Browsing by Subject "Niger"

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    Open Access
    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
    (BioMed Central, 2016-10-24) Denoeud-Ndam, Lise; Dicko, Alassane; Baudin, Elisabeth; Guindo, Ousmane; Grandesso, Francesco; Diawara, Halimatou; Sissoko, Sibiri; Sanogo, Koualy; Traoré, Seydou; Keita, Sekouba; Barry, Amadou; de Smet, Martin; Lasry, Estrella; Smit, Michiel; Wiesner, Lubbe; Barnes, Karen I; Djimde, Abdoulaye A; Guerin, Philippe J; Grais, Rebecca F; Doumbo, Ogobara K; Etard, Jean-François
    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.
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    Open Access
    A multi-center, open-label trial to compare the efficacy and pharmacokinetics of Artemether-Lumefantrine in children with severe acute malnutrition versus children without severe acute malnutrition: study protocol for the MAL-NUT study
    (BioMed Central Ltd, 2015) Denoeud-Ndam, Lise; Dicko, Alassane; Baudin, Elisabeth; Guindo, Ousmane; Grandesso, Francesco; Sagara, Issaka; Lasry, Estrella; Palma, Pedro; Parra, Angeles; Stepniewska, Kasia; Djimde, Abdoulaye; Barnes, Karen; Doumbo, Ogobara; Etard, Jean-Francois
    BACKGROUND:Malnutrition and malaria frequently coexist in sub-Saharan African countries. Studies on efficacy of antimalarial treatments usually follow the WHO standardized protocol in which severely malnourished children are systematically excluded.Few studies have assessed the efficacy of chloroquine, sulfadoxine-pyrimethamine and quinine in severe acute malnourished children. Overall, efficacy of these treatments appeared to be reduced, attributed to lower immunity and for some antimalarials altered pharmacokinetic profiles and lower drug concentrations. However, similar research on the efficacy and pharmacokinetic profiles of artemisinin-combination therapies (ACTs) and especially artemether-lumefantrine in malnourished children is currently lacking.The main objective of this study is to assess whether artemether-lumefantrine is less efficacious in children suffering from severe acute malnutrition (SAM) compared to non-SAM children, and if so, to what extent this can be attributed to a sub-optimal pharmacokinetic profile.METHODS/DESIGN:In two sites, Ouelessebougou, Mali and Maradi, Niger, children with uncomplicated microscopically-confirmed P. falciparum malaria aged between 6 and 59 months will be enrolled. Two non-SAM children will be enrolled after the enrolment of each SAM case. Children with severe manifestations of malaria or complications of acute malnutrition needing intensive treatment will be excluded.Treatment intakes will be supervised and children will be followed-up for 42 days, according to WHO guidance for surveillance of antimalarial drug efficacy. Polymerase Chain Reaction genotyping will be used to distinguish recrudescence from re-infection. SAM children will also benefit from the national nutritional rehabilitation program.Outcomes will be compared between the SAM and non-SAM populations. The primary outcome will be adequate clinical and parasitological response at day 28 after PCR correction, estimated by Kaplan-Meier analysis. To assess the pharmacokinetic profile of lumefantrine, a sparse sampling approach will be used with randomized allocation of sampling times (5 per child). A total of 180 SAM children and 360 non-SAM children will be recruited during the 2013 and 2014 malaria seasons.DISCUSSION:This study will provide important information that is currently lacking on the effect of SAM on therapeutic efficacy and pharmacokinetic profile of artemether-lumefantrine. If it shows lower therapeutic efficacy and decreased lumefantrine concentrations, it would inform dose optimization studies in SAM children.TRIAL REGISTRATION:ClinicalTrials.gov: NCT01958905
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    Niger's child survival success, contributing factors and challenges to sustainability: a retrospective analysis
    (Public Library of Science, 2016) Besada, Donela; Kerber, Kate; Leon, Natalie; Sanders, David; Daviaud, Emmanuelle; Rohde, Sarah; Rohde, Jon; Damme, Wim van; Kinney, Mary; Manda, Samuel; Oliphant, Nicholas P; Hachimou, Fatima; Ouedraogo, Adama; Ghali, Asma Yaroh; Doherty, Tanya
    BACKGROUND: Household surveys undertaken in Niger since 1998 have revealed steady declines in under-5 mortality which have placed the country 'on track' to reach the fourth Millennium Development goal (MDG). This paper explores Niger's mortality and health coverage data for children under-5 years of age up to 2012 to describe trends in high impact interventions and the resulting impact on childhood deaths averted. The sustainability of these trends are also considered. Methods and FINDINGS: Estimates of child mortality using the 2012 Demographic and Health Survey were developed and maternal and child health coverage indicators were calculated over four time periods. Child survival policies and programmes were documented through a review of documents and key informant interviews. The Lives Saved Tool (LiST) was used to estimate the number of child lives saved and identify which interventions had the largest impact on deaths averted. The national mortality rate in children under-5 decreased from 286 child deaths per 1000 live births (95% confidence interval 177 to 394) in the period 1989-1990 to 128 child deaths per 1000 live births in the period 2011-2012 (101 to 155), corresponding to an annual rate of decline of 3.6%, with significant declines taking place after 1998. Improvements in the coverage of maternal and child health interventions between 2006 and 2012 include one and four or more antenatal visits, maternal Fansidar and tetanus toxoid vaccination, measles and DPT3 vaccinations, early and exclusive breastfeeding, oral rehydration salts (ORS) and proportion of children sleeping under an insecticide-treated bed net (ITN). Approximately 26,000 deaths of children under-5 were averted in 2012 due to decreases in stunting rates (27%), increases in ORS (14%), the Hib vaccine (14%), and breastfeeding (11%). Increases in wasting and decreases in vitamin A supplementation negated some of those gains. Care seeking at the community level was responsible for an estimated 7,800 additional deaths averted in 2012. A major policy change occurred in 2006 enabling free health care provision for women and children, and in 2008 the establishment of a community health worker programme. CONCLUSION: Increases in access and coverage of care for mothers and children have averted a considerable number of childhood deaths. The 2006 free health care policy and health post expansion were paramount in reducing barriers to care. However the sustainability of this policy and health service provision is precarious in light of persistently high fertility rates, unpredictable GDP growth, a high dependence on donor support and increasing pressures on government funding.