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Modelling primaquine-induced haemolysis in G6PD deficiency

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Primaquine is the only drug available to prevent relapse in vivax malaria. The main adverse effect of primaquine which limits its use is erythrocyte age and dose dependent acute hemolytic anaemia in individuals with glucose-6-phosphate dehydrogenase deficiency (G6PDd). A compartmental model of the dynamics of red blood cell production and destruction was designed to characterize primaquine-induced haemolysis using a holistic analysis of all published data on primaquine-induced haemolysis to predict a safer alternative regimen to the current weekly regimen for vivax radical cure in G6PD deficiency. The model was fitted to data from a recent study of the effects of weekly high-dose primaquine (0.75 mg PQ base/kg body weight) in G6PD deficient vivax malaria patients from Cambodia. The model suggests that a step-wise increase in daily administered primaquine dose would be safe and would not require testing for G6PDd.