Caracterização sorológica e detecção molecular do HTLV em amostras de pacientes com distúrbios neurológicos no Estado do Pará, Brasil (1996-2005)

Detalhes bibliográficos
Ano de defesa: 2006
Autor(a) principal: LIMA, Telma Vitorina Ribeiro lattes
Orientador(a): LINHARES, Alexandre da Costa lattes
Banca de defesa: Não Informado pela instituição
Tipo de documento: Dissertação
Tipo de acesso: Acesso aberto
Idioma: por
Instituição de defesa: Universidade Federal do Pará
Programa de Pós-Graduação: Programa de Pós-Graduação em Doenças Tropicais
Departamento: Núcleo de Medicina Tropical
País: Brasil
Palavras-chave em Português:
Área do conhecimento CNPq:
Link de acesso: http://repositorio.ufpa.br/jspui/handle/2011/3701
Resumo: Human T-lymphotropic virus tipe 1 is recognized as the etiologic agent of tropical spastic paraparesis/HTLV-1 associated myelopathy (TSP/HAM). A very similar clinical disease has been increasingly associated to HTLV-2, whose pathogenicity still requires further assessments. This transversal, retrospective epidemiological survey aimed to determine the prevalence of HTLV among individuals with neurological disturbances and further evaluate cases of inconclusive serology using molecular biology methods. The present study involved patients inhabitants of Pará State and/or admitted at health institutions of the and who were referred to the Virology Section of Instituto Evandro Chagas (IEC) by local doctors between January of 1996 and December 2005, to search for the presence of HTLV-1/2 serum antibodies. Of these patients 353 were selected, with age between 9 months and 79 years, who presented at least one signal or symptom of the Marsh’s Complex (1996), as well as had HTLV-1/2 positive serology at screening and confirmatory ELISA. The overall prevalence of HTLV antibodies by ELISA as 8,8% (31/353), with rates of 10,6% (19/179) and 6,9% (12/174) for female and male patients, respectively. Among HTLV-1/2 the 31 ELISA-positive patients it was noted that 15 (48.4%) of 31 had paresis (n = 8), parestesis (n = 5), and paraplegia (n = 3). Of these 31 HTLV ELISA positive patients, 25 could be submitted to WB for assessment of viral types, which were distributed as follow: 80% (20/25) were HTLV-1, 12% (3/25) were HTLV-2, one case was of HTLV-1+HTLV-2 infection (4%), and serum from one patient yielded an indeterminate profile (4%). Only 14 of these 25 patients could be re-localised for collection of an additional sample for molecular analysis. It was observed that 78.6% of samples typed by WB had the proviral TAX region successfully amplified by nested-PCR. In addition, types were confirmed as based on results obtained from the amplification of the POL region using real-time PCR; this denoted good specificity and sensitivity of the WB used in this study. The sample defined as HTLV-1+HTLV-2 infection by WB was amplified in its TAX region but real time PCR confirmed HTLV-1 infection only. The patient with WB indeterminate profile and one of samples typed as HTLV-2 by WB were amplified by nested-PCR but the real time PCR was negative for HTLV-1 and HTLV-2 in both samples. One patient presenting clinical manifestations of crural myalgia and parestesia with duration of about 7 years reacted HTLV-2-positive by both WB and real-time PCR, a denoting a clear HTLV-2- related chronic myelopathy. This study has identified a case of possible vertical transmission in two distinct situations: a patient whose mother presented antibodies for HTLV-1 by WB and two sisters who reacted HTLV-1-positive by WB and real-time PCR. Although of epidemiological relevance, results from this study warrant further and broader analyses concerning the molecular epidemiology of HTLV types and subtypes HTLV. In addition, a more complete clinical assessment of neurological symptoms should be further performed, in order to better characterise cases of HTLV-related chronic myelopathy in our region.
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spelling 2013-04-18T13:15:20Z2013-04-18T13:15:20Z2006-07-07LIMA, Telma Vitorina Ribeiro. Caracterização sorológica e detecção molecular do HTLV em amostras de pacientes com distúrbios neurológicos no Estado do Pará, Brasil (1996-2005). 2006. 101 f. Dissertação (Mestrado) - Universidade Federal do Pará, Núcleo de Medicina Tropical, Belém, 2006. Programa de Pós-Graduação em Doenças Tropicais.http://repositorio.ufpa.br/jspui/handle/2011/3701Human T-lymphotropic virus tipe 1 is recognized as the etiologic agent of tropical spastic paraparesis/HTLV-1 associated myelopathy (TSP/HAM). A very similar clinical disease has been increasingly associated to HTLV-2, whose pathogenicity still requires further assessments. This transversal, retrospective epidemiological survey aimed to determine the prevalence of HTLV among individuals with neurological disturbances and further evaluate cases of inconclusive serology using molecular biology methods. The present study involved patients inhabitants of Pará State and/or admitted at health institutions of the and who were referred to the Virology Section of Instituto Evandro Chagas (IEC) by local doctors between January of 1996 and December 2005, to search for the presence of HTLV-1/2 serum antibodies. Of these patients 353 were selected, with age between 9 months and 79 years, who presented at least one signal or symptom of the Marsh’s Complex (1996), as well as had HTLV-1/2 positive serology at screening and confirmatory ELISA. The overall prevalence of HTLV antibodies by ELISA as 8,8% (31/353), with rates of 10,6% (19/179) and 6,9% (12/174) for female and male patients, respectively. Among HTLV-1/2 the 31 ELISA-positive patients it was noted that 15 (48.4%) of 31 had paresis (n = 8), parestesis (n = 5), and paraplegia (n = 3). Of these 31 HTLV ELISA positive patients, 25 could be submitted to WB for assessment of viral types, which were distributed as follow: 80% (20/25) were HTLV-1, 12% (3/25) were HTLV-2, one case was of HTLV-1+HTLV-2 infection (4%), and serum from one patient yielded an indeterminate profile (4%). Only 14 of these 25 patients could be re-localised for collection of an additional sample for molecular analysis. It was observed that 78.6% of samples typed by WB had the proviral TAX region successfully amplified by nested-PCR. In addition, types were confirmed as based on results obtained from the amplification of the POL region using real-time PCR; this denoted good specificity and sensitivity of the WB used in this study. The sample defined as HTLV-1+HTLV-2 infection by WB was amplified in its TAX region but real time PCR confirmed HTLV-1 infection only. The patient with WB indeterminate profile and one of samples typed as HTLV-2 by WB were amplified by nested-PCR but the real time PCR was negative for HTLV-1 and HTLV-2 in both samples. One patient presenting clinical manifestations of crural myalgia and parestesia with duration of about 7 years reacted HTLV-2-positive by both WB and real-time PCR, a denoting a clear HTLV-2- related chronic myelopathy. This study has identified a case of possible vertical transmission in two distinct situations: a patient whose mother presented antibodies for HTLV-1 by WB and two sisters who reacted HTLV-1-positive by WB and real-time PCR. Although of epidemiological relevance, results from this study warrant further and broader analyses concerning the molecular epidemiology of HTLV types and subtypes HTLV. In addition, a more complete clinical assessment of neurological symptoms should be further performed, in order to better characterise cases of HTLV-related chronic myelopathy in our region.O vírus linfotrópico de células de T humanas tipo 1 (HTLV-1) é reconhecido como agente etiológico da paraparesia espástica tropical/mielopatia associada ao HTLV-1 (PET/MAH). Quadro clínico muito similar a este vem sendo crescentemente associado ao HTLV-2, cuja patogenicidade ainda requer maiores esclarecimentos. Este inquérito epidemiológico transversal objetivou determinar a prevalência do HTLV entre indivíduos com distúrbios neurológicos e esclarecer, por métodos de biologia molecular, os casos de sorologia inconclusiva. O presente estudo envolveu pacientes residentes no Estado do Pará e/ou internados em instituições de saúde esse Estado, e que tenham sido encaminhados à Seção de Virologia (SEVIR) do Instituto Evandro Chagas (IEC) por médicos locais, entre janeiro de 1996 e dezembro 2005, com vistas à pesquisa de anticorpos específicos para HTLV-1/2. Dessa população foram selecionados 353 pacientes, com idades entre 9 meses e 79 anos, que apresentassem pelo menos um sinal ou sintoma do Complexo de Marsh(1996), bem como sorologia positiva para os testes de triagem e confirmatório de EIE específico para HTLV-1/2. A prevalência geral de anticorpos específicos para HTLV por EIE foi de 8,8% (31/353), com taxas de 10,6% (19/179) e 6,9% (12/174) nos sexos feminino e masculino, respectivamente. Entre os pacientes positivos para HTLV-1/2 por EIE, verificou-se que, tomadas em conjunto, as manifestações de paresia (n = 8), parestesia (n = 5) e paraplegia (n = 3) ocorreram em 48,4% (15/31) dos casos. Dos 31 pacientes positivos para HTLV por EIE, 25 puderam ser submetidos ao WB para definição do tipo viral, encontrando: 80% (20/25) de HTLV- 1, 12% (3/25), HTLV-2, uma infecção mista (4%) e um perfil indeterminado (4%). Destes 25 indivíduos, apenas 14 puderam ser re-localizados para coleta de nova amostra visando-s à análise molecular. Verificou-se que 78,6% das amostras tipadas por WB revelaram amplificação da região TAX pró-viral pela nested-PCR e foram confirmadas quanto à tipagem pela pesquisa da região POL por PCR em tempo real, denotando especificidade e sensibilidade satisfatórias do método de WB empregado no estudo. A amostra definida como infecção mista por WB foi amplificada para região TAX, porém a PCR em tempo real confirmou infecção apenas pelo HTLV-1. O paciente com perfil indeterminado e uma das amostras tipadas como HTLV-2 por WB foram amplificadas pela nested-PCR, porém a PCR em tempo real não detectou genoma pró-viral de HTLV-1, nem do -2 em quaisquer das duas amostras. Uma paciente, portadora de quadro de mialgia e parestesia crural com duração de aproximadamente 7 anos se apresentou positiva para HTLV-2 por WB e PCR em tempo real, caracterizando um quadro compatível com mielopatia associada a esse tipo. Registraram-se indícios de transmissão vertical em dois casos distintos: um paciente cuja mãe apresentou anticorpos para HTLV-1 por WB e duas irmãs com diagnóstico de HTLV-1 por WB e PCR em tempo real. Os resultados deste trabalho evidenciam a necessidade de análises mais profundas acerca da epidemiologia molecular dos tipos e subtipos do HTLV, bem como avaliações clínicas mais rigorosas do ponto de vista neurológico, visando a melhor caracterizar a associação do vírus à condição mórbida designada mielopatia crônica.CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível SuperiorporUniversidade Federal do ParáPrograma de Pós-Graduação em Doenças TropicaisUFPABrasilNúcleo de Medicina TropicalCNPQ::CIENCIAS DA SAUDE::SAUDE COLETIVA::SAUDE PUBLICACNPQ::CIENCIAS BIOLOGICAS::IMUNOLOGIACNPQ::CIENCIAS BIOLOGICAS::GENETICA::GENETICA MOLECULAR E DE MICROORGANISMOSCNPQ::CIENCIAS DA SAUDE::MEDICINA::CLINICA MEDICA::DOENCAS INFECCIOSAS E PARASITARIASVírus linfotrópico de células T humanas tipo 1Vírus 2 linfotrópico T humanoParaparesia espástica tropicalTécnicas de diagnóstico molecularImunoensaioPará - EstadoAmazônia brasileiraCaracterização sorológica e detecção molecular do HTLV em amostras de pacientes com distúrbios neurológicos no Estado do Pará, Brasil (1996-2005)info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisLINHARES, Alexandre da Costahttp://lattes.cnpq.br/3316632173870389http://lattes.cnpq.br/1121064397042189LIMA, Telma Vitorina Ribeiroinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFPAinstname:Universidade Federal do Pará (UFPA)instacron:UFPAORIGINALDissertacao_CaracterizacaoSorologicaDeteccao.pdfDissertacao_CaracterizacaoSorologicaDeteccao.pdfapplication/pdf2500353http://repositorio.ufpa.br/oai/bitstream/2011/3701/1/Dissertacao_CaracterizacaoSorologicaDeteccao.pdffd2fb2f2fcdd6056ea361eaf6b1607a6MD51CC-LICENSElicense_urllicense_urltext/plain; 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dc.title.pt_BR.fl_str_mv Caracterização sorológica e detecção molecular do HTLV em amostras de pacientes com distúrbios neurológicos no Estado do Pará, Brasil (1996-2005)
title Caracterização sorológica e detecção molecular do HTLV em amostras de pacientes com distúrbios neurológicos no Estado do Pará, Brasil (1996-2005)
spellingShingle Caracterização sorológica e detecção molecular do HTLV em amostras de pacientes com distúrbios neurológicos no Estado do Pará, Brasil (1996-2005)
LIMA, Telma Vitorina Ribeiro
CNPQ::CIENCIAS DA SAUDE::SAUDE COLETIVA::SAUDE PUBLICA
CNPQ::CIENCIAS BIOLOGICAS::IMUNOLOGIA
CNPQ::CIENCIAS BIOLOGICAS::GENETICA::GENETICA MOLECULAR E DE MICROORGANISMOS
CNPQ::CIENCIAS DA SAUDE::MEDICINA::CLINICA MEDICA::DOENCAS INFECCIOSAS E PARASITARIAS
Vírus linfotrópico de células T humanas tipo 1
Vírus 2 linfotrópico T humano
Paraparesia espástica tropical
Técnicas de diagnóstico molecular
Imunoensaio
Pará - Estado
Amazônia brasileira
title_short Caracterização sorológica e detecção molecular do HTLV em amostras de pacientes com distúrbios neurológicos no Estado do Pará, Brasil (1996-2005)
title_full Caracterização sorológica e detecção molecular do HTLV em amostras de pacientes com distúrbios neurológicos no Estado do Pará, Brasil (1996-2005)
title_fullStr Caracterização sorológica e detecção molecular do HTLV em amostras de pacientes com distúrbios neurológicos no Estado do Pará, Brasil (1996-2005)
title_full_unstemmed Caracterização sorológica e detecção molecular do HTLV em amostras de pacientes com distúrbios neurológicos no Estado do Pará, Brasil (1996-2005)
title_sort Caracterização sorológica e detecção molecular do HTLV em amostras de pacientes com distúrbios neurológicos no Estado do Pará, Brasil (1996-2005)
author LIMA, Telma Vitorina Ribeiro
author_facet LIMA, Telma Vitorina Ribeiro
author_role author
dc.contributor.advisor1.fl_str_mv LINHARES, Alexandre da Costa
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/3316632173870389
dc.contributor.authorLattes.fl_str_mv http://lattes.cnpq.br/1121064397042189
dc.contributor.author.fl_str_mv LIMA, Telma Vitorina Ribeiro
contributor_str_mv LINHARES, Alexandre da Costa
dc.subject.cnpq.fl_str_mv CNPQ::CIENCIAS DA SAUDE::SAUDE COLETIVA::SAUDE PUBLICA
CNPQ::CIENCIAS BIOLOGICAS::IMUNOLOGIA
CNPQ::CIENCIAS BIOLOGICAS::GENETICA::GENETICA MOLECULAR E DE MICROORGANISMOS
CNPQ::CIENCIAS DA SAUDE::MEDICINA::CLINICA MEDICA::DOENCAS INFECCIOSAS E PARASITARIAS
topic CNPQ::CIENCIAS DA SAUDE::SAUDE COLETIVA::SAUDE PUBLICA
CNPQ::CIENCIAS BIOLOGICAS::IMUNOLOGIA
CNPQ::CIENCIAS BIOLOGICAS::GENETICA::GENETICA MOLECULAR E DE MICROORGANISMOS
CNPQ::CIENCIAS DA SAUDE::MEDICINA::CLINICA MEDICA::DOENCAS INFECCIOSAS E PARASITARIAS
Vírus linfotrópico de células T humanas tipo 1
Vírus 2 linfotrópico T humano
Paraparesia espástica tropical
Técnicas de diagnóstico molecular
Imunoensaio
Pará - Estado
Amazônia brasileira
dc.subject.por.fl_str_mv Vírus linfotrópico de células T humanas tipo 1
Vírus 2 linfotrópico T humano
Paraparesia espástica tropical
Técnicas de diagnóstico molecular
Imunoensaio
Pará - Estado
Amazônia brasileira
description Human T-lymphotropic virus tipe 1 is recognized as the etiologic agent of tropical spastic paraparesis/HTLV-1 associated myelopathy (TSP/HAM). A very similar clinical disease has been increasingly associated to HTLV-2, whose pathogenicity still requires further assessments. This transversal, retrospective epidemiological survey aimed to determine the prevalence of HTLV among individuals with neurological disturbances and further evaluate cases of inconclusive serology using molecular biology methods. The present study involved patients inhabitants of Pará State and/or admitted at health institutions of the and who were referred to the Virology Section of Instituto Evandro Chagas (IEC) by local doctors between January of 1996 and December 2005, to search for the presence of HTLV-1/2 serum antibodies. Of these patients 353 were selected, with age between 9 months and 79 years, who presented at least one signal or symptom of the Marsh’s Complex (1996), as well as had HTLV-1/2 positive serology at screening and confirmatory ELISA. The overall prevalence of HTLV antibodies by ELISA as 8,8% (31/353), with rates of 10,6% (19/179) and 6,9% (12/174) for female and male patients, respectively. Among HTLV-1/2 the 31 ELISA-positive patients it was noted that 15 (48.4%) of 31 had paresis (n = 8), parestesis (n = 5), and paraplegia (n = 3). Of these 31 HTLV ELISA positive patients, 25 could be submitted to WB for assessment of viral types, which were distributed as follow: 80% (20/25) were HTLV-1, 12% (3/25) were HTLV-2, one case was of HTLV-1+HTLV-2 infection (4%), and serum from one patient yielded an indeterminate profile (4%). Only 14 of these 25 patients could be re-localised for collection of an additional sample for molecular analysis. It was observed that 78.6% of samples typed by WB had the proviral TAX region successfully amplified by nested-PCR. In addition, types were confirmed as based on results obtained from the amplification of the POL region using real-time PCR; this denoted good specificity and sensitivity of the WB used in this study. The sample defined as HTLV-1+HTLV-2 infection by WB was amplified in its TAX region but real time PCR confirmed HTLV-1 infection only. The patient with WB indeterminate profile and one of samples typed as HTLV-2 by WB were amplified by nested-PCR but the real time PCR was negative for HTLV-1 and HTLV-2 in both samples. One patient presenting clinical manifestations of crural myalgia and parestesia with duration of about 7 years reacted HTLV-2-positive by both WB and real-time PCR, a denoting a clear HTLV-2- related chronic myelopathy. This study has identified a case of possible vertical transmission in two distinct situations: a patient whose mother presented antibodies for HTLV-1 by WB and two sisters who reacted HTLV-1-positive by WB and real-time PCR. Although of epidemiological relevance, results from this study warrant further and broader analyses concerning the molecular epidemiology of HTLV types and subtypes HTLV. In addition, a more complete clinical assessment of neurological symptoms should be further performed, in order to better characterise cases of HTLV-related chronic myelopathy in our region.
publishDate 2006
dc.date.issued.fl_str_mv 2006-07-07
dc.date.accessioned.fl_str_mv 2013-04-18T13:15:20Z
dc.date.available.fl_str_mv 2013-04-18T13:15:20Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/masterThesis
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dc.identifier.citation.fl_str_mv LIMA, Telma Vitorina Ribeiro. Caracterização sorológica e detecção molecular do HTLV em amostras de pacientes com distúrbios neurológicos no Estado do Pará, Brasil (1996-2005). 2006. 101 f. Dissertação (Mestrado) - Universidade Federal do Pará, Núcleo de Medicina Tropical, Belém, 2006. Programa de Pós-Graduação em Doenças Tropicais.
dc.identifier.uri.fl_str_mv http://repositorio.ufpa.br/jspui/handle/2011/3701
identifier_str_mv LIMA, Telma Vitorina Ribeiro. Caracterização sorológica e detecção molecular do HTLV em amostras de pacientes com distúrbios neurológicos no Estado do Pará, Brasil (1996-2005). 2006. 101 f. Dissertação (Mestrado) - Universidade Federal do Pará, Núcleo de Medicina Tropical, Belém, 2006. Programa de Pós-Graduação em Doenças Tropicais.
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