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

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dc.contributor	Epicentre, Paris, France. francesco.checchi@lshtm.ac.uk
dc.creator	Checchi, F
dc.creator	Piola, P
dc.creator	Fogg, C
dc.creator	Bajunirwe, F
dc.creator	Biraro, S
dc.creator	Grandesso, F
dc.creator	Ruzagira, E
dc.creator	Babigumira, J
dc.creator	Kigozi, I
dc.creator	Kiguli, J
dc.creator	Kyomuhendo, J
dc.creator	Ferradini, L
dc.creator	Taylor, W R J
dc.creator	Guthmann, J P
dc.date	2006
dc.date.accessioned	2017-01-31T07:10:10Z
dc.date.available	2017-01-31T07:10:10Z
dc.identifier	Supervised versus unsupervised antimalarial treatment with six-dose artemether-lumefantrine: pharmacokinetic and dosage-related findings from a clinical trial in Uganda. 2006, 5:59 Malar. J.
dc.identifier	1475-2875
dc.identifier	16854236
dc.identifier	10.1186/1475-2875-5-59
dc.identifier	http://hdl.handle.net/10144/18902
dc.identifier	http://fieldresearch.msf.org/msf/handle/10144/18902
dc.identifier	Malaria Journal
dc.identifier.uri	http://dspace.mediu.edu.my:8181/xmlui/handle/10144/18902
dc.description	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.
dc.language	en
dc.publisher	BioMed Central
dc.relation	http://www.malariajournal.com
dc.rights	Archived on this site by Open Access permission
dc.title	Supervised versus unsupervised antimalarial treatment with six-dose artemether-lumefantrine: pharmacokinetic and dosage-related findings from a clinical trial in Uganda.