Thalassemia and malaria: New insights into an old problem

The hemoglobinopathies are probably the world's most common genetic disease s: The World Health Organization has estimated that at least 5% of the popu lation are carriers for one or other of the most serious forms, the alpha- and beta-thalassemias and the structural variant hemoglobins S, C, and E, w hich an found at polymorphic frequencies in many countries. All these hemog lobinopathies are believed to provide protection against malaria, and it is thought that, in malarial regions of the world, natural selection has been responsible for elevating and maintaining their gene frequencies, an idea first proposed 50 years ago by J.B.S. Haldane. Epidemiological studies undertaken in the 1950s on hemoglobin S in Africa p rovided support for the "malaria hypothesis," but until recently it has pro ved extremely difficult to verify it for the thalassemias. The application of molecular methods has, however, provided new opportunities to address th is old question. Population and molecular genetic analysis of thalassemia v ariants, and microepidemiological studies of the relationship between alpha -thalassemia and malaria in the southwest Pacific, have provided unequivoca l evidence for protection. Surprisingly, some of this protection appears to derive from enhanced susceptibility in very young thalassemic children to both Plasmodium falciparum and, especially, P. vivax, and this early exposu re appears to provide the basis for better protection in later life.