Abstract
BackgroundHaemolysis risk with single dose or short course primaquine was evaluated in glucose-6-phosphate dehydrogenase (G6PD) deficient people.MethodsMajor electronic databases (to August 2016) were searched for single or short course 8-aminoquinolines (8-AQ) in (1) randomized comparisons against placebo in G6PD deficient people; and (2) observational comparisons in G6PD deficient compared to replete people. Two authors independently assessed eligibility, risk-of-bias, and extracted data.ResultsFive randomized controlled trials and four controlled observational cohorts were included. In G6PD deficient individuals, high-dose (0.75 mg/kg) PQ resulted in lower average haemoglobin levels at 7 days (mean difference [MD] −1.45 g/dl, 95% CI −2.17 to −0.74, 2 trials) and larger percentage fall from baseline to day 7 (MD −10.31%, 95% CI −17.69 to −2.92, 3 trials) compared to placebo. In G6PD deficient compared to replete people, average haemoglobin was lower at 7 days (MD −1.19 g/dl, 95% CI −1.94 to −0.44, 2 trials) and haemoglobin change from baseline to day 7 was greater (MD −9.10%, 95% CI −12.55 to −5.65, 5 trials). One small trial evaluated mid-range PQ dose (0.4–0.5 mg/kg) in G6PD deficient people, with no difference detected in average haemoglobin at day 7 compared to placebo. In one cohort comparing G6PD deficient and replete people there was a greater fall with G6PD deficiency (MD −4.99%, 95% CI −9.96 to −0.02). For low-dose PQ (0.1–0.25 mg/kg) in G6PD deficient people, haemoglobin change from baseline was similar to the placebo group (MD 1.72%, 95% CI −1.89 to 5.34, 2 trials). Comparing low dose PQ in G6PD deficient with replete people, the average haemoglobin was lower in the G6PD deficient group at 7 days (−0.57 g (95% CI −0.97 to −0.17, 1 trial)); although change from baseline was similar (MD −1.45%, 95% CI −5.69 to 2.78, 3 trials).ConclusionsFalls in average haemoglobin are less marked with the 0.1 to 0.25 mg/kg PQ than with the 0.75 mg/kg dose, and severe haemolytic events are not common. However, data were limited and the evidence GRADE was low or very low certainty.
Highlights
Haemolysis risk with single dose or short course primaquine was evaluated in glucose-6-phosphate dehydrogenase (G6PD) deficient people
Four studies reported that they used the fluorescent spot test (FST) for screening [27, 29,30,31], and one study used the rapid test rather than FST [28]
With the 0.75 mg/kg single dose in G6PD deficient people there is an average 1.45 g/dl greater fall in haemoglobin by day 7 compared to placebo, and risks of anaemia (20% drop in haemoglobin) are increased 11-fold
Summary
Haemolysis risk with single dose or short course primaquine was evaluated in glucose-6-phosphate dehydrogenase (G6PD) deficient people. Primaquine (PQ) has been used widely since the 1950s to prevent relapse from Plasmodium vivax. In the malaria endemic countries of sub-Saharan Africa and Asia [6] makes the drug potentially unsafe within these populations. In 2010, the World Health Organization (WHO) reaffirmed a recommendation made many years previously for a single dose of 0.75 mg/kg of PQ to be administered with primary treatment for falciparum malaria to reduce transmission [7]. The WHO lowered the recommended single dose for gametocytocidal effect to 0.25 mg/kg in 2012, and limited PQ’s use to areas threatened by artemisinin resistance or areas of low endemicity approaching elimination [8]. In 2015, the policy recommendation was changed to recommend use in ‘low transmission areas’ and it was explicitly stated that G6PD testing was not required before single dose use [9]
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