Nitric oxide, malaria, and anemia: Inverse relationship between nitric oxide production and hemoglobin concentration in asymptomatic, malaria-exposedchildren

The cause of the anemia associated with chronic, intermittent, asymptomatic , low-level parasitemia in children in malaria-endemic endemic areas is not well understood. Nitric oxide (NO) decreases erythropoiesis, and it is lik ely an important mediator of anemia of chronic disease. Production of NO is decreased in acute uncomplicated and cerebral malaria, but it is increased in asymptomatic Tanzanian children (with or without parasitemia). We hypot hesized that chronic overproduction of NO in these asymptomatic children co ntributes to the anemia associated with subclinical/subpatent malaria. In 4 4 fasting, asymptomatic, malaria-exposed, Tanzanian children, NO production (measured using fasting urine NOx excretion) was inversely associated with hemoglobin concentration (P = 0.03, controlling for age and gender). Using multiple linear regression, hemoglobin concentration was negatively associ ated with parasitemia (P = 0.005). After controlling for age and parasitemi a, NO was no longer an independent predictor of anemia. One of the mechanis ms of parasite-related anemia in such children may be through the adverse h ematologic effects of parasite-induced NO production.