The effect of dose on the antimalarial efficacy of artemether-lumefantrine: a systematic review and pooled analysis of individual patient data.
Details
Serval ID
serval:BIB_44E162F82DC6
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
The effect of dose on the antimalarial efficacy of artemether-lumefantrine: a systematic review and pooled analysis of individual patient data.
Journal
Lancet. Infectious Diseases
Working group(s)
Worldwide Antimalarial Resistance Network (WWARN) AL Dose Impact Study Group, Anstey NM;, Price RN;, Davis TME;, Karunajeewa HA;, Mueller I;, Karunajeewa HA;, D'Alessandro U;, Massougbodji A;, Nikiema F;, Ouedraogo JB;, Tinto H;, Zongo I;, Ouedraogo JB;, Tinto H;, Same-Ekobo A;, Kone M;, Menan H;, Toure AO;, Yavo W;, Yavo W;, Kofoed PE;, Alemayehu BH;, Jima D;, Baudin E;, Espie E;, Nabasumba C;, Pinoges L;, Schramm B;, Cot M;, Deloron P;, Faucher JF;, Cot M;, Deloron P;, Faucher JF;, Faucher JF;, Guthmann JP;, Lell B;, Borrmann S;, Lell B;, Adjei GO;, Kofoed PE;, Ursing J;, Tjitra E;, Borrmann S;, Marsh K;, Peshu J;, Juma E;, Ogutu BR;, Omar SA;, Sawa P;, Talisuna AO;, Talisuna AO;, Khanthavong M;, Mayxay M;, Newton PN;, Mayxay M;, Piola P;, Djimde AA;, Doumbo OK;, Fofana B;, Sagara I;, Bassat Q;, Gonzalez R;, Menendez C;, Smithuis F;, Smithuis F;, Bousema T;, Kager PA;, Mens PF;
ISSN
1474-4457 (Electronic)
ISSN-L
1473-3099
Publication state
Published
Issued date
2015
Peer-reviewed
Oui
Volume
15
Number
6
Pages
692-702
Language
english
Notes
Publication types: Journal Article Publication Status: ppublish Document Type: Review
Abstract
BACKGROUND: Artemether-lumefantrine is the most widely used artemisinin-based combination therapy for malaria, although treatment failures occur in some regions. We investigated the effect of dosing strategy on efficacy in a pooled analysis from trials done in a wide range of malaria-endemic settings.
METHODS: We searched PubMed for clinical trials that enrolled and treated patients with artemether-lumefantrine and were published from 1960 to December, 2012. We merged individual patient data from these trials by use of standardised methods. The primary endpoint was the PCR-adjusted risk of Plasmodium falciparum recrudescence by day 28. Secondary endpoints consisted of the PCR-adjusted risk of P falciparum recurrence by day 42, PCR-unadjusted risk of P falciparum recurrence by day 42, early parasite clearance, and gametocyte carriage. Risk factors for PCR-adjusted recrudescence were identified using Cox's regression model with frailty shared across the study sites.
FINDINGS: We included 61 studies done between January, 1998, and December, 2012, and included 14 327 patients in our analyses. The PCR-adjusted therapeutic efficacy was 97·6% (95% CI 97·4-97·9) at day 28 and 96·0% (95·6-96·5) at day 42. After controlling for age and parasitaemia, patients prescribed a higher dose of artemether had a lower risk of having parasitaemia on day 1 (adjusted odds ratio [OR] 0·92, 95% CI 0·86-0·99 for every 1 mg/kg increase in daily artemether dose; p=0·024), but not on day 2 (p=0·69) or day 3 (0·087). In Asia, children weighing 10-15 kg who received a total lumefantrine dose less than 60 mg/kg had the lowest PCR-adjusted efficacy (91·7%, 95% CI 86·5-96·9). In Africa, the risk of treatment failure was greatest in malnourished children aged 1-3 years (PCR-adjusted efficacy 94·3%, 95% CI 92·3-96·3). A higher artemether dose was associated with a lower gametocyte presence within 14 days of treatment (adjusted OR 0·92, 95% CI 0·85-0·99; p=0·037 for every 1 mg/kg increase in total artemether dose).
INTERPRETATION: The recommended dose of artemether-lumefantrine provides reliable efficacy in most patients with uncomplicated malaria. However, therapeutic efficacy was lowest in young children from Asia and young underweight children from Africa; a higher dose regimen should be assessed in these groups.
FUNDING: Bill & Melinda Gates Foundation.
METHODS: We searched PubMed for clinical trials that enrolled and treated patients with artemether-lumefantrine and were published from 1960 to December, 2012. We merged individual patient data from these trials by use of standardised methods. The primary endpoint was the PCR-adjusted risk of Plasmodium falciparum recrudescence by day 28. Secondary endpoints consisted of the PCR-adjusted risk of P falciparum recurrence by day 42, PCR-unadjusted risk of P falciparum recurrence by day 42, early parasite clearance, and gametocyte carriage. Risk factors for PCR-adjusted recrudescence were identified using Cox's regression model with frailty shared across the study sites.
FINDINGS: We included 61 studies done between January, 1998, and December, 2012, and included 14 327 patients in our analyses. The PCR-adjusted therapeutic efficacy was 97·6% (95% CI 97·4-97·9) at day 28 and 96·0% (95·6-96·5) at day 42. After controlling for age and parasitaemia, patients prescribed a higher dose of artemether had a lower risk of having parasitaemia on day 1 (adjusted odds ratio [OR] 0·92, 95% CI 0·86-0·99 for every 1 mg/kg increase in daily artemether dose; p=0·024), but not on day 2 (p=0·69) or day 3 (0·087). In Asia, children weighing 10-15 kg who received a total lumefantrine dose less than 60 mg/kg had the lowest PCR-adjusted efficacy (91·7%, 95% CI 86·5-96·9). In Africa, the risk of treatment failure was greatest in malnourished children aged 1-3 years (PCR-adjusted efficacy 94·3%, 95% CI 92·3-96·3). A higher artemether dose was associated with a lower gametocyte presence within 14 days of treatment (adjusted OR 0·92, 95% CI 0·85-0·99; p=0·037 for every 1 mg/kg increase in total artemether dose).
INTERPRETATION: The recommended dose of artemether-lumefantrine provides reliable efficacy in most patients with uncomplicated malaria. However, therapeutic efficacy was lowest in young children from Asia and young underweight children from Africa; a higher dose regimen should be assessed in these groups.
FUNDING: Bill & Melinda Gates Foundation.
Pubmed
Web of science
Create date
12/06/2015 16:21
Last modification date
20/08/2019 13:49
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