A comparative, randomized clinical trial of artemisinin/naphtoquine twice daily one day versus artemether/lumefantrine six doses regimen in children and adults with uncomplicated falciparum malaria in Côte d'Ivoire

<p>Abstract</p> <p>Background</p> <p>Drug resistance in <it>Plasmodium falciparum </it>poses a major threat to malaria control. Combination anti-malarial therapy, including artemisinins, has been advocated to improve efficacy and limit the spread of resistance. The fixed combination of oral artemether-lumefantrine (AL) is highly effective and well-tolerated. Artemisinin/naphtoquine (AN) is a fixed-dose ACT that has recently become available in Africa.</p> <p>The objectives of the study were to compare the efficacy and safety of AN and AL for the treatment of uncomplicated <it>falciparum </it>malaria in a high transmission-intensity site in Ivory Coast.</p> <p>Methods</p> <p>We enrolled 122 participants aged 6 months or more with uncomplicated <it>falciparum </it>malaria. Participants were randomized to receive either artemisinin/naphtoquine or artemether/lumefantrine with variable dose according to their weight. Primary endpoints were the risks of treatment failure within 28 days, either unadjusted or adjusted by genotyping to distinguish recrudescence from new infection.</p> <p>Results</p> <p>Among 125 participants enrolled, 123 (98.4%) completed follow-up. Clinical evaluation of the 123 participants showed that cumulative PCR-uncorrected cure rate on day 28 was 100% for artemisinin/naphtoquine and 98.4% for artemether/lumefantrine. Both artemisinin-based combinations effected rapid fever and parasite clearance.</p> <p>Interpretation</p> <p>These data suggest that Arco^®could prove to be suitable for use as combination antimalarial therapy. Meanwhile, pharmacokinetic studies and further efficacy assessment should be conducted before its widespread use can be supported.</p

Genotyping of S and C Mutated Beta Globin Gene: Development of a Set of Primers for Use with DfV'VnG PCR Systems

International audienceSickle cell disease is a genetic disorder that affects nearly 5% of world population. In ivory coast, SCD is a real problem of health and screening is not systematic after born. Here, we designed a set of primers to detect abnormal hemoglobin S and C which can be used both in conventional and quantitative PCR (by curves combinations analysed). A total of 60 blood samples including 13 AA, 23 AS, 9 SS, 12 SC and 3 CC hemoglobin type were screened using hemoglobin electrophoresis and PCR. The universal control primer HBU/R4 was successfully amplified for all of 60 samples. In conventional PCR, for typing of allele S sensibility and specificity of primers were respectively 86.36% and 87.50%. For allele C, sensibility and specificity of this pair were respectively 53.33% and 91.11%. In qPCR, specificity and sensitivity of primers were greater than 85% for allele S and C specific primers

Artemisinin derivative-containing therapies and abnormal hemoglobin: Do we need to adapt the treatment?

International audienceBackground: Artemisinin-based treatment in malaria patients with abnormal hemoglobin may be ineffective because of their genetic particularity, which could lead to resistance. The main purpose of this study was to assess the effect of artemisinin derivatives on in vivo parasite clearance according to erythrocyte variants. In vivo response was investigated through retrospective data obtained over a 42-day artemether-lumefantrine/artesunate amodiaquine efficacy protocol conducted from 2012 to 2016. Results: A total of 770 patients in Côte d’Ivoire attending the hospitals of Anonkoua-koute (Abidjan), Petit Paris (Korhogo), Libreville (Man), Dar es salam (Bouaké), Ayamé and Yamoussoukro with acute uncomplicated falciparum malaria were selected for successful hemoglobin typing. HbAS, HbSS, HbAC, and HbSC genotypes were found. Parasite clearance time was obtained for 414 patients. In the population with abnormal hemoglobin, parasite densities on admission and parasite clearance rates were significantly lower in the HbSC group compared to HbAA (p = 0.02 and p = 0.007, respectively). After PCR correction on day 42, the acute treatment rate was 100% for each group. Parasite half-life and time for initial parasitaemia to decline by 50 and 99% were longer for the HbSC group (p < 0.05). The study also investigated the prevalence of K13-propeller polymorphisms across different hemoglobin genotype groups. A total of 185 and 63 samples were sequenced in the HbAA group and patients with abnormal Hb, respectively. Only two nonsynonymous mutations D559N and V510M were found in the HbAA group. Conclusion: Although this study proved good efficacy of artemether-lumefantrine and artesunate amodiaquine in the treatment of uncomplicated Plasmodium falciparum malaria in patients with abnormal hemoglobin, the increased delay of parasite clearance may represent a threat to health in these patients in relation with sickle cell crisis, which could support selection of parasites resistant to artemisinin

Map of Africa illustrating the emergence of CQ resistance in East, Central and West Africa detected through travellers’ surveillance from the late 1970s to the early 1980s.

<p>The dates of detection of index cases are displayed. The red arrows show the spread of antimalarial resistance from East Africa to West Africa.</p

Summary of the molecular and <i>in vitro</i> field studies in the four endemic countries included in the analysis (both published and unpublished).

<p>Summary of the molecular and <i>in vitro</i> field studies in the four endemic countries included in the analysis (both published and unpublished).</p

Observed data, fitted model (by logistic regression) and 95% confidence interval (shaded area) for the prevalence of the <i>pfcrt</i> 76 mutant isolates from 2000 to 2011 for travellers (red) and field studies (blue) for A-Senegal, B-Mali, C-Cote d’Ivoire and D-Cameroon.

<p>Each data point represents the prevalence of resistant isolates per year for travellers’ data and per study for field studies, where the size of the circle is proportional to the number of isolates in the sample.</p

Observed data, fitted model (by logistic regression) and 95% confidence interval (shaded area) for the prevalence of the <i>pfdhfr</i> 108 mutant isolates from 1996 to 2011 for travellers (red) and field studies (blue) for A-Senegal, B-Mali, C-Cote d’Ivoire and D-Cameroon.

<p>Each data point represents the prevalence of resistant isolates per year for travellers’ data and per study for field studies, where the size of the circle is proportional to the number of isolates in the sample.</p