Theses and Dissertations Collection

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    Interactions oe host immune responses, iron status and genetic backgrounds in the pathogenesis of malarial anaemia in children
    (Sokoine University of Agriculture, 2008) Moses, Gwamaka
    In search for pathophysiological mechanisms of malarial anaemia, this study investigated several serum soluble factors (cytokines, growth factors, iron markers) and mechanisms (red cell aging, complement regulation, genetic red cell disorders) that may explain why some children with malaria develop anaemia. Among anaemic malaria patients, children with inappropriate reticulocyte responses were compared to those with normal reticulocyte responses for the differences in serum soluble factor levels. Serum soluble factors were analyzed by multiplex bead-based platform with custom sandwich or competitive assay kits. Children with inappropriate reticulocyte responses had higher IL-1, IL-6, TNI-'-a. IL-10 and TNF-a/IL-10 ratio, and lower erythropoietin levels. In multivariate logistic regression analyses, only erythropoietin remained significantly associated and inversely related to poor reticulocyte response suggesting that erythropoietin influences rcticulocytosis during malaria. RBC membrane surface molecules were measured by cytolluorometry and analyzed for their relationship with cytokine levels. RBC age and anaemia during acute malaria. Phosphatidylserine. IgG, CD35. CD55 and CD59 levels were not associated with cytokine levels, whereas TNF-a/IL-10 ratio associated positively with CD59 only. Loss of CD55 and CD59 occurs during erythrocyte ageing but this effect docs not explain the changes occurring during malarial anaemia. CD55 levels were significantly lower in anaemic children and correlated positively with haemoglobin level, suggesting that the loss of CD55 may contribute to malarial anaemia. Immune responses to P.falciparum malaria in children with different genetic backgrounds were studied before and during first malaria episodes. Haemoglobin levels did not varyiii according to the genetic backgrounds before malaria infection. Parasitemia. haemoglobin and cytokine levels (IL-1. IL-6. IFN-y and IL-5) were significantly higher in age-matched children with normal haemoglobin than sickle cell carriers during malaria. Levels of TNF-a and ferritin varied on the basis of thalassemia status, and none of the serum soluble factors levels varied on the basis of G6PD genotypes. The results suggest that genetic red cell disorders vary in their effects to modulate immune response and these variations may be influencing disease outcomes. From these data it is concluded that several host factors interact to contribute to acute malarial anaemia including EPO response, CrP levels on RBC and genetic backgrounds.