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- Title
Hemolytic Dynamics of Weekly Primaquine Antirelapse Therapy Among Cambodians With Acute Plasmodium vivax Malaria With or Without Glucose-6-Phosphate Dehydrogenase Deficiency.
- Authors
Taylor, Walter R J; Kheng, Sim; Muth, Sinoun; Tor, Pety; Kim, Saorin; Bjorge, Steven; Topps, Narann; Kosal, Khem; Sothea, Khon; Souy, Phum; Char, Chuor Meng; Vanna, Chan; Ly, Po; Khieu, Virak; Christophel, Eva; Kerleguer, Alexandra; Pantaleo, Antonella; Mukaka, Mavuto; Menard, Didier; Baird, J Kevin
- Abstract
<bold>Background: </bold>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]).<bold>Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusions: </bold>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.<bold>Clinical Trials Registration: </bold>ACTRN12613000003774.
- Subjects
SOUTHEAST Asia; CAMBODIA; GLUCOSE-6-phosphate dehydrogenase deficiency; WORLD Health Organization; PLASMODIUM vivax; CLINICAL trial registries; PRIMAQUINE; GLUCOSE-6-phosphate dehydrogenase
- Publication
Journal of Infectious Diseases, 2019, Vol 220, Issue 11, p1750
- ISSN
0022-1899
- Publication type
journal article
- DOI
10.1093/infdis/jiz313