Artemether-lumefantrine versus dihydroartemisinin-piperaquine for falciparum malaria: a longitudinal, randomized trial in young Ugandan children.
BACKGROUND
Artemisinin-based combination therapies are now widely recommended as first-line treatment for uncomplicated malaria. However, which therapies are optimal is a matter of debate. We aimed to compare the short- and longer-term efficacy of 2 leading therapies in a cohort of young Ugandan children.


METHODS
A total of 351 children aged 6 weeks to 12 months were enrolled and followed up for up to 1 year. Children who were at least 4 months of age, weighted at least 5 kg, and had been diagnosed as having their first episode of uncomplicated malaria were randomized to receive artemether-lumefantrine or dihydroartemisinin-piperaquine. The same treatment was given for all subsequent episodes of uncomplicated malaria. Recrudescent and new infections were distinguished by polymerase chain reaction genotyping. Outcomes included the risk of recurrent malaria after individual treatments and the incidence of malaria treatments for individual children after randomization.


RESULTS
A total of 113 children were randomized to artemether-lumefantrine and 119 to dihydroartemisinin-piperaquine, resulting in 320 and 351 treatments for uncomplicated falciparum malaria, respectively. Artemether-lumefantrine was associated with a higher risk of recurrent malaria after 28 days (35% vs 11%; P = .001]). When the duration of follow-up was extended, differences in the risk of recurrent malaria decreased such that the overall incidence of malaria treatments was similar for children randomized to artemether-lumefantrine, compared with those randomized to dihydroartemisinin-piperaquine (4.82 vs 4.61 treatments per person-year; P = .63). The risk of recurrent malaria due to recrudescent parasites was similarly low in both treatment arms.


CONCLUSIONS
Artemether-lumefantrine and dihydroartemisinin-piperaquine were both efficacious and had similar long-term effects on the risk of recurrent malaria. Clinical trials registration. NCT00527800.
Arinaitwe
Emmanuel
E
Makerere University-University of California San Francisco Research Collaboration, University of California, San Francisco 94143, USA.
Sandison
Taylor G
TG
Wanzira
Humphrey
H
Kakuru
Abel
A
Homsy
Jaco
J
Kalamya
Julius
J
Kamya
Moses R
MR
Vora
Neil
N
Greenhouse
Bryan
B
Rosenthal
Philip J
PJ
Tappero
Jordan
J
Dorsey
Grant
G
D000962:Antimalarials / Q000627:therapeutic use*; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins / Q000627:therapeutic use*; D002675:Child, Preschool; D004338:Drug Combinations; D004983:Ethanolamines / Q000627:therapeutic use*; D005449:Fluorenes / Q000627:therapeutic use*; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000188:drug therapy*; D011804:Quinolines / Q000627:therapeutic use*; D016896:Treatment Outcome; D014454:Uganda; D010879:Piperazines
D000962:Antimalarials; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins; D004338:Drug Combinations; D004983:Ethanolamines; D005449:Fluorenes; D011804:Quinolines; C039060:artenimol; C034759:piperaquine; D010879:Piperazines