Primaquine-sensitive individuals

Distribution of Primaquine-Sensitive Individuals in the Various Population Groups. Primaquine sensitivity was found in Negroes (B7, B19, C3, C7, G6, G7, G18, H21, M7), Caucasians (G18, L3, M7, W3), and certain Jewish tribes (S21, S23). The phenomenon could be detected in 4.6% of an unselected population of 305 North Americans. In healthy Negroes the sensitivity was more common (7.2%) than in Caucasians (1.3%) (G18). In the Jewish population, the defect was found in 20% of the non-Ashkenazic Jews originating from Iraq and Persia, in 5% from Yemen and Turkey, and in 2% from North Africa. Also 3% of the Arabs in Israel showed drug sensitivity. 

In primaquine-sensitive individuals haemolytic anaemia may occur. There have been four reports on this side effect since 1962 . The daily dose varied between 200 and 800 mg of nitrofurantoin and the duration of treatment ranged from three to fourteen days. In all patients, erythrocyte glucose-6-phosphate dehydrogenase values were reduced. Glutathione blood levels were also found to be depressed . It must be assumed, however, that this side effect, which occurs only in the Negro, is extremely rare and is also reversible. 

In cases of primaquine sensitivity, erythrocytes were shown to be deficient in G-6-PDH activity and thus there is not sufficient NADPH2 for the reduction of GSSG by its reductase system. In such individuals lowered GSH levels in erythrocytes were found (B6, B8, Bll, S8, S24, and others). Furthermore, it can be shown that in these cases, when erythrocytes are incubated with acetylphenylhydrazine (B6, G18), the maintenance of even a lowered GSH level is not possible. The GSH stability test is based on this fact it measures virtually the G-6-PDH activity and not that of GSSGR. 

Chloroquine is the drug of choice in the treatment of nonfalciparum and sensitive falciparum malaria. It rapidly terminates fever (in 24-48 hours) and clears parasitemia (in 48-72 hours) caused by sensitive parasites. It is still used to treat falciparum malaria in some areas with widespread resistance, in particular much of Africa, owing to its safety, low cost, antipyretic properties, and partial activity, but continued use of chloroquine for this purpose is discouraged, especially in nonimmune individuals. Chloroquine has been replaced by other drugs, principally artemisinin-based combination therapies, as the standard therapy to treat falciparum malaria in most endemic countries. Chloroquine does not eliminate dormant liver forms of P vivax and P ovale, and for that reason primaquine must be added for the radical cure of these species. 

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