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The hemoglobinopathies, disorders of hemoglobin structure and production, protect against death from malaria. In sub-Saharan Africa, two such conditions occur at particularly high frequencies: presence of the structural variant hemoglobin S and alpha(+)-thalassemia, a condition characterized by reduced production of the normal alpha-globin component of(More)
Although the alpha+ thalassemias almost certainly confer protection against death from malaria, this has not been formally documented. We have conducted a study involving 655 case patients with rigorously defined severe malaria and 648 controls, frequency matched on area of residence and ethnic group. The prevalence of both heterozygous and homozygous(More)
BACKGROUND Haptoglobin (Hp) genotype determines the efficiency of hemoglobin clearance after malaria-induced hemolysis and alters antioxidant and immune functions. The Hp2 allele is thought to have spread under strong selection pressure, but it is unclear whether this is due to protection from malaria or other diseases. METHODS We monitored the incidence(More)
Funding: This study received financial support from the Wellcome Trust. TNW and KM are supported by the Wellcome Trust. DJW is supported through a grant from the Leverhulme Trust. Competing Interests: The authors have declared that no competing interests exist. þ-thalassaemia on the incidence of malaria and other diseases in children living on the coast of(More)
BACKGROUND In sub-Saharan Africa, more than 90% of children with sickle-cell anaemia die before the diagnosis can be made. The causes of death are poorly documented, but bacterial sepsis is probably important. We examined the risk of invasive bacterial diseases in children with sickle-cell anaemia. METHODS This study was undertaken in a rural area on the(More)
BACKGROUND Many investigators have suggested that malaria infection predisposes individuals to bacteraemia. We tested this hypothesis with mendelian randomisation studies of children with the malaria-protective phenotype of sickle-cell trait (HbAS). METHODS This study was done in a defined area around Kilifi District Hospital, Kilifi, Kenya. We did a(More)
Hepcidin is the master regulatory hormone that governs iron homeostasis and has a role in innate immunity. Although hepcidin has been studied extensively in model systems, there is less information on hepcidin regulation in global health contexts where iron deficiency (ID), anemia, and high infectious burdens (including malaria) all coexist but fluctuate(More)
Although malaria is widely considered a major cause of death in young children born with sickle cell anemia (SCA) in sub-Saharan Africa, this is poorly quantified. We attempted to investigate this question through 4 large case-control analyses involving 7164 children living on the coast of Kenya. SCA was associated with an increased risk of admission to(More)
BACKGROUND The alpha-thalassaemias are the commonest genetic disorders of humans. It is generally believed that this high frequency reflects selection through a survival advantage against death from malaria; nevertheless, the epidemiological description of the relationships between alpha-thalassaemia, malaria, and other common causes of child mortality(More)
Both the sickle cell trait (HbAS) and alpha(+)-thalassaemia are common in many tropical areas. While their individual haematological effects are well described, few studies describe their effects when inherited together. We present data from the Kenyan coast, which suggest that HbAS and alpha(+)-thalassaemia may interact to produce specific effects on(More)