Persistence of vaccine immunity against the hepatitis B virus and response to evaccination in vertically HlV-infected adolescents on highly active antiretroviral therapy

Detalhes bibliográficos
Autor(a) principal: Pessoa, Silvana Duarte
Data de Publicação: 2022
Outros Autores: Succi, Regina Célia de Menezes, Moraes-Pinto, Maria Isabel de
Tipo de documento: Artigo
Idioma: por
eng
spa
Título da fonte: Revista Pan-Amazônica de Saúde (RPAS)
Texto Completo: https://ojs.iec.gov.br/rpas/article/view/1401
Resumo: INTRODUCTION: Children infected with the human immunodeficiency virus (HIV) present alterations both in their humoral and cellular immune responses. These changes might lead to an inefficient immune response against certain specific vaccine antigens and/or to an early reduction in the antibody levels considered protective after immunization. This low immune protection against vaccine antigens is due to a deficiency in the treatment of antigens, a failure in the generation of the immunologic memory and/or the quantitative and functional loss of T and B memory cells. In addition, the introduction of highly active antiretroviral therapy (HAART) leads to the suppression of viral replication and to a partial restoration of the immunologic function, including the immune response against vaccine antigens. Recent studies have demonstrated that only a low percentage of children vertically infected with HIV treated with HAART maintain levels of protective antibodies after the primary immunization against the hepatitis B virus (HBV); however, the factors associated with the persistence of protective antibodies after primary vaccination and with the response to revaccination have not been clarified.OBJECTIVE: To evaluate the persistence of the levels of protective antibodies against HBV in adolescents vertically infected with HIV treated with HAART and their response to vaccination.MATERIAL AND METHODS: This study was approved by the Ethics Committee of the Universidade Federal de São Paulo (UNIFESP/EPM). It was performed in the AIDS pediatric outpatient facilities of the institution. From January 2006 to August 2007, 40 adolescents vertically infected with HIV (HIV group) were selected for a prospective, longitudinal, controlled and intervention study. Twenty-three healthy HIV-negative adolescents were selected as the control group. The inclusion criteria for the groups were as follows: 10-20 years of age, absence of a previous history of hepatitis B and full immunization against HBV at least four years before the beginning of this study. The exclusion criteria were blood and blood products transfusion up to six months before the beginning of the study, acute febrile disease seven days prior to inclusion in the study, previous history or serologic evidence of HBV infection (i.e., the presence of anti-HBc antibodies). Furthermore, all the adolescents of both groups had received three doses of the recombinant vaccine against hepatitis B in the primary immunization. The adolescents with anti-HBs antibody levels of < 10 mUI/mL were revaccinated against HBV with up to six doses over an interval of 30-60 days. The adolescents in the HIV group received a double dose of the recombinant vaccine against HBV (20 µg of Euvax-B®, LG Chemical Ltd., from Korea). The adolescents in the control group were revaccinated with a standard dose of the Brazilian recombinant vaccine against HBV (10 µg of Butang®, by Instituto Butantã de São Paulo, São Paulo). The maturation of lymphocytes was assessed by flow cytometry through the phenotypic profile. Statistical analysis was executed using SPSS version 12.0, with a significance level of p < 0.05.RESULTS: In the beginning of the study, anti-HBs antibody levels ≥ 10 mUI/mL were observed in 18/40 (40.5%) of the HIV-infected adolescents and in 18/23 (78.3%) of the adolescents in the control group. The adolescents in the HIV group with anti-HBs ≥ 10 mUI/mL presented a higher percentage of TCD4+ cells, a higher percentage of central memory and of naïve TCD8+ cells and a lower immune activation. After revaccination, 18/12 (66.7%) adolescents in the HIV group presented anti-HBs antibody levels > 10 mUI/mL. The adolescents who did not respond to the vaccination course presented with a lower percentage of TCD4+ cells, a higher immune activation and a detectable viral load.CONCLUSION: These findings suggest that a higher percentage of TCD4+ cells, a lower immune activation and a better control of the replication of the HIV might be associated with a better vaccine response against the HBV
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spelling Persistence of vaccine immunity against the hepatitis B virus and response to evaccination in vertically HlV-infected adolescents on highly active antiretroviral therapyPersistencia de la inmunidad vacunal contra el virus de la hepatitis B y respuesta a la revacunación en adolescentes infectados por el VIH por transmisión vertical en uso de terapia antirretroviral potentePersistência da imunidade vacinal contra o vírus da hepatite B e resposta à revacinação em adolescentes infectados pelo HIV por transmissão vertical em uso de terapia antirretroviral potente*Vacunas contra Hepatitis BVIHAntígenos CD38Vacinas contra Hepatite BHIVAntígenos CD38Hepatitis B VaccinesHIVAntigens, CD38INTRODUCTION: Children infected with the human immunodeficiency virus (HIV) present alterations both in their humoral and cellular immune responses. These changes might lead to an inefficient immune response against certain specific vaccine antigens and/or to an early reduction in the antibody levels considered protective after immunization. This low immune protection against vaccine antigens is due to a deficiency in the treatment of antigens, a failure in the generation of the immunologic memory and/or the quantitative and functional loss of T and B memory cells. In addition, the introduction of highly active antiretroviral therapy (HAART) leads to the suppression of viral replication and to a partial restoration of the immunologic function, including the immune response against vaccine antigens. Recent studies have demonstrated that only a low percentage of children vertically infected with HIV treated with HAART maintain levels of protective antibodies after the primary immunization against the hepatitis B virus (HBV); however, the factors associated with the persistence of protective antibodies after primary vaccination and with the response to revaccination have not been clarified.OBJECTIVE: To evaluate the persistence of the levels of protective antibodies against HBV in adolescents vertically infected with HIV treated with HAART and their response to vaccination.MATERIAL AND METHODS: This study was approved by the Ethics Committee of the Universidade Federal de São Paulo (UNIFESP/EPM). It was performed in the AIDS pediatric outpatient facilities of the institution. From January 2006 to August 2007, 40 adolescents vertically infected with HIV (HIV group) were selected for a prospective, longitudinal, controlled and intervention study. Twenty-three healthy HIV-negative adolescents were selected as the control group. The inclusion criteria for the groups were as follows: 10-20 years of age, absence of a previous history of hepatitis B and full immunization against HBV at least four years before the beginning of this study. The exclusion criteria were blood and blood products transfusion up to six months before the beginning of the study, acute febrile disease seven days prior to inclusion in the study, previous history or serologic evidence of HBV infection (i.e., the presence of anti-HBc antibodies). Furthermore, all the adolescents of both groups had received three doses of the recombinant vaccine against hepatitis B in the primary immunization. The adolescents with anti-HBs antibody levels of < 10 mUI/mL were revaccinated against HBV with up to six doses over an interval of 30-60 days. The adolescents in the HIV group received a double dose of the recombinant vaccine against HBV (20 µg of Euvax-B®, LG Chemical Ltd., from Korea). The adolescents in the control group were revaccinated with a standard dose of the Brazilian recombinant vaccine against HBV (10 µg of Butang®, by Instituto Butantã de São Paulo, São Paulo). The maturation of lymphocytes was assessed by flow cytometry through the phenotypic profile. Statistical analysis was executed using SPSS version 12.0, with a significance level of p < 0.05.RESULTS: In the beginning of the study, anti-HBs antibody levels ≥ 10 mUI/mL were observed in 18/40 (40.5%) of the HIV-infected adolescents and in 18/23 (78.3%) of the adolescents in the control group. The adolescents in the HIV group with anti-HBs ≥ 10 mUI/mL presented a higher percentage of TCD4+ cells, a higher percentage of central memory and of naïve TCD8+ cells and a lower immune activation. After revaccination, 18/12 (66.7%) adolescents in the HIV group presented anti-HBs antibody levels > 10 mUI/mL. The adolescents who did not respond to the vaccination course presented with a lower percentage of TCD4+ cells, a higher immune activation and a detectable viral load.CONCLUSION: These findings suggest that a higher percentage of TCD4+ cells, a lower immune activation and a better control of the replication of the HIV might be associated with a better vaccine response against the HBVINTRODUCCIÓN: Niños infectados por el virus de inmunodeficiencia humana (VIH) presentan alteraciones, tanto en la inmunidad humoral como en la inmunidad celular, que pueden conducir a una respuesta inmunológica ineficaz a determinados antígenos vacunales específicos y/o a una reducción precoz de los niveles de anticuerpos considerados protectores, luego de la inmunización. Esta baja protección inmunológica contra antígenos vacunales se debe a un defecto en el procesamiento de los antígenos, una falla en la generación de memoria inmunológica y/o a la pérdida cuantitativa y funcional y a células T y B de memoria. Por otro lado, la introducción de la terapia antirretroviral potente (HAART) conduce a una supresión de la replicación viral y a la restauración parcial de la función inmunológica, incluyendo la respuesta inmune a antígenos vacunales. Estudios recientes han demostrado que apenas un pequeño porcentaje de niños infectados verticalmente por el VIH en uso de HAART mantienen niveles de anticuerpos protectores luego de inmunización primaria contra el virus de la hepatitis B (VHB). Sin embargo, los factores asociados a la persistencia de anticuerpos protectores luego de vacunación primaria y de respuesta a la revacunación, son aún poco aclarados.OBJETIVO: Evaluar la persistencia de los niveles de anticuerpos protectores contra el VHB en adolescentes infectados verticalmente por el VIH en uso de HAART y respuesta a la revacunación.MATERIALES Y MÉTODOS: El presente estudio fue aprobado por el Comité de Ética de la Universidad Federal de São Paulo (UNIFESP/EPM) y realizado en el ambulatorio pediátrico de SIDA de la misma institución. En el período de enero de 2006 a agosto de 2007, 40 adolescentes infectados verticalmente por VIH (grupo VIH) fueron reclutados en un estudio prospectivo, longitudinal, controlado e intervencionista. Veintitrés adolescentes saludables VIH-negativos fueron seleccionados para formar el grupo de control. Los criterios de inclusión para ambos grupos fueron: edad de 10 a 20 años; ausencia de historia previa de enfermedad hepatitis B; e inmunización completa contra el VHB desde, por lo menos, cuatro años antes del inicio del estudio. Los criterios de exclusión fueron: transfusión de sangre y hemoderivados en el plazo de seis meses antes del inicio del estudio; enfermedad febril aguda siete días antes de la entrada al estudio, historia previa o evidencia serológica de infección por el VHB (presencia de anticuerpos anti-HBc). Además, todos los adolescentes de ambos grupos habían recibido, al menos, tres dosis de la vacuna recombinante contra hepatitis B en la inmunización primaria. Los adolescentes con niveles de anticuerpos anti-HBs < 10 mUI/mL fueron revacunados contra VHB con hasta un máximo de seis dosis, en un intervalo de 30-60 días. Los adolescentes del grupo VIH fueron vacunados con una doble dosis de la vacuna recombinante contra el VHB (20 |ig de Euvax-B®, LG Chemical Ltd., de Corea). Los adolescentes del grupo control fueron revacunados con la vacuna recombinante brasileña contra el VHB, en la dosis estándar (10 |ig de Butang®, del Instituto Butantã de São Paulo, São Paulo). La maduración de los linfocitos se evaluó por el perfil fenotípico, por el método de citometría de flujo. El análisis estadístico se realizó con el software SPSS versión 12.0, con un nivel de significancia de p < 0,05.RESULTADOS: En la inclusión del estudio, los niveles de anticuerpos anti-HBs > 10 mUI/mL fueron hallados en 18/40 (40,5%) de los adolescentes infectados por VIH y en 18/23 (78,3%) de los adolescentes del grupo control. Los adolescentes del grupo VIH con anti-HBs > 10 mUI/mL presentaron mayor porcentaje de células TCD4 + , mayor porcentaje de células TCD8+ naive y de memoria central, y menor activación inmunológica. En la revacunación, 18/12 (66,7%) adolescentes del grupo VIH presentaron niveles de anticuerpos anti-HBs > 10 mUI/mL. Los adolescentes que no respondieron a la revacunación presentaron un menor porcentaje de células TCD4 + , mayor activación inmunológica y carga viral detectable.CONCLUSIÓN: Esos hallazgos sugieren que el mayor porcentaje de células TCD4 + , la menor activación inmunológica y el mejor control de la replicación del VIH pueden estar asociados a una mejor respuesta vacunal contra el virus de la hepatitis B.INTRODUÇÃO: Crianças infectadas pelo vírus da imunodeficiência humana (HIV) apresentam alterações, tanto na imunidade humoral como na imunidade celular, que podem levam a uma resposta imunológica ineficaz a determinados antígenos vacinais específicos e/ou a uma redução precoce dos níveis de anticorpos considerados protetores após a imunização. Esta baixa proteção imunológica contra antígenos vacinais deve-se a um defeito no processamento de antígenos, uma falha na geração de memória imunológica e/ou à perda quantitativa e funcional e células T e B de memória. Por outro lado, a introdução da terapia antirretroviral potente (HAART) leva a uma supressão da replicação viral e à restauração parcial da função imunológica, incluindo a resposta imune a antígenos vacinais. Estudos recentes têm demonstrado que apenas uma pequena porcentagem de crianças infectadas verticalmente pelo HIV em uso de HAART mantém níveis de anticorpos protetores após a imunização primária contra o vírus da hepatite B (VHB). Entretanto, os fatores associados à persistência de anticorpos protetores após a vacinação primária e de resposta à revacinação são pouco esclarecidos.OBJETIVO: Avaliar a persistência dos níveis de anticorpos protetores contra o VHB em adolescentes infectados verticalmente pelo HIV em uso de HAART e resposta à revacinação.MATERIAIS E MÉTODOS: O presente estudo foi aprovado pelo Comitê de Ética da Universidade Federal de São Paulo (UNIFESP/EPM) e realizado no Ambulatório Pediátrico de Aids da própria instituição. No período de janeiro de 2006 a agosto de 2007, 40 adolescentes infectados verticalmente pelo HIV (grupo HIV) foram recrutados em um estudo prospectivo, longitudinal, controlado e intervencionista. Vinte e três adolescentes saudáveis HIV-negativos foram selecionados para constituir o grupo controle. Os critérios de inclusão para ambos os grupos foram: idade de 10 a 20 anos; ausência de história prévia de doença hepatite B; e imunização completa contra o VHB pelo menos quatro anos antes do início do estudo. Os critérios de exclusão foram: transfusão de sangue e hemoderivados no prazo de seis meses antes do início do estudo; doença febril aguda sete dias antes da entrada do estudo, história prévia ou evidência sorológica de infecção pelo VHB (presença de anticorpos anti-HBc). Além disso, todos os adolescentes de ambos os grupos tinham recebido pelo menos três doses da vacina recombinante contra hepatite B na imunização primária. Os adolescentes com níveis de anticorpos anti-HBs < 10 mUI/mL foram revacinados contra VHB até um máximo de seis doses, no intervalo de 30 a 60 dias. Os adolescentes do grupo HIV foram vacinados com dose dupla da vacina recombinante contra o VHB (20 µg de Euvax-B®, LG Chemical Ltd., da Coréia). Os adolescentes do grupo controle foram revacinados com a vacina recombinante brasileira contra o VHB, na dose padrão (10 µg de Butang®, do Instituto Butantã de São Paulo, São Paulo). A maturação de linfócitos foi avaliada por meio do perfil fenotípico pelo método de citometria de fluxo. A análise estatística foi realizada pelo programa SPSS versão 12.0, com nível de significância p < 0,05.RESULTADOS: Na inclusão do estudo, os níveis de anticorpos anti-HBs ≥ 10 mUl/mL foram encontrados em 18/40 (40,5%) dos adolescentes infectados pelo HIV e 18/23 (78,3%) dos adolescentes do grupo controle. Os adolescentes do grupo HIV com anti-HBs ≥ 10 mUl/mL apresentaram maior porcentagem de células TCD4 + , maior porcentagem de células TCD8+ naive e de memória central, menor ativação imunológica. Na revacinação, 18/12 (66,7%) adolescentes do grupo HIV apresentaram níveis de anticorpos anti-HBs ≥ 10 mUl/mL. Os adolescentes que não responderam à revacinação apresentaram uma menor porcentagem de células TCD4 + , maior ativação imunológica e carga viral detectável.CONCLUSÃO: Esses achados sugerem que a maior porcentagem de células TCD4+, a menor ativação imunológica e o melhor controle da replicação do HIV podem estar associados à melhor resposta vacinal contra o vírus da hepatite B.Instituto Evandro Chagas/SCTIE/MS2022-08-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersiontext/xmlapplication/pdfapplication/pdfapplication/pdfhttps://ojs.iec.gov.br/rpas/article/view/140110.5123/S2176-62232010000300020Revista Pan-Amazônica de Saúde; v. 1 n. 3 (2010): jul-set; 2Pan-Amazonian Journal of Health; Vol. 1 No. 3 (2010): jul-set; 2Revista Pan-Amazônica de Saúde; Vol. 1 Núm. 3 (2010): jul-set; 22176-62232176-6215reponame:Revista Pan-Amazônica de Saúde (RPAS)instname:Instituto Evandro Chagas (IEC)instacron:IECporengspahttps://ojs.iec.gov.br/rpas/article/view/1401/1036https://ojs.iec.gov.br/rpas/article/view/1401/1037https://ojs.iec.gov.br/rpas/article/view/1401/1038https://ojs.iec.gov.br/rpas/article/view/1401/1039Pessoa, Silvana DuarteSucci, Regina Célia de MenezesMoraes-Pinto, Maria Isabel de info:eu-repo/semantics/openAccess2022-08-09T13:57:26Zoai:revista.iec.gov.br:article/1401Revistahttp://revista.iec.gov.br/PRIhttps://ojs.iec.gov.br/index.php/rpas/oairevista@iec.gov.br2176-62152176-6223opendoar:2022-08-09T13:57:26Revista Pan-Amazônica de Saúde (RPAS) - Instituto Evandro Chagas (IEC)false
dc.title.none.fl_str_mv Persistence of vaccine immunity against the hepatitis B virus and response to evaccination in vertically HlV-infected adolescents on highly active antiretroviral therapy
Persistencia de la inmunidad vacunal contra el virus de la hepatitis B y respuesta a la revacunación en adolescentes infectados por el VIH por transmisión vertical en uso de terapia antirretroviral potente
Persistência da imunidade vacinal contra o vírus da hepatite B e resposta à revacinação em adolescentes infectados pelo HIV por transmissão vertical em uso de terapia antirretroviral potente*
title Persistence of vaccine immunity against the hepatitis B virus and response to evaccination in vertically HlV-infected adolescents on highly active antiretroviral therapy
spellingShingle Persistence of vaccine immunity against the hepatitis B virus and response to evaccination in vertically HlV-infected adolescents on highly active antiretroviral therapy
Pessoa, Silvana Duarte
Vacunas contra Hepatitis B
VIH
Antígenos CD38
Vacinas contra Hepatite B
HIV
Antígenos CD38
Hepatitis B Vaccines
HIV
Antigens, CD38
title_short Persistence of vaccine immunity against the hepatitis B virus and response to evaccination in vertically HlV-infected adolescents on highly active antiretroviral therapy
title_full Persistence of vaccine immunity against the hepatitis B virus and response to evaccination in vertically HlV-infected adolescents on highly active antiretroviral therapy
title_fullStr Persistence of vaccine immunity against the hepatitis B virus and response to evaccination in vertically HlV-infected adolescents on highly active antiretroviral therapy
title_full_unstemmed Persistence of vaccine immunity against the hepatitis B virus and response to evaccination in vertically HlV-infected adolescents on highly active antiretroviral therapy
title_sort Persistence of vaccine immunity against the hepatitis B virus and response to evaccination in vertically HlV-infected adolescents on highly active antiretroviral therapy
author Pessoa, Silvana Duarte
author_facet Pessoa, Silvana Duarte
Succi, Regina Célia de Menezes
Moraes-Pinto, Maria Isabel de
author_role author
author2 Succi, Regina Célia de Menezes
Moraes-Pinto, Maria Isabel de
author2_role author
author
dc.contributor.author.fl_str_mv Pessoa, Silvana Duarte
Succi, Regina Célia de Menezes
Moraes-Pinto, Maria Isabel de
dc.subject.por.fl_str_mv Vacunas contra Hepatitis B
VIH
Antígenos CD38
Vacinas contra Hepatite B
HIV
Antígenos CD38
Hepatitis B Vaccines
HIV
Antigens, CD38
topic Vacunas contra Hepatitis B
VIH
Antígenos CD38
Vacinas contra Hepatite B
HIV
Antígenos CD38
Hepatitis B Vaccines
HIV
Antigens, CD38
description INTRODUCTION: Children infected with the human immunodeficiency virus (HIV) present alterations both in their humoral and cellular immune responses. These changes might lead to an inefficient immune response against certain specific vaccine antigens and/or to an early reduction in the antibody levels considered protective after immunization. This low immune protection against vaccine antigens is due to a deficiency in the treatment of antigens, a failure in the generation of the immunologic memory and/or the quantitative and functional loss of T and B memory cells. In addition, the introduction of highly active antiretroviral therapy (HAART) leads to the suppression of viral replication and to a partial restoration of the immunologic function, including the immune response against vaccine antigens. Recent studies have demonstrated that only a low percentage of children vertically infected with HIV treated with HAART maintain levels of protective antibodies after the primary immunization against the hepatitis B virus (HBV); however, the factors associated with the persistence of protective antibodies after primary vaccination and with the response to revaccination have not been clarified.OBJECTIVE: To evaluate the persistence of the levels of protective antibodies against HBV in adolescents vertically infected with HIV treated with HAART and their response to vaccination.MATERIAL AND METHODS: This study was approved by the Ethics Committee of the Universidade Federal de São Paulo (UNIFESP/EPM). It was performed in the AIDS pediatric outpatient facilities of the institution. From January 2006 to August 2007, 40 adolescents vertically infected with HIV (HIV group) were selected for a prospective, longitudinal, controlled and intervention study. Twenty-three healthy HIV-negative adolescents were selected as the control group. The inclusion criteria for the groups were as follows: 10-20 years of age, absence of a previous history of hepatitis B and full immunization against HBV at least four years before the beginning of this study. The exclusion criteria were blood and blood products transfusion up to six months before the beginning of the study, acute febrile disease seven days prior to inclusion in the study, previous history or serologic evidence of HBV infection (i.e., the presence of anti-HBc antibodies). Furthermore, all the adolescents of both groups had received three doses of the recombinant vaccine against hepatitis B in the primary immunization. The adolescents with anti-HBs antibody levels of < 10 mUI/mL were revaccinated against HBV with up to six doses over an interval of 30-60 days. The adolescents in the HIV group received a double dose of the recombinant vaccine against HBV (20 µg of Euvax-B®, LG Chemical Ltd., from Korea). The adolescents in the control group were revaccinated with a standard dose of the Brazilian recombinant vaccine against HBV (10 µg of Butang®, by Instituto Butantã de São Paulo, São Paulo). The maturation of lymphocytes was assessed by flow cytometry through the phenotypic profile. Statistical analysis was executed using SPSS version 12.0, with a significance level of p < 0.05.RESULTS: In the beginning of the study, anti-HBs antibody levels ≥ 10 mUI/mL were observed in 18/40 (40.5%) of the HIV-infected adolescents and in 18/23 (78.3%) of the adolescents in the control group. The adolescents in the HIV group with anti-HBs ≥ 10 mUI/mL presented a higher percentage of TCD4+ cells, a higher percentage of central memory and of naïve TCD8+ cells and a lower immune activation. After revaccination, 18/12 (66.7%) adolescents in the HIV group presented anti-HBs antibody levels > 10 mUI/mL. The adolescents who did not respond to the vaccination course presented with a lower percentage of TCD4+ cells, a higher immune activation and a detectable viral load.CONCLUSION: These findings suggest that a higher percentage of TCD4+ cells, a lower immune activation and a better control of the replication of the HIV might be associated with a better vaccine response against the HBV
publishDate 2022
dc.date.none.fl_str_mv 2022-08-09
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10.5123/S2176-62232010000300020
url https://ojs.iec.gov.br/rpas/article/view/1401
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dc.relation.none.fl_str_mv https://ojs.iec.gov.br/rpas/article/view/1401/1036
https://ojs.iec.gov.br/rpas/article/view/1401/1037
https://ojs.iec.gov.br/rpas/article/view/1401/1038
https://ojs.iec.gov.br/rpas/article/view/1401/1039
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dc.publisher.none.fl_str_mv Instituto Evandro Chagas/SCTIE/MS
publisher.none.fl_str_mv Instituto Evandro Chagas/SCTIE/MS
dc.source.none.fl_str_mv Revista Pan-Amazônica de Saúde; v. 1 n. 3 (2010): jul-set; 2
Pan-Amazonian Journal of Health; Vol. 1 No. 3 (2010): jul-set; 2
Revista Pan-Amazônica de Saúde; Vol. 1 Núm. 3 (2010): jul-set; 2
2176-6223
2176-6215
reponame:Revista Pan-Amazônica de Saúde (RPAS)
instname:Instituto Evandro Chagas (IEC)
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instname_str Instituto Evandro Chagas (IEC)
instacron_str IEC
institution IEC
reponame_str Revista Pan-Amazônica de Saúde (RPAS)
collection Revista Pan-Amazônica de Saúde (RPAS)
repository.name.fl_str_mv Revista Pan-Amazônica de Saúde (RPAS) - Instituto Evandro Chagas (IEC)
repository.mail.fl_str_mv revista@iec.gov.br
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