Efficacy and Effectiveness of Artemether-Lumefantrine after Initial and Repeated Treatment in Children < 5 Years of Age with Acute Uncomplicated Plasmodium falciparum Malaria in Rural Tanzania: A Randomized Trial

Document Type



Pathology (East Africa)


Background. We assessed the efficacy, effectiveness and safety of artemether-lumefantrine, which is the most widely used artemisinin-based combination therapy in Africa, against Plasmodium falciparum malaria during an extended follow-up period after initial and repeated treatment.

Methods. We performed an open-label randomized trial of artemether-lumefantrine with supervised (n = 180) and unsupervised intake (n = 179) in children(PCR)–corrected cure rates by day 56 and day 42 after initial and repeated treatment, respectively, as estimated by survival analysis.

Results. The PCR-corrected cure rate after initial treatment was 98.1% (95% confidence interval [CI], 94.2%–99.4%) after supervised and 95.1% (95% CI, 90.7%–98.1%) after unsupervised intake (P = .29). After retreatment of recurrent infections, the cure rates were 92.9% (95% CI, 81.8%–97.3%) and 97.6% (95% CI, 89.3%–98.8%), respectively (P = .58). Reinfections occurred in 46.9% (82 of 175) versus 50.9 % of the patients (relative risk [RR], 0.92 [95% CI, 0.74–1.14]; P = .46) after initial therapy and 32.4% (24 of 74) versus 39.0% (32 of 82) (RR, 0.83 [95% CI, 0.54–1.27]; P = .39) after retreatment. Median blood lumefantrine concentrations in supervised and unsupervised patients on day 7 were 304 versus 194 ng/mL (P < .001) after initial treatment and 253 versus 164 ng/mL (P = .001) after retreatment. Vomiting was the most commonly reported drug-related adverse event (in 1% of patients) after both initial and repeated treatment.

Conclusions. Artemether-lumefantrine was highly efficacious even after unsupervised administration, despite significantly lower lumefantrine concentrations, compared with concentration achieved with supervised intake, and was well-tolerated and safe after initial and repeated treatment


This work was published before the author joined Aga Khan University.

Publication (Name of Journal)

Clinical Infectious Diseases