Anemia is an important complication of malaria, and its pathogenesis is not well understood. To gain insight into potential age-related relationships between tumor necrosis factor alpha (TNF-␣), interleukin 10 (IL-10), erythropoietin, and anemia during acute malaria, 273 children of ages 12 to 120 months presenting with acute, uncomplicated malaria in Kampala, Uganda, were monitored at enrollment and 3 and 7 days later. Younger children had higher geometric mean erythropoietin, TNF-␣, and ␣ 1 -acid glycoprotein (AGP) concentrations than older children. Univariate regression analysis revealed that age, log 10 erythropoietin levels, IL-10/TNF-␣ ratio, and AGP levels were each significantly associated with hemoglobin levels at baseline. Hemoglobin concentrations were inversely correlated with the log 10 erythropoietin level at all three visits. For the older age groups, higher levels of TNF-␣ were significantly associated with higher IL-10 levels at all three visits, but this relationship was significant only at baseline for younger children. These data suggest that younger children do not maintain IL-10 production in response to the inflammatory process, and this mechanism may contribute to the more severe anemia found in younger children. Acute malaria is an illness whose incidence and severity are largely age dependent. Further studies are needed to understand the relationships between age-related immune responses to malaria and their role in the pathogenesis of malarial anemia.

Abstract. Although antioxidant status has been implicated in the pathogenesis of malaria, these factors need further characterization. A longitudinal study was conducted involving 273 children 1-10 years of age with acute, uncomplicated malaria in Kampala, Uganda. Plasma vitamin A, carotenoids, and vitamin E were measured at enrollment and on day 7. Malaria parasitemia was measured at enrollment, on day 3, and on day 7. Malaria parasitemia had completely cleared in 57.1% and 85.3% of children by day 3 and day 7, respectively. Plasma vitamin A, ␣-carotene, ␤-carotene, lycopene, lutein/zeaxanthin, and vitamin E were depressed at enrollment and increased by day 7. Multivariate analyses showed that higher plasma lycopene concentrations at enrollment were associated with clearance of parasitemia between enrollment and day 3 (odds ratio ϭ 1.46, 95% confidence interval ϭ 1.07-2.06, per 0.10 mol/L of lycopene). This study suggests that children with acute malaria have depressed plasma concentrations of antioxidants, and that higher plasma lycopene is associated with more rapid clearance of malaria parasitemia.