Efficacy of Primaquine for the Radical Cure of Plasmodium vivax Malaria in Northeast Myanmar and the Impact of Cytochrome P450 2D6 Genotypes.

Abstract

Background: The antirelapse activity of primaquine (PQ) for Plasmodium vivax malaria depends on the host cytochrome P450 2D6 (CYP2D6) enzyme activity. This study aimed to assess the efficacy of PQ for the radical cure of P. vivax malaria in the Greater Mekong Subregion and determine the association of the post-PQ recurrences with CYP2D6 genotypes.

Methods: In 2014-2017, a total of 239 patients with uncomplicated P. vivax malaria in northeastern Myanmar were prospectively enrolled to receive a standard regimen of 3-day chloroquine and 14-day low-dose PQ (total dose, 3.5 mg/kg) as directly observed therapy. Patients were followed up biweekly for 1 year. A nested case-control study was designed to compare 49 patients with P. vivax malaria recurrences and 49 without recurrence. The CYP2D6 genotype-predicted activity score (AS) was used to estimate the unadjusted odds ratio of recurrence.

Results: During the 1-year follow-up, 54 recurrences were recorded with 65% occurring within 6 months after PQ treatment. The cumulative risk of recurrence was 17.3% (95% confidence interval, 11.9%-22.7%) at 6 months and 25.6% (19.3%-31.9%) at 1 year. Most recurrences were asymptomatic, with reduced parasitemia and gametocytemia. The CYP2D6*36+*10 tandem type with decreased function was the most prevalent allele (34.7%). Patients with an AS ≤1.25 had a significantly higher risk of recurrence (odds ratio, 6.53 [95% confidence interval, 2.0-21]; P < .001).

Conclusions: More than 75% of patients with vivax malaria in this region carried CYP2D6 alleles with an AS ≤1.25, suggesting the consideration for higher PQ doses.