13 research outputs found

    Deep-sequencing reveals broad subtype-specific HCV resistance mutations associated with treatment failure

    Get PDF
    A percentage of hepatitis C virus (HCV)-infected patients fail direct acting antiviral (DAA)-based treatment regimens, often because of drug resistance-associated substitutions (RAS). The aim of this study was to characterize the resistance profile of a large cohort of patients failing DAA-based treatments, and investigate the relationship between HCV subtype and failure, as an aid to optimizing management of these patients. A new, standardized HCV-RAS testing protocol based on deep sequencing was designed and applied to 220 previously subtyped samples from patients failing DAA treatment, collected in 39 Spanish hospitals. The majority had received DAA-based interferon (IFN) a-free regimens; 79% had failed sofosbuvir-containing therapy. Genomic regions encoding the nonstructural protein (NS) 3, NS5A, and NS5B (DAA target regions) were analyzed using subtype-specific primers. Viral subtype distribution was as follows: genotype (G) 1, 62.7%; G3a, 21.4%; G4d, 12.3%; G2, 1.8%; and mixed infections 1.8%. Overall, 88.6% of patients carried at least 1 RAS, and 19% carried RAS at frequencies below 20% in the mutant spectrum. There were no differences in RAS selection between treatments with and without ribavirin. Regardless of the treatment received, each HCV subtype showed specific types of RAS. Of note, no RAS were detected in the target proteins of 18.6% of patients failing treatment, and 30.4% of patients had RAS in proteins that were not targets of the inhibitors they received. HCV patients failing DAA therapy showed a high diversity of RAS. Ribavirin use did not influence the type or number of RAS at failure. The subtype-specific pattern of RAS emergence underscores the importance of accurate HCV subtyping. The frequency of “extra-target” RAS suggests the need for RAS screening in all three DAA target regions

    Proyecto de lucha contra las grandes endemias : informe technico final

    No full text
    Objective: Data on the epidemiology of the Teniasis/Cysticercosis complex in the Department of a Paz, Bolivia, are very scarce, even if #Taenia solium is known to be endemic in the area. Thus, in the present study, we tried to identify the way of contamination of the human by the larvae of #Taenia solium, and to evaluate the prevalence of teniasis in several communities located in the Altiplano. Methods: A cross-sectional survey has been concluted in three rural communities located in the privince of Los Andes. the prevalence of taeniasis has been measured through coprological examinations including a direct microscopic examination and examination using Ritchie's concentration methods. A questionnaire has been aplied to collect information on the socio-economic environment, the displacements and the nutritional habits of each person. Another questionnaire, elaborated by the IENT, will be applied to identify people who suffer of epilepsy and to characterize the clinical presentation of the latter. The a CT-scan examination and a serodetection of antigens of #T. soliumwillbeperformedonpeoplewithepilepsyinordertoidentifythosepatientswithneurocysticercosis.Thestudyofthecontaminantpotentialinordertoidentifythosepatientswithneurocysticercosis.Thestudyofthecontaminantpotentialoffoodwasrealizedinaruralcommunity,aswellasinthecitiesofLaPazandElAlto.Samplesofcookedigmeathadbeenbought,dissected(thickness0.5cmwide)andtheviabilityofthecysticercipresentinthepiecesofmeathasbeenanalyzed.TheinfectivepotentialoftheparasitewasassessedbythecapacityofevaginationofthecysticercipreciouslywashedwithasalinesolutionandlefttoincubateinaPetriboxcontainingasalinesolutionat20 will be performed on people with epilepsy in order to identify those patients with neurocysticercosis. The study of the contaminant potential in order to identify those patients with neurocysticercosis. The study of the contaminant potential of food was realized in a rural community, as well as in the cities of La Paz and El Alto. Samples of cooked ig meat had been bought, dissected (thickness 0.5 cm wide) and the viability of the cysticerci present in the pieces of meat has been analyzed. The infective potential of the parasite was assessed by the capacity of evagination of the cysticerci preciously washed with a saline solution and left to incubate in a Petri box containing a saline solution at 20% of fresh bovine bile diluted in physiological serum. Results: A total of 269 faecal samples has been collected among the three communities visited. No egg of #Taenia sp. was found neither by direct examination of stools nor by te Ritchie's concentration techniques. Three cases of infection by helminth parasites have been recorded: two cases with #Hymenolepis nana(1,! (1,!%) and one with #Enterobius vermicularis (0,4%). In addition, the patients showed high rates of infection by protozoan parasites: #Entamoeba coli(59,8 (59,8%), #Endolimx nana (49,8%), #Blastocystis hominis(47,6 (47,6%), #Chilomastix mesnili (14,1%), #Giardia lamblia(10,8 (10,8%), #Entamoeba histolytica (10,8%) and #Iodamoeba butschlii$ (9,7%). A rigorous disection of the 120 food samples was made. 75 samples were bought in La Paz, 38 in El Alto and 7 in the village of Batallas on the Altiplano. Cysticerci were found in only one of the 75 samples which represents 0,8% of all the samples. The 10 cysticerci found were incubated during 24h in bovine bile diluted in physiological serum for testing their viability. None of them started to evaginate, thus they were al non-viable. Conclusion: According to our results, the prevalence of teniasis is very low in this part of the Bolivian Altiplano. A decrease of the prevalence of taeniasis probably occurred durging this last years, thanks to the National Programme for the Prevention and Control of Teniasis-Cysticercosis started in 1994. The apparent low rate of porcine infection by cysticercosis in this region may be due to changes in the husbandry practices or to an improvement in hygiene habits (90% of the population have latrines). No contaminating food was found during the study. the contamination of the human by infectious food may occur at Chrstmas when the marketing of pork meat increases dramatically in the city. (résumé d'auteur

    A Classification System for Colombian Wetlands: an Essential Step Forward in Open Environmental Policy-Making

    No full text
    Knowledge about the distribution and diversity of wetlands has become an essential tool for environmental management and policy-making. Yet, while recent estimates indicate that 27% of the area of Colombia is covered by wetlands and despite a number of regional studies, information about the diversity of wetlands nationally is scarce. In response, we present a national wetland classification system that is based on an ecological approach, from the perspective of wetland scientists, and which builds upon the assumptions underlying the flood pulse concept and hydrogeomorphic approach. Thus, the approach and structure of the Brazilian wetland classification system are used, with geomorphological adjustments made according to Colombia’s topography. The classification is hierarchical, multi-scale, functional, and organized according to four levels (system, macroregion, subsystem, and class), with the wetland diversity of Colombia represented nationally by 89 macrohabitats across marine-coastal, inland, and anthropogenic systems. The primary purpose of this classification is to provide integrated and organized information on the distribution and diversity of Colombian wetlands that will serve as a baseline for transparent environmental policy-making. © 2019, Society of Wetland Scientists

    Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility

    No full text
    Fasting glucose and insulin are intermediate traits for type 2 diabetes. Here we explore the role of coding variation on these traits by analysis of variants on the HumanExome BeadChip in 60,564 non-diabetic individuals and in 16,491 T2D cases and 81,877 controls. We identify a novel association of a low-frequency nonsynonymous SNV in GLP1R (A316T; rs10305492; MAF=1.4%) with lower FG (β=-0.09±0.01mmoll-1, P=3.4 × 10-12), T2D risk (OR[95%CI]=0.86[0.76-0.96], P=0.010), early insulin secretion (β=-0.07±0.035pmolinsulin mmolglucose-1, P=0.048), but higher 2-h glucose (β=0.16±0.05mmoll-1, P=4.3 × 10-4). We identify a gene-based association with FG at G6PC2 (p SKAT =6.8 × 10-6) driven by four rare protein-coding SNVs (H177Y, Y207S, R283X and S324P). We identify rs651007 (MAF=20%) in the first intron of ABO at the putative promoter of an antisense lncRNA, associating with higher FG (β=0.02±0.004mmoll-1, P=1.3 × 10-8). Our approach identifies novel coding variant associations and extends the allelic spectrum of variation underlying diabetes-related quantitative traits and T2D susceptibility. © 2015 Macmillan Publishers Limited. All rights reserved
    corecore