Chloroquine or dihydroartemisinin-piperaquine with either a 7- or 14-day primaquine regimen provided highly effective radical cure of Plasmodium vivax malaria on the Thailand-Myanmar border, suggesting that short-course and higher-dose primaquine regimens for P vivax malaria radical cure may aid efficacy by improving adherence, according to a study recently published in Clinical Infectious Diseases.
P vivax is the most geographically dispersed of the strains of malaria that affect humans, with chloroquine being the first-line treatment for more than 70 years. However, low-grade chloroquine resistance, which is manifested by earlier appearance of relapse, has been reported increasingly in recent years, whereas high-grade resistance remains confined to Oceania and Indonesia. Piperaquine, a slowly eliminated bisquinoline, combined with dihydroartemisinin is well tolerated and highly effective against chloroquine-resistant P vivax malaria, and has replaced chloroquine as first-line treatment in Indonesia. The current 2-way, randomized controlled trial compared the radical curative efficacy of short-course 7-day high-dose primaquine with that of the standard 14-day high-dose regimen.
Between 2012 and 2014, 654 patients with uncomplicated P vivax malaria on the Thailand-Myanmar border were recruited and randomly assigned to either chloroquine (25 mg base/kg) or dihydroartemisinin-piperaquine (dihydroartemisinin 7 mg/kg and piperaquine 55 mg/kg) plus primaquine, either .5 mg/kg/day for 14 days or 1 mg/kg/day for 7 days. Adverse events within 42 days and 1-year recurrence rates were compared and their relationship with day 6 drug concentrations was assessed.
P vivax recurrences occurred in 12% of patients and there was no difference between treatments. Fever resolution was faster in the dihydroartemisinin-piperaquine groups (mean difference .5 days; P <.001). Parasite clearance was also faster in the dihydroartemisinin-piperaquine groups (mean difference .7 days; P <.001). Of the analyzed patients, 20% did not complete the 6-month follow-up, and a further 17% did not complete the 1-year follow-up. In the multivariable Cox regression model, independent risk factors for premature discontinuation were being >15 years old (P =.037 compared with 0-4 years old), being male (P =.002), and taking dihydroartemisinin-piperaquine (P =.009). There were no significant differences in reported adverse events among the 4 groups, with the exception of abdominal pain.
Overall, the study authors concluded that, “The radical curative efficacy in P vivax malaria of 7-day high-dose primaquine is similar to the standard 14-day high dose regimen.”
Chu CS, Phyo AP, Turner C, et al. Chloroquine versus dihydroartemisinin-piperaquine with standard high dose primaquine given either for 7 days or 14 days in Plasmodium vivax malaria [published online August 24, 2018] Clin Infect Dis. doi: 10.1093/cid/ciy735