Protective Efficacy and Safety of Three Antimalarial Regimens for the Prevention of Malaria in Young Ugandan Children: A Randomized Controlled Trial doi:10.1371/journal.pmed.1001689
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Date
2014
Journal Title
Journal ISSN
Volume Title
Publisher
PLoS medicine
Abstract
Chemoprevention offers a promising strategy for prevention of malaria in African children. However, the optimal chemoprevention drug and dosing strategy is unclear in areas of year-round transmission and resistance to many
antimalarial drugs. To compare three available regimens, we conducted an open-label randomized controlled trial of chemoprevention in Ugandan children. Methods and Findings: This study was conducted between June 28, 2010, and September 25, 2013. 400 infants were enrolled and 393 randomized at 6 mo of age to no chemoprevention, monthly sulfadoxine-pyrimethamine (SP), daily
trimethoprim-sulfamethoxazole (TS), or monthly dihydroartemisinin-piperaquine (DP). Study drugs were administered at home without supervision. Piperaquine (PQ) levels were used as a measure of compliance in the DP arm. Participants were
given insecticide-treated bednets, and caregivers were encouraged to bring their child to a study clinic whenever they were Chemoprevention was stopped at 24 mo of age, and participants followed-up an additional year. Primary outcome was the incidence of malaria during the intervention period. During the intervention, the incidence of malaria in the no
chemoprevention arm was 6.95 episodes per person-year at risk. Protective efficacy was 58% (95% CI, 45%–67%, p,0.001)
for DP, 28% (95% CI, 7%–44%, p = 0.01) for TS, and 7% for SP (95% CI, 219% to 28%, p = 0.57). PQ levels were below the
detection limit 52% of the time when malaria was diagnosed in the DP arm, suggesting non-adherence. There were no differences between the study arms in the incidence of serious adverse events during the intervention and the incidence of malaria during the 1-y period after the intervention was stopped.Conclusions: For preventing malaria in children living in an area of high transmission intensity, monthly DP was the mostefficacious and safe, although adherence may pose a problem.Monthly SP and daily TS may not be appropriate in areas with high transmission intensity and frequent resistance to antifolates.
Description
Keywords
Antimalarial Regimens, Prevention, Malaria, Young Children
Citation
Bigira, V., Kapisi, J., Clark, T. D., Kinara, S., Mwangwa, F., Muhindo, M. K., ... & Dorsey, G. (2014). Protective efficacy and safety of three antimalarial regimens for the prevention of malaria in young Ugandan children: a randomized controlled trial. PLoS medicine, 11(8), e1001689.