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1.
Antiviral Res ; 182: 104859, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32649965

RESUMO

The outbreaks of Zika virus (ZIKV) infection in Brazil, 2015-2016, were associated with severe congenital malformations. Our translational study aimed to test the efficacy of the antiviral agent sofosbuvir (SOF) against vertical transmission of ZIKV and the associated congenital syndrome (CZS), using a rhesus monkey model. Eight pregnant macaques were successfully infected during the organogenesis phase with a Brazilian ZIKV strain; five of them received SOF from two to fifteen days post-infection. Both groups of dams showed ZIKV-associated clinical signals, detectable ZIKV RNA in several specimens, specific anti-ZIKV IgM and IgG antibodies, and maternal neutralizing antibodies. However, malformations occurred only among non-treated dam offspring. Compared to non-treated animals, all SOF-treated dams had a shorter ZIKV viremia and four of five neonates had undetectable ZIKV RNA in blood and tissue samples. These results support further clinical evaluations aiming for the prevention of CZS.


Assuntos
Antivirais/uso terapêutico , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Sofosbuvir/uso terapêutico , Infecção por Zika virus/prevenção & controle , Infecção por Zika virus/transmissão , Zika virus/efeitos dos fármacos , Animais , Anticorpos Antivirais/sangue , Antivirais/administração & dosagem , Brasil , Feminino , Macaca mulatta , Gravidez , Complicações Infecciosas na Gravidez/prevenção & controle , Complicações Infecciosas na Gravidez/virologia , Sofosbuvir/administração & dosagem , Pesquisa Translacional Biomédica , Viremia/tratamento farmacológico , Viremia/prevenção & controle , Zika virus/imunologia , Infecção por Zika virus/congênito , Infecção por Zika virus/tratamento farmacológico
2.
BMC Infect Dis ; 13: 495, 2013 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-24148233

RESUMO

BACKGROUND: Hepatitis E virus (HEV) has been described as an emerging pathogen in Brazil and seems to be widely disseminated among swine herds. An autochthonous human case of acute hepatitis E was recently reported. To obtain a better understanding of the phenotypic profiles of both human and swine HEV strains, a experimental study was conducted using the animal model, Macaca fascicularis. METHODS: Six cynomolgus monkeys (Macaca fascicularis) were inoculated intravenously with swine HEV genotype 3 that was isolated from naturally and experimentally infected pigs in Brazil and the Netherlands. Two other monkeys were inoculated with HEV genotype 3 that was recovered from Brazilian and Argentinean patients with locally acquired acute and fulminant hepatitis E. The haematological, biochemical, and virological parameters of all animals were monitored for 67 days. RESULTS: Subclinical hepatitis was observed in all monkeys after inoculation with HEV genotype 3 that was recovered from the infected swine and human patients. HEV RNA was detected in the serum and/or faeces of 6 out of the 8 cynomolgus monkeys between 5 and 53 days after inoculation. The mild inflammation of liver tissues and elevations of discrete liver enzymes were observed. Seroconversions to anti-HEV IgM and/or IgG were detected in 7 animals. Reactivities to anti-HEV IgA were also detected in the salivary samples of 3 animals. Interestingly, all of the infected monkeys showed severe lymphopenia and a trend toward monocytosis, which coincided with elevations in alanine aminotransferase and antibody titres. CONCLUSIONS: The ability of HEV to cross the species barrier was confirmed for both the swine (Brazilian and Dutch) and human (Argentinean) strains, thus reinforcing the zoonotic risk of hepatitis E in South America. Cynomolgus monkeys that were infected with HEV genotype 3 developed subclinical hepatitis that was associated with haematological changes. Haematological approaches should be considered in future studies of HEV infection.


Assuntos
Vírus da Hepatite E/patogenicidade , Hepatite E/veterinária , Hepatite E/virologia , Falência Hepática/virologia , Doenças dos Suínos/virologia , Adulto , Animais , Feminino , Hepatite E/sangue , Vírus da Hepatite E/classificação , Humanos , Lactente , Contagem de Leucócitos , Falência Hepática/sangue , Macaca fascicularis , Masculino , Especificidade da Espécie , Suínos , Doenças dos Suínos/sangue
3.
BMC Infect Dis ; 11: 15, 2011 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-21226945

RESUMO

BACKGROUND: The anti-HCV antibody response has not been well characterized during the early phase of HCV infection and little is known about its relationship to the clinical course during this period. METHODS: We analyzed serial anti-HCV antibodies longitudinally obtained from a prospective cohort of 65 patients with acute HCV infection by using a microparticle enzyme immunoassay AxSYM HCV 3.0 (Abbott Diagnostics) during the first 12 months from HCV acquisition in Rio de Janeiro, Brazil. Spontaneous viral clearance (SVC) was defined as undetectable HCV RNA in serum, in the absence of treatment, for three consecutive HCV PCR tests within 12-months of follow-up. RESULTS: Baseline antibody values were similar among patient groups with self-limiting HCV evolution (n = 34) and persistent viremia (n = 31) [median (interquartile range) signal/cut-off ratio (s/co) 78.7 (60.7-93.8) vs. 93.9 (67.8-111.9), p = 0.26]. During 12-months follow-up, patients with acute spontaneous resolving HCV infection showed significantly lower serial antibody response in comparison to individuals progressing to chronic infection [median (interquartile range) s/co 62.7 (35.2-85.0) vs. 98.4 (70.4-127.4), p < 0.0001]. In addition, patients with self-limiting HCV evolution exhibited an expeditious, sharp decline of serial antibody values after SVC in comparison to those measured before SVC [median (interquartile range) s/co 56.0 (25.4-79.3) vs. 79.4 (66.3-103.0), p < 0.0001]. CONCLUSION: Our findings indicate a rapid short-term decline of antibody values in patients with acute spontaneous resolving HCV infection.


Assuntos
Hepacivirus/imunologia , Anticorpos Anti-Hepatite C/imunologia , Hepatite C/imunologia , Adulto , Idoso , Brasil , Estudos de Coortes , Feminino , Seguimentos , Hepacivirus/genética , Hepacivirus/isolamento & purificação , Hepatite C/virologia , Humanos , Masculino , Pessoa de Meia-Idade , RNA Viral/sangue , RNA Viral/genética , Adulto Jovem
4.
Mem Inst Oswaldo Cruz ; 98(1): 13-7, 2003 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-12700856

RESUMO

Furnas dos Dionísios is an Afro-Brazilian black community whose descendants were mainly fugitive slaves that established themselves in the State of Mato Grosso do Sul (MS), Brazil. The population is comprised mainly of low socioeconomic individuals who are engaged in agricultural activities. The objective of this study was to investigate the prevalence of hepatitis B (HB) and its correlation with epidemiological data obtained from the community. The studied population totaled 260 individuals with ages varying from 1 to 79 years (median 20). One hundred thirty-three (51.2%) were females and 127 (48.8%) were males. A high prevalence for anti-HBc was observed (42.7%), with present infection detected in 9.2% of the subjects who were also HB surface antigens (HBs Ag) positive; 27.3% were anti-HBc and anti-HBs reactive, and 6.2% had anti-HBc as only marker. The prevalence for anti-HBc was proportional to age, reaching its highest peak in age categories greater than 50. No serological marker was detected in children under the age of 2 years, however anti-HBc was present in 12 subjects with ages between 2 and 14 years, of these 8 (7.4%) were HBsAg positive. Among individuals over the age of 15 years, 99 were anti-HBc reactive, of these 16 (10.5%) were also HBsAg positive, thus suggesting an increased prevalence of HBV carriers among children and adolescents. The risk factors observed in this community that were significantly associated with anti-HBc positivity were age (over 20 years) and having an anti-HBc positive mother. Both HBeAg and anti-HBe were detected in 44.4% of the samples tested. HBsAg subtypes found in the studied population were adw2 (77.7%) and ayw2 (23.3%). While intrafamilial transmission was most likely responsible for HBV infection among children, other routes such as sexual contact might be considered for individuals with ages over 15 years.


Assuntos
Hepatite B/etnologia , Adolescente , Adulto , África/etnologia , Idoso , Brasil/epidemiologia , Criança , Pré-Escolar , Métodos Epidemiológicos , Feminino , Hepatite B/epidemiologia , Anticorpos Anti-Hepatite B/sangue , Antígenos de Superfície da Hepatite B/sangue , Vírus da Hepatite B/imunologia , Vírus da Hepatite B/isolamento & purificação , Humanos , Lactente , Masculino , Pessoa de Meia-Idade
5.
Mem. Inst. Oswaldo Cruz ; 98(1): 13-17, Jan. 30, 2003. tab, graf
Artigo em Inglês | LILACS | ID: lil-331376

RESUMO

Furnas dos Dionísios is an Afro-Brazilian black community whose descendants were mainly fugitive slaves that established themselves in the State of Mato Grosso do Sul (MS), Brazil. The population is comprised mainly of low socioeconomic individuals who are engaged in agricultural activities. The objective of this study was to investigate the prevalence of hepatitis B (HB) and its correlation with epidemiological data obtained from the community. The studied population totaled 260 individuals with ages varying from 1 to 79 years (median 20). One hundred thirty-three (51.2 percent) were females and 127 (48.8 percent) were males. A high prevalence for anti-HBc was observed (42.7 percent), with present infection detected in 9.2 percent of the subjects who were also HB surface antigens (HBs Ag) positive; 27.3 percent were anti-HBc and anti-HBs reactive, and 6.2 percent had anti-HBc as only marker. The prevalence for anti-HBc was proportional to age, reaching its highest peak in age categories greater than 50. No serological marker was detected in children under the age of 2 years, however anti-HBc was present in 12 subjects with ages between 2 and 14 years, of these 8 (7.4 percent) were HBsAg positive. Among individuals over the age of 15 years, 99 were anti-HBc reactive, of these 16 (10.5 percent) were also HBsAg positive, thus suggesting an increased prevalence of HBV carriers among children and adolescents. The risk factors observed in this community that were significantly associated with anti-HBc positivity were age (over 20 years) and having an anti-HBc positive mother. Both HBeAg and anti-HBe were detected in 44.4 percent of the samples tested. HBsAg subtypes found in the studied population were adw2 (77.7 percent) and ayw2 (23.3 percent). While intrafamilial transmission was most likely responsible for HBV infection among children, other routes such as sexual contact might be considered for individuals with ages over 15 years


Assuntos
Humanos , Masculino , Feminino , Lactente , Pré-Escolar , Criança , Adolescente , Adulto , Pessoa de Meia-Idade , Hepatite B , África , Brasil , Métodos Epidemiológicos , Hepatite B , Anticorpos Anti-Hepatite B , Antígenos de Superfície da Hepatite B , Vírus da Hepatite B
8.
Mem Inst Oswaldo Cruz ; 97(5): 643-4, 2002 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-12219127

RESUMO

In order to investigate the hepatitis C virus (HCV) infection prevalence and risk factors in hemophiliacs in Central Brazil, 90 patients were interviewed and serum samples tested for HCV RNA and anti-HCV antibodies. An overall prevalence of 63.3% (CI 95%: 53.0-72.7) was found. Multivariate analysis of risk factors showed that number of blood transfusions was significantly associated with this infection. Most hemophiliacs received locally produced cryoprecipitate. All infected patients were transfused before the screening of blood units for anti-HCV. However, hemophiliacs who received exclusively screened cryoprecipitate were HCV negative. It confirms the expected decline in transfusion-acquired hepatitis C.


Assuntos
Hemofilia A/virologia , Anticorpos Anti-Hepatite C/sangue , Hepatite C/epidemiologia , Adolescente , Adulto , Biomarcadores/sangue , Brasil/epidemiologia , Criança , Pré-Escolar , Intervalos de Confiança , Ensaio de Imunoadsorção Enzimática , Hemofilia A/epidemiologia , Hemofilia A/terapia , Hepatite C/sangue , Humanos , Pessoa de Meia-Idade , Análise Multivariada , Prevalência , RNA Viral/sangue , Diálise Renal , Fatores de Risco
9.
Mem. Inst. Oswaldo Cruz ; 97(5): 643-644, July 2002. tab
Artigo em Inglês | LILACS | ID: lil-321206

RESUMO

In order to investigate the hepatitis C virus (HCV) infection prevalence and risk factors in hemophiliacs in Central Brazil, 90 patients were interviewed and serum samples tested for HCV RNA and anti-HCV antibodies. An overall prevalence of 63.3 percent (CI 95 percent: 53.0-72.7) was found. Multivariate analysis of risk factors showed that number of blood transfusions was significantly associated with this infection. Most hemophiliacs received locally produced cryoprecipitate. All infected patients were transfused before the screening of blood units for anti-HCV. However, hemophiliacs who received exclusively screened cryoprecipitate were HCV negative. It confirms the expected decline in transfusion-acquired hepatitis C


Assuntos
Humanos , Pré-Escolar , Criança , Adolescente , Adulto , Pessoa de Meia-Idade , Hepatite C , Anticorpos Anti-Hepatite C , Diálise Renal , Biomarcadores , Brasil , Intervalos de Confiança , Ensaio de Imunoadsorção Enzimática , Hemofilia A , Hepatite C , Análise Multivariada , Prevalência , Fatores de Risco , RNA Viral
10.
Rev. saúde pública ; 27(1): 30-5, fev. 1993. tab
Artigo em Português | LILACS | ID: lil-117677

RESUMO

Como parte de uma investigaçäo epidemiológica de campo, sobre hepatite B num município de características rurais do Estado de Säo Paulo, Brasil, foi estudada a distribuiçäo de marcadores sorológicos dessa doença segundo a área de residência e o local de nascimento dos indivíduos. Para o município estudado como um todo, a prevalência encontrada para um ou mais dos marcadores sorológicos de hepatite B foi de 7,7 por cento, com os habitantes rurais apresentando risco mais elevado que os urbanos (9,8 por cento e 4,9 por cento, respectivamente). A análise da positividade, de acordo com o local de nascimento, mostrou valores mais altos entre os migrantes provenientes de outros Estados do país (15,8 por cento), seguidos dos oriundos de outros municípios de Säo Paulo (9,2 por cento): entre os nascidos no município estudado e, particularmente em Ribeiräo Preto, centro urbano de localizaçäo próxima ao mesmo, observaram-se as menores prevalências (5,2 por cento e 2,5 por cento, respectivamente). Discute-se a importância de se analisar em estudos epidemiológicos, a procedência dos indivíduos, variável capaz de influir na história natural da hepatite B numa comunidade, e, eventualmente, explicar diferenças nas distribuiçöes de marcadores dessa infecçäo em populaçöes aparentemente semelhantes.


Assuntos
Humanos , Hepatite B/epidemiologia , Características de Residência , Migração Interna , Brasil , Hepatite B/transmissão , Anticorpos Anti-Hepatite B/análise , População Rural
11.
Rev. saúde pública ; 27(1): 36-42, fev. 1993. tab
Artigo em Português | LILACS | ID: lil-117678

RESUMO

A associaçäo entre prevalência de marcadores sorológicos de hepatite B e local de nascimento, verificado em estudo realizado num município de características rurais do Estado de Säo Paulo, Cássia dos Coqueiros, sugere existirem diferenças entre migrantes e näo-migrantes no que diz respeito a fatores de risco para hepatite B. Esses dois grupos foram analisados segundo as variáveis escolaridade, ocupaçäo profissional, número de hospitalizaçöes, antecedente de transfusöes sangüíneas e tipo de tratamento dentário prévio. A comparaçäo entre os grupos mostra que migrantes, particularmente de outros Estados do país, apresentam baixos níveis de escolaridade, elevadas proporçöes de lavradores empregados, maior número de internaçöes prévias e maiores exposiçöes a transfusöes sangüíneas e a procedimentos odontológicos mais agressivos. Observaram-se ainda associaçöes entre a prevalência de marcadores de hepatite B e as variáveis escolaridade, ocupaçäo profissional, número de hospitalizaçöes e tipo de tratamento odontológico, muito embora as duas últimas näo justifiquem as maiores prevalências entre os migrantes. A distribuiçäo de marcadores de hepatite B parece ser resultado da pior condiçäo socioeconômica dos migrantes, refletida pelo seu nível inferior de escolaridade e pela predominância de ocupaçöes secundárias


Assuntos
Humanos , Fatores Socioeconômicos , Hepatite B/epidemiologia , Migração Interna , Brasil , Fatores de Risco , Hepatite B/transmissão , Características de Residência , População Rural
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