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Efficacy of artemether–lumefantrine and dihydroartemisinin–piperaquine for the treatment of uncomplicated malaria in Papua New Guinea

BACKGROUND: In 2009, the Papua New Guinea (PNG) Department of Health adopted artemether–lumefantrine (AL) and dihydroartemisinin–piperaquine (DHA-PPQ) as the first- and second-line treatments for uncomplicated malaria, respectively. This study was conducted to assess the efficacy of both drugs follo...

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Autores principales: Tavul, Livingstone, Hetzel, Manuel W., Teliki, Albina, Walsh, Dorish, Kiniboro, Benson, Rare, Lawrence, Pulford, Justin, Siba, Peter M., Karl, Stephan, Makita, Leo, Robinson, Leanne, Kattenberg, Johanna H., Laman, Moses, Oswyn, Gilchrist, Mueller, Ivo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6173938/
https://www.ncbi.nlm.nih.gov/pubmed/30290825
http://dx.doi.org/10.1186/s12936-018-2494-z
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author Tavul, Livingstone
Hetzel, Manuel W.
Teliki, Albina
Walsh, Dorish
Kiniboro, Benson
Rare, Lawrence
Pulford, Justin
Siba, Peter M.
Karl, Stephan
Makita, Leo
Robinson, Leanne
Kattenberg, Johanna H.
Laman, Moses
Oswyn, Gilchrist
Mueller, Ivo
author_facet Tavul, Livingstone
Hetzel, Manuel W.
Teliki, Albina
Walsh, Dorish
Kiniboro, Benson
Rare, Lawrence
Pulford, Justin
Siba, Peter M.
Karl, Stephan
Makita, Leo
Robinson, Leanne
Kattenberg, Johanna H.
Laman, Moses
Oswyn, Gilchrist
Mueller, Ivo
author_sort Tavul, Livingstone
collection PubMed
description BACKGROUND: In 2009, the Papua New Guinea (PNG) Department of Health adopted artemether–lumefantrine (AL) and dihydroartemisinin–piperaquine (DHA-PPQ) as the first- and second-line treatments for uncomplicated malaria, respectively. This study was conducted to assess the efficacy of both drugs following adoption of the new policy. METHODS: Between June 2012 and September 2014, a therapeutic efficacy study was conducted in East Sepik and Milne Bay Provinces of PNG in accordance with the standard World Health Organization (WHO) protocol for surveillance of anti-malarial drug efficacy. Patients ≥ 6 months of age with microscopy confirmed Plasmodium falciparum or Plasmodium vivax mono-infections were enrolled, treated with AL or DHA-PPQ, and followed up for 42 days. Study endpoints were adequate clinical and parasitological response (ACPR) on days 28 and 42. The in vitro efficacy of anti-malarials and the prevalence of selected molecular markers of resistance were also determined. RESULTS: A total of 274 P. falciparum and 70 P. vivax cases were enrolled. The day-42 PCR-corrected ACPR for P. falciparum was 98.1% (104/106) for AL and 100% (135/135) for DHA-PPQ. The day-42 PCR-corrected ACPR for P. vivax was 79.0% (15/19) for AL and 92.3% (36/39) for DHA-PPQ. Day 3 parasite clearance of P. falciparum was 99.2% with AL and 100% with DHA-PPQ. In vitro testing of 96 samples revealed low susceptibility to chloroquine (34% of samples above IC(50) threshold) but not to lumefantrine (0%). Molecular markers assessed in a sub-set of the study population indicated high rates of chloroquine resistance in P. falciparum (pfcrt SVMNT: 94.2%, n = 104) and in P. vivax (pvmdr1 Y976F: 64.8%, n = 54). CONCLUSIONS: AL and DHA-PPQ were efficacious as first- and second-line treatments for uncomplicated malaria in PNG. Continued in vivo efficacy monitoring is warranted considering the threat of resistance to artemisinin and partner drugs in the region and scale-up of artemisinin-based combination therapy in PNG. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12936-018-2494-z) contains supplementary material, which is available to authorized users.
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spelling pubmed-61739382018-10-15 Efficacy of artemether–lumefantrine and dihydroartemisinin–piperaquine for the treatment of uncomplicated malaria in Papua New Guinea Tavul, Livingstone Hetzel, Manuel W. Teliki, Albina Walsh, Dorish Kiniboro, Benson Rare, Lawrence Pulford, Justin Siba, Peter M. Karl, Stephan Makita, Leo Robinson, Leanne Kattenberg, Johanna H. Laman, Moses Oswyn, Gilchrist Mueller, Ivo Malar J Research BACKGROUND: In 2009, the Papua New Guinea (PNG) Department of Health adopted artemether–lumefantrine (AL) and dihydroartemisinin–piperaquine (DHA-PPQ) as the first- and second-line treatments for uncomplicated malaria, respectively. This study was conducted to assess the efficacy of both drugs following adoption of the new policy. METHODS: Between June 2012 and September 2014, a therapeutic efficacy study was conducted in East Sepik and Milne Bay Provinces of PNG in accordance with the standard World Health Organization (WHO) protocol for surveillance of anti-malarial drug efficacy. Patients ≥ 6 months of age with microscopy confirmed Plasmodium falciparum or Plasmodium vivax mono-infections were enrolled, treated with AL or DHA-PPQ, and followed up for 42 days. Study endpoints were adequate clinical and parasitological response (ACPR) on days 28 and 42. The in vitro efficacy of anti-malarials and the prevalence of selected molecular markers of resistance were also determined. RESULTS: A total of 274 P. falciparum and 70 P. vivax cases were enrolled. The day-42 PCR-corrected ACPR for P. falciparum was 98.1% (104/106) for AL and 100% (135/135) for DHA-PPQ. The day-42 PCR-corrected ACPR for P. vivax was 79.0% (15/19) for AL and 92.3% (36/39) for DHA-PPQ. Day 3 parasite clearance of P. falciparum was 99.2% with AL and 100% with DHA-PPQ. In vitro testing of 96 samples revealed low susceptibility to chloroquine (34% of samples above IC(50) threshold) but not to lumefantrine (0%). Molecular markers assessed in a sub-set of the study population indicated high rates of chloroquine resistance in P. falciparum (pfcrt SVMNT: 94.2%, n = 104) and in P. vivax (pvmdr1 Y976F: 64.8%, n = 54). CONCLUSIONS: AL and DHA-PPQ were efficacious as first- and second-line treatments for uncomplicated malaria in PNG. Continued in vivo efficacy monitoring is warranted considering the threat of resistance to artemisinin and partner drugs in the region and scale-up of artemisinin-based combination therapy in PNG. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12936-018-2494-z) contains supplementary material, which is available to authorized users. BioMed Central 2018-10-05 /pmc/articles/PMC6173938/ /pubmed/30290825 http://dx.doi.org/10.1186/s12936-018-2494-z Text en © The Author(s) 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Tavul, Livingstone
Hetzel, Manuel W.
Teliki, Albina
Walsh, Dorish
Kiniboro, Benson
Rare, Lawrence
Pulford, Justin
Siba, Peter M.
Karl, Stephan
Makita, Leo
Robinson, Leanne
Kattenberg, Johanna H.
Laman, Moses
Oswyn, Gilchrist
Mueller, Ivo
Efficacy of artemether–lumefantrine and dihydroartemisinin–piperaquine for the treatment of uncomplicated malaria in Papua New Guinea
title Efficacy of artemether–lumefantrine and dihydroartemisinin–piperaquine for the treatment of uncomplicated malaria in Papua New Guinea
title_full Efficacy of artemether–lumefantrine and dihydroartemisinin–piperaquine for the treatment of uncomplicated malaria in Papua New Guinea
title_fullStr Efficacy of artemether–lumefantrine and dihydroartemisinin–piperaquine for the treatment of uncomplicated malaria in Papua New Guinea
title_full_unstemmed Efficacy of artemether–lumefantrine and dihydroartemisinin–piperaquine for the treatment of uncomplicated malaria in Papua New Guinea
title_short Efficacy of artemether–lumefantrine and dihydroartemisinin–piperaquine for the treatment of uncomplicated malaria in Papua New Guinea
title_sort efficacy of artemether–lumefantrine and dihydroartemisinin–piperaquine for the treatment of uncomplicated malaria in papua new guinea
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6173938/
https://www.ncbi.nlm.nih.gov/pubmed/30290825
http://dx.doi.org/10.1186/s12936-018-2494-z
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