It has long been recognized that certain ordinarily salutary drugs may produce an acute hemolytic anemia in some susceptible individuals. The 8-aminoquinoline antimalarial, pamaquine (plasmoquine), was such a medication. It was the investigation of the hemolytic effect of pamaquine and its derivatives which led to the recognition that hereditary red cell enzyme deficiencies could produce hemolytic disease.

Glucose-6-phosphate dehydrogenase deficiency.

A Genetic Differentiation

Primary infantile glaucoma (congenital glaucoma).

Glucose-6-phosphate dehydrogenase (G6PD) is a potentially pathogenic inherited enzyme abnormality and, similar to other human red blood cell polymorphisms, is particularly prevalent in historically malaria endemic countries. The spatial extent of Plasmodium vivax malaria overlaps widely with that of G6PD deficiency; unfortunately the only drug licensed for the radical cure and relapse prevention of P. vivax, primaquine, can trigger severe haemolytic anaemia in G6PD deficient individuals. This chapter reviews the past and current data on this unique pharmacogenetic association, which is becoming increasingly important as several nations now consider strategies to eliminate malaria transmission rather than control its clinical burden. G6PD deficiency is a highly variable disorder, in terms of spatial heterogeneity in prevalence and molecular variants, as well as its interactions with P. vivax and primaquine. Consideration of factors including aspects of basic physiology, diagnosis, and clinical triggers of primaquine-induced haemolysis is required to assess the risks and benefits of applying primaquine in various geographic and demographic settings. Given that haemolytically toxic antirelapse drugs will likely be the only therapeutic options for the coming decade, it is clear that we need to understand in depth G6PD deficiency and primaquine-induced haemolysis to determine safe and effective therapeutic strategies to overcome this hurdle and achieve malaria elimination.

G6PD Deficiency: Global Distribution, Genetic Variants and Primaquine Therapy

Primaquine is the only generally available anti-malarial that prevents relapse in vivax and ovale malaria, and the only potent gametocytocide in falciparum malaria. Primaquine becomes increasingly important as malaria-endemic countries move towards elimination, and although it is widely recommended, it is commonly not given to malaria patients because of haemolytic toxicity in subjects who are glucose-6-phosphate dehydrogenase (G6PD) deficient (gene frequency typically 3-30% in malaria endemic areas; >180 different genetic variants). In six decades of primaquine use in approximately 200 million people, 14 deaths have been reported. Confining the estimate to reports with known denominators gives an estimated mortality of one in 621,428 (upper 95% CI: one in 407,807). All but one death followed multiple dosing to prevent vivax malaria relapse. Review of dose-response relationships and clinical trials of primaquine in G6PD deficiency suggests that the currently recommended WHO single low dose (0.25 mg base/kg) to block falciparum malaria transmission confers a very low risk of haemolytic toxicity.

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Primaquine: the risks and the benefits

Zinc Nutrition of Children in Fars Province of Iran

enzyme Glucose-6-phosphate dehydrogenase (G-6-PD). This enzyme deficiency is qualitatively and quantitatively not always the same among affected individuals and the process of hemolysis is more severe among Caucasians than among American Negroes. If malaria prophylaxis and treatment with agents such as primaquine, which is capable of producing this kind of hemolytic reaction, is to be tried on a global basis, its safety must first be established. Without clear evidence, it is commonly stated that in the recommended doses for prophylaxis no harmful effect is to be anticipated from the combined administration

Malaria Prophylaxis and Treatment in G-6-PD Deficiency: An Observation on the Toxicity of Primaquine and Chloroquine

Optic Disc in Normal Newborns

Studies in the present decade are mak ing it clear that some manifestations of malnutrition in the Middle Eastern coun tries closely resemble the changes seen in naturally-occurring or experimentally- induced deficiency of this trace metal in animals. This review points out the pos sible role of zinc in the nutrition of chil dren, based on metabolic studies still in progress in Iran.

Mohsen Ziai

Papers

Zinc Nutrition of Children in Fars Province of Iran

Malaria Prophylaxis and Treatment in G-6-PD Deficiency: An Observation on the Toxicity of Primaquine and Chloroquine

Optic Disc in Normal Newborns

Nutrition Review : Zinc Metabolism The Possible Roles Played by Zinc Deficiency in Malnutrition of Children

Tetanus Neonatorum in Iran: Notes on Etiology, Manifestations and Therapy