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.7672023-03-30T10:40:04Z Efficacy and day 7 plasma piperaquine concentrations in African children treated for uncomplicated malaria with dihydroartemisinin-piperaquine. Zongo, Issaka Some, Fabrice A. Somda, Serge A. M. Parikh, Sunil Rouamba, Noel Rosenthal, Philip J. Tarning, Joel Lindegardh, Niklas Nosten, Franc¸ois Oue´draogo, Jean Bosco Oue´draogo, Jean Bosco Mahidol University. Faculty of Tropical Medicine. Mahidol-Oxford Tropical Medicine Research Unit. Mahidol University. Faculty of Tropical Medicine. Mahidol-Oxford Tropical Medicine Research Unit. Shoklo Malaria Research Unit. African children Concentrations Dihydroartemisinin-Piperaquine Malaria Plasma Open Access article 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. 2015-02-24T04:12:03Z 2016-10-05T07:03:08Z 2015-02-24T04:12:03Z 2016-10-05T07:03:08Z 2014 2015-02-20 2014-08-18 Article Zongo I, Somé FA, Somda SA, Parikh S, Rouamba N, Rosenthal PJ, et al. Efficacy and day 7 plasma piperaquine concentrations in African children treated for uncomplicated malaria with dihydroartemisinin-piperaquine. PLoS One. 2014 Aug 18;9(8):e103200. 10.1371/journal.pone.0103200 1932-6203 (electronic) https://repository.li.mahidol.ac.th/handle/123456789/767 eng Mahidol University PloS one application/pdf |
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African children Concentrations Dihydroartemisinin-Piperaquine Malaria Plasma Open Access article Zongo, Issaka Some, Fabrice A. Somda, Serge A. M. Parikh, Sunil Rouamba, Noel Rosenthal, Philip J. Tarning, Joel Lindegardh, Niklas Nosten, Franc¸ois Oue´draogo, Jean Bosco Efficacy and day 7 plasma piperaquine concentrations in African children treated for uncomplicated malaria with dihydroartemisinin-piperaquine. |
description |
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. |
author2 |
Oue´draogo, Jean Bosco |
author_facet |
Oue´draogo, Jean Bosco Zongo, Issaka Some, Fabrice A. Somda, Serge A. M. Parikh, Sunil Rouamba, Noel Rosenthal, Philip J. Tarning, Joel Lindegardh, Niklas Nosten, Franc¸ois Oue´draogo, Jean Bosco |
format |
Article |
author |
Zongo, Issaka Some, Fabrice A. Somda, Serge A. M. Parikh, Sunil Rouamba, Noel Rosenthal, Philip J. Tarning, Joel Lindegardh, Niklas Nosten, Franc¸ois Oue´draogo, Jean Bosco |
author_sort |
Zongo, Issaka |
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 |
2015 |
url |
https://repository.li.mahidol.ac.th/handle/123456789/767 |
_version_ |
1763492936914305024 |