Evaluation de l'activité antipaludique de 21 plantes utilisées en médecine traditionnelle ivoirienne (fractionnement biodirigé des extraits les plus actifs)

La propagation de la résistance aux antipaludiques est un frein évident à la lutte contre le paludisme dans le monde. D'où la nécessité et l'urgence d'élaborer de nouveaux médicaments de faible coût, efficaces contre les souches multirésistantes de P. falciparum. Dans cette étude nous avons évalué l'activité antiplamodiale de 21 plantes couramment utilisées en médecine traditionnelle ivoirienne contre le paludisme. Les composés actifs ont été isolés par fractionnement biodirigé des extraits les plus intéressants. C'est ainsi que nous avons isolé la cryptolépine et l'acide ellagique respectivement à partir de Sida acuta et Alchornea cordifolia. Ces molécules ont montré in vitro une meilleure activité que la chloroquine contre une souche chloroquino-résistante FcM29. L'acide ellagique a montré une activité in vivo contre P. vinckei petteri qui est cependant plus faible que celle de la chloroquine. L'ensemble de cette étude a fait l'objet de 3 publications dans des revues internationales.MONTPELLIER-BU Pharmacie (341722105) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF

Efficacy and Safety of Artesunate-Amodiaquine versus Artemether-Lumefantrine in the Treatment of Uncomplicated Plasmodium falciparum Malaria in Sentinel Sites across Côte d’Ivoire

Two years after the introduction of free Artesunate-Amodiaquine (ASAQ) and Artemether-Lumefantrine (AL) for the treatment of uncomplicated malaria in public health facilities in Côte d’Ivoire, we carried out this study to compare their efficacy and tolerability in three surveillance sites. It was a multicentre open randomised clinical trial of 3-day ASAQ treatment against AL for the treatment of 2 parallel groups of patients aged 2 years and above. The endpoints were (1) Adequate Clinical and Parasitological Response (ACPR) at day 28 and (2) the clinical and biological tolerability. Of the 300 patients who were enrolled 289, with 143 (49.5%) and 146 (50.5%) in the ASAQ and AL groups, respectively, correctly followed the WHO 2003 protocol we used. The PCR-corrected ACPR was 99.3% for each group. More than 94% of patients no longer showed signs of fever, 48 hours after treatment. Approximately 78% of the people in the ASAQ group had a parasite clearance time of 48 hours or less compared to 81% in the AL group (p=0.496). Both drugs were found to be well tolerated by the patients. This study demonstrates the effectiveness and tolerability of ASAQ and AL supporting their continuous use for the treatment of uncomplicated P. falciparum malaria infection in Côte d’Ivoire

Clinical Study Efficacy and Safety of Artesunate-Amodiaquine versus Artemether-Lumefantrine in the Treatment of Uncomplicated Plasmodium falciparum Malaria in Sentinel Sites across Côte d'Ivoire

Two years after the introduction of free Artesunate-Amodiaquine (ASAQ) and Artemether-Lumefantrine (AL) for the treatment of uncomplicated malaria in public health facilities in Côte d'Ivoire, we carried out this study to compare their efficacy and tolerability in three surveillance sites. It was a multicentre open randomised clinical trial of 3-day ASAQ treatment against AL for the treatment of 2 parallel groups of patients aged 2 years and above. The endpoints were (1) Adequate Clinical and Parasitological Response (ACPR) at day 28 and (2) the clinical and biological tolerability. Of the 300 patients who were enrolled 289, with 143 (49.5%) and 146 (50.5%) in the ASAQ and AL groups, respectively, correctly followed the WHO 2003 protocol we used. The PCR-corrected ACPR was 99.3% for each group. More than 94% of patients no longer showed signs of fever, 48 hours after treatment. Approximately 78% of the people in the ASAQ group had a parasite clearance time of 48 hours or less compared to 81% in the AL group ( = 0.496). Both drugs were found to be well tolerated by the patients. This study demonstrates the effectiveness and tolerability of ASAQ and AL supporting their continuous use for the treatment of uncomplicated P. falciparum malaria infection in Côte d'Ivoire

Improved Protocol for Continuous Culture of Plasmodium falciparum Reference Strains

Parasitic biobank of Plasmodium falciparum is almost germinal in Côte d’Ivoire. However, several high-level research topics on this parasite involve the taking into account of nature isolates but also chemo-sensitive or resistant reference strains for a better validation of results. In addition, acquisition of these reference strains is still arduous for laboratories in developing countries due to complexity of administrative procedures. For those reasons, this study aimed in to combine several procedures into a consolidated one in order to enhance the multiplication of P. falciparum reference strains. Continuous culture of plasmodial strains was based on the Trager and Jensen procedures. The CELL culture protocols used are those of the Swiss TPH described by Sergio Wittlin; the “Growing Plasmodium falciparum cultures at high parasitemia” and the “Stockholm sorbitol method” of Methods in Malaria Research-6th edition 2013; and the INV-01 and INV-02 procedures of the Worldwide Antimalarial Resistance Network (WWARN). Reference Plasmodium falciparum strains NF54 sensitive to chloroquine (CQs) and K1 resistant to chloroquine (CQr) were received from the Swiss Tropical Institute and Public Health (Swiss TPH). The CQs NF54 strain reacted more quickly to the protocol unlike the CQr K1 strain. Parasitic densities (DP) obtained with NF54 strain were ranged from 0.4% at day zero (D0) to 11.4% at day eight (D8). Strain K1 finally adapted successfully after one month of follow-up. Related DPs ranged from less than 0.1% to more than 20% in just three growth cycles after adaptation. A joint protocol (from this work) called “CRLP-SwissTPH-Pasteur_001” is available and allows to efficiently multiply reference strains NF54 and K1. It is planned to spread out the tests to other plasmodial strains as well as to wild isolates in order to standardize this procedure

Cryptococcus genetic diversity and mixed infections in Ivorian HIV patients: A follow up study

International audienceGenetic diversity analyses were performed by sero-genotyping and multi-locus sequence typing on 252 cryptococcal isolates from 13 HIV-positive Ivorian patients followed-up for cryptococcal meningitis. Antifungal susceptibility analyses were performed according to the CLSI M27A3 method. The majority (67.8%) of the isolates belonged to the Cryptococcus neoformans (serotype A) species complex, with 93% being VNI and 7% being VNII. Cryptococcus deuterogattii VGII (serotype B) represented 16.7% of the strains, while C. neoformans/C. deneoformans VNIII (serotype AD) hybrids accounted for 15.1% of the strains. One strain (0.4%) was not identifiable. Nine different sequence types (STs 5, 6, 23, 40, 93, 207, 311, and a new ST; 555) were identified in the C. neoformans population, while the C. deuterogattii population comprised the single ST 173. The distribution of the strains showed that, while the majority of patients (9/13) harboured a single sequence type, 4 patients showed mixed infections. These patients experienced up to 4 shifts in strain content either at the species and/or ST level during their follow-up. This evolution of diversity over time led to the co-existence of up to 3 different Cryptococcus species and 4 different ST within the same individual during the course of infection. Susceptibility testing showed that all strains were susceptible to amphotericin B while 3.6% of them had a none-wild type phenotype to 5-flucytosine. Concerning fluconazole, 2.9% of C.neoformans serotype A strains and 2.4% of C. deuterogattii had also respectively a none-wild type phenotype to this molecule. All C. neoformans x C. deneoformans serotype AD hybrids had however a wild type phenotype to fluconazole. The present study showed that mixed infections exist and could be of particular importance for care outcomes. Indeed, (i) the different Cryptococcus species are known to exhibit different virulence and different susceptibility patterns to antifungal drugs and (ii) the strains genetic diversity within the samples may influence the susceptibility to antifungal treatment