Consideration of ethics in primaquine therapy against malaria transmission

Epidemiology and Infectivity of Plasmodium falciparum and Plasmodium vivax Gametocytes in Relation to Malaria Control and Elimination

“…Control interventions that specifically aim to reduce transmission would, on the other hand, target all individuals who contribute to malaria transmission, including individuals who are apparently healthy. These types of interventions are considered by some to be altruistic in the sense that they do not protect individuals themselves but the community as a whole, and therefore they require additional ethical considerations (20) and a new degree of community awareness and engagement (109). For P. vivax elimination strategies, a major challenge in elimination efforts is the clearance of hypnozoites that form reservoirs of infection that persist in the livers of infected people.…”

“…At an individual level, concerns with drug use are particularly acute for PQ. As discussed above, this drug is unique in it that it has a strong gametocytocidal effect (363,412,438), but it also induces hemolysis that is related to G6PD deficiency (20,92,381,414). Hemolysis may occur after a single dose in G6PD-deficient individuals (381,412,414) and may be particularly severe in individuals with the Mediterranean (BϪ) G6PD genotype (20,158).…”

“…As discussed above, this drug is unique in it that it has a strong gametocytocidal effect (363,412,438), but it also induces hemolysis that is related to G6PD deficiency (20,92,381,414). Hemolysis may occur after a single dose in G6PD-deficient individuals (381,412,414) and may be particularly severe in individuals with the Mediterranean (BϪ) G6PD genotype (20,158). Although the effect of PQ on hemoglobin levels is generally mild (412,414) and self-limiting (110,412), severe and life-threatening hemolysis may occur in some individuals (158,381).…”

“…Although the effect of PQ on hemoglobin levels is generally mild (412,414) and self-limiting (110,412), severe and life-threatening hemolysis may occur in some individuals (158,381). Our current understanding of PQ sensitivity phenotypes is incomplete (20,414), and Baird and Surjadjaja recently stressed that the reliable information is currently "inadequate by almost any contemporary standard of safety in chemotherapeutics, especially in the context of dosing demonstrably vulnerable populations" (20). Further safety data are particularly important for regions where malaria is endemic, where not only the prevalence of G6PD deficiency is high (316) but also mild and severe anemia can be common due to infections (e.g., malaria and helminth infections) and other genetic conditions (e.g., thalassemia and sickle-cell anemia).…”

Diagnosis and Treatment of Plasmodium vivax Malaria

“…120,121 However, the safety of the weekly regimen in non-A− variants was not established. 122,123 Only very recently were 18 Cambodian men with G6PDd (17/18 with Viangchan variant) and acute P. vivax malaria given the 0.75 mg/kg PQ dose weekly for 8 weeks. 124 All hemolyzed steeply after the first dose, but not dangerously, except for one subject who required hospitalization and transfusion.…”