Supervised versus unsupervised antimalarial treatment with six-dose artemether-lumefantrine: pharmacokinetic and dosage-related findings from a clinical trial in Uganda

Francesco Checchi; Patrice Piola; Carole Fogg; Francis Bajunirwe; Samuel Biraro; Francesco Grandesso; Eugene Ruzagira; Joseph Babigumira; Isaac Kigozi; James Kiguli; Juliet Kyomuhendo; Laurent Ferradini; Walter R. J. Taylor; Jean-Paul Guthmann

doi:10.1186/1475-2875-5-59

Supervised versus unsupervised antimalarial treatment with six-dose artemether-lumefantrine: pharmacokinetic and dosage-related findings from a clinical trial in Uganda

Francesco Checchi, Patrice Piola, Carole Fogg, Francis Bajunirwe, Samuel Biraro, Francesco Grandesso, Eugene Ruzagira, Joseph Babigumira, Isaac Kigozi, James Kiguli, Juliet Kyomuhendo, Laurent Ferradini, Walter R. J. Taylor, Jean-Paul Guthmann

Research output: Contribution to journal › Article › peer-review

109 Downloads (Pure)

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.

Original language	English
Journal	Malaria Journal
Volume	5
Issue number	59
Early online date	19 Jul 2006
DOIs	https://doi.org/10.1186/1475-2875-5-59
Publication status	Published - Jul 2006

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1186/1475-2875-5-59

1475-2875-5-59.pdfFinal published version, 254 KB

Cite this

Checchi, F., Piola, P., Fogg, C., Bajunirwe, F., Biraro, S., Grandesso, F., Ruzagira, E., Babigumira, J., Kigozi, I., Kiguli, J., Kyomuhendo, J., Ferradini, L., Taylor, W. R. J., & Guthmann, J.-P. (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). https://doi.org/10.1186/1475-2875-5-59

@article{3ac3b05b36ba4755aaae369d717165fc,

title = "Supervised versus unsupervised antimalarial treatment with six-dose artemether-lumefantrine: pharmacokinetic and dosage-related findings from a clinical trial in Uganda",

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.",

author = "Francesco Checchi and Patrice Piola and Carole Fogg and Francis Bajunirwe and Samuel Biraro and Francesco Grandesso and Eugene Ruzagira and Joseph Babigumira and Isaac Kigozi and James Kiguli and Juliet Kyomuhendo and Laurent Ferradini and Taylor, {Walter R. J.} and Jean-Paul Guthmann",

note = "BioMed Central license agreement In submitting an article to any of the journals published by BioMed Central I certify that: 1. I am authorized by my co-authors to enter into these arrangements. 2. I warrant, on behalf of myself and my co-authors, that: the article is original, has not been formally published in any other peer-reviewed journal, is not under consideration by any other journal and does not infringe any existing copyright or any other third party rights; I am/we are the sole author(s) of the article and have full authority to enter into this agreement and in granting rights to BioMed Central are not in breach of any other obligation. the article contains nothing that is unlawful, libellous, or which would, if published, constitute a breach of contract or of confidence or of commitment given to secrecy; I/we have taken due care to ensure the integrity of the article. To my/our - and currently accepted scientific - knowledge all statements contained in it purporting to be facts are true and any formula or instruction contained in the article will not, if followed accurately, cause any injury, illness or damage to the user. I agree to BioMed Central's Open Data policy 3. I, and all authors, agree that the article, if editorially accepted for publication, shall be licensed under the Creative Commons Attribution License 4.0. If the law requires that the article be published in the public domain, I/we will notify BioMed Central at the time of submission upon which the article shall be released under the Creative Commons 1.0 Public Domain Dedication waiver. For the avoidance of doubt it is stated that sections 1 and 2 of this license agreement shall apply and prevail regardless of whether the article is published under Creative Commons Attribution License 4.0 or the Creative Commons 1.0 Public Domain Dedication waiver.",

year = "2006",

month = jul,

doi = "10.1186/1475-2875-5-59",

language = "English",

volume = "5",

journal = "Malaria Journal",

issn = "1475-2875",

publisher = "BioMed Central",

number = "59",

}

Checchi, F, Piola, P, Fogg, C, Bajunirwe, F, Biraro, S, Grandesso, F, Ruzagira, E, Babigumira, J, Kigozi, I, Kiguli, J, Kyomuhendo, J, Ferradini, L, Taylor, WRJ & Guthmann, J-P 2006, 'Supervised versus unsupervised antimalarial treatment with six-dose artemether-lumefantrine: pharmacokinetic and dosage-related findings from a clinical trial in Uganda', Malaria Journal, vol. 5, no. 59. https://doi.org/10.1186/1475-2875-5-59

TY - JOUR

T1 - Supervised versus unsupervised antimalarial treatment with six-dose artemether-lumefantrine

T2 - pharmacokinetic and dosage-related findings from a clinical trial in Uganda

AU - Checchi, Francesco

AU - Piola, Patrice

AU - Fogg, Carole

AU - Bajunirwe, Francis

AU - Biraro, Samuel

AU - Grandesso, Francesco

AU - Ruzagira, Eugene

AU - Babigumira, Joseph

AU - Kigozi, Isaac

AU - Kiguli, James

AU - Kyomuhendo, Juliet

AU - Ferradini, Laurent

AU - Taylor, Walter R. J.

AU - Guthmann, Jean-Paul

N1 - BioMed Central license agreement In submitting an article to any of the journals published by BioMed Central I certify that: 1. I am authorized by my co-authors to enter into these arrangements. 2. I warrant, on behalf of myself and my co-authors, that: the article is original, has not been formally published in any other peer-reviewed journal, is not under consideration by any other journal and does not infringe any existing copyright or any other third party rights; I am/we are the sole author(s) of the article and have full authority to enter into this agreement and in granting rights to BioMed Central are not in breach of any other obligation. the article contains nothing that is unlawful, libellous, or which would, if published, constitute a breach of contract or of confidence or of commitment given to secrecy; I/we have taken due care to ensure the integrity of the article. To my/our - and currently accepted scientific - knowledge all statements contained in it purporting to be facts are true and any formula or instruction contained in the article will not, if followed accurately, cause any injury, illness or damage to the user. I agree to BioMed Central's Open Data policy 3. I, and all authors, agree that the article, if editorially accepted for publication, shall be licensed under the Creative Commons Attribution License 4.0. If the law requires that the article be published in the public domain, I/we will notify BioMed Central at the time of submission upon which the article shall be released under the Creative Commons 1.0 Public Domain Dedication waiver. For the avoidance of doubt it is stated that sections 1 and 2 of this license agreement shall apply and prevail regardless of whether the article is published under Creative Commons Attribution License 4.0 or the Creative Commons 1.0 Public Domain Dedication waiver.

PY - 2006/7

Y1 - 2006/7

N2 - 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.

AB - 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.

U2 - 10.1186/1475-2875-5-59

DO - 10.1186/1475-2875-5-59

M3 - Article

SN - 1475-2875

VL - 5

JO - Malaria Journal

JF - Malaria Journal

IS - 59

ER -

Supervised versus unsupervised antimalarial treatment with six-dose artemether-lumefantrine: pharmacokinetic and dosage-related findings from a clinical trial in Uganda

Abstract

UN SDGs

Access to Document

Fingerprint

Cite this