Immediately after the discovery of the particular distribution in the world of the different thalassaemias, a narrow correspondence of geographic distribution between the thalassaemic areas and the malarial endemia has emerged. Also in Italy there is an absolute coincidence that is clearly recognizable in the geographical distribution of the thalassaemic sources (Delta Padano, Sardinia, Sicily, Calabria, Basilicata, Puglia).

On the base of this relief, it made to hypothesize that, for the thalassaemia as for other two genetic defects (the sickle cell anaemia and the lack of the G6PD enzyme activity), a greater resistance toward the pernicious malaria and therefore a survival of the thalassaemic heterozygote greater than the normal homozygote has acted as a positive selective factor, in the past. This factor has allowed the appearance and then the permanence during the centuries of dense thalassaemia sources, despite the losses of the thalassaemic genes that happens in each generation because of the missed reproduction of the thalassaemic homozygotes. However, the pathogenetic mechanism of this greater resistance to the malaria has not been identified yet.