Efficacy of artemether-lumefantrine in relation to drug exposure in children with and without severe acute malnutrition: an open comparative intervention study in Mali and Niger.

Denoeud-Ndam L Dicko A Baudin E Guindo O Grandesso F Diawara H Sissoko S Sanogo K Traoré S Keita S Barry A de Smet M Lasry E Smit M Wiesner L Barnes KI Djimde AA Guerin PJ Grais RF Doumbo OK Etard JF
BMC medicine 2016 10 24; 14(1); 167. doi: 10.1186/s12916-016-0716-1. Epub 2016 10 24
Artemether-lumefantrine Mali Niger Pharmacokinetics Plasmodium falciparum malaria Severe acute malnutrition Treatment outcome


BACKGROUND: Severe acute malnutrition (SAM) affects almost all organs and has been associated with reduced intestinal absorption of medicines. However, very limited information is available on the pharmacokinetic properties of antimalarial drugs in this vulnerable population. We assessed artemether-lumefantrine (AL) clinical efficacy in children with SAM compared to those without.

METHODS: Children under 5 years of age with uncomplicated P. falciparum malaria were enrolled between November 2013 and January 2015 in Mali and Niger, one third with uncomplicated SAM and two thirds without. AL was administered under direct observation with a fat intake consisting of ready-to-use therapeutic food (RUTF - Plumpy'Nut®) in SAM children, twice daily during 3 days. Children were followed for 42 days, with PCR-corrected adequate clinical and parasitological response (ACPR) at day 28 as the primary outcome. Lumefantrine concentrations were assessed in a subset of participants at different time points, including systematic measurements on day 7.

RESULTS: A total of 399 children (360 in Mali and 39 in Niger) were enrolled. Children with SAM were younger than their non-SAM counterparts (mean 17 vs. 28 months, P 

CONCLUSIONS: This study shows comparable therapeutic efficacy of AL in children without SAM and in those with SAM when given in combination with RUTF, but a higher risk of reinfection in older children suffering from SAM. This could be associated with poorer exposure to the antimalarials as documented by a lower lumefantrine concentration on day 7.

TRIAL REGISTRATION: ClinicalTrials.gov: NCT01958905 , registration date: October 7, 2013.