Discussion
anemia, acute disease, parasitaemia, G6PD deficiency, hemolysis, anorexia
EVENT, RECRUITMENT, ANEMIA, ACUTE DISEASE, G6PD DEFICIENCY, HEMOLYSIS, ANOREXIA
Our study represents the largest study to date on the use of the 8-week primaquine regimen for the radical cure of Defining antirelapse efficacy of primaquine and tafenoquine is confounded by the frequency and timing of hypnozoite reactivation and recurrent parasitaemia, which vary with hypnozoite load, and parasite strains in a geographical region [Few studies have estimated the efficacy of weekly primaquine. In the 1960s, 10% (2/11) of patients experimentally challenged with the Chesson strain of The current WHO guidelines recommend a daily dose of PQ in adults of 15 mg (0.25 mg/kg) or 30 mg (0.5 mg/kg) for the 14 day regimen and weekly 45 mg (0.75mg/kg) in the 8 week regimen. The weekly dose of PQ in our study was weight adjusted to provide a total mg/kg dose of approximately 7mg/kg (The primary safety concern for primaquine relates to its ability to cause severe hemolysis in patients with G6PD deficiency [Weekly spacing of PQ administration allows some haematological recovery between drug exposures. Two male patients with Mediterranean and Kaiping variants had a fall in Hb >5g/dL, but both started with high baseline Hb concentrations, neither had a fall in Hb below 10g/dL or reported concomitant symptoms, and both recovered quickly while completing their course of primaquine. By contrast, a 16-year old male with the Kaiping variant had a 33% fall in Hb to 9.0 g/dL, associated with general malaise, anorexia and reduced oral intake requiring intravenous fluid administration in hospital. A similar event occurred in a Cambodian trial, in which a male with the Viangchan variant was treated with PQ8W and had a fractional fall of 25% (from 10 to 7.5 g/dL) resulting in symptomatic anemia necessitating a blood transfusion [Our study has several limitations. We were unable to measure the enzyme activity by spectrophotometry at all sites and thus relied on screening with the FST. This qualitative assay only detects G6PD deficiency in patients with less than 30% enzyme activity and is vulnerable to subjective visual discrimination [Another limitation of our analysis is the relatively low patient recruitment into the study. Despite being the largest study of primaquine in patients with G6PDd, the sample size is relatively small for an antimalarial clinical trial conducted over multiple sites. This limitation has confounded previous clinical trials seeking to enrol intermediate or severely G6PD deficient patients and likely reflects the protective effect of G6PDd against acute disease [In conclusion, our study provides important new evidence on the tolerability, safety and efficacy of PQ8W in Asian and African patients with G6PDd. PQ8W was highly effective in preventing 