Efficacy and Safety of Pyronaridine-Artesunate plus Single-Dose Primaquine for the Treatment of Malaria in Western Cambodia

Abstract

This single-arm trial (n = 104) in western Cambodia showed high efficacy for 3-day treatment with pyronaridine-artesunate plus single-dose primaquine in Plasmodium falciparum malaria. Day 42 PCR-adjusted adequate clinical and parasitological response (ACPR) was 98.3% (58/59) (95% confidence interval [CI], 90.9 to 100.0) in Trapeng Chau in Kampong Speu and 100% (41/41) (95% CI, 91.4 to 100) in Veal Veng in Pursat; 80.6% (83/103) of the patients had P. falciparum with drug resistance molecular markers. For Plasmodium vivax malaria, pyronaridine-artesunate day 28 ACPR was 98.3% (59/60) (95% CI, 91.1 to 100) and 100% (60/60) (95% CI, 94.0 to 100), respectively. (This study is registered in the Australian New Zealand Clinical Trials Registry [ANZCTR] under reference no. ACTRN12618001999224.)

Efficacy and Safety of Pyronaridine–Artesunate for the Treatment of Uncomplicated Plasmodium falciparum and Plasmodium vivax Malaria in Myanmar

“…This was seen for P. falciparum in Cambodia with a dominant artemisinin/ piperaquine multidrug-resistant haplotype emerging within months of dihydroartemisinin-piperaquine being introduced as first-line therapy. 3 The most recent data from the GMS indicate that pyronaridine-artesunate retains good efficacy in Cambodia and Vietnam against multidrug-resistant P. falciparum, [14][15][16] and the current study confirms excellent efficacy in Myanmar. These findings are reassuring, potentially allowing the diversification of antimalarial therapy, and suggesting an alternative option should resistance undermine the efficacy of currently recommended antimalarial drugs.…”

“…This is in contrast to Cambodia–Laos–Vietnam, where a multidrug-resistant haplotype conferring high-level resistance to artemisinin and piperaquine has reached near fixation in some regions. 1 , 3 , 14 – 16 Correspondingly, day-3 parasite positivity rates are relatively high, for example, 35.6–46.7% in eastern regions of Cambodia and 28.6–41.7% in the west. 14 , 15 Moreover, high clinical failure rates are observed for dihydroartemisinin–piperaquine.…”

“… 1 , 3 , 14 – 16 Correspondingly, day-3 parasite positivity rates are relatively high, for example, 35.6–46.7% in eastern regions of Cambodia and 28.6–41.7% in the west. 14 , 15 Moreover, high clinical failure rates are observed for dihydroartemisinin–piperaquine. 4 A limitation of this study was that molecular markers of P. falciparum resistance to piperaquine and mefloquine were not investigated.…”

“…3,4 The ACT pyronaridine-artesunate has shown good efficacy for uncomplicated falciparum and vivax malaria in large-scale clinical trials conducted in Asia and Africa. [5][6][7][8][9][10][11][12] Within the GMS, pyronaridine-artesunate PCR-corrected day-42 adequate clinical and parasitological response (ACPR) rates against falciparum malaria in western Cambodia were 87.9% (95% CI: 80.6, 93.2) in 2014-2015, 13 but more recently > 98% efficacy was noted for this region (2018) 14 and efficacy was > 96% in eastern Cambodia (1997), 15 and > 96% in Vietnam (2017-2018). 16 Thus, pyronaridine-artesunate can remain a valuable treatment option for uncomplicated falciparum malaria in regions where the utility of other antimalarial drugs has been compromised by drug resistance.…”

“… 18 , 19 Pyronaridine–artesunate is the first ACT specifically registered for P. vivax malaria, with demonstrated high clinical efficacy across Southeast Asia. 12 , 14 Chloroquine resistance has been reported in Myanmar, 20 – 23 and to plan effective P. vivax elimination programs, the efficacy of alternative therapies requires confirmation.…”