Effects of foetal haemoglobin on susceptibility of red cells to Plasmodium falciparum

Abstract

HIGH gene frequencies for the sickling disorders and β thalassaemia may be due to the relative protection against Plasmodium falciparum malaria which has been afforded to heterozygous carriers¹. In sickling disorders the properties of the abnormal haemoglobin may be responsible for this phenomenon^2–4 but the red cells of adult β thalassaemia heterozygotes contain reduced amounts of normal haemoglobin⁵ and are indistinguishable from normal red cells with respect to the rates of invasion and growth of P. falciparum (G.P., D.J.W. and R.J.M., in preparation). Hence it is not clear how the β thalassaemia polymorphism has been maintained. There is a possible explanation, however. At birth red cells contain mainly foetal haemoglobin (Hb F); adult haemoglobin (Hb A) replaces Hb F during the first year of life. The rate of decline of Hb F production during this period is retarded in infants heterozygous for β thalassaemia as compared with normal infants⁶. If the presence of Hb F were to protect red cells against P. falciparum, β thalassaemia carriers aged 6–18 months might be at an advantage when passive immunity to P. falciparum is waning but active immunity is not fully established and mortality from malaria is high⁷. To test this hypothesis we have compared the rates of invasion and growth of P. falciparum in red cells containing Hb A with those containing Hb F using a modification of the in vitro culture system^8–10.