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

• Published in: Malaria Journal
• Main Authors: Ruzagira Eugene, Grandesso Francesco, Biraro Samuel, Bajunirwe Francis, Fogg Carole, Piola Patrice, Checchi Francesco, Babigumira Joseph, Kigozi Isaac, Kiguli James, Kyomuhendo Juliet, Ferradini Laurent, Taylor Walter RJ, Guthmann Jean-Paul
• Format: Article in Journal/Newspaper
• Language: English
• Published: BMC 2006
• Subjects: Arctic medicine. Tropical medicine; RC955-962; Infectious and parasitic diseases; RC109-216; Arctic
• Online Access: https://doi.org/10.1186/1475-2875-5-59; https://doaj.org/article/93350b5783bb4facae0e7c63c839d20d

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.