
VL - 10
SP - 672
EP - 680
JO - TROP MED INT HEALTH
JF - TROP MED INT HEALTH
SN - 1360-2276
IS - 7
M1 - 7
ER -
