Artemisinin-based combination therapy effective against asymptomatic malaria

Patients with asymptomatic Plasmodium falciparum infection may benefit from the artemisinin-based combination therapy pyronaridine/artesunate, which appears highly effective even at incomplete 2-day regimen, according to a phase II trial.

The trial, which was conducted in The Gambia and Zambia, randomized 303 patients (mean age 15.8 years, 51.2 percent female) to receive a 3-day (n=101), 2-day (n=100), or 1-day (n=102) treatment regimen of pyronaridine/artesunate (180:60 mg), dosed according to bodyweight.

In the per-protocol population, the primary efficacy outcome of polymerase chain reaction-adjusted adequate parasitological response at day 28 was high—at 100 percent with both the 3-day (98/98) and 2-day regimens (96/96) and 96.8 percent (89/94) for the 1-day regimen.

At day 63, efficacy was sustained at 100 percent in both the 3-day and 2-day treatment groups, whereas it dropped to 94.4 percent (84/89) in the 1-day group.

Adverse events (AEs) occurred with similar frequency in the 3-day (52/101, 51.5 percent), 2-day (52/99, 52.5 percent), and 1-day (56/103, 54.4 percent) groups. Most AEs were mild to moderate (grade 1 or 2: 136/160, 85 percent).

Overall, few patients developed asymptomatic, transient increases (>3xULN) in alanine transaminase/aspartate transaminase (6/301, 2.0 percent).

Despite the 3-day and 2-day regimens showing similar efficacy, the researchers stressed that good adherence to the 3-day regimen should be encouraged. The only reason for studying incomplete regimens was to evaluate the efficacy of pyronaridine/artesunate when given for community-based interventions aimed at reducing the human reservoir of malaria infection (eg, mass drug administration or mass testing and treatment).

As such, the findings are reassuring given that treated individuals may take only 1 or 2 days of treatment especially in cases where treatment is not directly supervised.