Iron delocalisation in the pathogenesis of malarial anaemia.
There is consensus that the pathophysiology of malaria-associated anaemia is multifactorial, but the precise mechanisms behind many of the haematological changes during malaria remain unclear. In this review, we attempt to build a composite picture of the pathophysiology of malarial anaemia using evidence from experimental, human and animal studies. We propose that cytokine- and hepcidin-mediated iron delocalisation, a principal mechanism in the anaemia of inflammation, plays an important role in the aetiology of malarial anaemia, and can explain some of the clinical and laboratory findings. These mechanisms interact with other aetiological determinants, such as dietary iron and micronutrient supply, helminth load, other infections and genetic variation, in determining the severity and associated features of anaemia. We suggest that iron delocalisation as a mechanism for malarial anaemia could be exploited for the development of alternative therapeutic strategies for post-malaria anaemia.
Nweneka
Chidi V
CV
Nutrition Programme, MRC Keneba, P.O. Box 273, Banjul, The Gambia. cnweneka@mrc.gm <cnweneka@mrc.gm>
Doherty
Conor P
CP
Cox
Sharon
S
Prentice
Andrew
A
D000740:Anemia / Q000097:blood* / Q000209:etiology; D018798:Anemia, Iron-Deficiency / Q000097:blood / Q000209:etiology*; D023181:Antimicrobial Cationic Peptides / Q000378:metabolism; D027682:Cation Transport Proteins / Q000378:metabolism; D002648:Child; D016207:Cytokines / Q000378:metabolism; D004907:Erythrocyte Deformability; D064451:Hepcidins; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D008288:Malaria / Q000150:complications*; D009569:Nitric Oxide / Q000378:metabolism; D010961:Plasmodium / Q000472:pathogenicity; D000098742:Ferroportin
D023181:Antimicrobial Cationic Peptides; D027682:Cation Transport Proteins; D016207:Cytokines; C578702:HAMP protein, human; D064451:Hepcidins; D000098742:Ferroportin; D009569:Nitric Oxide; D007501:Iron