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dc.contributor.author
WWARN Gametocyte Study Group
dc.contributor.author
Abdulla, Salim
dc.contributor.author
Taylor, Walter R.
dc.contributor.author
et al.
dc.date.accessioned
2019-06-27T15:53:59Z
dc.date.available
2017-06-12T07:00:55Z
dc.date.available
2019-06-27T15:53:59Z
dc.date.issued
2016
dc.identifier.issn
1741-7015
dc.identifier.other
10.1186/s12916-016-0621-7
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/117101
dc.identifier.doi
10.3929/ethz-b-000117101
dc.description.abstract
Background Gametocytes are responsible for transmission of malaria from human to mosquito. Artemisinin combination therapy (ACT) reduces post-treatment gametocyte carriage, dependent upon host, parasite and pharmacodynamic factors. The gametocytocidal properties of antimalarial drugs are important for malaria elimination efforts. An individual patient clinical data meta-analysis was undertaken to identify the determinants of gametocyte carriage and the comparative effects of four ACTs: artemether-lumefantrine (AL), artesunate/amodiaquine (AS-AQ), artesunate/mefloquine (AS-MQ), and dihydroartemisinin-piperaquine (DP). Methods Factors associated with gametocytaemia prior to, and following, ACT treatment were identified in multivariable logistic or Cox regression analysis with random effects. All relevant studies were identified through a systematic review of PubMed. Risk of bias was evaluated based on study design, methodology, and missing data. Results The systematic review identified 169 published and 9 unpublished studies, 126 of which were shared with the WorldWide Antimalarial Resistance Network (WWARN) and 121 trials including 48,840 patients were included in the analysis. Prevalence of gametocytaemia by microscopy at enrolment was 12.1 % (5887/48,589), and increased with decreasing age, decreasing asexual parasite density and decreasing haemoglobin concentration, and was higher in patients without fever at presentation. After ACT treatment, gametocytaemia appeared in 1.9 % (95 % CI, 1.7–2.1) of patients. The appearance of gametocytaemia was lowest after AS-MQ and AL and significantly higher after DP (adjusted hazard ratio (AHR), 2.03; 95 % CI, 1.24–3.12; P = 0.005 compared to AL) and AS-AQ fixed dose combination (FDC) (AHR, 4.01; 95 % CI, 2.40–6.72; P < 0.001 compared to AL). Among individuals who had gametocytaemia before treatment, gametocytaemia clearance was significantly faster with AS-MQ (AHR, 1.26; 95 % CI, 1.00–1.60; P = 0.054) and slower with DP (AHR, 0.74; 95 % CI, 0.63–0.88; P = 0.001) compared to AL. Both recrudescent (adjusted odds ratio (AOR), 9.05; 95 % CI, 3.74–21.90; P < 0.001) and new (AOR, 3.03; 95 % CI, 1.66–5.54; P < 0.001) infections with asexual-stage parasites were strongly associated with development of gametocytaemia after day 7. Conclusions AS-MQ and AL are more effective than DP and AS-AQ FDC in preventing gametocytaemia shortly after treatment, suggesting that the non-artemisinin partner drug or the timing of artemisinin dosing are important determinants of post-treatment gametocyte dynamics.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
BioMed Central
en_US
dc.rights.uri
http://creativecommons.org/licenses/by/4.0/
dc.subject
Drug resistance
en_US
dc.subject
Gametocyte
en_US
dc.subject
Malaria
en_US
dc.subject
Plasmodium falciparum
en_US
dc.title
Gametocyte carriage in uncomplicated Plasmodium falciparum malaria following treatment with artemisinin combination therapy: A systematic review and meta-analysis of individual patient data
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 4.0 International
dc.date.published
2016-05-24
ethz.journal.title
BMC Medicine
ethz.journal.volume
14
en_US
ethz.journal.abbreviated
BMC med.
ethz.pages.start
79
en_US
ethz.size
18 p.
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.wos
ethz.identifier.scopus
ethz.identifier.nebis
004717944
ethz.publication.place
London
en_US
ethz.publication.status
published
en_US
ethz.date.deposited
2017-06-12T07:02:10Z
ethz.source
ECIT
ethz.identifier.importid
imp593654723de9594577
ethz.ecitpid
pub:178999
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2017-07-26T22:04:14Z
ethz.rosetta.lastUpdated
2019-06-27T15:54:08Z
ethz.rosetta.versionExported
true
ethz.COinS
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