RESUMO
Direct acting antiviral (DAA) therapy against hepatitis C virus (HCV) increases sustained virologic response rates. Nevertheless, drug resistance has occasionally been associated with failure to DAA. However, the information about the prevalence of NS5A and NS5B resistance-associated substitutions (RASs) in Argentina is very scarce. In this study, we determine the prevalence of NS5A and NS5B resistances to treatment in Argentinean DAA treatment-naïve patients chronically infected with genotype 1 (HCV-1). In this retrospective cross-sectional study, 108 HCV-1-infected patients were studied. RASs in NS5A and NS5B were analyzed by Sanger at baseline and phylogenetic analysis was performed. NS5A and NS5B RASs were detected in 25.8% and 6.3% of the analyzed sequences, respectively. The most frequent primary RASs for NS5A were L31M (7.5%) and Y93H (3.2%) and for NS5B was L159F (3.8%). No association between the presence of RASs and the outcome of DAA treatment was found in this study. Additionally, most of the Argentinean samples were randomly distributed among sequences around the world in the phylogenetic analysis. Only one significant Argentinean cluster was observed in both regions but without any particular RASs pattern. Baseline RASs in NS5A and NS5B were frequently observed in HCV-1-infected patients from Buenos Aires, Argentina but not related to treatment outcome. No clusters related to RASs transmission were observed in the phylogenetic analysis. The frequency of RASs detected in this study supports the need for more molecular epidemiology studies on RASs to adjust local treatment guidelines with the incorporation of autochthonous data.
Assuntos
Substituição de Aminoácidos , Antivirais/uso terapêutico , Farmacorresistência Viral/genética , Hepacivirus/genética , Proteínas não Estruturais Virais/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Argentina/epidemiologia , Estudos Transversais , Feminino , Genótipo , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/epidemiologia , Hepatite C Crônica/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Filogenia , Prevalência , Estudos RetrospectivosRESUMO
The aim of the present study was to gather information regarding the molecular epidemiology of Human papillomavirus (HPV) and related risk factors in a group of women with low- and high-grade cervical lesions and cancer from the coastal region of Ecuador. In addition, we studied the evolution of HPV variants from the most prevalent types and provided a temporal framework for their emergence, which may help to trace the source of dissemination within the region. We analyzed 166 samples, including 57 CIN1, 95 CIN2/3 and 14 cancer cases. HPV detection and typing was done by PCR-sequencing (MY09/MY11). HPV variants and estimation of the time to most recent common ancestor (tMRCA) was assessed through phylogeny and coalescence analysis. HPV DNA was found in 54.4% of CIN1, 74.7% of CIN2/3 and 78.6% of cancer samples. HPV16 (38.9%) and HPV58 (19.5%) were the most prevalent types. Risk factors for the development of cervical lesions/cancer were the following: three or more pregnancies (OR = 4.3), HPV infection (OR = 3.7 for high-risk types; OR = 3.5 for HPV16), among others. With regard to HPV evolution, HPV16 isolates belonged to lineages A (69%) and D (31%) whereas HPV58 isolates belonged only to lineage A. The period of emergence of HPV16 was in association with human populations (tMRCA = 91 052 years for HPV16A and 27000 years for HPV16D), whereas HPV58A preceded Homo sapiens evolution (322 257 years). This study provides novel data on HPV epidemiology and evolution in Ecuador, which will be fundamental in the vaccine era.
El objetivo del presente estudio fue aportar información sobre la epidemiología molecular del virus del papiloma humano (human papillomavirus [HPV]) y los factores de riesgo asociados al desarrollo de lesiones cervicales y cáncer en mujeres de la costa del Ecuador. Además, se estudiaron la evolución de las variantes de los HPV más prevalentes y el marco temporal de su emergencia, para ayudar a rastrear la fuente de dispersión en la región. Se analizaron 166 muestras, incluyendo 57 y 95 casos de neoplasia intraepitelial cervical tipo 1 (CIN1) y tipo 2/3 (CIN2/3), respectivamente, y 14 de casos de cáncer. La detección/tipificación de HPV se realizó por PCR-secuenciación (MY09/MY11). La caracterización de variantes y la datación del ancestro común más reciente (tMRCA) se realizaron mediante filogenia y coalescencia. Se encontró ADN de HPV en el 54,4% de las muestras de CIN1, el 74,7% de las muestras de CIN2/3 y el 78,6% de las muestras de cáncer. Los tipos HPV16 (38,9%) y HPV58 (19,5%) fueron los más frecuentes. Los factores de riesgo para el desarrollo de lesiones cervicales/cáncer fueron 3 o más embarazos (OR = 4,3) e infección por HPV (O = 3,7 para HPV de alto riesgo, OR = 3,5 para HPV16), entre otros. En cuanto a la evolución viral, los aislados del HPV16 pertenecían a los linajes A (69%) y D (31%), mientras que los aislados del HPV58 pertenecían únicamente al linaje A. El período de emergencia del HPV16 estuvo asociado a poblaciones humanas (tMRCA = 91.052 años para HPV16Ay 27.000 para HPV16D), mientras que el del HPV58A precedió a la evolución de Homo sapiens (322.257 años). Este estudio proporciona datos novedosos sobre la epidemiología y la evolución del HPV en Ecuador, los cuales serán fundamentales en la era de la vacuna.
Assuntos
Feminino , Humanos , Filogenia , Neoplasias do Colo do Útero , Epidemiologia Molecular , Infecções por Papillomavirus , Papillomaviridae , DNA Viral/análise , Neoplasias do Colo do Útero/virologia , Infecções por Papillomavirus/genética , Infecções por Papillomavirus/epidemiologia , Equador/epidemiologiaRESUMO
.(AU)
Bacterial richness in maritime Antarctica has been poorly described to date. Phylogenetic affiliation of seawater free-living microbial assemblages was studied from three locations near the Argentinean Jubany Station during two Antarctic summers. Sixty 16S RNA cloned sequences were phylogenetically affiliated to Alphaproteobacteria (30/60 clones), Gammaproteobacteria(19/60 clones), Betaproteobacteria and Cytophaga-Flavobacteriia- Bacteroides (CFB), which were (2/60) and (3/60) respectively. Furthermore, six out of 60 clones could not be classified. Both, Alphaproteobacteria and Gammaproteobacteria, showed several endemic and previously undescribed sequences. Moreover, the absence of Cyanobacteria sequences in our samples is remarkable. In conclusion, we are reporting a rich sequence assemblage composed of widely divergent isolates among themselves and distant from the most closely related sequences currently deposited in data banks.(AU)
RESUMO
.
Bacterial richness in maritime Antarctica has been poorly described to date. Phylogenetic affiliation of seawater free-living microbial assemblages was studied from three locations near the Argentinean Jubany Station during two Antarctic summers. Sixty 16S RNA cloned sequences were phylogenetically affiliated to Alphaproteobacteria (30/60 clones), Gammaproteobacteria(19/60 clones), Betaproteobacteria and Cytophaga-Flavobacteriia- Bacteroides (CFB), which were (2/60) and (3/60) respectively. Furthermore, six out of 60 clones could not be classified. Both, Alphaproteobacteria and Gammaproteobacteria, showed several endemic and previously undescribed sequences. Moreover, the absence of Cyanobacteria sequences in our samples is remarkable. In conclusion, we are reporting a rich sequence assemblage composed of widely divergent isolates among themselves and distant from the most closely related sequences currently deposited in data banks.