Protective Efficacy and Safety of Three Antimalarial Regimens for the Prevention of Malaria in Young Ugandan Children: A Randomized Controlled Trial

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Background:
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 ill. 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, −19% 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 most efficacious 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.

Trial registration:
www.ClinicalTrials.gov NCT00948896

Please see later in the article for the Editors' Summary

Vyšlo v časopise: Protective Efficacy and Safety of Three Antimalarial Regimens for the Prevention of Malaria in Young Ugandan Children: A Randomized Controlled Trial. PLoS Med 11(8): e32767. doi:10.1371/journal.pmed.1001689
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pmed.1001689

Souhrn

Trial registration:
www.ClinicalTrials.gov NCT00948896

Please see later in the article for the Editors' Summary

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