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

Abstract 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–lume...

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Main Authors: Johanna M. Roth, Patrick Sawa, George Omweri, Victor Osoti, Nicodemus Makio, John Bradley, Teun Bousema, Henk D. F. H. Schallig, Pètra F. Mens
Format: Article
Language:English
Published: BMC 2018-06-01
Series:Malaria Journal
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Online Access:http://link.springer.com/article/10.1186/s12936-018-2373-7
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author Johanna M. Roth
Patrick Sawa
George Omweri
Victor Osoti
Nicodemus Makio
John Bradley
Teun Bousema
Henk D. F. H. Schallig
Pètra F. Mens
author_facet Johanna M. Roth
Patrick Sawa
George Omweri
Victor Osoti
Nicodemus Makio
John Bradley
Teun Bousema
Henk D. F. H. Schallig
Pètra F. Mens
author_sort Johanna M. Roth
collection DOAJ
description Abstract 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
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spelling doaj.art-e7b5dd92fde04f3b85817ca1b1a9e4a82022-12-22T01:48:29ZengBMCMalaria Journal1475-28752018-06-0117111110.1186/s12936-018-2373-7Plasmodium falciparum gametocyte dynamics after pyronaridine–artesunate or artemether–lumefantrine treatmentJohanna M. Roth0Patrick Sawa1George Omweri2Victor Osoti3Nicodemus Makio4John Bradley5Teun Bousema6Henk D. F. H. Schallig7Pètra F. Mens8Department of Medical Microbiology, Laboratory for Clinical Parasitology, Academic Medical CenterHuman Health Division, International Centre of Insect Physiology and EcologyHuman Health Division, International Centre of Insect Physiology and EcologyHuman Health Division, International Centre of Insect Physiology and EcologyHuman Health Division, International Centre of Insect Physiology and EcologyMedical Research Council Tropical Epidemiology Group, London School of Hygiene and Tropical MedicineRadboud Institute for Health Sciences, Radboud University Medical CenterDepartment of Medical Microbiology, Laboratory for Clinical Parasitology, Academic Medical CenterDepartment of Medical Microbiology, Laboratory for Clinical Parasitology, Academic Medical CenterAbstract 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=1http://link.springer.com/article/10.1186/s12936-018-2373-7Plasmodium falciparumGametocytesArtemether–lumefantrinePyronaridine–artesunate
spellingShingle Johanna M. Roth
Patrick Sawa
George Omweri
Victor Osoti
Nicodemus Makio
John Bradley
Teun Bousema
Henk D. F. H. Schallig
Pètra F. Mens
Plasmodium falciparum gametocyte dynamics after pyronaridine–artesunate or artemether–lumefantrine treatment
Malaria Journal
Plasmodium falciparum
Gametocytes
Artemether–lumefantrine
Pyronaridine–artesunate
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 Plasmodium falciparum
Gametocytes
Artemether–lumefantrine
Pyronaridine–artesunate
url http://link.springer.com/article/10.1186/s12936-018-2373-7
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