33 research outputs found
Esofagite por Candida: distribuição da espécie e fatores de risco para a infecção
Although Candida albicans is the main cause of fungal esophagitis, other species such as C. tropicalis, C. krusei and C. stellatoidea have also been implicated. Several studies have identified risk factors for C. albicans esophagitis. However, data for non-C. albicans species is still sparse. The aim of this study was to determine the etiology of Candida esophagitis in our medical centre over an 18-month period. Additionally, we aimed to investigate predisposing conditions for esophageal candidosis caused by different Candida species. A total of 21,248 upper gastroscopies were performed in Santa Casa Complexo Hospitalar between January 2005 and July 2006. The prevalence of Candida esophagitis was 0.74% (n = 158). C. albicans caused the vast majority of infections (96.2%), followed by C. tropicalis (2.5%), C. lusitaniae (0.6%) and C. glabrata (0.6%). There were 81 women (51.3%) and 77 men (48.7%). No case of mixed infection occurred. Concomitant oral candidosis was documented for 10.8% (n = 17). Most of cases (55.1%) involved outpatients. Around one fifth of patients in our cohort had no identifiable risk factors for esophageal candidosis (20.8%). Since nearly all infections were caused by C. albicans we were not able to determine risk factors for esophagitis caused by other Candida species.Embora Candida albicans seja a principal causa de esofagite fĂșngica, outras espĂ©cies como C. tropicalis, C. krusei e C. stellatoidea tambĂ©m tĂȘm sido implicadas. O objetivo desse estudo foi descrever espĂ©cies causadoras de esofagite fĂșngica em nosso centro durante um perĂodo de 18 meses, alĂ©m de comparar condiçÔes predisponentes para candidose esofĂĄgica causadas por diferentes espĂ©cies de Candida. De janeiro de 2005 a julho de 2006, 21.248 endoscopias digestivas altas foram realizadas no Complexo Hospitalar Santa Casa (Porto Alegre, Brasil). A prevalĂȘncia de esofagite por Candida foi de 0,74% (n = 158). C. albicans foi a causadora da maioria das infecçÔes (96,2%), seguida por C. tropicalis (2,5%), C. lusitaniae (0,6%) e C. glabrata (0,6%). Candidose oral concomitante foi documentada em 10,8% (n = 17). Cerca de 21% dos pacientes nĂŁo teve qualquer fator de risco identificĂĄvel para candidose esofĂĄgica. Em função do pequeno nĂșmero de pacientes infectados por espĂ©cies nĂŁo-Candida albicans, nĂŁo foi possĂvel determinarmos fatores de risco para estas infecçÔes
Polymorphisms and resistance mutations of hepatitis C virus on sequences in the European hepatitis C virus database
AIM: To evaluate the occurrence of resistant mutations in treatment-naĂŻve hepatitis C virus (HCV) sequences deposited in the European hepatitis C virus database (euHCVdb).
METHODS: The sequences were downloaded from the euHCVdb (https://euhcvdb.ibcp.fr/euHCVdb/). The search was performed for full-length NS3 protease, NS5A and NS5B polymerase sequences of HCV, separated by genotypes 1a, 1b, 2a, 2b and 3a, and resulted in 798 NS3, 708 NS5A and 535 NS5B sequences from HCV genotypes 1a, 1b, 2a, 2b and 3a, after the exclusion of sequences containing errors and/or gaps or incomplete sequences, and sequences from patients previously treated with direct antiviral agents (DAA). The sequence alignment was performed with MEGA 6.06 MAC and the resulting protein sequences were then analyzed using the BioEdit 7.2.5. for mutations associated with resistance. Only positions that have been described as being associated with failure in treatment in in vivo studies, and/or as conferring a more than 2-fold change in replication in comparison to the wildtype reference strain in in vitro phenotypic assays were included in the analysis.
RESULTS: The Q80K variant in the NS3 gene was the most prevalent mutation, being found in 44.66% of subtype 1a and 0.25% of subtype 1b. Other frequent mutations observed in more than 2% of the NS3 sequences were: I170V (3.21%) in genotype 1a, and Y56F (15.93%), V132I (23.28%) and I170V (65.20%) in genotype 1b. For the NS5A, 2.21% of the genotype 1a sequences have the P58S mutation, 5.95% of genotype 1b sequences have the R30Q mutation, 15.79% of subtypes 2a sequences have the Q30R mutation, 23.08% of subtype 2b sequences have a L31M mutation, and in subtype 3a sequences, 23.08% have the M31L resistant variants. For the NS5B, the V321L RAV was identified in 0.60% of genotype 1a and in 0.32% of genotype 1b sequences, and the N142T variant was observed in 0.32% of subtype 1b sequences. The C316Y, S556G, D559N RAV were identified in 0.33%, 7.82% and 0.32% of genotype 1b sequences, respectively, and were not observed in other genotypes.
CONCLUSION: HCV mutants resistant to DAAs are found in low frequency, nevertheless they could be selected and therapy could fail due resistance substitutions in HCV genome
Polymorphisms and resistance mutations of hepatitis C virus on sequences in the European hepatitis C virus database
AIM: To evaluate the occurrence of resistant mutations in treatment-naĂŻve hepatitis C virus (HCV) sequences deposited in the European hepatitis C virus database (euHCVdb).
METHODS: The sequences were downloaded from the euHCVdb (https://euhcvdb.ibcp.fr/euHCVdb/). The search was performed for full-length NS3 protease, NS5A and NS5B polymerase sequences of HCV, separated by genotypes 1a, 1b, 2a, 2b and 3a, and resulted in 798 NS3, 708 NS5A and 535 NS5B sequences from HCV genotypes 1a, 1b, 2a, 2b and 3a, after the exclusion of sequences containing errors and/or gaps or incomplete sequences, and sequences from patients previously treated with direct antiviral agents (DAA). The sequence alignment was performed with MEGA 6.06 MAC and the resulting protein sequences were then analyzed using the BioEdit 7.2.5. for mutations associated with resistance. Only positions that have been described as being associated with failure in treatment in in vivo studies, and/or as conferring a more than 2-fold change in replication in comparison to the wildtype reference strain in in vitro phenotypic assays were included in the analysis.
RESULTS: The Q80K variant in the NS3 gene was the most prevalent mutation, being found in 44.66% of subtype 1a and 0.25% of subtype 1b. Other frequent mutations observed in more than 2% of the NS3 sequences were: I170V (3.21%) in genotype 1a, and Y56F (15.93%), V132I (23.28%) and I170V (65.20%) in genotype 1b. For the NS5A, 2.21% of the genotype 1a sequences have the P58S mutation, 5.95% of genotype 1b sequences have the R30Q mutation, 15.79% of subtypes 2a sequences have the Q30R mutation, 23.08% of subtype 2b sequences have a L31M mutation, and in subtype 3a sequences, 23.08% have the M31L resistant variants. For the NS5B, the V321L RAV was identified in 0.60% of genotype 1a and in 0.32% of genotype 1b sequences, and the N142T variant was observed in 0.32% of subtype 1b sequences. The C316Y, S556G, D559N RAV were identified in 0.33%, 7.82% and 0.32% of genotype 1b sequences, respectively, and were not observed in other genotypes.
CONCLUSION: HCV mutants resistant to DAAs are found in low frequency, nevertheless they could be selected and therapy could fail due resistance substitutions in HCV genome
Polymorphisms and resistance mutations of hepatitis C virus on sequences in the European hepatitis C virus database
AIM: To evaluate the occurrence of resistant mutations in treatment-naĂŻve hepatitis C virus (HCV) sequences deposited in the European hepatitis C virus database (euHCVdb).
METHODS: The sequences were downloaded from the euHCVdb (https://euhcvdb.ibcp.fr/euHCVdb/). The search was performed for full-length NS3 protease, NS5A and NS5B polymerase sequences of HCV, separated by genotypes 1a, 1b, 2a, 2b and 3a, and resulted in 798 NS3, 708 NS5A and 535 NS5B sequences from HCV genotypes 1a, 1b, 2a, 2b and 3a, after the exclusion of sequences containing errors and/or gaps or incomplete sequences, and sequences from patients previously treated with direct antiviral agents (DAA). The sequence alignment was performed with MEGA 6.06 MAC and the resulting protein sequences were then analyzed using the BioEdit 7.2.5. for mutations associated with resistance. Only positions that have been described as being associated with failure in treatment in in vivo studies, and/or as conferring a more than 2-fold change in replication in comparison to the wildtype reference strain in in vitro phenotypic assays were included in the analysis.
RESULTS: The Q80K variant in the NS3 gene was the most prevalent mutation, being found in 44.66% of subtype 1a and 0.25% of subtype 1b. Other frequent mutations observed in more than 2% of the NS3 sequences were: I170V (3.21%) in genotype 1a, and Y56F (15.93%), V132I (23.28%) and I170V (65.20%) in genotype 1b. For the NS5A, 2.21% of the genotype 1a sequences have the P58S mutation, 5.95% of genotype 1b sequences have the R30Q mutation, 15.79% of subtypes 2a sequences have the Q30R mutation, 23.08% of subtype 2b sequences have a L31M mutation, and in subtype 3a sequences, 23.08% have the M31L resistant variants. For the NS5B, the V321L RAV was identified in 0.60% of genotype 1a and in 0.32% of genotype 1b sequences, and the N142T variant was observed in 0.32% of subtype 1b sequences. The C316Y, S556G, D559N RAV were identified in 0.33%, 7.82% and 0.32% of genotype 1b sequences, respectively, and were not observed in other genotypes.
CONCLUSION: HCV mutants resistant to DAAs are found in low frequency, nevertheless they could be selected and therapy could fail due resistance substitutions in HCV genome
Genetic Barrier to Direct Acting Antivirals in HCV Sequences Deposited in the European Databank
Background & Aims: Development of resistance results from mutations in the viral genome, and the presence of selective drug pressure leads to the emergence of a resistant virus population. The aim of this study was to analyze the impact of genetic variability on the genetic barrier to drug resistance to DAAs.
Methods: The genetic barrier was quantified based on the number and type of nucleotide mutations required to impart resistance, considering full-length HCV NS3, NS5A and NS5B regions segregated by genotype into subtypes 1a, 1b, 2a, 2b and 3a. This study analyzed 789 NS3 sequences, 708 sequences and 536 NS5B sequences deposited in the European Hepatitis C Virus Database, in the following resistance-associated positions: NS3: F43/I/L/ S/V, Q80K/R, R155K/G, A156G/S/T and D168A/C/E/G/H/N/T/V/Y; NS5A: L/M28A/T/V, Q30E/H/R, L31F/I/M/V, H58D or P58S and Y93C/F/H/N/S; NS5B: S282P/R/T, C316H/N/Y, S368T, Y448C/H, S556G/R, D559R.
Results: Variants that require only one transversion in NS3 were found in 4 positions and include F43S, R80K, R155K/G and A156T. The genetic barrier to resistance shows subtypic differences at position 155 of the NS3 gene where a single transition is necessary in subtype 1a. In the NS5A gene, 5 positions where only one nucleotide change can confer resistance were found, such as L31M which requires one transversion in all subtypes, except in 0.28% of 1b sequences; and R30H, generated by a single transition, which was found in 10.25% of the sequences of genotype 1b. Other subtypic differences were observed at position 58, where resistance is less likely in genotype 1a because a transversion is required to create the variant 58S. For the NS5B inhibitors, the genetic barrier at positions conferring resistance was nearly identical in subtypes 1a and 1b, and single transitions or transversions were necessary in 5 positions to generate a drug-resistant variant of HCV. The positions C316Y and S556D required only one transition in all genotypes, Y448H and S556 G/N/R positions required only one transition for up to 98.8%of the sequences analyzed. A single variant in position 448 in genotype 1a is less likely to become the resistance variant 448H because it requires two transversions. Also, in the position 559D a transversion and a transition were necessary to generate the resistance mutant D559H.
Conclusion: Results revealed that in 14 out of 16 positions, conversion to a drug-resistant variant of HCV required only one single nucleotide substitutions threatening direct acting antivirals from all three classes
Tratamento de cromoblastomicose severa com a associação itraconazole e 5-flucitosina
Cromoblastomicose Ă© uma infecção fĂșngica crĂŽnica do tecido subcutĂąneo causada pela inoculação traumĂĄtica de um grupo especĂfico de fungos atravĂ©s da pele, encontrados eventualmente em trabalhadores do campo descalços em paĂses de clima tropical e subtropical. Relatamos aqui o caso de um paciente do sexo masculino com uma lesĂŁo dermatolĂłgica de crescimento lento e pruriginosa nos membros inferiores por 20 anos, diagnosticada e tratada com sucesso para cromoblastomicose. Apesar da prevalĂȘncia desta doença em nossa regiĂŁo, o tratamento ainda Ă© um desafio.Chromoblastomycosis is a chronic human melanized fungi infection of the subcutaneous tissue caused by traumatic inoculation of a specific group of dematiaceous fungi through the skin, often found in barefooted agricultural workers, in tropical and subtropical climate countries. We report the case of a male patient presenting a slow-growing pruriginous lesion on the limbs for 20 years, mistreated over that time, which was diagnosed and successfully treated as chromoblastomycosis. Besides the prevalence of this disease, treatment is still a clinical challenge
FREQUENCY OF THE MDR1 GENE POLYMORPHISM RS1045642 (C3435T) IN HCV-HIV CO-INFECTED PATIENTS
Relative validity of a food frequency questionnaire in patients coinfected with hepatitis C virus and human immunodeficiency virus
Candidose esofågica : distribuição de espécies e fatores de risco em hospital terciårio de Porto Alegre
INTRODUĂĂO: a incidĂȘncia de esofagite fĂșngica tem se elevado nos Ășltimos anos, com diversos casos sendo relatados em indivĂduos sem qualquer fator de risco. Embora Candida albicans seja o principal agente etiolĂłgico da esofagite fĂșngica, outras espĂ©cies como C. tropicalis, C. krusei e C. stellatoidea tĂȘm sido implicadas como agentes etiolĂłgicos. OBJETIVO: descrever as espĂ©cies de fungos causadores de esofagite em nosso centro durante um perĂodo de 18 meses; avaliar os fatores de risco para candidose esofĂĄgica; comparar as condiçÔes predisponentes para diferentes espĂ©cies de Candida; analisar a suscetibilidade das espĂ©cies Ă s drogas antifĂșngicas e avaliar a prevalĂȘncia de outros gĂȘneros fĂșngicos em pacientes com esofagite MĂTODOS: de janeiro de 2005 a julho de 2006, foram realizadas 21.248 endoscopias digestivas altas na Santa Casa Complexo Hospitalar (Porto Alegre, RS Brasil), sendo diagnosticada esofagite fĂșngica em 159 pacientes. Os espĂ©cimes clĂnicos obtidos atravĂ©s de biĂłpsia ou escovado esofĂĄgico foram encaminhado para exame micolĂłgico direto e cultivo. A identificação das espĂ©cies foi realizada pela formação de tubo germinativo e atravĂ©s do sistema automatizado VITEK ID 32C (bioMĂ©rieux Marcy lâEtoile, França). Os testes de suscetibilidade ao fluconazol foram realizados utilizando ensaios de microdiluição, de acordo com a metodologia recomendada pelo CLSI (Clinical and Laboratory Standards Institute), documento M27-A. RESULTADOS: A prevalĂȘncia de candidose esofĂĄgica foi de 0,74% (n=158). C. albicans foi a espĂ©cie causadora da maioria das infecçÔes (96,2%), seguida por C. tropicalis (2,5%), C. lusitaniae (0,6%) e C. glabrata (0,6%). Houve apenas um caso (0,63%) de esofagite por outro gĂȘnero. LesĂ”es orais compatĂveis com candidose foram concomitantemente documentadas em 10,8% (n=17). Cerca de um quinto dos pacientes nĂŁo teve qualquer fator de risco identificĂĄvel para candidose esofĂĄgica. Exceto por um isolado de Candida, todos os demais foram considerados sensĂveis ao fluconazol. Em função do pequeno nĂșmero de pacientes infectados por espĂ©cies nĂŁo-C. albicans, nĂŁo foi possĂvel determinar fatores de risco para estas infecçÔes. CONCLUSĂES: C. albicans foi o principal agente etiolĂłgico de esofagite fĂșngica, sendo que esofagite causada por outros gĂȘneros de fungos foram pouco freqĂŒentes. ResistĂȘncia aos antifĂșngicos imidazĂłlicos nĂŁo foi observada.INTRODUTION: the incidence of fungal oesophagitis has increased in the last years, with many cases occurring in patients without any identifiable risk factor. Although Candida albicans is the main cause of fungal oesophagitis, other species such as C. tropicalis, C. krusei and C. stellatoidea have also been implicated. OBJETIVE: to describe the fungal species causing oesophagitis in our medical centre over an 18-month period; to evaluate the risk factors for Candida oesophagitis; to describe predisposing conditions for oesophageal candidosis caused by different Candida species; to evaluate the prevalence of non-C. albicans species as the cause of fungal oesophagitis; and to analyse the susceptibility of Candida species to antifungal agents. METHODS: During January 2005 and July 2006, a total of 21,248 upper gastroscopies were performed in Santa Casa Complexo Hospitalar (Porto Alegre, Brazil). Fungal oesophagitis was diagnosed in 159 patients. Samples were sent in saline solution to the mycology laboratory. The germ tube test was used to differentiate C. albicans from other Candida species, which were identified at the species level with ID 32C kit (bioMĂ©rieux Marcy lâEtoile, France). Susceptibility testing to antifungal drugs was performed by microdiluition, according to the document M27-A (CLSI, Clinical and Laboratory Standards Institute). RESULTS: The prevalence of Candida oesophagitis was 0.74% (n=158). The vast majority of infections were caused by C. albicans (96.2%), followed by C. tropicalis (2.5%), C. lusitaniae (0.6%) and C. glabrata (0.6%). All but one case of fungal oesophagitis were caused by Candida species. There were 81 women (51.3%) and 77 men (48.7%). Oral candidosis was diagnosed in 10.8% of patients (n=17). Around one fifth of patients had no identifiable risk factors for oesophageal candidosis. All but one isolate were fluconazole-sensitive. Statistical analyses were hampered by the limited number of oesophagitis caused by non-C. albicans species. CONCLUSION: C. albicans was to be the main aetiology of fugal oesophagitis in our medical centre, with other fungi being uncommonly implicated. Resistance to triazolic antimicotic drugs was not observed
Candidose esofågica : distribuição de espécies e fatores de risco em hospital terciårio de Porto Alegre
INTRODUĂĂO: a incidĂȘncia de esofagite fĂșngica tem se elevado nos Ășltimos anos, com diversos casos sendo relatados em indivĂduos sem qualquer fator de risco. Embora Candida albicans seja o principal agente etiolĂłgico da esofagite fĂșngica, outras espĂ©cies como C. tropicalis, C. krusei e C. stellatoidea tĂȘm sido implicadas como agentes etiolĂłgicos. OBJETIVO: descrever as espĂ©cies de fungos causadores de esofagite em nosso centro durante um perĂodo de 18 meses; avaliar os fatores de risco para candidose esofĂĄgica; comparar as condiçÔes predisponentes para diferentes espĂ©cies de Candida; analisar a suscetibilidade das espĂ©cies Ă s drogas antifĂșngicas e avaliar a prevalĂȘncia de outros gĂȘneros fĂșngicos em pacientes com esofagite MĂTODOS: de janeiro de 2005 a julho de 2006, foram realizadas 21.248 endoscopias digestivas altas na Santa Casa Complexo Hospitalar (Porto Alegre, RS Brasil), sendo diagnosticada esofagite fĂșngica em 159 pacientes. Os espĂ©cimes clĂnicos obtidos atravĂ©s de biĂłpsia ou escovado esofĂĄgico foram encaminhado para exame micolĂłgico direto e cultivo. A identificação das espĂ©cies foi realizada pela formação de tubo germinativo e atravĂ©s do sistema automatizado VITEK ID 32C (bioMĂ©rieux Marcy lâEtoile, França). Os testes de suscetibilidade ao fluconazol foram realizados utilizando ensaios de microdiluição, de acordo com a metodologia recomendada pelo CLSI (Clinical and Laboratory Standards Institute), documento M27-A. RESULTADOS: A prevalĂȘncia de candidose esofĂĄgica foi de 0,74% (n=158). C. albicans foi a espĂ©cie causadora da maioria das infecçÔes (96,2%), seguida por C. tropicalis (2,5%), C. lusitaniae (0,6%) e C. glabrata (0,6%). Houve apenas um caso (0,63%) de esofagite por outro gĂȘnero. LesĂ”es orais compatĂveis com candidose foram concomitantemente documentadas em 10,8% (n=17). Cerca de um quinto dos pacientes nĂŁo teve qualquer fator de risco identificĂĄvel para candidose esofĂĄgica. Exceto por um isolado de Candida, todos os demais foram considerados sensĂveis ao fluconazol. Em função do pequeno nĂșmero de pacientes infectados por espĂ©cies nĂŁo-C. albicans, nĂŁo foi possĂvel determinar fatores de risco para estas infecçÔes. CONCLUSĂES: C. albicans foi o principal agente etiolĂłgico de esofagite fĂșngica, sendo que esofagite causada por outros gĂȘneros de fungos foram pouco freqĂŒentes. ResistĂȘncia aos antifĂșngicos imidazĂłlicos nĂŁo foi observada.INTRODUTION: the incidence of fungal oesophagitis has increased in the last years, with many cases occurring in patients without any identifiable risk factor. Although Candida albicans is the main cause of fungal oesophagitis, other species such as C. tropicalis, C. krusei and C. stellatoidea have also been implicated. OBJETIVE: to describe the fungal species causing oesophagitis in our medical centre over an 18-month period; to evaluate the risk factors for Candida oesophagitis; to describe predisposing conditions for oesophageal candidosis caused by different Candida species; to evaluate the prevalence of non-C. albicans species as the cause of fungal oesophagitis; and to analyse the susceptibility of Candida species to antifungal agents. METHODS: During January 2005 and July 2006, a total of 21,248 upper gastroscopies were performed in Santa Casa Complexo Hospitalar (Porto Alegre, Brazil). Fungal oesophagitis was diagnosed in 159 patients. Samples were sent in saline solution to the mycology laboratory. The germ tube test was used to differentiate C. albicans from other Candida species, which were identified at the species level with ID 32C kit (bioMĂ©rieux Marcy lâEtoile, France). Susceptibility testing to antifungal drugs was performed by microdiluition, according to the document M27-A (CLSI, Clinical and Laboratory Standards Institute). RESULTS: The prevalence of Candida oesophagitis was 0.74% (n=158). The vast majority of infections were caused by C. albicans (96.2%), followed by C. tropicalis (2.5%), C. lusitaniae (0.6%) and C. glabrata (0.6%). All but one case of fungal oesophagitis were caused by Candida species. There were 81 women (51.3%) and 77 men (48.7%). Oral candidosis was diagnosed in 10.8% of patients (n=17). Around one fifth of patients had no identifiable risk factors for oesophageal candidosis. All but one isolate were fluconazole-sensitive. Statistical analyses were hampered by the limited number of oesophagitis caused by non-C. albicans species. CONCLUSION: C. albicans was to be the main aetiology of fugal oesophagitis in our medical centre, with other fungi being uncommonly implicated. Resistance to triazolic antimicotic drugs was not observed