On the relation between malaria and G-6-PD deficiency

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Abstract
In regions where favism is present, a high correlation apparently exists between endemic malaria and the frequency of G-6-PD G-6-P dehydrogenase deficiency, (Huheey and Martin). The hemolytic event in a malarial environment may be a favorable selective factor. The fitness of the G-6-PD-deficient individual who shows hemolysis is higher than that of those who do not show hemolysis. Modiano (1976) suggested that hemolysis may not be a negative component of the selective forces which act on the G-6-PD-deficient variants. Some facts which make these hypotheses unlikely are considered and other, more promising lines for the analysis of the complex relation between malaria and G-6-PD deficiency are suggested. In Sardinia and in the area of the Po Delta [Italy] even though favism is present, there is a very low correlation between the frequency of G-6-PD deficiency and past malarial morbidity. The situation is similar to that observed in other parts of the world, in which malaria is highly endemic, but where favism is absent. Some facts seem to be in contrast with the possibility that hemolysis could by itself be a favorable event. In hemizygous males, hemolysis due to favism is generally severe and there is a high mortality rate. In heterozygous females, the erythrocytes with G-6-PD deficiency seem to show a low parasite rate compared to normal cells and only the normal erythrocytes are destroyed during the hemolytic crisis. In malarial environments, enzymopenic variants associated with continuous hemolysis have not been selected. A positive selection of such variants would be expected if hemolysis was by itself a positive factor. The G-6-PD system apparently interacts with various factors, both genetical (thalassemia, erythrocyte acid phosphatase, adenosine deaminase) and environmental (Vicia faba, altitude, viral and protozoal diseases). In a malarial environment, therefore, the fitness of the different G-6-PD genotypes depends on numerous variables. This could explain the low correlation generally observed between the degree of malarial endemicity and the frequency of G-6-PD deficiency. Further analysis of the above interactions could elucidate the mechanisms which brought about the selection of certain types of enzymopenic variants in malarial regions.