Higher-Dose Primaquine to Prevent Relapse of <i>Plasmodium vivax</i> Malaria
Nathália Nogueira Chamma-Siqueira, Suiane C. Negreiros, Sarah-Blythe Ballard, Sâmela Farias, Sandro Patroca da Silva, Stella M. Chenet, Eduardo José Melo dos Santos, Luann Wendel Pereira de Sena, Flávia Póvoa da Costa, Amanda G.N. Cardoso-Mello, Paola Marchesini, Cássio Peterka, Giselle Maria Rachid Viana, Alexandre Macedo de Oliveira
Abstract
BACKGROUND: malaria is primaquine at a total dose of 3.5 mg per kilogram of body weight, despite evidence of only moderate efficacy. METHODS: monoinfection. All the patients received directly observed chloroquine for 3 days (total dose, 25 mg per kilogram). Group 1 received a total primaquine dose of 3.5 mg per kilogram (0.5 mg per kilogram per day) over 7 days with unobserved administration; group 2 received the same regimen as group 1 but with observed administration; and group 3 received a total primaquine dose of 7.0 mg per kilogram over 14 days (also 0.5 mg per kilogram per day) with observed administration. We monitored the patients for 168 days. RESULTS: recurrences were observed: 2 in group 1 and 1 in group 2. By day 168, a total of 70 recurrences had occurred: 24 in group 1, 34 in group 2, and 12 in group 3. No serious adverse events were noted. On day 168, the percentage of patients without recurrence was 58% (95% confidence interval [CI], 44 to 70) in group 1, 59% (95% CI, 47 to 69) in group 2, and 86% (95% CI, 76 to 92) in group 3. Survival analysis showed a difference in the day 168 recurrence-free percentage of 27 percentage points (97.5% CI, 10 to 44; P<0.001) between group 1 and group 3 and a difference of 27 percentage points (97.5% CI, 12 to 42; P<0.001) between group 2 and group 3. CONCLUSIONS: malaria than a total dose of 3.5 mg per kilogram through day 168. (Supported by the U.S. Agency for International Development; ClinicalTrials.gov number, NCT03610399.).