Haemolysis after a single dose of primaquine co-administered with an artemisinin is not restricted to glucose-6-phosphate dehydrogenase (G6PD A- variant) deficient individuals in Tanzania.


Shekalaghe, SA; ter Braak, R; Daou, M; Kavishe, R; van den Bijllaardt, W; van den Bosch, S; Koenderink, JB; Luty, AJ; Whitty, CJ; Drakeley, C; Sauerwein, RW; Bousema, T; (2010) Haemolysis after a single dose of primaquine co-administered with an artemisinin is not restricted to glucose-6-phosphate dehydrogenase (G6PD A- variant) deficient individuals in Tanzania. Antimicrobial agents and chemotherapy, 54 (5). pp. 1762-8. ISSN 0066-4804 DOI: https://doi.org/10.1128/AAC.01135-09

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Abstract

: The current interest in malaria elimination has led to a renewed interest in drugs that can be used for mass administration to minimize malaria transmission. Primaquine (PQ) is the only generally available drug with a strong activity against mature Plasmodium falciparum gametocytes, the parasite stage responsible for transmission. Despite concerns about PQ-induced hemolysis in glucose-6-phosphate dehydrogenase (G6PD)-deficient individuals, a single dose of PQ may be safe and efficacious in clearing gametocytes that persist after conventional treatment. As part of a mass drug intervention, we determined the hemolytic effect of sulfadoxine-pyrimethamine (SP) plus artesunate (AS) plus a single dose of primaquine (PQ; 0.75 mg/kg of body weight) in children aged 1 to 12 years. Children were randomized to receive SP+AS+PQ or placebo; those with a hemoglobin (Hb) level below 8 g/dl were excluded from receiving PQ and received SP+AS. The Hb concentration was significantly reduced 7 days after SP+AS+PQ treatment but not after placebo or SP+AS treatment. This reduction in Hb was most pronounced in G6PD-deficient (G6PD A-) individuals (-2.5 g/dl; 95% confidence interval [95% CI], -1.2 to -3.8 g/dl) but was also observed in heterozygotes (G6PD A) (-1.6 g/dl; 95% CI, -0.9 to -2.2 g/dl) and individuals with the wild-type genotype (G6PD B) (-0.5 g/dl; 95% CI, -0.4 to -0.6 g/dl). Moderate anemia (Hb level of <8 g/dl) was observed in 40% (6/15 individuals) of the G6PD A-, 11.1% (3/27 individuals) of the G6PD A, and 4.5% (18/399 individuals) of the G6PD B individuals; one case of severe anemia (Hb level of <5 g/dl) was observed. PQ may cause moderate anemia when coadministered with artemisinins, and excluding individuals based on G6PD status alone may not be sufficient to prevent PQ-induced hemolysis.<br/>

Item Type: Article
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Immunology and Infection
Faculty of Infectious and Tropical Diseases > Dept of Clinical Research
Research Centre: Malaria Centre
PubMed ID: 20194698
Web of Science ID: 276804300015
URI: http://researchonline.lshtm.ac.uk/id/eprint/4047

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