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Dihydroartemisinin-Piperaquine as Chemoprevention for Uncomplicated Malaria in Young Ugandan Children: an Adherence and Pharmacodynamic Analysis
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. University of California San Francisco. (Margareta Hammarlund-Udenaes)
2014 (English)Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
Abstract [en]

Introduction: The majority of the malaria related deaths occurs in young African children. When the promising antimalarial dihydroartemisinin-piperaquine (DHA-PQ) was administered with a directly observed therapy (DOT) as chemoprevention to healthy adults in Thailand, DHA-PQ reviled a protective efficacy (PE) of 98% when compared to a no chemoprevention arm. However, in a recently published study of DHA-PQ given to 98 young African children in Uganda without DOT, the PE was only 56%, which was much lower than expected and suggests a less than optimal adherence. Aim: To estimate an average adherence score per child and investigate whether adherence was predictive of the risk for uncomplicated malaria in the Tororo cohort of children. Materials and Methods: Based on observed PQ concentrations collected at random times during the Tororo trial between 2010 and 2012, pharmacokinetic profiles of PQ with variability were simulated using a previously described pharmacometric population model for the same drug and drug regimen given to Thai children. An adherence score was assigned to each of the collected pharmacokinetic measurements. Results: When the PE was reanalysed, this time stratified by 4 adherence quartiles generated from the average adherence scores per child, the greatest PE (88%, 95% CI, 0.07%-0.21%, p<0.001) was calculated for the most adherent quartile. Conclusions:  Despite the fact that several assumptions had to be made in order to accomplish this analysis, this report presents a method to retrospectively measure the impact of adherence on the overall effect of DHA-PQ in the completed Tororo trial, something that this trial was not designed to measure initially. This new adherence info sheds new light on the effectiveness of DHA-PQ for this paediatric population. 

Place, publisher, year, edition, pages
2014. , 23 p.
Keyword [en]
Malaria, Chemoprevention, Children, Dihydroartemisinin-Piperaquine
National Category
Other Medical Sciences not elsewhere specified
URN: urn:nbn:se:uu:diva-241997OAI: oai:DiVA.org:uu-241997DiVA: diva2:782023
Subject / course
Educational program
Master of Science Programme in Pharmacy
Available from: 2015-01-21 Created: 2015-01-19 Last updated: 2015-01-21Bibliographically approved

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