Trial reportMalaria journal2015
Variable piperaquine exposure significantly impacts protective efficacy of monthly dihydroartemisinin-piperaquine for the prevention of malaria in Ugandan children.
Trial report in Malaria journal, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00948896 (A Randomized Controlled Trial of Monthly Dihydroartemisinin-piperaquine Versus Monthly Sulfadoxine-pyrimethamine Versus Daily Trimethoprim-sulfamethoxazole Versus No Therapy for the Prevention of Malaria), which is not on this map. Cited by 18 papers, 3 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Randomized Controlled Trial of Monthly Dihydroartemisinin-piperaquine Versus Monthly Sulfadoxine-pyrimethamine Versus Daily Trimethoprim-sulfamethoxazole Versus No Therapy for the Prevention of Malaria
Who cites it
18 citing papers in PubMed, 3 syntheses or guidelines pooled it, 25 citations in OpenAlex.
- Intermittent preventive treatment for malaria in infants.The Cochrane database of systematic reviews · 2021Pooled it
- Intermittent preventive treatment for malaria in infants.The Cochrane database of systematic reviews · 2019Pooled it
- Impact of Plasmodium falciparum malaria and intermittent preventive treatment of malaria in pregnancy on the risk of malaria in infants: a systematic review.Malaria journal · 2019Pooled it
- Dihydroartemisinin-piperaquine effectiveness for seasonal malaria chemoprevention in settings with extended seasonal malaria transmission in Tanzania.Scientific reports · 2024Trial
- Interplay among malnutrition, chemoprevention, and the risk of malaria in young Ugandan children: Longitudinal pharmacodynamic and growth analysis.CPT: pharmacometrics & systems pharmacology · 2023Trial
- Trial
- Intermittent preventive treatment with dihydroartemisinin-piperaquine and risk of malaria following cessation in young Ugandan children: a double-blind, randomised, controlled trial.The Lancet. Infectious diseases · 2019Trial
- Optimal dosing of dihydroartemisinin-piperaquine for seasonal malaria chemoprevention in young children.Nature communications · 2019Trial
- Dihydroartemisinin-piperaquine for intermittent preventive treatment of malaria during pregnancy and risk of malaria in early childhood: A randomized controlled trial.PLoS medicine · 2018Trial
- Effective Antimalarial Chemoprevention in Childhood Enhances the Quality of CD4+ T Cells and Limits Their Production of Immunoregulatory Interleukin 10.The Journal of infectious diseases · 2016Trial
- Frequent Malaria Drives Progressive Vδ2 T-Cell Loss, Dysfunction, and CD16 Up-regulation During Early Childhood.The Journal of infectious diseases · 2016Trial
- Impact of Dolutegravir-, Lopinavir/Ritonavir-, and Efavirenz-Based Antiretrovirals on Piperaquine Pharmacokinetics in Ugandan Children Living with HIV.Clinical pharmacology and therapeutics · 2026Article
- Agent-based simulation of seasonal malaria chemoprevention strategy in Southern Tanzania: comparing dihydroartemisinin-piperaquine with or without primaquine.Malaria journal · 2026Article
- Impact of population based indoor residual spraying in combination with mass drug administration on malaria incidence and test positivity in a high transmission setting in north eastern Uganda.Malaria journal · 2023Article
- Reduced Exposure to Piperaquine, Compared to Adults, in Young Children Receiving Dihydroartemisinin-Piperaquine as Malaria Chemoprevention.Clinical pharmacology and therapeutics · 2019Article
- Sickle Cell Disease Clinical Trials and Phenotypes.Journal of tropical diseases & public health · 2018Article
- Sickle Cell Disease.The New England journal of medicine · 2017Article
- Rethinking Dosing Regimen Selection of Piperaquine for Malaria Chemoprevention: A Simulation Study.PloS one · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
Abstract
backgroundAnti-malarial chemoprevention with dihydroartemisinin-piperaquine (DHA/PQ) is a promising tool for malaria control, but its efficacy in children may be limited by inadequate drug exposure.
methodsChildren were enrolled in a non directly-observed trial of DHA/PQ chemoprevention in a high transmission setting in Uganda. Children were randomized at 6 months of age to no chemoprevention (n = 89) or monthly DHA/PQ (n = 87) and followed through 24 months of age, with pharmacokinetic sampling performed at variable times following monthly dosing of DHA/PQ. A previously published pharmacokinetic model was used to estimate piperaquine (PQ) exposure in each child, and associations between PQ exposure and the protective efficacy (PE) of DHA/PQ were explored.
resultsThe incidence of malaria was 6.83 and 3.09 episodes per person year at risk in the no chemoprevention and DHA/PQ arms, respectively (PE 54 %, 95 % CI 39-66 %, P < 0.001). Among children randomized to DHA/PQ, 493 pharmacokinetic samples were collected. Despite nearly 100 % reported adherence to study drug administration at home, there was wide variability in PQ exposure, and children were stratified into three groups based on average PQ exposure during the intervention that was determined by model generated percentiles (low, n = 40; medium, n = 37, and high, n = 10). Gender and socioeconomic factors were not significantly associated with PQ exposure. In multivariate models, the PE of DHA/PQ was 31 % in the low PQ exposure group (95 % CI 6-49 %, P = 0.02), 67 % in the medium PQ exposure group (95 % CI 54-76 %, P < 0.001), and 97 % in the high PQ exposure group (95 % CI 89-99 %, P < 0.001).
conclusionsThe protective efficacy of DHA/PQ chemoprevention in young children was strongly associated with higher drug exposure; in children with the highest PQ exposure, monthly DHA/PQ chemoprevention was nearly 100 % protective against malaria. Strategies to ensure good adherence to monthly dosing and optimize drug exposure are critical to maximize the efficacy of this promising malaria control strategy.
trial registrationCurrent Controlled Trials Identifier NCT00948896.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.