Repeated artemisinin-based combination therapies in a malaria hyperendemic area of Mali: efficacy, safety, and public health impact

Abstract

Artemisinin-based combination therapies (ACTs) are the first-line treatment of uncomplicated malaria. The public health benefit and safety of repeated administration of a given ACT are poorly studied. We conducted a randomized trial comparing artemether-lumefantrine, artesunate plus amodiaquine (AS+AQ) and artesunate plus sulfadoxine-pyrimethamine (AS+SP) in patients 6 months of age and older with uncomplicated malaria in Mali from July 2005 to July 2007. The patient received the same initial treatment of each subsequent uncomplicated malaria episode except for treatment failures where quinine was used. Overall, 780 patients were included. Patients in the AS+AQ and AS+SP arms had significantly less risk of having malaria episodes; risk ratio (RR) = 0.84 (P = 0.002) and RR = 0.80 (P = 0.001), respectively. The treatment efficacy was similar and above 95% in all arms. Although all drugs were highly efficacious and well tolerated, AS+AQ and AS+SP were associated with less episodes of malaria.

Figure 1.

Study trial profile.

Figure 2.

Per protocol non-polymerase chain reaction (PCR) corrected adequate clinical and parasitological responses (ACPRs) per study arm, per season, and per year. Non-PCR corrected ACPRs per study arm, per season, and per year. The numbers of patients (n/N) with non-corrected ACPRs were 51/105, 82/105, and 90/107, respectively, for AL, AS+AQ, and AS+SP in July–September 2005, 68/120, 87/107, and 114/121 in October–December 2005; 29/29, 25/25, and 22/22 in January–March 2006; 31/43, 33/45, and 47/53 in April–June 2006; 115/188, 127/176, and 163/191 in July–September 2006; 75/126, 94/119, and 140/150 in October–December 2006; 32/33, 24/24, and 16/16 in January–March 2007; 11/13, 13/13, and 12/12 in April–June 2007.