The effect of dosing strategies on the therapeutic efficacy of artesunate-amodiaquine for uncomplicated malaria: a meta-analysis of individual patient data
Abstract:BackgroundArtesunate-amodiaquine (AS-AQ) is one of the most widely used artemisinin-based combination therapies (ACTs) to treat uncomplicated Plasmodium falciparum malaria in Africa. We investigated the impact of different dosing strategies on the efficacy of this combination for the treatment of falciparum malaria.MethodsIndividual patient data from AS-AQ clinical trials were pooled using the WorldWide Antimalarial Resistance Network (WWARN) standardised methodology. Risk factors for treatment failure were id… Show more
“…Age acts as a strong confounder in investigating this association. It has been negatively associated with lumefantrine concentration in this study and others [31, 33], and children < 3 years have usually lower exposure to lumefantrine [15]. Additionally, unmeasured factors linked to age modulate the exposition and susceptibility to malaria: different exposure to mosquito bites in relation to behavioral changes in older children possibly mediated by different utilization of insecticide-treated nets [34], and different immune premunition switching from transmitted maternal immunity via breastfeeding to acquired host immunity.…”
Section: Discussionsupporting
confidence: 73%
“…We confirmed here that the relation between the dose-weight received and the lumefantrine concentration measured in blood is not straightforward, the higher dose-weight received in younger SAM children resulted in a lower day 7 concentration [31]. Though not correlated with a higher risk of treatment failure or reinfection in our study, the low concentration achieved in SAM and young children is still a concern, as sub-optimal exposure to antimalarials is the first step to the emergence of parasite resistance [35].…”
Section: Discussionsupporting
confidence: 71%
“…Of note, older SAM children were also those who experienced more reinfections. A day-7 concentration over 200 ng/mL (previously pointed by WWARN as an efficacy threshold) [31], was achieved in 57.1 % of younger SAM, 66.7 % of younger non-SAM, 75.0 % of older SAM, and 82.8 % of older non-SAM ( P = 0.002 overall) patients. We did not find a statistically significant association between lumefantrine concentration on day 7 and protection from reinfection by day 28 (in Cox modelling, HR = 1.05, 95 % CI, 0.68–1.64, P = 0.818 for the measure of association between reinfection and log-transformed lumefantrine concentration in continuous variables, after adjusting for age).Fig.…”
Section: Resultsmentioning
confidence: 92%
“…A recent meta-analysis conducted by WWARN also pointed out that day 7 lumefantrine concentration was lower in younger and underweight children, though it did not investigate the effect of SAM specifically [31]. …”
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.
“…Age acts as a strong confounder in investigating this association. It has been negatively associated with lumefantrine concentration in this study and others [31, 33], and children < 3 years have usually lower exposure to lumefantrine [15]. Additionally, unmeasured factors linked to age modulate the exposition and susceptibility to malaria: different exposure to mosquito bites in relation to behavioral changes in older children possibly mediated by different utilization of insecticide-treated nets [34], and different immune premunition switching from transmitted maternal immunity via breastfeeding to acquired host immunity.…”
Section: Discussionsupporting
confidence: 73%
“…We confirmed here that the relation between the dose-weight received and the lumefantrine concentration measured in blood is not straightforward, the higher dose-weight received in younger SAM children resulted in a lower day 7 concentration [31]. Though not correlated with a higher risk of treatment failure or reinfection in our study, the low concentration achieved in SAM and young children is still a concern, as sub-optimal exposure to antimalarials is the first step to the emergence of parasite resistance [35].…”
Section: Discussionsupporting
confidence: 71%
“…Of note, older SAM children were also those who experienced more reinfections. A day-7 concentration over 200 ng/mL (previously pointed by WWARN as an efficacy threshold) [31], was achieved in 57.1 % of younger SAM, 66.7 % of younger non-SAM, 75.0 % of older SAM, and 82.8 % of older non-SAM ( P = 0.002 overall) patients. We did not find a statistically significant association between lumefantrine concentration on day 7 and protection from reinfection by day 28 (in Cox modelling, HR = 1.05, 95 % CI, 0.68–1.64, P = 0.818 for the measure of association between reinfection and log-transformed lumefantrine concentration in continuous variables, after adjusting for age).Fig.…”
Section: Resultsmentioning
confidence: 92%
“…A recent meta-analysis conducted by WWARN also pointed out that day 7 lumefantrine concentration was lower in younger and underweight children, though it did not investigate the effect of SAM specifically [31]. …”
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.
“…Neutropenia and elevation of ALT were considered AEs of special interest [42–44]. An independent data monitoring committee comprised of 3 renowned experts reviewed the study protocol and evaluated the results of efficacy and safety analyses.…”
SummaryIn the Brazilian Amazon, the artesunate–amodiaquine combination was more effective in preventing Plasmodium vivax recurrence. With a favorable safety profile, this antimalarial treatment proved to be a good first-line alternative. Chloroquine resistance is probably underestimated in the area.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.