The Hemoglobinopathy and Iron Metabolism Unit, is designed to provide, for Research Projects 1, 2 and 3, identification of the hemoglobin phenotype and characterization of the abnormalities in iron metabolism in patients with cerebral malaria who enter the clinic trial in Project 1. In addition, blood samples will be obtained from uninfected patients with defined hemoglobinopathies for use in the studies in vitro in Project 3. The available evidence from epidemiological, clinical and laboratory studies suggest that the hemoglobin phenotype may be an important determinant of both (i) the susceptibility of an individual patient to infection with P. falciparum, and, perhaps, to the development of the cerebral malaria, (ii) the sensitivity of the intraerythrocytic parasite to some types of antimalarial chemotherapy. As a result, determination of the hemoglobin phenotype is of critical importance for the evaluation of the clinical response to therapy with the three regimens to be evaluated in Project 1, for the assessment of the pathological findings in Project 2, and for the interpretation of the results of studies in vitro in Project 3. In addition, to assess the effect of each regimen on the disordered iron metabolism that develops with cerebral malaria, this Core will be responsible for measurements of haptoglobin, hemopexin, ferritin, iron total iron-binding capacity and transferrin receptor concentrations in the plasma, and for erythrocyte zinc protoporphyrin and erythrocyte ferritin in the red cells of these patients. These measurements will be made on the samples collected by Asawamohasakda's Core from the patients with cerebral malaria who receive, with appropriate placebo administration, (i) desferrioxamine and quinine, (ii) single therapy with artesunate, or (ii) single therapy with quinine.
The specific aims are:
Aim 1 : to determine the hemoglobin phenotype of patients with cerebral malaria in the clinical trial of Project 1, measure the proportions of normal and abnormal hemoglobins presents in red cells and provide this data for the studies in Projects 2 and 3;
Aim 2 : to provide blood samples from patients with defined hemoglobinopathies for the studies in vitro in Project 3;
Aim 3 : to characterize the disordered iron metabolism in patients with cerebral malaria in the clinical trial and determine the effects of the therapy with desferrioxamine and quinine, artesunate alone and quinine alone. Results of these studies will contribute to our understanding of the interaction of hemoglobin phenotype with the treatment of cerebral malaria with endoperoxides such as artesunate and iron-chelating agents such as desferrioxamine.
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