Comparative Efficacy of Artemether-Lumefantrine and Dihydroartemisinin-Piperaquine for the Treatment of Uncomplicated Malaria in Ugandan Children.
Antimalarials
/ adverse effects
Artemether, Lumefantrine Drug Combination
/ adverse effects
Artemisinins
/ adverse effects
Child, Preschool
Comparative Effectiveness Research
Drug Combinations
Drug Resistance
/ genetics
Female
Genotype
Humans
Infant
Malaria, Falciparum
/ drug therapy
Male
Membrane Transport Proteins
/ genetics
Multidrug Resistance-Associated Proteins
/ genetics
Parasitemia
/ drug therapy
Plasmodium falciparum
/ genetics
Protozoan Proteins
/ genetics
Quinolines
/ adverse effects
Recurrence
Single-Blind Method
Uganda
Treatment efficacy
Uganda
artemether-lumefantrine
dihydroartemisinin-piperaquine
malaria
Journal
The Journal of infectious diseases
ISSN: 1537-6613
Titre abrégé: J Infect Dis
Pays: United States
ID NLM: 0413675
Informations de publication
Date de publication:
15 03 2019
15 03 2019
Historique:
received:
31
07
2018
accepted:
01
11
2018
pubmed:
13
11
2018
medline:
14
1
2020
entrez:
13
11
2018
Statut:
ppublish
Résumé
In Uganda, artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DHA-PQ) showed excellent treatment efficacy for uncomplicated malaria in prior trials. Because the frequency of resistance to artemisinins and piperaquine is increasing in Southeast Asia and the prevalence of Plasmodium falciparum polymorphisms associated with resistance has changed, we reassessed treatment efficacies at 3 sites in Uganda. For this randomized, single-blinded clinical trial, children aged 6-59 months with uncomplicated falciparum malaria were assigned treatment with AL or DHA-PQ and followed for 42 days. Primary end points were risks of recurrent parasitemia, either unadjusted or adjusted to distinguish recrudescence from new infection. We assessed selection by study regimens of relevant P. falciparum genetic polymorphisms associated with drug resistance. Of 599 patients enrolled, 578 completed follow-up. There were no early treatment failures. The risk of recurrent parasitemia was lower with DHA-PQ as compared to AL at all 3 sites at 42 days (26.0% vs 47.0%; P < .001). Recrudescent infections were uncommon in both the DHA-PQ and AL arms (1.1% and 2.2%, respectively; P = .25). Neither regimen selected for pfcrt or pfmdr1 polymorphisms associated with drug resistance. AL and DHA-PQ remain effective for the treatment of malaria in Uganda. Neither regimen selected for genetic polymorphisms associated with drug resistance. ISRCTN15793046.
Sections du résumé
BACKGROUND
In Uganda, artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DHA-PQ) showed excellent treatment efficacy for uncomplicated malaria in prior trials. Because the frequency of resistance to artemisinins and piperaquine is increasing in Southeast Asia and the prevalence of Plasmodium falciparum polymorphisms associated with resistance has changed, we reassessed treatment efficacies at 3 sites in Uganda.
METHODS
For this randomized, single-blinded clinical trial, children aged 6-59 months with uncomplicated falciparum malaria were assigned treatment with AL or DHA-PQ and followed for 42 days. Primary end points were risks of recurrent parasitemia, either unadjusted or adjusted to distinguish recrudescence from new infection. We assessed selection by study regimens of relevant P. falciparum genetic polymorphisms associated with drug resistance.
RESULTS
Of 599 patients enrolled, 578 completed follow-up. There were no early treatment failures. The risk of recurrent parasitemia was lower with DHA-PQ as compared to AL at all 3 sites at 42 days (26.0% vs 47.0%; P < .001). Recrudescent infections were uncommon in both the DHA-PQ and AL arms (1.1% and 2.2%, respectively; P = .25). Neither regimen selected for pfcrt or pfmdr1 polymorphisms associated with drug resistance.
CONCLUSIONS
AL and DHA-PQ remain effective for the treatment of malaria in Uganda. Neither regimen selected for genetic polymorphisms associated with drug resistance.
CLINICAL TRIALS REGISTRATION
ISRCTN15793046.
Identifiants
pubmed: 30418593
pii: 5174239
doi: 10.1093/infdis/jiy637
pmc: PMC7868963
doi:
Substances chimiques
Antimalarials
0
Artemether, Lumefantrine Drug Combination
0
Artemisinins
0
Drug Combinations
0
Mdr1 protein, Plasmodium falciparum
0
Membrane Transport Proteins
0
Multidrug Resistance-Associated Proteins
0
PfCRT protein, Plasmodium falciparum
0
Protozoan Proteins
0
Quinolines
0
artenimol
6A9O50735X
piperaquine
A0HV2Q956Y
Banques de données
ISRCTN
['ISRCTN15793046']
Types de publication
Comparative Study
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1112-1120Subventions
Organisme : NIAID NIH HHS
ID : R01 AI075045
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI089674
Pays : United States
Informations de copyright
© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.
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