title: In Tanzania, hemolysis after a single dose of primaquine coadministered with an artemisinin is not restricted to glucose-6-phosphate dehydrogenase-deficient (G6PD A-) individuals.
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.
authors.affiliation: Department of Medical Microbiology, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands.
authors.forename: Seif A
authors.initials: SA
authors.lastname: Shekalaghe
authors.forename: Roel
authors.initials: R
authors.lastname: ter Braak
authors.forename: Modibo
authors.initials: M
authors.lastname: Daou
authors.forename: Reginald
authors.initials: R
authors.lastname: Kavishe
authors.forename: Wouter
authors.initials: W
authors.lastname: van den Bijllaardt
authors.forename: Sven
authors.initials: S
authors.lastname: van den Bosch
authors.forename: Jan B
authors.initials: JB
authors.lastname: Koenderink
authors.forename: Adrian J F
authors.initials: AJ
authors.lastname: Luty
authors.forename: Christopher J M
authors.initials: CJ
authors.lastname: Whitty
authors.forename: Chris
authors.initials: C
authors.lastname: Drakeley
authors.forename: Robert W
authors.initials: RW
authors.lastname: Sauerwein
authors.forename: Teun
authors.initials: T
authors.lastname: Bousema
mesh_terms: D000740:Anemia / Q000139:chemically induced* / Q000453:epidemiology; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000009:adverse effects; D000962:Antimalarials / Q000008:administration & dosage / Q000009:adverse effects*; D037621:Artemisinins / Q000008:administration & dosage / Q000009:adverse effects*; D000077332:Artesunate; D002648:Child; D002675:Child, Preschool; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D005500:Follow-Up Studies; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D005955:Glucosephosphate Dehydrogenase Deficiency / Q000453:epidemiology; D006454:Hemoglobins / Q000378:metabolism; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000453:epidemiology / Q000517:prevention & control*; D015999:Multivariate Analysis; D015995:Prevalence; D011319:Primaquine / Q000008:administration & dosage / Q000009:adverse effects*; D011739:Pyrimethamine / Q000008:administration & dosage / Q000009:adverse effects; D012044:Regression Analysis; D012307:Risk Factors; D013413:Sulfadoxine / Q000008:administration & dosage / Q000009:adverse effects; D013636:Tanzania
chemical_list: D000890:Anti-Infective Agents; D000962:Antimalarials; D037621:Artemisinins; D004338:Drug Combinations; D006454:Hemoglobins; C001205:fanasil, pyrimethamine drug combination; D000077332:Artesunate; D013413:Sulfadoxine; C031327:artemisinin; D005954:Glucosephosphate Dehydrogenase; D011319:Primaquine; D011739:Pyrimethamine