La lutte contre les schistosomoses en Afrique de l'Ouest

L'éducation pour la santé a été une composante importante du programme de lutte contre la bilharziose urinaire au Niger dès son démarrage. L'objectif était de faire percevoir le rôle de la population dans le maintien de la schistosomose au sein des périmètres irrigués. L'éducation pour la santé était étroitement associée à l'assainissement et à l'approvisionnement en eau potable. L'ensemble s'inscrivait dans le cadre de la participation communautaire aux soins de santé primaire. Les difficultés rencontrées sont décrites et expliquent en grande partie la médiocrité des résultats dans ce domaine. (Résumé d'auteur

La lutte contre les schistosomoses en Afrique de l'Ouest

Le programme de lutte contre la bilharziose urinaire au Niger a été initié en 1980 pour réduire la morbidité de la bilharziose urinaire dans la zone de périmètres irrigués de la vallée du fleuve Niger où des rizières avaient été aménagées. Quatre stratégies ont été utilisées : traitement des populations par le praziquantel, éducation pour la santé, formation et assainissement du milieu. Plus de 110 000 personnes réparties dans 171 villages étaient concernées par ce projet. Le projet a été progressivement décentralisé pour être intégré aux structures nationales de santé. Parallèlement, une recherche opérationnelle a permis de définir des indicateurs de prévalence et de morbidité tant pour l'évaluation de l'endémie avant intervention et la définition des stratégies de contrôle, que pour la surveillance du programme de lutte lui-même. La formation des agents chargés de poursuivre ce programme après sa dévolution a été conduite sur le terrain et a impliqué le personnel de santé, les enseignants et les membres des coopératives agricoles. La sensibilisation de la population a été faite à l'aide d'un matériel pédagogique créé pour la circonstance. Les mesures d'assainissement ont été limitées par l'absence de motivation de la population. Le traitement de la population a été organisé par le projet mais effectué par le personnel de santé du district qui a mis en place le recouvrement des coûts dans le but de pérenniser l'intervention. Les difficultées rencontrées et les remèdes possibles sont discutés. (Résumé d'auteur

Restauration de plages nues d’une brousse tachetée au Niger

Un essai de restauration de plages nues dfune brousse tachetee degradee du Parc National du W au sudouest du Niger a ete installe en 2007. Cet article etablit le bilan de cette restauration realisee par la plantation dfespeces locales dans des ouvrages antierosifs du type tranchees sylvopastorales. Dans la zonetemoin et dans la zone mise en defens par une cloture, le taux de survie des plants mis en place, leur croissance en hauteur et en diametre, la composition et la diversite floristique des herbacees ont ete suivis pendant trois ans (2007-2009). Lfeffet des ouvrages antierosifs sur lfhumidite du sol a ete evalue pendant lapremiere annee. Les analyses demontrent une amelioration nette des conditions ecologiques du site dfexperimentation, qui evolue progressivement vers lfetat dfune brousse tachetee, qui est lfecosysteme de reference. Lfamelioration de lfhumidite du sol induit des conditions beaucoup plus favorables pour la couverture vegetale. La richesse floristique dans la zone-temoin est passee en trois annees de 16 a 49, la diversite ƒ¿ de 2,1 a 4,42 et lfequitabilite de Pielou de 0,59 a 0,78. Dans la zone cloturee (mise en defens), la richesse floristique, la diversite ƒ¿ et lfequitabilite de Pielou sont respectivement passees en trois ans de 14 a 43, de 2,26 a 4,22 et de 0,53 a 0,79, ce qui traduit une amelioration progressive de la flore. Acacia senegal et Bauhinia rufescens ont enregistre les plus forts taux de survie et les plus importantes croissances en hauteur et en diametre. Les mortalites elevees des A. seyal et Ziziphus mauritiana sont vraisemblablement liees a la forte concentration de rongeurs que la presence dfune cloture ne gene guere. La pose couteuse dfune cloture nfest efficace que contre les grands mammiferes, ce qui se traduit toujourspar une croissance en diametre et en hauteur superieure pour la zone cloturee.Mots-cles : restauration ecologique, brousse tachetee, Acacia senegal, Acacia seyal, Bauhinia rufescens, Ziziphus mauritiana, ouvrage antierosif

Helicobacter pullorum cytolethal distending toxin targets vinculin and cortactin and triggers formation of lamellipodia in intestinal epithelial cells

Helicobacter pullorum, a bacterium initially isolated from poultry, has been associated with human digestive disorders. However, the factor responsible for its cytopathogenic effects on epithelial cells has not been formally identified. The cytopathogenic alterations induced by several human and avian H. pullorum strains were investigated on human intestinal epithelial cell lines. Moreover, the effects of the cytolethal distending toxin (CDT) were evaluated first by using a wild-type strain and its corresponding cdtB isogenic mutant and second by delivering the active CdtB subunit of the CDT directly into the cells. All of the H. pullorum strains induced cellular distending phenotype, actin cytoskeleton remodeling, and G2/M cell cycle arrest. These effects were dependent on the CDT, as they were (1) not observed in response to a cdtB isogenic mutant strain and (2) present in cells expressing CdtB. CdtB also induced an atypical delocalization of vinculin from focal adhesions to the perinuclear region, formation of cortical actin-rich large lamellipodia with an upregulation of cortactin, and decreased cellular adherence. In conclusion, the CDT of H. pullorum is responsible for major cytopathogenic effects in vitro, confirming its role as a main virulence factor of this emerging human pathogen.This work was supported by the Institut national de la santé et de la recherche médicale, the University Bordeaux Segalen, the Conseil Régional d’Aquitaine (grants 20030304002FA and 20040305003 FA), the Société Nationale Française de Gastroentérologie, the European Union (FEDER no. 2003227

Membrane phospholipids control gating of the mechanosensitive potassium leak channel TREK1

Tandem pore domain (K2P) potassium channels modulate resting membrane potentials and shape cellular excitability. For the mechanosensitive subfamily of K2Ps, the composition of phospholipids within the bilayer strongly influences channel activity. To examine the molecular details of K2P lipid modulation, we solved cryo-EM structures of the TREK1 K2P channel bound to either the anionic lipid phosphatidic acid (PA) or the zwitterionic lipid phosphatidylethanolamine (PE). At the extracellular face of TREK1, a PA lipid inserts its hydrocarbon tail into a pocket behind the selectivity filter, causing a structural rearrangement that recapitulates mutations and pharmacology known to activate TREK1. At the cytoplasmic face, PA and PE lipids compete to modulate the conformation of the TREK1 TM4 gating helix. Our findings demonstrate two distinct pathways by which anionic lipids enhance TREK1 activity and provide a framework for a model that integrates lipid gating with the effects of other mechanosensitive K2P modulators

Novel Survivin Inhibitor for Suppressing Pancreatic Cancer Cells Growth via Downregulating Sp1 and Sp3 Transciption Factors

Background/Aims: Targeting survivin, an anti-apoptotic protein and mitotic regulator, is considered as an effective therapeutic option for pancreatic cancer (PaCa). Tolfenamic acid (TA) showed anti-cancer activity in pre-clinical studies. A recent discovery demonstrated a copper(II) complex of TA (Cu-TA) can result in higher activity. In this study, the ability of Cu-TA to inhibit survivin and its transcription factors, Specificity protein (Sp) 1 and 3 in PaCa cell lines and tumor growth in mouse xenograft model were evaluated. Methods: Cell growth inhibition was measured in MIA PaCa-2 and Panc1 cells for 2 days using CellTiter-Glo kit. Sp1, Sp3 and survivin expression (by Western blot and qPCR), apoptotic cells and cell cycle phase distribution (by flow cytometry) were evaluated. A pilot study was performed using athymic nude mice [treated with vehicle/Cu-TA (25 or 50 mg/kg) 3 times/week for 4 weeks. Results: The IC50 value for Cu-TA was about half than TA. Both agents repressed the protein expression of Sp1/Sp3/survivin, Cu-TA was more effective than TA. Especially effect on survivin inhibition was 5.2 (MIA PaCa-2) or 6.4 (Panc1) fold higher and mRNA expression of only survivin was decreased. Apoptotic cells increased with Cu-TA treatment in both cell lines, while Panc1 showed both effect on apoptosis and cell cycle (G2/M) arrest. Cu-TA decreased the tumor growth in mouse xenografts (25 mg/kg: 48%; 50 mg/kg: 68%). Additionally, there was no change observed in mice body weights, indicating no overt toxicity was occurring. Conclusion: These results show that Cu-TA can serve as an effective survivin inhibitor for inhibiting PaCa cell growth

Evaluating Short-Term Patient Outcomes after HIV Care Interventions in a Low Resource Setting: Preparing for an HIV Vaccine Trial Site in Bamako, Mali

Poster Presentation From AIDS Vaccine 2012 Boston, MA, USA. 9-12 September 201

Protocol, rationale and design of PEOPLE (Post ExpOsure Prophylaxis for LEprosy in the Comoros and Madagascar): A cluster randomized trial on effectiveness of different modalities of implementation of post-exposure prophylaxis of leprosy contacts

Background: Leprosy is an ancient infectious disease with a global annual incidence that has plateaued above 200,000 new cases since over a decade. New strategies are required to overcome this stalemate. Post-exposure prophylaxis (PEP) with a single dose of Rifampicin (SDR) has conditionally been recommended by the World Health Organization (WHO), based on a randomized-controlled-Trial in Bangladesh. More evidence is required. The Post ExpOsure Prophylaxis for Leprosy (PEOPLE) trial will assess effectiveness of different modalities of PEP on the Comoros and Madagascar. Methods: PEOPLE is a cluster-randomized trial with villages selected on previous leprosy-incidence and randomly allocated to four arms. Four annual door-To-door surveys will be performed in all arms. All consenting permanent residents will be screened for leprosy. Leprosy patients will be treated according to international guidelines and eligible contacts will be provided with SDR-PEP. Arm-1 is the comparator in which no PEP will be provided. In arms 2, 3 and 4, SDR-PEP will be provided at double the regular dose (20 mg/kg) to eligible contacts aged two years and above. In arm 2 all household-members of incident leprosy patients are eligible. In arm 3 not only household-members but also neighbourhood contacts living within 100-m of an incident case are eligible. In arm 4 such neighbourhood contacts are only eligible if they test positive to anti-PGL-I, a serological marker. Incidence rate ratios calculated between the comparator arm 1 and each of the intervention arms will constitute the primary outcome. Discussion: Different trials on PEP have yielded varying results. The pivotal COLEP trial in Bangladesh showed a 57% reduction in incidence over a two-year period post-intervention without any rebound in the following years. A study in a high-incidence setting in Indonesia showed no effect of PEP provided to close contacts but a major effect of PEP provided as a blanket measure to an entire island population. High background incidence could be the reason of the lack of effect of PEP provided to individual contacts. The PEOPLE trial will assess effectiveness of PEP in a high incidence setting and will compare three different approaches, to identify who benefits most from PEP. Trial registration: Clinicaltrials.Gov. NCT03662022. Initial Protocol Version 1.2, 27-Aug-2018