Efficacy and day 7 plasma piperaquine concentrations in African children treated for uncomplicated malaria with dihydroartemisinin-piperaquine
Background: One promising new Artemisinin-based combination therapies (ACTs) is dihydroartemisinin-piperaquine (DHA-PQ). However, the pharmacokinetics of piperaquine and the relationship between drug levels and clinical efficacy are incompletely characterized, particularly in children. Methods: We p...
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th-mahidol.329952018-11-09T08:51:03Z Efficacy and day 7 plasma piperaquine concentrations in African children treated for uncomplicated malaria with dihydroartemisinin-piperaquine Issaka Zongo Fabrice A. Somé Serge A.M. Somda Sunil Parikh Noel Rouamba Philip J. Rosenthal Joel Tarning Niklas Lindegardh François Nosten Jean Bosco Ouédraogo Bobo-Dioulasso Centre MURAZ Yale University University of California, San Francisco Mahidol University Nuffield Department of Clinical Medicine Agricultural and Biological Sciences Biochemistry, Genetics and Molecular Biology Background: One promising new Artemisinin-based combination therapies (ACTs) is dihydroartemisinin-piperaquine (DHA-PQ). However, the pharmacokinetics of piperaquine and the relationship between drug levels and clinical efficacy are incompletely characterized, particularly in children. Methods: We performed a single-arm open-label trial in Bobo-Dioulasso, Burkina Faso. A total of 379 participants aged 6 months or more with uncomplicated falciparum malaria were enrolled. Each participant received daily dose of DHA-PQ for three days and followed for 42 days. Parasitological efficacy was analyzed, considering rates of recrudescence and overall recurrence. PK was an exploratory endpoint and a priori, no sample size had been determined. Day 7 capillary and venous plasma concentrations of piperaquine were measured in children aged 2-10 years. Results: Of the 379 participants, 365 (96.3%) completed 42 days of follow-up. The median daily dose of PQ was 18.5 mg/kg [6.5-24]. Treatment with DHA-PQ was well tolerated with fever and parasitemia resolution within 48 hours in nearly all children. Recurrent malaria within 42 days of follow-up occurred in 31.3% (10/34) of children less than 2 years old, 16.0% (16/106) of those aged 2-5 years, 9.4% (15/160) of those aged 5-10 years, and none (0/68) of those over 10 years old. After genotyping, 3 of 41 recurrent episodes were recrudescence. An exploratory analysis shows that children with successful treatment outcomes had significantly higher median plasma concentrations of PQ compared to those with recurrent malaria within 42 days after therapy, considering either capillary samples (68 ng/ml [50-85] compared to 48 ng/ml [36-55], p<0.001) or venous samples (42 ng/ml [29-59] compared to 25 ng/ml [19-44], p<0.001). Conclusion: DHA-PQ was effective for uncomplicated P. falciparum malaria treatment and offers an alternative to other ACTs. Recurrent malaria was mainly due to new infections after treatment and was correlated with low day 7 PQ concentration in the youngest patients. Trial Registration: Controlled-Trials.com ISRCTN59761234 © 2014 Zongo et al. 2018-11-09T01:44:06Z 2018-11-09T01:44:06Z 2014-08-18 Article PLoS ONE. Vol.9, No.8 (2014) 10.1371/journal.pone.0103200 19326203 2-s2.0-84929138444 https://repository.li.mahidol.ac.th/handle/123456789/32995 Mahidol University SCOPUS https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84929138444&origin=inward |
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Agricultural and Biological Sciences Biochemistry, Genetics and Molecular Biology Issaka Zongo Fabrice A. Somé Serge A.M. Somda Sunil Parikh Noel Rouamba Philip J. Rosenthal Joel Tarning Niklas Lindegardh François Nosten Jean Bosco Ouédraogo Efficacy and day 7 plasma piperaquine concentrations in African children treated for uncomplicated malaria with dihydroartemisinin-piperaquine |
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Background: One promising new Artemisinin-based combination therapies (ACTs) is dihydroartemisinin-piperaquine (DHA-PQ). However, the pharmacokinetics of piperaquine and the relationship between drug levels and clinical efficacy are incompletely characterized, particularly in children. Methods: We performed a single-arm open-label trial in Bobo-Dioulasso, Burkina Faso. A total of 379 participants aged 6 months or more with uncomplicated falciparum malaria were enrolled. Each participant received daily dose of DHA-PQ for three days and followed for 42 days. Parasitological efficacy was analyzed, considering rates of recrudescence and overall recurrence. PK was an exploratory endpoint and a priori, no sample size had been determined. Day 7 capillary and venous plasma concentrations of piperaquine were measured in children aged 2-10 years. Results: Of the 379 participants, 365 (96.3%) completed 42 days of follow-up. The median daily dose of PQ was 18.5 mg/kg [6.5-24]. Treatment with DHA-PQ was well tolerated with fever and parasitemia resolution within 48 hours in nearly all children. Recurrent malaria within 42 days of follow-up occurred in 31.3% (10/34) of children less than 2 years old, 16.0% (16/106) of those aged 2-5 years, 9.4% (15/160) of those aged 5-10 years, and none (0/68) of those over 10 years old. After genotyping, 3 of 41 recurrent episodes were recrudescence. An exploratory analysis shows that children with successful treatment outcomes had significantly higher median plasma concentrations of PQ compared to those with recurrent malaria within 42 days after therapy, considering either capillary samples (68 ng/ml [50-85] compared to 48 ng/ml [36-55], p<0.001) or venous samples (42 ng/ml [29-59] compared to 25 ng/ml [19-44], p<0.001). Conclusion: DHA-PQ was effective for uncomplicated P. falciparum malaria treatment and offers an alternative to other ACTs. Recurrent malaria was mainly due to new infections after treatment and was correlated with low day 7 PQ concentration in the youngest patients. Trial Registration: Controlled-Trials.com ISRCTN59761234 © 2014 Zongo et al. |
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Bobo-Dioulasso |
author_facet |
Bobo-Dioulasso Issaka Zongo Fabrice A. Somé Serge A.M. Somda Sunil Parikh Noel Rouamba Philip J. Rosenthal Joel Tarning Niklas Lindegardh François Nosten Jean Bosco Ouédraogo |
format |
Article |
author |
Issaka Zongo Fabrice A. Somé Serge A.M. Somda Sunil Parikh Noel Rouamba Philip J. Rosenthal Joel Tarning Niklas Lindegardh François Nosten Jean Bosco Ouédraogo |
author_sort |
Issaka Zongo |
title |
Efficacy and day 7 plasma piperaquine concentrations in African children treated for uncomplicated malaria with dihydroartemisinin-piperaquine |
title_short |
Efficacy and day 7 plasma piperaquine concentrations in African children treated for uncomplicated malaria with dihydroartemisinin-piperaquine |
title_full |
Efficacy and day 7 plasma piperaquine concentrations in African children treated for uncomplicated malaria with dihydroartemisinin-piperaquine |
title_fullStr |
Efficacy and day 7 plasma piperaquine concentrations in African children treated for uncomplicated malaria with dihydroartemisinin-piperaquine |
title_full_unstemmed |
Efficacy and day 7 plasma piperaquine concentrations in African children treated for uncomplicated malaria with dihydroartemisinin-piperaquine |
title_sort |
efficacy and day 7 plasma piperaquine concentrations in african children treated for uncomplicated malaria with dihydroartemisinin-piperaquine |
publishDate |
2018 |
url |
https://repository.li.mahidol.ac.th/handle/123456789/32995 |
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1763488045117472768 |