Artemether-lumefantrine versus dihydroartemisinin-piperaquine for treatment of malaria: a randomized trial.
OBJECTIVE
To compare the efficacy and safety of artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DP) for treating uncomplicated falciparum malaria in Uganda.


METHODS
Randomized single-blinded clinical trial.


METHODS
Apac, Uganda, an area of very high malaria transmission intensity.


METHODS
Children aged 6 mo to 10 y with uncomplicated falciparum malaria.


METHODS
Treatment of malaria with AL or DP, each following standard 3-d dosing regimens.


METHODS
Risks of recurrent parasitemia at 28 and 42 d, unadjusted and adjusted by genotyping to distinguish recrudescences and new infections.


RESULTS
Of 421 enrolled participants, 417 (99%) completed follow-up. The unadjusted risk of recurrent falciparum parasitemia was significantly lower for participants treated with DP than for those treated with AL after 28 d (11% versus 29%; risk difference [RD] 18%, 95% confidence interval [CI] 11%-26%) and 42 d (43% versus 53%; RD 9.6%, 95% CI 0%-19%) of follow-up. Similarly, the risk of recurrent parasitemia due to possible recrudescence (adjusted by genotyping) was significantly lower for participants treated with DP than for those treated with AL after 28 d (1.9% versus 8.9%; RD 7.0%, 95% CI 2.5%-12%) and 42 d (6.9% versus 16%; RD 9.5%, 95% CI 2.8%-16%). Patients treated with DP had a lower risk of recurrent parasitemia due to non-falciparum species, development of gametocytemia, and higher mean increase in hemoglobin compared to patients treated with AL. Both drugs were well tolerated; serious adverse events were uncommon and unrelated to study drugs.


CONCLUSIONS
DP was superior to AL for reducing the risk of recurrent parasitemia and gametocytemia, and provided improved hemoglobin recovery. DP thus appears to be a good alternative to AL as first-line treatment of uncomplicated malaria in Uganda. To maximize the benefit of artemisinin-based combination therapy in Africa, treatment should be integrated with aggressive strategies to reduce malaria transmission intensity.
Kamya
Moses R
MR
Department of Medicine, Makerere University, Kampala, Uganda. mkamya@infocom.co.ug
Yeka
Adoke
A
Bukirwa
Hasifa
H
Lugemwa
Myers
M
Rwakimari
John B
JB
Staedke
Sarah G
SG
Talisuna
Ambrose O
AO
Greenhouse
Bryan
B
Nosten
François
F
Rosenthal
Philip J
PJ
Wabwire-Mangen
Fred
F
Dorsey
Grant
G