Tafenoquine for radical cure of P vivax

N Engl J Med. 2019 Jan 17;380(3):215-228

Contributed by Dr Abi Manesh

Hypnozoites, the dormant liver malarial parasites are important causes of recurrent Plasmodium vivax infections. Primaquine, an 8-aminoquinoline given at 15 mg base per day for 14 days has been the standard of care to eliminate hypnozoites, to produce ‘radical cure’. Primaquine treatment is complicated by poor adherence and hemolysis among patients with G6PD deficiency. Tafenoquine, a recently FDA approved 8-aminoquinoline is characterized by a longer half-life (15 days vs 5 hours) and shares the ability to produce hemolysis among G6PD deficient. G6PD deficiency is X linked - male hemizygotes and female homozygotes remain clinically deficient while the female heterozygotes are genetic mosaics with varying degree of deficiency. Approximately, 10% of malaria endemic population in the world has G6PD deficiency. Qualitative testing for G6PD may miss some of the female heterozygotes – thereby putting them at risk of life-threatening hemolysis with long-acting tafenoquine. Hence, quantitative tests ensuring G6PD activity is more than 70% is required before tafenoquine is administered. Such rapid tests are not commonly available in field settings.

The investigators studied the role of tafenoquine to ensure ‘radical cure’ in an RCT involving 522 patients from Ethiopia, Peru, Brazil, Cambodia, Thailand, and the Philippines. All patients received a 3-day course of chloroquine (total dose of 1500 mg). In addition, patients were assigned to receive a single 300-mg dose of tafenoquine on day 1 or 2 (260 patients), placebo (133 patients), or a 15-mg dose of primaquine once daily for 14 days (129 patients). The primary outcome was the Kaplan–Meier estimated percentage of patients who were free from recurrence at 6 months, defined as P. vivax clearance without recurrent parasitemia.

The percentage of patients free from recurrence at 6 months was 62.4% in the tafenoquine group (95% confidence interval [CI], 54.9 to 69.0), 27.7% in the placebo group (95% CI, 19.6 to 36.6), and 69.6% in the primaquine group (95% CI, 60.2 to 77.1). The hazard ratio for the risk of recurrence was 0.30 (95% CI, 0.22 to 0.40) with tafenoquine as compared with placebo (P<0.001) and 0.26 (95% CI, 0.18 to 0.39) with primaquine as compared with placebo (P<0.001).

In summary, provided optimal G6PD testing strategies are available, tafenoquine is a more convenient alternative for primaquine to ensure radical cure in P. vivax malaria.