Protective efficacy and safety of three antimalarial regimens for the prevention of malaria in young Ugandan children: a randomized controlled trial.
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...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-08-01
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| Series: | PLoS Medicine |
| Online Access: | http://europepmc.org/articles/PMC4122345?pdf=render |
| _version_ | 1818025148592160768 |
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| author | Victor Bigira James Kapisi Tamara D Clark Stephen Kinara Florence Mwangwa Mary K Muhindo Beth Osterbauer Francesca T Aweeka Liusheng Huang Jane Achan Diane V Havlir Philip J Rosenthal Moses R Kamya Grant Dorsey |
| author_facet | Victor Bigira James Kapisi Tamara D Clark Stephen Kinara Florence Mwangwa Mary K Muhindo Beth Osterbauer Francesca T Aweeka Liusheng Huang Jane Achan Diane V Havlir Philip J Rosenthal Moses R Kamya Grant Dorsey |
| author_sort | Victor Bigira |
| collection | DOAJ |
| description | 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.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.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.www.ClinicalTrials.gov NCT00948896 Please see later in the article for the Editors' Summary. |
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| issn | 1549-1277 1549-1676 |
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| spelling | doaj.art-962cb667668946d18dad8a18d96013f62022-12-22T02:02:43ZengPublic Library of Science (PLoS)PLoS Medicine1549-12771549-16762014-08-01118e100168910.1371/journal.pmed.1001689Protective efficacy and safety of three antimalarial regimens for the prevention of malaria in young Ugandan children: a randomized controlled trial.Victor BigiraJames KapisiTamara D ClarkStephen KinaraFlorence MwangwaMary K MuhindoBeth OsterbauerFrancesca T AweekaLiusheng HuangJane AchanDiane V HavlirPhilip J RosenthalMoses R KamyaGrant DorseyChemoprevention 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.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.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.www.ClinicalTrials.gov NCT00948896 Please see later in the article for the Editors' Summary.http://europepmc.org/articles/PMC4122345?pdf=render |
| spellingShingle | Victor Bigira James Kapisi Tamara D Clark Stephen Kinara Florence Mwangwa Mary K Muhindo Beth Osterbauer Francesca T Aweeka Liusheng Huang Jane Achan Diane V Havlir Philip J Rosenthal Moses R Kamya Grant Dorsey Protective efficacy and safety of three antimalarial regimens for the prevention of malaria in young Ugandan children: a randomized controlled trial. PLoS Medicine |
| title | Protective efficacy and safety of three antimalarial regimens for the prevention of malaria in young Ugandan children: a randomized controlled trial. |
| title_full | Protective efficacy and safety of three antimalarial regimens for the prevention of malaria in young Ugandan children: a randomized controlled trial. |
| title_fullStr | Protective efficacy and safety of three antimalarial regimens for the prevention of malaria in young Ugandan children: a randomized controlled trial. |
| title_full_unstemmed | Protective efficacy and safety of three antimalarial regimens for the prevention of malaria in young Ugandan children: a randomized controlled trial. |
| title_short | Protective efficacy and safety of three antimalarial regimens for the prevention of malaria in young Ugandan children: a randomized controlled trial. |
| title_sort | protective efficacy and safety of three antimalarial regimens for the prevention of malaria in young ugandan children a randomized controlled trial |
| url | http://europepmc.org/articles/PMC4122345?pdf=render |
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