Interactions between Thalassaemias and Malaria
Why has investigation of the interaction between thalassaemias and malaria remained inconclusive despite our best efforts? For ß-thalassaemia, it is only in a limited part of West Africa that it continues to co-exist with malaria. Malaria has been eradicated from most other regions where ß-thalassaemia is common. The findings of Willcox et al. support a protective role for ß-thalassaemia, in which heterozygotes one-to-four years old appear to have a reduced risk of malaria, using an arbitrary density criterion of 1 × 10 9/l relative to controls (relative risk, 0.45; upper 95% confidence interval, 0.79). By contrast, α +-thalassaemia (in which one or two of the four α-globin genes are deleted) is exceedingly common throughout sub-Saharan Africa, an area of high malarial transmission. However, thus far, the effects of α +-thalassaemia on the clinical manifestations of malaria in this area have not been extensively studied. And the few studies that have been carried out on the relationship between α +-thalassaemia and malaria have not provided an all-encompassing and plausible cellular mechanism for protection.
There are many gaps in our knowledge of whether thalassaemia might protect against malaria.Malarial parasites can certainly invade and multiply within a +-thalassaemic cells. They also appear to cytoadhere equally well to endothelial cells as do parasitized normal red cells. So how does thalassaemia protect against malaria? Carlson and colleagues proposed (with supporting evidence) that thalassaemic cells have a reduced ability to form rosettes (a process in which uninfected red cells bind to infected cells), which causes harm perhaps by aiding and abetting the obstruction of capillary blood flow and leading to sequestration of schizont-infected red cells in vital organs. Thalassaemic red cells also appear to bind increased amounts of immunoglobulin, which might favour early removal of those red cells containing parasites; perhaps, they bind less complement, sparing those cells with reduced complement. We just do not know why thalassaemia protects against malaria, leaving our current knowledge in a state of conjecture. While study of the association of disease with genetic polymorphisms may be intellectually attractive, some would argue that it is of little clinical relevance
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