Facteurs prédictifs de l’échec de traitement antituberculeux en Guinée Conakry

La tuberculose est un véritable problème de santé publique. C'est une maladie guérissable et cette  guérison passe par une bonne prise en charge thérapeutique. Il arrive parfois on assiste à l'échec thérapeutique, d'où l'intérêt de notre étude portant sur les facteurs prédictifs de ses échecs. Dans  l'espace d'une année sur 1300 cas de tuberculose toute forme confondue, 700 cas de tuberculose  pulmonaire à microscopie positive ont été répertorié dont 100 cas transférés. La tranche d'âge de 15-25  ans a été la plus touchée avec un sexe-ratio de 2 en faveur des hommes et 41,66% de nos malades ont été les ouvriers suivis de 20,83% des commerçants. La majorité de nos patients provenait de Conakry  soit 99, 5%. Sur 600 patients suivis les nouveaux cas  représentaient 83,33% et l'échec thérapeutique représentait 12 cas soit 2%. L'interruption du traitement  représente le principal facteur de l'échec. Les facteurs qui ont influencé la régularité des malades au  traitement ont été multiples. Des facteurs liés à l'organisation du système de santé, la rupture des  médicaments antituberculeux, l'éducation sanitaire insuffisante, les contraintes de la supervision du traitement, l'implication insuffisante et la vente des médicaments par le personnel de santé. Des facteurs liés aux patients euxmêmes, la crainte de perte d'emploi, les contraintes financières. Les renforcements de  l'organisation du système sanitaire et l'éducation thérapeutiques pourront réduire le taux d'échec du  traitement antituberculeux. L'amélioration de la qualité de la prise en charge des malades en situation d'échec devrait passer par une culture systématique des expectorations avec antibiogramme.Key words: Facteurs prédictifs, Echec, Antituberculeux, Tuberculose.

Effect of premature rupture of membranes on the maternal and fetal prognosis during childbirth at the gynecology-obstetrics department of the Matam Communal Medical Center, Conakry, Guinea

Background: Premature rupture of membranes (RPM) is defined by rupture of the amnion and chorion before entering labor within 24 hours leading to vaginal discharge of amniotic fluid without uterine contractions. Objective of this study was to improving the management of premature Ruptures of the membranes received in the service.Methods: This was a descriptive and analytical prospective study lasting six months from January 1 to June 30 2016.Results: During the study period, we collected 108 cases of RPM out of 1543 deliveries, representing a hospital frequency of 7%. RPM had more frequently concerned pregnant women aged 25-29 (37.04%), housewife (37.03%), primiparous (45.37%) and referral (52.78%). 95.37% were single pregnancies with cephalic presentation (80%) received between 37-42 weeks (84.26%). Management mainly consisted of antibiotic prophylaxis (100%), fetal pulmonary maturation and childbirth. The vagina was the main mode of delivery (62.04%). The maternal prognosis was dominated by chorioamnionitis (12.96%). The fetal one was made up of respiratory distress (40.71%) and prematurity (12.39%).Conclusions: RPM is frequent at the Matam municipal medical center. It is essential for its prevention to ensure health education of the population in general and genital hygiene in particular, to make a coherent prenatal follow-up while putting a particular accent on the detection and the treatment of genital infections

CD209 Genetic Polymorphism and Tuberculosis Disease

BACKGROUND: Tuberculosis causes significant morbidity and mortality worldwide, especially in sub-Saharan Africa. DC-SIGN, encoded by CD209, is a receptor capable of binding and internalizing Mycobacterium tuberculosis. Previous studies have reported that the CD209 promoter single nucleotide polymorphism (SNP)-336A/G exerts an effect on CD209 expression and is associated with human susceptibility to dengue, HIV-1 and tuberculosis in humans. The present study investigates the role of the CD209 -336A/G variant in susceptibility to tuberculosis in a large sample of individuals from sub-Saharan Africa. METHODS AND FINDINGS: A total of 2,176 individuals enrolled in tuberculosis case-control studies from four sub-Saharan Africa countries were genotyped for the CD209 -336A/G SNP (rs4804803). Significant overall protection against pulmonary tuberculosis was observed with the -336G allele when the study groups were combined (n = 914 controls vs. 1262 cases, Mantel-Haenszel 2 x 2 chi(2) = 7.47, P = 0.006, odds ratio = 0.86, 95%CI 0.77-0.96). In addition, the patients with -336GG were associated with a decreased risk of cavitory tuberculosis, a severe form of tuberculosis disease (n = 557, Pearson's 2x2 chi(2) = 17.34, P = 0.00003, odds ratio = 0.42, 95%CI 0.27-0.65). This direction of association is opposite to a previously observed result in a smaller study of susceptibility to tuberculosis in a South African Coloured population, but entirely in keeping with the previously observed protective effect of the -336G allele. CONCLUSION: This study finds that the CD209 -336G variant allele is associated with significant protection against tuberculosis in individuals from sub-Saharan Africa and, furthermore, cases with -336GG were significantly less likely to develop tuberculosis-induced lung cavitation. Previous in vitro work demonstrated that the promoter variant -336G allele causes down-regulation of CD209 mRNA expression. Our present work suggests that decreased levels of the DC-SIGN receptor may therefore be protective against both clinical tuberculosis in general and cavitory tuberculosis disease in particular. This is consistent with evidence that Mycobacteria can utilize DC-SIGN binding to suppress the protective pro-inflammatory immune response

La langue pulaar en France (variation des pratiques et des formes dans les intéractions familiales)

La pulaar reste une langue qui se transmet bien en France. Cependant, on observe des variations au niveau des pratiques et des formes dans les interactions familiales. L'origine géographique des locuteurs, leurs réseaux de relations ainsi que le courant migratoire dont ils sont issus sont des éléments importants de différenciation des usages linguistiques des immigrés. Ainsi, les anciens immigrés originaires des villages et adoptant un mode de vie ethno-communautaire maintiennent un pulaar plus ancien et plus archaïque. Les nouveaux immigrés originaires des villes parlent un pulaar plus moderne. Par ailleurs, les variétés de pulaar des anciens immigrés ou des membres de l'Association Kawtal (une association de défense de la langue pulaar en France) se distinguent des variétés en usage dans les régions d'origines des locuteurs. En effet, le contact avec des nouvelles réalités fait évoluer le pulaar de France d'une manière différente. Dans les nouvelles formes, on note des néologismes, des formes archaïsantes (antiquating forms) ou des glissements sémantiques.Pulaar continues to be a well-transmitted immigrant language in France. However, a closer look at Pulaar forms and usage during family interactions shows marked generational variations. This stems naturally from differences in the language use of Pulaar immigrants from different geographical regions, who seek out suitable settlement sites in France based on relational networks. Earlier generations who migrate straight from villages and settle into ethnic communities tend to maintain an older and more archaic form of Pulaar. Newer immigrants from cities speak a more modernized form of Pulaar. Even then, the varieties of Pulaar spoken by older immigrants or members of the Kawtal Association - an association for the defense of the Pulaar language in France - are distinguishable from varieties in use in these speakerrs' regions of origin. In fact, contact with new realities on the ground lead to a different evolution of Pulaar in France. Notable in new Pulaar forms are neologisms, archaisms and semantic shifts.PARIS5-Bib. SHS Descartes CNRS (751062113) / SudocSudocFranceF

Variants of the CD40 ligand gene are not associated with increased susceptibility to tuberculosis in West Africa.

Evidence for linkage between tuberculosis and human chromosomal region Xq26 has previously been described. The costimulatory molecule CD40 ligand, encoded by TNFSF5 and located at Xq26.3, is a promising positional candidate. Interactions between CD40 ligand and CD40 are involved in the development of humoral- and cell-mediated immunity, as well as the activation of macrophages, which are the primary host and effector cells for Mycobacterium tuberculosis. We hypothesised that common variation within TNFSF5 might affect susceptibility to tuberculosis disease and, thus, might be responsible for the observed linkage to Xq26. Sequencing 32 chromosomes from a Gambian population identified nine common polymorphisms within the coding, 3' and 5' regulatory sequences of the gene. Six single nucleotide polymorphisms (SNPs) and a 3' microsatellite were genotyped in 121 tuberculosis patients and their available parents. No association with tuberculosis was detected for these variants using a transmission disequilibrium test, although one SNP at -726 showed some evidence of association in males. This finding, however, did not replicate in a separate case control study of over 1,200 West African individuals. We conclude that common genetic variation in TNFSF5 is not likely to affect tuberculosis susceptibility in West Africa and the linkage observed in this region is not due to variation in TNFSF5

Effect of efavirenz-based antiretroviral therapy and high-dose rifampicin on the pharmacokinetics of isoniazid and acetyl-isoniazid.

Objectives: To describe the pharmacokinetics of isoniazid and acetyl-isoniazid in TB/HIV-coinfected patients, and assess the effects of efavirenz co-administration and a 50% increase in the dose of rifampicin on the pharmacokinetic parameters of isoniazid and acetyl-isoniazid. Methods: TB/HIV-coinfected patients participating in the three-treatment-arm RAFA randomized controlled trial conducted in West Africa were recruited into the pharmacokinetics sub-study. Five serial blood samples were collected on a single visit between 4 and 8 weeks after initiation of antituberculosis treatment. Concentration-time data for isoniazid and acetyl-isoniazid were analysed using non-linear mixed-effects models. Results: Isoniazid concentrations from 150 patients were available for analysis, and 79 of these (53%) also had concentrations of acetyl-isoniazid. Isoniazid pharmacokinetics was best described with a two-compartment disposition model with lagged first-order absorption and elimination using a semi-mechanistic model describing hepatic extraction. The model identified two elimination pathways, separating formation of acetyl-isoniazid from other routes of metabolism. The predicted AUC0-24 is reduced by 29% in patients who are fast acetylators of isoniazid and receiving efavirenz-based ART (6.73 versus 4.68 mg·h/L). In slow acetylators, efavirenz-based ART had no effect on isoniazid exposure (AUC0-24 = 17.5 mg·h/L). Conclusions: Efavirenz-based ART affects the acetylation metabolic pathway amongst rapid acetylators, resulting in reduced exposure to isoniazid. Pharmacokinetics of isoniazid and acetyl-isoniazid were not influenced by the 50% increase in rifampicin dose

Shifts in Mycobacterial Populations and Emerging Drug-Resistance in West and Central Africa.

In this study, we retrospectively analysed a total of 605 clinical isolates from six West or Central African countries (Benin, Cameroon, Central African Republic, Guinea-Conakry, Niger and Senegal). Besides spoligotyping to assign isolates to ancient and modern mycobacterial lineages, we conducted phenotypic drug-susceptibility-testing for each isolate for the four first-line drugs. We showed that phylogenetically modern Mycobacterium tuberculosis strains are more likely associated with drug resistance than ancient strains and predict that the currently ongoing replacement of the endemic ancient by a modern mycobacterial population in West/Central Africa might result in increased drug resistance in the sub-region

IFN-gamma-inducible protein 10 and pentraxin 3 plasma levels are tools for monitoring inflammation and disease activity in Mycobacterium tuberculosis infection

IFN-gamma-inducible protein 10 (IP-10/CXCL10) is a chemokine involved in delayed-type hypersensitivity and attraction of monocytes and activated T lymphocytes at inflammatory foci, whereas pentraxin 3 (PTX3) is part of the innate immune response. In the Republic of Guinea, 220 newly diagnosed, HIV-negative, pulmonary tuberculosis (TB) patients were studied together with 220 healthy household controls and 220 community controls. CXCL10 and PTX3 blood levels were assessed by ELISA at diagnosis, after 2 months and at the end of treatment. In untreated patients, both CXCL 10 and PTX3 levels were higher (P < 0.0001) than in controls, although household controls had higher (P < 0.0001) CXCL10 and PTX3 levels than community controls, but lower (P < 0.0001) than those of patients. At the end of treatment, 186 cured patients showed reduction (P < 0.0001) in both CXCL10 and PTX3 levels. In 34 patients with treatment failure, both CXCL10 and PTX3 levels increased further. In five previously healthy households who developed TB during the follow-up and in two patients who relapsed after treatment, a remarkable increase in both CXCL10 and PTX3 plasma levels was observed. Active TB is associated with increased CXCL 10 and PTX3 levels in the plasma. Although not specific for TB, measurement of these proteins may help the monitoring of disease activity and efficacy of therapy. (C) 2004 Elsevier SAS. All rights reserved