Supervised versus unsupervised antimalarial treatment with six-dose artemether-lumefantrine: pharmacokinetic and dosage-related findings from a clinical trial in Uganda
Supervised versus unsupervised antimalarial treatment with six-dose artemether-lumefantrine: pharmacokinetic and dosage-related findings from a clinical trial in Uganda
Background: A six-dose antimalarial regimen of artemether-lumefantrine (A/L) may soon become one of the most widely used drug combination in Africa, despite possible constraints with adherence and poor absorption due to inadequate nutrition, and a lack of pharmacokinetic and effectiveness data.Methods: Within a trial of supervised versus unsupervised A/L treatment in a stable Ugandan Plasmodium falciparum transmission setting, plasma lumefantrine concentrations were measured in a subset of patients on day 3 (C [lum]day3) and day 7 (C [lum]day7) post-inclusion. Predictors of lumefantrine concentrations were analysed to show how both C [lum]day7 and the weight-adjusted lumefantrine dose affect 28-day recrudescence and re-infection risks. The implications of these novel findings are discussed in terms of the emergence of lumefantrine-resistant strains in Africa.Results: C [lum]day3 and C [lum]day7 distributions among 241 supervised and 238 unsupervised patients were positively skewed. Unsupervised treatment and decreasing weight-adjusted lumefantrine dose were negatively associated with C [lum]day3. Unsupervised treatment and decreasing age showed strong negative associations with C [lum]day7. Both models were poorly predictive (R-squared <0.25). There were no recrudescences in either arm, but decreasing lumefantrine dose per Kg resulted in up to 13-fold higher adjusted risks of re-infection. Re-infections occurred only among patients with C [lum]day7 below 400 ng/mL (p <0.001).Conclusion: Maintaining the present six-dose regimen and ensuring high adherence and intake are essential to maximize the public health benefits of this valuable drug combination.
1-8
Checchi, Francesco
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Piola, Patrice
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Fogg, Carole
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Bajunirwe, Francis
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Biraro, Samuel
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Grandesso, Francesco
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Ruzagira, Eugene
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Babigumira, Joseph
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Kigozi, Isaac
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Kiguli, James
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Kyomuhendo, Juliet
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Ferradini, Laurent
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Taylor, Walter R. J.
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Guthmann, Jean-Paul
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19 July 2006
Checchi, Francesco
e404c8bf-de19-4af1-b6c1-85c1ebee95e6
Piola, Patrice
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Fogg, Carole
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Bajunirwe, Francis
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Biraro, Samuel
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Grandesso, Francesco
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Ruzagira, Eugene
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Babigumira, Joseph
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Kigozi, Isaac
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Kiguli, James
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Kyomuhendo, Juliet
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Ferradini, Laurent
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Taylor, Walter R. J.
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Guthmann, Jean-Paul
ae239f74-b3b4-4f18-95fb-d5690d062d67
Checchi, Francesco, Piola, Patrice, Fogg, Carole, Bajunirwe, Francis, Biraro, Samuel, Grandesso, Francesco, Ruzagira, Eugene, Babigumira, Joseph, Kigozi, Isaac, Kiguli, James, Kyomuhendo, Juliet, Ferradini, Laurent, Taylor, Walter R. J. and Guthmann, Jean-Paul
(2006)
Supervised versus unsupervised antimalarial treatment with six-dose artemether-lumefantrine: pharmacokinetic and dosage-related findings from a clinical trial in Uganda.
Malaria Journal, 5 (59), .
(doi:10.1186/1475-2875-5-59).
Abstract
Background: A six-dose antimalarial regimen of artemether-lumefantrine (A/L) may soon become one of the most widely used drug combination in Africa, despite possible constraints with adherence and poor absorption due to inadequate nutrition, and a lack of pharmacokinetic and effectiveness data.Methods: Within a trial of supervised versus unsupervised A/L treatment in a stable Ugandan Plasmodium falciparum transmission setting, plasma lumefantrine concentrations were measured in a subset of patients on day 3 (C [lum]day3) and day 7 (C [lum]day7) post-inclusion. Predictors of lumefantrine concentrations were analysed to show how both C [lum]day7 and the weight-adjusted lumefantrine dose affect 28-day recrudescence and re-infection risks. The implications of these novel findings are discussed in terms of the emergence of lumefantrine-resistant strains in Africa.Results: C [lum]day3 and C [lum]day7 distributions among 241 supervised and 238 unsupervised patients were positively skewed. Unsupervised treatment and decreasing weight-adjusted lumefantrine dose were negatively associated with C [lum]day3. Unsupervised treatment and decreasing age showed strong negative associations with C [lum]day7. Both models were poorly predictive (R-squared <0.25). There were no recrudescences in either arm, but decreasing lumefantrine dose per Kg resulted in up to 13-fold higher adjusted risks of re-infection. Re-infections occurred only among patients with C [lum]day7 below 400 ng/mL (p <0.001).Conclusion: Maintaining the present six-dose regimen and ensuring high adherence and intake are essential to maximize the public health benefits of this valuable drug combination.
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1475-2875-5-59
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Accepted/In Press date: 19 July 2006
Published date: 19 July 2006
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Local EPrints ID: 436998
URI: http://eprints.soton.ac.uk/id/eprint/436998
ISSN: 1475-2875
PURE UUID: 5ad1b64e-fb6f-4430-b2cf-fdaa5ac7e478
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Date deposited: 14 Jan 2020 18:35
Last modified: 17 Mar 2024 03:56
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Author:
Francesco Checchi
Author:
Patrice Piola
Author:
Francis Bajunirwe
Author:
Samuel Biraro
Author:
Francesco Grandesso
Author:
Eugene Ruzagira
Author:
Joseph Babigumira
Author:
Isaac Kigozi
Author:
James Kiguli
Author:
Juliet Kyomuhendo
Author:
Laurent Ferradini
Author:
Walter R. J. Taylor
Author:
Jean-Paul Guthmann
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