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.