Longitudinal outcomes in a cohort of Ugandan children randomized to artemether-lumefantrine versus dihydroartemisinin-piperaquine for the treatment of malaria.
BACKGROUND
Artemisinin-based combination therapy (ACT) has become the standard of care for the treatment of uncomplicated Plasmodium falciparum malaria. Although several ACT regimens are approved, data guiding optimal choices of ACTs are limited. We compared short- and long-term outcomes in a cohort of young Ugandan children randomized to 2 leading ACTs.


METHODS
Overall, 312 children were randomized to artemether-lumefantrine or dihydroartemisinin-piperaquine (DP) at the time of the first episode of uncomplicated malaria (median age, 10.5 months). The same treatment was given for all subsequent episodes of uncomplicated malaria and children were followed until they reached 5 years of age. The cohort included a subgroup that was human immunodeficiency virus (HIV) infected (n = 44) or HIV exposed (n = 175) and prescribed trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis. Outcomes included time to recurrent malaria following individual treatments and the overall incidences of treatments for malaria, complicated malaria, and hospitalizations.


RESULTS
Among children not prescribed TMP-SMX prophylaxis, 4443 treatments for malaria were given over 790 person-years following randomization. Treatment with DP was associated with a lower hazard of recurrent malaria over the 84 days after treatment (hazard ratio, 0.66; 95% confidence interval [CI], .61-.70; P < .001). Children randomized to DP had a lower incidence of all treatments for malaria (incidence rate ratio [IRR], 0.85; 95% CI, .75-.96; P = .01), complicated malaria (IRR, 0.12; 95% CI, .04-.39; P < .001), and hospitalizations (IRR, 0.31; 95% CI, .13-.77; P = .01). Among children prescribed TMP-SMX prophylaxis, there were no significant differences in longitudinal outcomes.


CONCLUSIONS
Compared to artemether-lumefantrine, the use of DP to treat uncomplicated malaria delayed the time to recurrent malaria and reduced the incidences of treatments for malaria, complicated malaria, and hospitalizations.


BACKGROUND
NCT00527800.
Infectious Diseases Research Collaboration, Kampala, Uganda.
Humphrey
H
Wanzira
Infectious Diseases Research Collaboration, Kampala, Uganda.
Abel
A
Kakuru
Infectious Diseases Research Collaboration, Kampala, Uganda.
Emmanuel
E
Arinaitwe
Infectious Diseases Research Collaboration, Kampala, Uganda.
Victor
V
Bigira
Infectious Diseases Research Collaboration, Kampala, Uganda.
Mary K
MK
Muhindo
Department of Medicine, University of California, San Francisco.
Melissa
M
Conrad
Department of Medicine, University of California, San Francisco.
Philip J
PJ
Rosenthal
Department of Medicine, Makerere University College of Health Sciences, Kampala, Uganda.
Moses R
MR
Kamya
Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia.
Jordan W
JW
Tappero
Department of Medicine, University of California, San Francisco.
Grant
G
Dorsey
D000962:Antimalarials / Q000627:therapeutic use*; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins / Q000627:therapeutic use*; D002675:Child, Preschool; D015331:Cohort Studies; D004338:Drug Combinations; D004359:Drug Therapy, Combination / Q000379:methods; D004983:Ethanolamines / Q000627:therapeutic use*; D005260:Female; D005449:Fluorenes / Q000627:therapeutic use*; D015658:HIV Infections / Q000150:complications; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D007223:Infant; D008137:Longitudinal Studies; D016778:Malaria, Falciparum / Q000188:drug therapy*; D008297:Male; D011804:Quinolines / Q000627:therapeutic use*; D012008:Recurrence; D013997:Time Factors; 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
Uganda; artemether-lumefantrine; cohort; dihydroartemisinin-piperaquine; malaria