161 research outputs found

    Resistance to Dihydroartemisinin

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    Mouvements sociaux, organisations et stratégies

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    En France, les « mouvements sociaux » renvoient souvent, dans le langage commun, Ă  une rĂ©alitĂ© nĂ©gative, synonyme de protestations sociales, qui seraient soit le produit principal du corporatisme de certains corps de mĂ©tier (les « cheminots »), soit la voie que choisissent d’emprunter les salariĂ©s afin de rĂ©agir face Ă  des situations dĂ©sespĂ©rĂ©es comme les fermetures sauvages d’entreprises ou les dĂ©localisations massives. [PremiĂšres lignes de l'article

    Lack of association between putative transporter gene polymorphisms in Plasmodium falciparum and chloroquine resistance in imported malaria isolates from Africa

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    BACKGROUND: Plasmodium falciparum drug resistance represents a major health problem in malaria endemic countries. The mechanisms of resistance are not fully elucidated. Recently, an association between putative transporter gene polymorphisms and in vitro response to chloroquine (CQ) and quinine has been reported in culture-adapted, cloned isolates from various geographical origins. However, this was not confirmed in another study performed on isolates from a defined region in Thailand. METHODS: This study tried to find an association between putative transporters gene polymorphisms with in vitro response to CQ and pfcrt genotype in isolates originating from various African countries. To avoid biases of parasites adaptation in culture, fresh isolates obtained from symptomatic, malaria-infected travellers returning from Africa to France were used. Monoclonal isolates included in the study were selected using a msp-2 fragment analysis method. In vitro susceptibility to CQ, single nucleotide polymorphisms and microsatellite polymorphisms in pfcrt, pfmdr1 and six putative transporter genes were established in 27 isolates and three reference strains. RESULTS: Polymorphism of pfcrt at positions 76 and 220 showed a significant association with in vitro chloroquine resistance (P < .02 and P < .05 respectively). Polymorphism of pfmdr1 at position 86 showed an equally significant association with in vitro chloroquine response (P < .05). No association was found between SNPs or microsatellite polymorphisms of putative transporter genes and in vitro CQR or pfcrt genotype in imported malaria isolates from Africa. CONCLUSION: The previously described association between putative transporter gene polymorphisms and in vitro response to chloroquine (CQ) was not confirmed in the present study

    Évaluer l&apos;impact du vieillissement des digues sur les mĂ©canismes et scĂ©narios de rupture

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    Digues Maritimes et Fluviales de Protection contre les Inondations : Digues 2019, AIX EN PROVENCE, FRANCE, 20-/03/2019 - 21/03/2019Les scĂ©narios de rupture des digues sont basĂ©s sur des hypothĂšses d&apos;enchaĂźnement de dĂ©gradations ou de ruptures partielles de diffĂ©rentes parties des ouvrages. Ainsi, pour qu&apos;une dĂ©faillance intervienne sur un tronçon de digue, il faut que certaines parties d&apos;ouvrage arrivent Ă  la limite de leur &apos;bon&apos; fonctionnement et que leurs propriĂ©tĂ©s passent en-dessous d&apos;un certain niveau de performance. L&apos;Ă©volution des propriĂ©tĂ©s et des performances n&apos;est cependant pas toujours &apos;binaire&apos; : l&apos;ouvrage semble ĂȘtre dans un Ă©tat correct puis, instantanĂ©ment, arrive Ă  la rupture. Cet article propose une discussion sur les mĂ©canismes de vieillissement des matĂ©riaux utilisĂ©s notamment pour leur fonction d&apos;Ă©tanchĂ©itĂ©, Ă  partir d&apos;exemples concrets. Le vieillissement est un phĂ©nomĂšne normal qui apparaĂźt soit par un usage rĂ©pĂ©tĂ© de l&apos;ouvrage soit par des phĂ©nomĂšnes normaux de dĂ©gradation et d&apos;usure par le temps et les conditions extĂ©rieures. Ce vieillissement normal peut ĂȘtre identifiĂ© au travers de mĂ©canismes de dĂ©gradation qui seraient classĂ©s par type de dĂ©gradation (mĂ©tĂ©orologique, interaction avec le vivant, interaction avec des masses d&apos;eau), par intensitĂ© (fort, moyen, faible) et par cinĂ©tique (trĂšs long, rapide, instantanĂ©). Ces mĂ©canismes de dĂ©gradations seraient dĂ©pendants de la localisation gĂ©ographique de l&apos;ouvrage, de la nature des composants et de la qualitĂ© initiale de la rĂ©alisation de l&apos;ouvrage

    Plasmodium falciparum Malaria and Atovaquone-Proguanil Treatment Failure

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    We noticed overrepresentation of atovaquone-proguanil therapeutic failures among Plasmodium falciparum–infected travelers weighing >100 kg. We report here 1 of these cases, which was not due to resistant parasites or impaired drug bioavailability. The follow-up of such patients should be strengthened

    Rapid Dissemination of Plasmodium falciparum Drug Resistance Despite Strictly Controlled Antimalarial Use

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    BACKGROUND: Inadequate treatment practices with antimalarials are considered major contributors to Plasmodium falciparum resistance to chloroquine, pyrimethamine and sulfadoxine. The longitudinal survey conducted in Dielmo, a rural Senegalese community, offers a unique frame to explore the impact of strictly controlled and quantified antimalarial use for diagnosed malaria on drug resistance. METHODOLOGY/PRINCIPAL FINDINGS: We conducted on a yearly basis a retrospective survey over a ten-year period that included two successive treatment policies, namely quinine during 1990–1994, and chloroquine (CQ) and sulfadoxine/pyrimethamine (SP) as first and second line treatments, respectively, during 1995–1999. Molecular beacon-based genotyping, gene sequencing and microsatellite analysis showed a low prevalence of Pfcrt and Pfdhfr-ts resistance alleles of Southeast Asian origin by the end of 1994 and their effective dissemination within one year of CQ and SP implementation. The Pfcrt resistant allele rose from 9% to 46% prevalence during the first year of CQ reintroduction, i.e., after a mean of 1.66 CQ treatment courses/person/year. The Pfdhfr-ts triple mutant rose from 0% to 20% by end 1996, after a mean of 0.35 SP treatment courses/person in a 16-month period. Both resistance alleles were observed at a younger age than all other alleles. Their spreading was associated with enhanced in vitro resistance and rapidly translated in an increased incidence of clinical malaria episodes during the early post-treatment period. CONCLUSION/SIGNIFICANCE: In such a highly endemic setting, selection of drug-resistant parasites took a single year after drug implementation, resulting in a rapid progression of the incidence of clinical malaria during the early post-treatment period. Controlled antimalarial use at the community level did not prevent dissemination of resistance haplotypes. This data pleads against reintroduction of CQ in places where resistant allele frequency has dropped to a very low level after CQ use has been discontinued, unless drastic measures are put in place to prevent selection and spreading of mutants during the post-treatment period

    As mĂșltiplas funçÔes da agricultura familiar: um estudo no assentamento Monte Alegre, regiĂŁo de Araraquara (SP).

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    A partir da emergĂȘncia da ideia de sustentabilidade, a agricultura adquiriu novas conotaçÔes, associadas nĂŁo apenas ao aspecto produtivo, mas tambĂ©m Ă  conservação dos recursos naturais e dos territĂłrios rurais, em um reconhecimento de sua multifuncionalidade. Com base nesta noção, que valoriza as funçÔes socioambientais desempenhadas pelas famĂ­lias rurais e pelas agriculturas praticadas, o presente artigo analisa um assentamento rural no estado de SĂŁo Paulo, buscando identificar quais sĂŁo e de que forma se expressam as funçÔes para alĂ©m da produção neste territĂłrio particular. Por meio de uma metodologia de cunho quali-quantitativo, observou-se que, no assentamento em foco, a agricultura encerra em si questĂ”es de coesĂŁo territorial, manutenção da segurança alimentar, conservação da agrobiodiversidade e de fomento a outras atividades produtivas, sendo o elemento central da reconstrução de um modo de vida rural neste ambiente

    In vitro susceptibility to pyrimethamine of DHFR I164L single mutant Plasmodium falciparum

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    <p>Abstract</p> <p>Background</p> <p>Recently, <it>Plasmodium falciparum </it>parasites bearing <it>Pfdhfr </it>I164L single mutation were found in Madagascar. These new mutants may challenge the use of antifolates for the intermittent preventive treatment of malaria during pregnancy (IPTp). Assays with transgenic bacteria suggested that I164L parasites have a wild-type phenotype for pyrimethamine but it had to be confirmed by testing the parasites themselves.</p> <p>Methods</p> <p>Thirty <it>Plasmodium falciparum </it>clinical isolates were collected in 2008 in the south-east of Madagascar. A part of <it>Pfdhfr </it>gene encompassing codons 6 to 206 was amplified by PCR and the determination of the presence of single nucleotide polymorphisms was performed by DNA sequencing. The multiplicity of infection was estimated by using an allelic family-specific nested PCR. Isolates that appeared monoclonal were submitted to culture adaptation. Determination of IC<sub>50s </sub>to pyrimethamine was performed on adapted isolates.</p> <p>Results</p> <p>Four different <it>Pfdhfr </it>alleles were found: the 164L single mutant-type (N = 13), the wild-type (N = 7), the triple mutant-type 51I/59R/108N (N = 9) and the double mutant-type 108N/164L (N = 1). Eleven out 30 (36.7%) of <it>P. falciparum </it>isolates were considered as monoclonal infection. Among them, five isolates were successfully adapted in culture and tested for pyrimethamine <it>in vitro </it>susceptibility. The wild-type allele was the most susceptible with a 50% inhibitory concentration (IC<sub>50</sub>) < 10 nM. The geometric mean of IC<sub>50 </sub>of the three I164L mutant isolates was 6-fold higher than the wild-type with 61.3 nM (SD = 3.2 nM, CI95%: 53.9-69.7 nM). These values remained largely below the IC<sub>50 </sub>of the triple mutant parasite (13,804 nM).</p> <p>Conclusion</p> <p>The IC<sub>50</sub>s of the I164L mutant isolates were significantly higher than those of the wild-type (6-fold higher) and close from those usually reported for simple mutants S108N (roughly10-fold higher than wild type). Given the observed values, the determination of IC<sub>50</sub>s directly on parasites did not confirm what has been found on transgenic bacteria. The prevalence increase of the <it>Pfdhfr </it>I164L single mutant parasite since 2006 could be explained by the selective advantage of this allele under sulphadoxine-pyrimethamine pressure. The emergence of highly resistant alleles should be considered in the future, in particular because an unexpected double mutant-type allele S108N/I164L has been already detected.</p

    Design and Characterization of an Electrically Powered Single Molecule on Gold

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    The surface diffusion of individual molecules is of paramount importance in self-assembly processes and catalytic processes. However, the fundamental understanding of molecule diffusion peculiarities considering conformations and adsorption sites remain poorly known at the atomic scale. Here, we probe the 4â€Č-(4-tolyl)-2,2â€Č:6â€Č,2″-terpyridine adsorbed on the Au(111) herringbone structure combining scanning tunneling microscopy and atomic force microscopy. Molecules are controllably translated by electrons excitations over the reconstruction, except at elbows acting as pinning centers. Experimental data supported by theoretical calculations show the formation of coordination bonds between the molecule and Au atoms of the surface. Using force spectroscopy, we quantify local variation of the surface potential and the lateral force required to move the molecule. We found an elevation of the diffusion barrier at elbows of the reconstruction of ∌100 meV compared to the rest of the surface

    Sulphadoxine/pyrimethamine versus amodiaquine for treating uncomplicated childhood malaria in Gabon: A randomized trial to guide national policy

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    <p>Abstract</p> <p>Background</p> <p>In Gabon, following the adoption of amodiaquine/artesunate combination (AQ/AS) as first-line treatment of malaria and of sulphadoxine/pyrimethamine (SP) for preventive intermittent treatment of pregnant women, a clinical trial of SP versus AQ was conducted in a sub-urban area. This is the first study carried out in Gabon following the WHO guidelines.</p> <p>Methods</p> <p>A random comparison of the efficacy of AQ (10 mg/kg/day × 3 d) and a single dose of SP (25 mg/kg of sulphadoxine/1.25 mg/kg of pyrimethamine) was performed in children under five years of age, with uncomplicated falciparum malaria, using the 28-day WHO therapeutic efficacy test. In addition, molecular genotyping was performed to distinguish recrudescence from reinfection and to determine the frequency of the <it>dhps </it>K540E mutation, as a molecular marker to predict SP-treatment failure.</p> <p>Results</p> <p>The day-28 PCR-adjusted treatment failures for SP and AQ were 11.6% (8/69; 95% IC: 5.5–22.1) and 28.2% (20/71; 95% CI: 17.7–38.7), respectively This indicated that SP was significantly superior to AQ (<it>P </it>= 0.019) in the treatment of uncomplicated childhood malaria and for preventing recurrent infections. Both treatments were safe and well-tolerated, with no serious adverse reactions recorded. The <it>dhps </it>K540E mutation was not found among the 76 parasite isolates tested.</p> <p>Conclusion</p> <p>The level of AQ-resistance observed in the present study may compromise efficacy and duration of use of the AQ/AS combination, the new first-line malaria treatment. Gabonese policy-makers need to plan country-wide and close surveillance of AQ/AS efficacy to determine whether, and for how long, these new recommendations for the treatment of uncomplicated malaria remain valid.</p
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