Comparative Efficacy of Artemether-Lumefantrine and Dihydroartemisinin-Piperaquine for the Treatment of Uncomplicated Malaria in Ugandan Children.


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
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

1112-1120

Subventions

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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Auteurs

Adoke Yeka (A)

School of Public Health, Makerere University College of Health Sciences.

Erika Wallender (E)

Department of Medicine, University of California, San Francisco.

Ronald Mulebeke (R)

School of Public Health, Makerere University College of Health Sciences.

Afizi Kibuuka (A)

School of Public Health, Makerere University College of Health Sciences.

Ruth Kigozi (R)

Malaria Action Programme for Districts, Malaria Consortium.

Agaba Bosco (A)

National Malaria Control Program, Ministry of Health, Uganda.

Paul Kyambadde (P)

National Malaria Control Program, Ministry of Health, Uganda.

Jimmy Opigo (J)

National Malaria Control Program, Ministry of Health, Uganda.

Simeon Kalyesubula (S)

East African Public Health Laboratories Networking Project, Kampala, Uganda.

Joseph Senzoga (J)

East African Public Health Laboratories Networking Project, Kampala, Uganda.

Joanna Vinden (J)

School of Public Health, University of California, Berkeley.

Melissa Conrad (M)

Department of Medicine, University of California, San Francisco.

Philip J Rosenthal (PJ)

Department of Medicine, University of California, San Francisco.

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Classifications MeSH