Perfil epidemiológico, molecular e filogenético do vírus da hepatite B circulantes no Estado de Roraima

Detalhes bibliográficos
Autor(a) principal: Sousa, Débora Dinelly de
Data de Publicação: 2018
Tipo de documento: Tese
Idioma: por
Título da fonte: Repositório Institucional da UFRR
Texto Completo: http://repositorio.ufrr.br:8080/jspui/handle/prefix/206
Resumo: The infection through Hepatitis B virus (HBV) is a serious global public health issue, presenting in Roraima high prevalence rates. It is parenterally and sexually transmitted primarily. Its genome consists of a circular and partially double-stranded DNA, with about 3.2 kb. HBV has a high degree of genetic diversity. HBV genotypes play an important role in the virus-host relationship. Mechanisms for the persistence of HBV infection involve several aspects, including immunogenic factors. The objective of the study was to perform the epidemiological characterization of HBV patients and genetics of circulating HBV strains from the partial sequencing of the S gene, allowing the detection of genotypes, possible changes in the genetic pattern of the strains and polymorphisms in a human gene (CCR5), relating to the clinical course, susceptibility or protection against infection. The study population consisted of patients with HBV and control subjects. Extraction of viral and genomic DNA was performed using commercial kits. The amplification of the S gene and polymorphism (CCR5 gene) was performed through the Polymerase Chain Reaction (PCR), using specific initiators. The positive fragments of the S gene were sequenced, genotyped and used in the phylogenetic study based on the Bayesian method. Most of the HBV patients were male (56.25%), aged between 31-50 years (54.29%). The brown race was prevalent in 45.31%, 29.68% had incomplete primary education, 44.53% were married and 66.40% were residents of the capital Boa Vista. Regarding the probable source/mechanism of infection, sexual transmission occurred in 26.97% of the cases. Vaccination was reported as ignored in 28.12% of those involved in the study, and among those who reported the information, the complete vaccination schedule represented 25%. Regarding the contact with HBV patients, 51.56% had no contact, and among those who had contact, 53.12% reported occupational contact. The detectable viral load <2000 IU/mL was found in 57.81% of patients, 51.13% were on treatment, and, among the drugs, the most frequent was Tenofovir, with 56.04%. Forty sequences were genotyped and the Maximum Clades Reliability (MCC) tree confirmed the presence of the A, D and F genotypes, with a prevalence for the A genotype (70%), p <0.0001. The sub genotypes found were A1, A2, D2, D3, D4, F2a and F3, the latter being detected for the first time in Brazil. As for the CCR5 gene, for the allelic and genotype frequencies of the analyzed groups, the HBV population was not in the Hardy-Weinberg equilibrium (p = 0.0139). No difference was observed in the frequency (2.6%) of the Δ32 allele between the groups (p = 0.9626). The frequency of the Δ32/Δ32 mutation was 0.53% in the HBV group and 0% in the control group. The study of HBV molecular diversity and epidemiology, in addition to the genetic standards of the general population, can contribute to a better understanding of the disease at a local level and allow the adoption of measures to prevent and control infection.
id UFRR-6_90437c0dce83968b93f804ea0c713b6b
oai_identifier_str oai:repositorio.ufrr.br:prefix/206
network_acronym_str UFRR-6
network_name_str Repositório Institucional da UFRR
repository_id_str
spelling Perfil epidemiológico, molecular e filogenético do vírus da hepatite B circulantes no Estado de RoraimaEpidemiologia molecularMolecular epidemiologyHepatite BHepatitis BCaracterização molecularMolecular characterizationGene CCR5RoraimaBrasilBrazilCNPQ::CIENCIAS BIOLOGICAS::BIOLOGIA GERALThe infection through Hepatitis B virus (HBV) is a serious global public health issue, presenting in Roraima high prevalence rates. It is parenterally and sexually transmitted primarily. Its genome consists of a circular and partially double-stranded DNA, with about 3.2 kb. HBV has a high degree of genetic diversity. HBV genotypes play an important role in the virus-host relationship. Mechanisms for the persistence of HBV infection involve several aspects, including immunogenic factors. The objective of the study was to perform the epidemiological characterization of HBV patients and genetics of circulating HBV strains from the partial sequencing of the S gene, allowing the detection of genotypes, possible changes in the genetic pattern of the strains and polymorphisms in a human gene (CCR5), relating to the clinical course, susceptibility or protection against infection. The study population consisted of patients with HBV and control subjects. Extraction of viral and genomic DNA was performed using commercial kits. The amplification of the S gene and polymorphism (CCR5 gene) was performed through the Polymerase Chain Reaction (PCR), using specific initiators. The positive fragments of the S gene were sequenced, genotyped and used in the phylogenetic study based on the Bayesian method. Most of the HBV patients were male (56.25%), aged between 31-50 years (54.29%). The brown race was prevalent in 45.31%, 29.68% had incomplete primary education, 44.53% were married and 66.40% were residents of the capital Boa Vista. Regarding the probable source/mechanism of infection, sexual transmission occurred in 26.97% of the cases. Vaccination was reported as ignored in 28.12% of those involved in the study, and among those who reported the information, the complete vaccination schedule represented 25%. Regarding the contact with HBV patients, 51.56% had no contact, and among those who had contact, 53.12% reported occupational contact. The detectable viral load <2000 IU/mL was found in 57.81% of patients, 51.13% were on treatment, and, among the drugs, the most frequent was Tenofovir, with 56.04%. Forty sequences were genotyped and the Maximum Clades Reliability (MCC) tree confirmed the presence of the A, D and F genotypes, with a prevalence for the A genotype (70%), p <0.0001. The sub genotypes found were A1, A2, D2, D3, D4, F2a and F3, the latter being detected for the first time in Brazil. As for the CCR5 gene, for the allelic and genotype frequencies of the analyzed groups, the HBV population was not in the Hardy-Weinberg equilibrium (p = 0.0139). No difference was observed in the frequency (2.6%) of the Δ32 allele between the groups (p = 0.9626). The frequency of the Δ32/Δ32 mutation was 0.53% in the HBV group and 0% in the control group. The study of HBV molecular diversity and epidemiology, in addition to the genetic standards of the general population, can contribute to a better understanding of the disease at a local level and allow the adoption of measures to prevent and control infection.A infecção pelo vírus da Hepatite B (HBV) é um sério problema de saúde pública global, e Roraima apresenta altas taxas de prevalência. É transmitido basicamente pelas vias parenteral e sexual. Seu genoma é constituído por um DNA circular parcialmente dupla fita, com cerca de 3,2 kb. O HBV apresenta um alto grau de diversidade genética. Os genótipos do HBV tem um papel importante na relação vírus-hospedeiro. Os mecanismos para a persistência da infecção pelo HBV envolvem vários aspectos, entre eles, vários fatores imunogenéticos do hospedeiro. O objetivo do estudo foi realizar a caracterização epidemiológica dos portadores de HBV e a identificação molecular das cepas de HBV circulantes, a partir do sequenciamento parcial do gene S, permitindo a detecção dos genótipos, possíveis alterações no padrão genético das cepas e polimorfismos do gene CCR5 nos portadores, relacionando ao curso clínico, de susceptibilidade ou proteção contra a infecção. A população do estudo foi constituída por pacientes portadores de HBV e indivíduos controle. A extração do DNA viral e genômico foi realizada com a utilização de kits comerciais. A amplificação do gene S e do polimorfismo (gene CCR5) foi realizada por Reação em cadeia da Polimerase (PCR), utilizando iniciadores específicos. Os fragmentos positivos do gene S foram sequenciados, genotipados e utilizados no estudo filogenético baseado no método Bayesiano. A maioria dos pacientes HBV eram do sexo masculino (56,25%), apresentavam entre 31-50 anos (54,29%), a raça parda foi a prevalente em 45,31%, 29,68% apresentavam ensino fundamental incompleto, 44,53% eram casados e 66,40% eram residentes na capital Boa Vista. Em relação à provável fonte/mecanismo de infecção, a transmissão sexual ocorreu em 26,97% dos casos. Em 28,12% dos envolvidos, a vacinação foi informada como ignorada, e entre os que apresentaram a informação, o esquema vacinal completo representou 25%. Quanto ao contato com portador de HBV, 51,56% não apresentavam nenhum contato, e entre os que apresentavam, 53,12% indicaram contato ocupacional. A carga viral detectável <2000 UI/mL foi encontrada em 57,81% dos pacientes, 51,13% estava em tratamento e, entre os medicamentos, o mais referido foi Tenofovir, com 56,04%. Quarenta sequências foram genotipadas e a árvore de Máxima Confiabilidade dos Clados (MCC) confirmou a presença dos genótipos A, D e F, com uma prevalência para o genótipo A (70%), p<0,0001. Os subgenótipos encontrados foram, A1, A2, D2, D3, D4, F2a e F3, sendo que este último, foi detectado pela primeira vez no Brasil. Quanto ao gene CCR5, para as frequências alélicas e genotípicas dos grupos analisados, a população HBV não estava em equilíbrio de Hardy-Weinberg (p=0,0139). Não foi observada diferença na frequência (2,6%) do alelo Δ32 entre os grupos (p=0,9626). A frequência da mutação Δ32/Δ32 foi de 0,53% no grupo HBV e de 0% no grupo controle. O estudo da diversidade molecular e epidemiologia do HBV, além dos padrões genéticos da população em geral, pode contribuir para um melhor entendimento da doença em nível local e permitir a adoção de medidas de prevenção e controle da infecção.Universidade Federal de RoraimaBrasilPPG-BIONORTE - Programa de Pós-Graduação em Biodiversidade e Biotecnologia da Rede BionortePPG-BIONORTE - Programa de Pós-Graduação em Biodiversidade e Biotecnologia da Amazônia LegalUFRRGranja, Fabianahttp://lattes.cnpq.br/7817030564952294Sousa, Débora Dinelly de2019-11-22T14:40:08Z2019-11-22T14:40:08Z2018info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesishttp://repositorio.ufrr.br:8080/jspui/handle/prefix/206porAttribution-NonCommercial-ShareAlike 3.0 Brazilhttp://creativecommons.org/licenses/by-nc-sa/3.0/br/info:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFRRinstname:Universidade Federal de Roraima (UFRR)instacron:UFRR2023-11-10T23:23:03Zoai:repositorio.ufrr.br:prefix/206Repositório InstitucionalPUBhttp://repositorio.ufrr.br:8080/oai/requestangelsenhora@gmail.comopendoar:2023-11-10T23:23:03Repositório Institucional da UFRR - Universidade Federal de Roraima (UFRR)false
dc.title.none.fl_str_mv Perfil epidemiológico, molecular e filogenético do vírus da hepatite B circulantes no Estado de Roraima
title Perfil epidemiológico, molecular e filogenético do vírus da hepatite B circulantes no Estado de Roraima
spellingShingle Perfil epidemiológico, molecular e filogenético do vírus da hepatite B circulantes no Estado de Roraima
Sousa, Débora Dinelly de
Epidemiologia molecular
Molecular epidemiology
Hepatite B
Hepatitis B
Caracterização molecular
Molecular characterization
Gene CCR5
Roraima
Brasil
Brazil
CNPQ::CIENCIAS BIOLOGICAS::BIOLOGIA GERAL
title_short Perfil epidemiológico, molecular e filogenético do vírus da hepatite B circulantes no Estado de Roraima
title_full Perfil epidemiológico, molecular e filogenético do vírus da hepatite B circulantes no Estado de Roraima
title_fullStr Perfil epidemiológico, molecular e filogenético do vírus da hepatite B circulantes no Estado de Roraima
title_full_unstemmed Perfil epidemiológico, molecular e filogenético do vírus da hepatite B circulantes no Estado de Roraima
title_sort Perfil epidemiológico, molecular e filogenético do vírus da hepatite B circulantes no Estado de Roraima
author Sousa, Débora Dinelly de
author_facet Sousa, Débora Dinelly de
author_role author
dc.contributor.none.fl_str_mv Granja, Fabiana
http://lattes.cnpq.br/7817030564952294
dc.contributor.author.fl_str_mv Sousa, Débora Dinelly de
dc.subject.por.fl_str_mv Epidemiologia molecular
Molecular epidemiology
Hepatite B
Hepatitis B
Caracterização molecular
Molecular characterization
Gene CCR5
Roraima
Brasil
Brazil
CNPQ::CIENCIAS BIOLOGICAS::BIOLOGIA GERAL
topic Epidemiologia molecular
Molecular epidemiology
Hepatite B
Hepatitis B
Caracterização molecular
Molecular characterization
Gene CCR5
Roraima
Brasil
Brazil
CNPQ::CIENCIAS BIOLOGICAS::BIOLOGIA GERAL
description The infection through Hepatitis B virus (HBV) is a serious global public health issue, presenting in Roraima high prevalence rates. It is parenterally and sexually transmitted primarily. Its genome consists of a circular and partially double-stranded DNA, with about 3.2 kb. HBV has a high degree of genetic diversity. HBV genotypes play an important role in the virus-host relationship. Mechanisms for the persistence of HBV infection involve several aspects, including immunogenic factors. The objective of the study was to perform the epidemiological characterization of HBV patients and genetics of circulating HBV strains from the partial sequencing of the S gene, allowing the detection of genotypes, possible changes in the genetic pattern of the strains and polymorphisms in a human gene (CCR5), relating to the clinical course, susceptibility or protection against infection. The study population consisted of patients with HBV and control subjects. Extraction of viral and genomic DNA was performed using commercial kits. The amplification of the S gene and polymorphism (CCR5 gene) was performed through the Polymerase Chain Reaction (PCR), using specific initiators. The positive fragments of the S gene were sequenced, genotyped and used in the phylogenetic study based on the Bayesian method. Most of the HBV patients were male (56.25%), aged between 31-50 years (54.29%). The brown race was prevalent in 45.31%, 29.68% had incomplete primary education, 44.53% were married and 66.40% were residents of the capital Boa Vista. Regarding the probable source/mechanism of infection, sexual transmission occurred in 26.97% of the cases. Vaccination was reported as ignored in 28.12% of those involved in the study, and among those who reported the information, the complete vaccination schedule represented 25%. Regarding the contact with HBV patients, 51.56% had no contact, and among those who had contact, 53.12% reported occupational contact. The detectable viral load <2000 IU/mL was found in 57.81% of patients, 51.13% were on treatment, and, among the drugs, the most frequent was Tenofovir, with 56.04%. Forty sequences were genotyped and the Maximum Clades Reliability (MCC) tree confirmed the presence of the A, D and F genotypes, with a prevalence for the A genotype (70%), p <0.0001. The sub genotypes found were A1, A2, D2, D3, D4, F2a and F3, the latter being detected for the first time in Brazil. As for the CCR5 gene, for the allelic and genotype frequencies of the analyzed groups, the HBV population was not in the Hardy-Weinberg equilibrium (p = 0.0139). No difference was observed in the frequency (2.6%) of the Δ32 allele between the groups (p = 0.9626). The frequency of the Δ32/Δ32 mutation was 0.53% in the HBV group and 0% in the control group. The study of HBV molecular diversity and epidemiology, in addition to the genetic standards of the general population, can contribute to a better understanding of the disease at a local level and allow the adoption of measures to prevent and control infection.
publishDate 2018
dc.date.none.fl_str_mv 2018
2019-11-22T14:40:08Z
2019-11-22T14:40:08Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/doctoralThesis
format doctoralThesis
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://repositorio.ufrr.br:8080/jspui/handle/prefix/206
url http://repositorio.ufrr.br:8080/jspui/handle/prefix/206
dc.language.iso.fl_str_mv por
language por
dc.rights.driver.fl_str_mv Attribution-NonCommercial-ShareAlike 3.0 Brazil
http://creativecommons.org/licenses/by-nc-sa/3.0/br/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Attribution-NonCommercial-ShareAlike 3.0 Brazil
http://creativecommons.org/licenses/by-nc-sa/3.0/br/
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Universidade Federal de Roraima
Brasil
PPG-BIONORTE - Programa de Pós-Graduação em Biodiversidade e Biotecnologia da Rede Bionorte
PPG-BIONORTE - Programa de Pós-Graduação em Biodiversidade e Biotecnologia da Amazônia Legal
UFRR
publisher.none.fl_str_mv Universidade Federal de Roraima
Brasil
PPG-BIONORTE - Programa de Pós-Graduação em Biodiversidade e Biotecnologia da Rede Bionorte
PPG-BIONORTE - Programa de Pós-Graduação em Biodiversidade e Biotecnologia da Amazônia Legal
UFRR
dc.source.none.fl_str_mv reponame:Repositório Institucional da UFRR
instname:Universidade Federal de Roraima (UFRR)
instacron:UFRR
instname_str Universidade Federal de Roraima (UFRR)
instacron_str UFRR
institution UFRR
reponame_str Repositório Institucional da UFRR
collection Repositório Institucional da UFRR
repository.name.fl_str_mv Repositório Institucional da UFRR - Universidade Federal de Roraima (UFRR)
repository.mail.fl_str_mv angelsenhora@gmail.com
_version_ 1802112035820929024