In summary, some changes associated with hydroxyurea treatment (increased NO and HbF and improved splenic function) would be expected to protect against malaria, but the data on hydroxyurea-related endothelial changes thought to be important in severe malaria pathogenesis (eg, ICAM-1, VWF, TNF-α) are less clear, with some studies suggesting that these factors might be increased with hydroxyurea and others suggesting no difference or even a decrease. This evidence concerns the gene TNF and malaria.