Tundun Williams, MD
Nominated From: University of Minnesota
Research Site: Uganda
Research Areas: Hematology, Inherited & Acquired Causes of Anemia
Primary Mentor: Chandy John, MD, MS (University of Minnesota)
Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency and Severe Malarial Anemia
In sub-Saharan Africa the prevalence of glucose-6-phosphate dehydrogenase (G6PD) deficiency ranges from 15 – 26%. G6PD is found in the cytoplasm of all cells and is responsible for the production of the reduced form of nicotinamide adenine dinucleotide phosphate (NADPH), a coenzyme that is crucial in protecting cells against oxidative damage. G6PD deficiency presents a significant public health burden, contributing infection- and drug-induced hemolysis and neonatal jaundice.
Studies have shown that G6PD deficiency protects against severe malarial anemia but data is unclear about whether this protection is afforded to only heterozygotes or to homozygotes and hemizygotes as well. Furthermore, the mechanism by which this protection is conferred is not well elucidated. Mechanisms that have been proposed include poor growth of Plasmodium falciparum in G6PD deficient erythrocytes, preferential phagocytosis of ring-stage parasitized erythrocytes and increased generation of oxygen radicals.
This study aims to elucidate the subset of G6PD deficient individuals that are protected against severe malarial anemia and to determine whether alterations in redox status are responsible for this protective mechanism.
Hydroxyurea Treatment of Children with Sickle Cell Anemia in a Malaria Endemic Area
Sickle cell anemia is highly prevalent in Africa and is a significant cause of morbidity and under-five mortality. Although the reasons are not clearly elucidated, the mortality from malaria is higher in children with sickle cell anemia. Dr. Chandy John and colleagues have proposed the Novel use Of Hydroxyurea in an African Region with Malaria (NOHARM) trial to determine if hydroxyurea is safe for use in children with sickle cell anemia living in malaria endemic areas and to investigate the mechanisms of potential risk of malaria in children with sickle cell anemia treated with hydroxyurea. During my year in Uganda, I look forward to being a part of this exciting and innovative trial.
A better understanding of the relationship between malaria and G6PD deficiency and malaria and sickle-cell anemia will guide treatment policy and lead to a decrease in G6PD- and sickle cell-related morbidity and mortality.
Advice for Potential Applicants
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