In the study, 69.6% in the primaquine group were free from recurrence at 6 months (HR 0.26; 95% CI, 0.18 to 0.39 vs. placebo; p<0.001). Tafenoquine was associated with asymptomatic declines in haemoglobin levels, which resolved without intervention.
Tafenoquine is a single-dose 8-aminoquinoline that was developed at the Walter Reed Army Institute of Research in the 1980s. According to an editorial, tafenoquine solves the potentially important problem of poor adherence to daily primaquine by providing a radical cure in a single dose but is also a weakness as the slow elimination (terminal half-life ~15 days) means that in patients with G6PD deficiency, haemolysis of the older erythrocytes continues until all susceptible cells have been destroyed. In contrast, primaquine (half-life ~5 hours) can be stopped at the first sign of clinically significant haemolysis. It adds that even with point-of-care testing, tafenoquine would still pose a significant risk to female heterozygotes who would be reported as “normal” by the screening tests but could still undergo substantial haemolysis. Thus tafenoquine is restricted to patients with greater than 70% of normal G6PD activity and a quantitative assessment of G6PD activity must be performed before tafenoquine is used. It notes that although point-of-care quantitative tests have been developed, they have not yet been tested extensively under field conditions.
The current study is one of two published in the New England Journal of Medicine, showing that with appropriate G6PD testing, tafenoquine can be given safely and its efficacy in preventing recurrence of P. vivax malaria was similar to that of the standard 14-day regimen of primaquine in South America and the Horn of Africa, but lower with tafenoquine than with primaquine in Southeast Asia. The editorial notes that the requirement for accurate quantitative G6PD assessments and the current prescribing restrictions (pregnancy, lactation, or age younger than 16 years) will limit the potential deployment of tafenoquine, at least in the immediate future but comments the developers of tafenoquine for persevering with this potentially valuable antimalarial drug, despite the difficulties. It concludes “it is too early to say whether tafenoquine can be used safely on a large scale in routine practice and thus fulfill its promise as a radical improvement in the treatment of malaria.”