Plasmodium vivax (P. vivax) malaria is a major cause of morbidity and mortality throughout the world. Primaquine, an 8-aminoquinoline, is the only widely available drug that prevents relapse, but its use is limited by the risk of acute hemolysis in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency in addition to poor awareness of the benefits of primaquine in preventing relapsing infections in high-transmission areas. Moreover, when it is prescribed, poor adherence is common due to its lengthy 14-day regimen. Shorter courses with higher daily doses have been hypothesized to improve adherence, and thus effectiveness, without reducing efficacy; however, randomized controlled trials assessing a shorter course have not been done. In this randomized, double-blind, non-inferiority trial, 2,336 patients with uncomplicated P. vivax malaria and normal G6PD as assessed by the fluorescent spot test were given standard blood schizontocidal treatment and then assigned in a 2:2:1 ratio to receive 7 days of supervised primaquine (1.0 mg/kg per day), 14 days of supervised primaquine (0.5 mg/kg per day), or placebo. The primary outcome was the incidence rate of symptomatic P. vivax parasitemia during the 1-year follow-up period, assessed in the intention-to-treat population. A margin of 0.07 recurrences per person-year was used to establish non-inferiority of the 7-day regimen compared with the 14-day regimen. Researchers found no difference in the incidence rate of symptomatic recurrent P. vivax malaria between the 7-day and 14-day primaquine regimens (7-day regimen: 0.18 recurrences per person-year, 95% CI 0.15 to 0.21; 14-day regimen: 0.16, 95% CI 0.13 to 0.18; between-group difference 0.02, 95% CI -0.02 to 0.05, p=0.3405). Potentially drug-related serious adverse events within 42 days of starting treatment were slightly more frequent in the 7-day group (9 total events (1.0%) in the 7-day group vs. 1 event (0.1%) in the 14-day group). In conclusion, results from this study support the use of a 7-day course of primaquine for P. vivax in patients in whom G6PD deficiency can be definitively ruled out.
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