# name
Artemether-lumefantrine treatment of uncomplicated Plasmodium
                falciparum malaria: a systematic review and meta-analysis of day
                7 lumefantrine concentrations and therapeutic response using
                individual patient data

# metadata.dc.description.abstract[].value
BACKGROUND: Achieving adequate antimalarial drug exposure is
                essential for curing malaria. Day 7 blood or plasma lumefantrine
                concentrations provide a simple measure of drug exposure that
                correlates well with artemether-lumefantrine efficacy. However,
                the 'therapeutic' day 7 lumefantrine concentration threshold
                needs to be defined better, particularly for important patient
                and parasite sub-populations. METHODS: The WorldWide
                Antimalarial Resistance Network (WWARN) conducted a large pooled
                analysis of individual pharmacokinetic-pharmacodynamic data from
                patients treated with artemether-lumefantrine for uncomplicated
                Plasmodium falciparum malaria, to define therapeutic day 7
                lumefantrine concentrations and identify patient factors that
                substantially alter these concentrations. A systematic review of
                PubMed, Embase, Google Scholar, ClinicalTrials.gov and
                conference proceedings identified all relevant studies. Risk of
                bias in individual studies was evaluated based on study design,
                methodology and missing data. RESULTS: Of 31 studies identified
                through a systematic review, 26 studies were shared with WWARN
                and 21 studies with 2,787 patients were included. Recrudescence
                was associated with low day 7 lumefantrine concentrations (HR
                1.59 (95% CI 1.36 to 1.85) per halving of day 7 concentrations)
                and high baseline parasitemia (HR 1.87 (95% CI 1.22 to 2.87) per
                10-fold increase). Adjusted for mg/kg dose, day 7 concentrations
                were lowest in very young children (<3 years), among whom
                underweight-for-age children had 23% (95% CI -1 to 41%) lower
                concentrations than adequately nourished children of the same
                age and 53% (95% CI 37 to 65%) lower concentrations than adults.
                Day 7 lumefantrine concentrations were 44% (95% CI 38 to 49%)
                lower following unsupervised treatment. The highest risk of
                recrudescence was observed in areas of emerging artemisinin
                resistance and very low transmission intensity. For all other
                populations studied, day 7 concentrations >/=200 ng/ml were
                associated with >98% cure rates (if parasitemia
                <135,000/muL). CONCLUSIONS: Current artemether-lumefantrine
                dosing recommendations achieve day 7 lumefantrine concentrations
                >/=200 ng/ml and high cure rates in most uncomplicated
                malaria patients. Three groups are at increased risk of
                treatment failure: very young children (particularly those
                underweight-for-age); patients with high parasitemias; and
                patients in very low transmission intensity areas with emerging
                parasite resistance. In these groups, adherence and treatment
                response should be monitored closely. Higher, more frequent, or
                prolonged dosage regimens should now be evaluated in very young
                children, particularly if malnourished, and in patients with
                hyperparasitemia.

# metadata.dc.rights[].value
cc by (c) WorldWide Antimalarial Resistance Network (WWARN) Lumefantrine PK/PD Study Group, 2015

# metadata.dc.source[].value
Articles publicats en revistes (ISGlobal)

# metadata.dc.title[].value
Artemether-lumefantrine treatment of uncomplicated Plasmodium
                falciparum malaria: a systematic review and meta-analysis of day
                7 lumefantrine concentrations and therapeutic response using
                individual patient data