Hemolytic Dynamics of Weekly Primaquine Antirelapse Therapy among Cambodians with Acute Plasmodium vivax Malaria with or Without Glucose-6-Phosphate Dehydrogenase Deficiency

Abstract

© 2019 The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. Background: Hemoglobin (Hb) data are limited in Southeast Asian glucose-6-phosphate dehydrogenase (G6PD) deficient (G6PD-) patients treated weekly with the World Health Organization-recommended primaquine regimen (ie, 0.75 mg/kg/week for 8 weeks [PQ 0.75]). Methods: We treated Cambodians who had acute Plasmodium vivax infection with PQ0.75 and a 3-day course of dihydroartemisinin/piperaquine and determined the Hb level, reticulocyte count, G6PD genotype, and Hb type. Results: Seventy-five patients (male sex, 63) aged 5-63 years (median, 24 years) were enrolled. Eighteen were G6PD deficient (including 17 with G6PD Viangchan) and 57 were not G6PD deficient; 26 had HbE (of whom 25 were heterozygous), and 6 had α-/β-Thalassemia. Mean Hb concentrations at baseline (ie, day 0) were similar between G6PD deficient and G6PD normal patients (12.9 g/dL [range, 9-16.3 g/dL] and 13.26 g/dL [range, 9.6-16 g/dL], respectively; P =. 46). G6PD deficiency (P = <.001), higher Hb concentration at baseline (P = <.001), higher parasitemia level at baseline (P =. 02), and thalassemia (P =. 027) influenced the initial decrease in Hb level, calculated as the nadir level minus the baseline level (range,-5.8-0 g/dL; mean,-1.88 g/dL). By day 14, the mean difference from the day 7 level (calculated as the day 14 level minus the day 7 level) was 0.03 g/dL (range,-0.25-0.32 g/dL). Reticulocyte counts decreased from days 1 to 3, peaking on day 7 (in the G6PD normal group) and day 14 (in the G6PD deficient group); reticulocytemia at baseline (P =. 001), G6PD deficiency (P = <.001), and female sex (P =. 034) correlated with higher counts. One symptomatic, G6PD-deficient, anemic male patient was transfused on day 4. Conclusions: The first PQ0.75 exposure was associated with the greatest decrease in Hb level and 1 blood transfusion, followed by clinically insignificant decreases in Hb levels. PQ0.75 requires monitoring during the week after treatment. Safer antirelapse regimens are needed in Southeast Asia. Clinical Trials Registration: ACTRN12613000003774.