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

Simple item page
dc.contributor.authorDenoeud-Ndam, Lise
dc.contributor.authorDicko, Alassane
dc.contributor.authorBaudin, Elisabeth
dc.contributor.authorGuindo, Ousmane
dc.contributor.authorGrandesso, Francesco
dc.contributor.authorDiawara, Halimatou
dc.contributor.authorSissoko, Sibiri
dc.contributor.authorSanogo, Koualy
dc.contributor.authorTraoré, Seydou
dc.contributor.authorKeita, Sekouba
dc.contributor.authorBarry, Amadou
dc.contributor.authorde Smet, Martin
dc.contributor.authorLasry, Estrella
dc.contributor.authorSmit, Michiel
dc.contributor.authorWiesner, Lubbe
dc.contributor.authorBarnes, Karen I
dc.contributor.authorDjimde, Abdoulaye A
dc.contributor.authorGuerin, Philippe J
dc.contributor.authorGrais, Rebecca F
dc.contributor.authorDoumbo, Ogobara K
dc.contributor.authorEtard, Jean-François
dc.date.accessioned2016-10-25T09:39:52Z
dc.date.available2016-10-25T09:39:52Z
dc.date.issued2016-10-24
dc.date.updated2016-10-24T18:04:10Z
dc.description.abstractBackground: 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 < 0.0001). PCR-corrected ACPR was 100 % (95 % CI, 96.8–100 %) in SAM at both day 28 and 42, versus 98.8 % (96.4–99.7 %) at day 28 and 98.3 % (95.6–99.4 %) at day 42 in non-SAM (P = 0.236 and 0.168, respectively). Compared to younger children, children older than 21 months experienced more reinfections and SAM was associated with a greater risk of reinfection until day 28 (adjusted hazard ratio = 2.10 (1.04–4.22), P = 0.038). Day 7 lumefantrine concentrations were significantly lower in SAM than non-SAM (median 251 vs. 365 ng/mL, P = 0.049). 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.
dc.identifier.apacitationDenoeud-Ndam, L., Dicko, A., Baudin, E., Guindo, O., Grandesso, F., Diawara, H., ... Etard, J. (2016). 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. <i>BMC Medicine</i>, http://hdl.handle.net/11427/22286en_ZA
dc.identifier.chicagocitationDenoeud-Ndam, Lise, Alassane Dicko, Elisabeth Baudin, Ousmane Guindo, Francesco Grandesso, Halimatou Diawara, Sibiri Sissoko, et al "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." <i>BMC Medicine</i> (2016) http://hdl.handle.net/11427/22286en_ZA
dc.identifier.citationBMC Medicine. 2016 Oct 24;14(1):167
dc.identifier.issn1741-7015
dc.identifier.ris TY - Journal Article AU - Denoeud-Ndam, Lise AU - Dicko, Alassane AU - Baudin, Elisabeth AU - Guindo, Ousmane AU - Grandesso, Francesco AU - Diawara, Halimatou AU - Sissoko, Sibiri AU - Sanogo, Koualy AU - Traoré, Seydou AU - Keita, Sekouba AU - Barry, Amadou AU - de Smet, Martin AU - Lasry, Estrella AU - Smit, Michiel AU - Wiesner, Lubbe AU - Barnes, Karen I AU - Djimde, Abdoulaye A AU - Guerin, Philippe J AU - Grais, Rebecca F AU - Doumbo, Ogobara K AU - Etard, Jean-François AB - 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 < 0.0001). PCR-corrected ACPR was 100 % (95 % CI, 96.8–100 %) in SAM at both day 28 and 42, versus 98.8 % (96.4–99.7 %) at day 28 and 98.3 % (95.6–99.4 %) at day 42 in non-SAM (P = 0.236 and 0.168, respectively). Compared to younger children, children older than 21 months experienced more reinfections and SAM was associated with a greater risk of reinfection until day 28 (adjusted hazard ratio = 2.10 (1.04–4.22), P = 0.038). Day 7 lumefantrine concentrations were significantly lower in SAM than non-SAM (median 251 vs. 365 ng/mL, P = 0.049). 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. DA - 2016-10-24 DB - OpenUCT DO - 10.1186/s12916-016-0716-1 DP - University of Cape Town J1 - BMC Medicine LK - https://open.uct.ac.za PB - University of Cape Town PY - 2016 SM - 1741-7015 T1 - 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 TI - 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 UR - http://hdl.handle.net/11427/22286 ER - en_ZA
dc.identifier.urihttp://dx.doi.org/10.1186/s12916-016-0716-1
dc.identifier.urihttp://hdl.handle.net/11427/22286
dc.identifier.vancouvercitationDenoeud-Ndam L, Dicko A, Baudin E, Guindo O, Grandesso F, Diawara H, et al. 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. BMC Medicine. 2016; http://hdl.handle.net/11427/22286.en_ZA
dc.language.rfc3066en
dc.publisherBioMed Central
dc.publisher.departmentDivision of Clinical Pharmacologyen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsCreative Commons Attribution 4.0 International License
dc.rights.holderThe Author(s).
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.sourceBMC Medicine
dc.source.urihttp://bmcmedicine.biomedcentral.com/
dc.subject.otherPlasmodium falciparum malaria
dc.subject.otherSevere acute malnutrition
dc.subject.otherArtemether-lumefantrine
dc.subject.otherTreatment outcome
dc.subject.otherPharmacokinetics
dc.subject.otherNiger
dc.subject.otherMali
dc.titleEfficacy 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
dc.typeJournal Article
uct.type.filetypeText
uct.type.filetypeImage
uct.type.resourceResearchen_ZA
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
Denoeud-Ndam_Article_2016.pdf
Size:
879.71 KB
Format:
Adobe Portable Document Format
Description:
Download
License bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
license.txt
Size:
1.72 KB
Format:
Item-specific license agreed upon to submission
Description:
Download
Collections
Journal Articles