The heritable haemoglobinopathy alpha(+)-thalassaemia is caused by the reduced synthesis of alpha-globin chains that form part of normal adult haemoglobin (Hb).Individuals homozygous for alpha(+)-thalassaemia have microcytosis and an increased erythrocyte count.Alpha(+)-thalassaemia homozygosity confers considerable protection against severe malaria, including severe malarial anaemia (SMA) (Hb concentration 1.
1 x 10(12)/l as a result of the reduced mean cell Hb in homozygous alpha(+)-thalassaemia.In addition, children homozygous for alpha(+)-thalassaemia require a 10% greater reduction in erythrocyte count Hog Ring Pliers than children of normal genotype (p = 0.02) for Hb concentration to fall to 50 g/l, the cutoff for SMA.
We estimated that the haematological profile in children homozygous for alpha(+)-thalassaemia reduces the risk of SMA during acute malaria compared to children of normal genotype (relative risk 0.52; 95% confidence interval enema-anal [CI] 0.24-1.
12, p = 0.09).The increased erythrocyte count and microcytosis in children homozygous for alpha(+)-thalassaemia may contribute substantially to their protection against SMA.
A lower concentration of Hb per erythrocyte and a larger population of erythrocytes may be a biologically advantageous strategy against the significant reduction in erythrocyte count that occurs during acute infection with the malaria parasite Plasmodium falciparum.This haematological profile may reduce the risk of anaemia by other Plasmodium species, as well as other causes of anaemia.Other host polymorphisms that induce an increased erythrocyte count and microcytosis may confer a similar advantage.