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Plasmodium falciparum gametocyte dynamics after pyronaridine–artesunate or artemether–lumefantrine treatment

BACKGROUND: Artemisinin-based combinations differ in their impact on gametocyte prevalence and density. This study assessed female and male gametocyte dynamics after treating children with uncomplicated Plasmodium falciparum malaria with either pyronaridine–artesunate (PA) or artemether–lumefantrine...

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Autores principales: Roth, Johanna M., Sawa, Patrick, Omweri, George, Osoti, Victor, Makio, Nicodemus, Bradley, John, Bousema, Teun, Schallig, Henk D. F. H., Mens, Pètra F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5987563/
https://www.ncbi.nlm.nih.gov/pubmed/29866116
http://dx.doi.org/10.1186/s12936-018-2373-7
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author Roth, Johanna M.
Sawa, Patrick
Omweri, George
Osoti, Victor
Makio, Nicodemus
Bradley, John
Bousema, Teun
Schallig, Henk D. F. H.
Mens, Pètra F.
author_facet Roth, Johanna M.
Sawa, Patrick
Omweri, George
Osoti, Victor
Makio, Nicodemus
Bradley, John
Bousema, Teun
Schallig, Henk D. F. H.
Mens, Pètra F.
author_sort Roth, Johanna M.
collection PubMed
description BACKGROUND: Artemisinin-based combinations differ in their impact on gametocyte prevalence and density. This study assessed female and male gametocyte dynamics after treating children with uncomplicated Plasmodium falciparum malaria with either pyronaridine–artesunate (PA) or artemether–lumefantrine (AL). METHODS: Kenyan children with uncomplicated Plasmodium falciparum malaria were included and randomly assigned to PA or AL treatment. Filter paper blood samples were collected as a source of RNA for quantitative reverse-transcription PCR (qRT-PCR) and nucleic acid sequence based amplification (QT-NASBA) to detect female gametocytes (targeting Pfs25 mRNA). Male gametocytes were detected by qRT-PCR (targeting PfMGET mRNA). Duration of gametocyte carriage, the female and male gametocyte response and the agreement between qRT-PCR and QT-NASBA were determined. RESULTS: The mean duration of female gametocyte carriage was significantly longer for PA (4.9 days) than for AL (3.8 days) as estimated by QT-NASBA (P = 0.036), but this difference was less clear when determined by Pfs25 qRT-PCR (4.5 days for PA and 3.7 for AL, P = 0.166). qRT-PCR based female gametocyte prevalence decreased from 100% (75/75) at baseline to 6.06% (4/66) at day 14 in the AL group and from 97.7% (83/85) to 13.9% (11/79) in the PA group. Male gametocyte prevalence decreased from 41.3% (31/75) at baseline to 19.7% (13/66) at day 14 in the AL group and from 35.3% (30/85) to 22.8% (18/79) in the PA group. There was good agreement between Pfs25 qRT-PCR and QT-NASBA female gametocyte prevalence (0.85, 95% CI 0.82–0.87). CONCLUSIONS: This study indicates that female gametocyte clearance may be slightly faster after AL compared to PA. Male gametocytes showed similar post-treatment clearance between study arms. Future studies should further address potential differences between the post-treatment transmission potential after PA compared to AL. Trial registration This study is registered at clinicaltrials.gov under NCT02411994. Registration date: 8 April 2015. https://clinicaltrials.gov/ct2/show/NCT02411994?term=pyronaridine-artesunate&cond=Malaria&cntry=KE&rank=1 ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12936-018-2373-7) contains supplementary material, which is available to authorized users.
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spelling pubmed-59875632018-07-10 Plasmodium falciparum gametocyte dynamics after pyronaridine–artesunate or artemether–lumefantrine treatment Roth, Johanna M. Sawa, Patrick Omweri, George Osoti, Victor Makio, Nicodemus Bradley, John Bousema, Teun Schallig, Henk D. F. H. Mens, Pètra F. Malar J Research BACKGROUND: Artemisinin-based combinations differ in their impact on gametocyte prevalence and density. This study assessed female and male gametocyte dynamics after treating children with uncomplicated Plasmodium falciparum malaria with either pyronaridine–artesunate (PA) or artemether–lumefantrine (AL). METHODS: Kenyan children with uncomplicated Plasmodium falciparum malaria were included and randomly assigned to PA or AL treatment. Filter paper blood samples were collected as a source of RNA for quantitative reverse-transcription PCR (qRT-PCR) and nucleic acid sequence based amplification (QT-NASBA) to detect female gametocytes (targeting Pfs25 mRNA). Male gametocytes were detected by qRT-PCR (targeting PfMGET mRNA). Duration of gametocyte carriage, the female and male gametocyte response and the agreement between qRT-PCR and QT-NASBA were determined. RESULTS: The mean duration of female gametocyte carriage was significantly longer for PA (4.9 days) than for AL (3.8 days) as estimated by QT-NASBA (P = 0.036), but this difference was less clear when determined by Pfs25 qRT-PCR (4.5 days for PA and 3.7 for AL, P = 0.166). qRT-PCR based female gametocyte prevalence decreased from 100% (75/75) at baseline to 6.06% (4/66) at day 14 in the AL group and from 97.7% (83/85) to 13.9% (11/79) in the PA group. Male gametocyte prevalence decreased from 41.3% (31/75) at baseline to 19.7% (13/66) at day 14 in the AL group and from 35.3% (30/85) to 22.8% (18/79) in the PA group. There was good agreement between Pfs25 qRT-PCR and QT-NASBA female gametocyte prevalence (0.85, 95% CI 0.82–0.87). CONCLUSIONS: This study indicates that female gametocyte clearance may be slightly faster after AL compared to PA. Male gametocytes showed similar post-treatment clearance between study arms. Future studies should further address potential differences between the post-treatment transmission potential after PA compared to AL. Trial registration This study is registered at clinicaltrials.gov under NCT02411994. Registration date: 8 April 2015. https://clinicaltrials.gov/ct2/show/NCT02411994?term=pyronaridine-artesunate&cond=Malaria&cntry=KE&rank=1 ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12936-018-2373-7) contains supplementary material, which is available to authorized users. BioMed Central 2018-06-04 /pmc/articles/PMC5987563/ /pubmed/29866116 http://dx.doi.org/10.1186/s12936-018-2373-7 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
Roth, Johanna M.
Sawa, Patrick
Omweri, George
Osoti, Victor
Makio, Nicodemus
Bradley, John
Bousema, Teun
Schallig, Henk D. F. H.
Mens, Pètra F.
Plasmodium falciparum gametocyte dynamics after pyronaridine–artesunate or artemether–lumefantrine treatment
title Plasmodium falciparum gametocyte dynamics after pyronaridine–artesunate or artemether–lumefantrine treatment
title_full Plasmodium falciparum gametocyte dynamics after pyronaridine–artesunate or artemether–lumefantrine treatment
title_fullStr Plasmodium falciparum gametocyte dynamics after pyronaridine–artesunate or artemether–lumefantrine treatment
title_full_unstemmed Plasmodium falciparum gametocyte dynamics after pyronaridine–artesunate or artemether–lumefantrine treatment
title_short Plasmodium falciparum gametocyte dynamics after pyronaridine–artesunate or artemether–lumefantrine treatment
title_sort plasmodium falciparum gametocyte dynamics after pyronaridine–artesunate or artemether–lumefantrine treatment
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5987563/
https://www.ncbi.nlm.nih.gov/pubmed/29866116
http://dx.doi.org/10.1186/s12936-018-2373-7
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