This study was conducted to analyse the course and the outcome of the liver disease in the co-infected animals in order to evaluate a possible synergic effect of human parvovirus B19 (B19V) and hepatitis A virus (HAV) co-infection. Nine adult cynomolgus monkeys were inoculated with serum obtained from a fatal case of B19V infection and/or a faecal suspension of acute HAV. The presence of specific antibodies to HAV and B19V, liver enzyme levels, viraemia, haematological changes, and necroinflammatory liver lesions were used for monitoring the infections. Seroconversion was confirmed in all infected groups. A similar pattern of B19V infection to human disease was observed, which was characterised by high and persistent viraemia in association with reticulocytopenia and mild to moderate anaemia during the period of investigation (59 days). Additionally, the intranuclear inclusion bodies were observed in pro-erythroblast cell from an infected cynomolgus and B19V Ag in hepatocytes. The erythroid hypoplasia and decrease in lymphocyte counts were more evident in the co-infected group. The present results demonstrated, for the first time, the susceptibility of cynomolgus to B19V infection, but it did not show a worsening of liver histopathology in the co-infected group.

O citomegalovírus humano (HCMV) apresenta variabilidade em diversas regiões do genoma, supostamente relacionada ao tropismo tecidual e imunopatogênese viral. Baseando-se na variação de seqüência do gene UL55 que codifica a glicoproteína gB, o HCMV pode ser classificado em um dos quatro genótipos. Estudos prévios têm investigado a associação destes genótipos a partir de cepas obtidas de pacientes imunossuprimidos. O presente estudo determinou os genótipos gB de cepas de HCMV obtidas de mulheres imunocompetentes em Vitória, Espírito Santo, Sudeste do Brasil. O genoma do HCMV foi extraído de secreção cervical, tecidos placentários fetais e maternos (vilosidade coriônica e decídua) obtidos de casos de aborto e de leucócitos do sangue periférico. A genotipagem foi realizada através da análise de polimorfismo de fragmentos de restrição do produto amplificado da região de alta variabilidade do gene UL55. Todos os quatro genótipos foram detectados na secreção cervical e na placenta, enquanto que somente o genótipo gB1 foi detectado em leucócitos. Genótipos gB1 e gB2 foram detectados em nove e seis das 23 cepas estudadas, respectivamente, enquanto gB3 e gB4 foram encontrados cada um em quatro casos. A diferença na freqüência de genótipos não foi estatisticamente significante. Infecção mista não foi detectada. Estes resultados indicam que os quarto genótipos de HCMV apresentam tropismo para os tecidos placentários e que todos eles circularam nas mulheres imunocompetentes no período e região geográfica do estudo.

Human cytomegalovirus (HCMV) displays genetic variability in several regions, supposed to be related with strain-specific tissue tropism and immunopathogenesis. Based on sequence variation in the UL55 gene that encodes gB glycoprotein, HCMV strains can be assigned to one of four genotypes. Previous studies have addressed gB genotyping mostly by investigating strains derived from immunosuppressed patients, sometimes without previous knowledge about genotype distribution in a geographic area. The present study verified the distribution of HCMV gB genotypes of strains obtained from immunocompetent women at Vitória City, Espírito Santo State, Southeastern, Brazil. The HCMV genome was extracted from their cervical secretion, fetal and maternal placenta tissues (chorionic villous and decidua) from abortion cases and from white blood cells (WBCs). HCMV genotyping was performed by restriction fragment length polymorphism analyses of amplified product from the high variability site of the UL55 gene. All four genotypes were observed in both cervical secretion and placenta, whereas in WBCs a single gB1 genotype was detected. HCMV gB1 and gB2 genotypes were detected, respectively, in nine and in six of the 23 studied samples, while gB3 and gB4 were each found in four separate samples of the total. The differences in genotype frequency were not considered statistically significant. No mixed genotype infection was observed. The results indicated that the four gB HCMV genotypes had no particular tropism for placenta tissues and that all genotypes circulated within immunocompetent women at the time and in the region of study.

Com o objetivo de medir a prevalência de anticorpos IgG contra o parvovírus B19 em gestantes com até 24 semanas de idade gestacional e detectar a ocorrência de casos de hidropisia fetal não-imune atribuídos a esse vírus, coletamos 249 amostras de soro em uma maternidade de referência na cidade do Rio de Janeiro, entre junho de 2003 e março de 2005. As gestantes foram acompanhadas até o termo da gestação, sendo detectados 17 casos de hidropisia fetal. Quatro casos foram atribuídos ao parvovírus B19 e dois destes ocorreram em gestantes residentes na zona oeste da cidade, em fevereiro de 2005. Resultados positivos para anticorpos IgG antiparvovírus B19 foram encontrados em 172 (71,6%) gestantes (IC 95% 65,5-77,7%), sendo esta prevalência de anticorpos comparável à encontrada em outras cidades brasileiras. A única variável associada com aquisição prévia de anticorpos IgG foi número de gestações anteriores maior que um(p= 0,02, IC 95% 0,36-0,94).

With the aim of measuring the prevalence of anti-parvovirus B19 IgG antibodies during pregnancy up to 24 weeks of gestation and detecting cases of nonimmune hydrops fetalis, 249 sera from pregnant women attending a reference hospital in Rio de Janeiro city, from June 2003 to November 2004 were collected. They were followed-up until the end of pregnancy, with 17 cases of fetal hydrops detected. Four cases were caused by parvovirus B19 and two of them occurred in pregnant women living in the western zone of the city, during February 2005. Anti-parvovirus B19 IgG antibodies were found in 172 (71.6%) pregnant women (CI 95% 65.5%-77.7%); this antibody prevalence is similar to results found for others Brazilian cities. The only variable associated with previous acquisition of IgG antibodies to parvovirus B19 was number of pregnancies greater than one (p= 0.02, CI 95% 0.36-0.94).

Sondas marcadas com biotina foram utilizadas neste trabalho para detecção de infecção viral por hibridização in situ em tecidos fixados com formalina e embebidos em parafina de 11 casos obtidos de abortamento. Sondas para citomegalovírus humano (HCMV), parvovírus B19 humano (B19) e adenovírus humano tipo 2 (HAd2), foram marcadas com biotina-11-dUTP através da reação de nick-translation. Estreptavidina conjugada com fosfatase alcalina (SAP) seguida por solução de 4-nitro-azul de tetrazolio/5-bromo-4-cloro-3-indolil fosfato (NBT/BCIP) foram utilizadas para detecção da biotina após a reação de hibridização. Reação positiva foi observada no núcleo de células do epitélio glandular da decídua tanto no controle positivo quanto no negativo em tecidos de primeiro e segundo trimestre gestacional. Esta reação não foi inibida com solução bloqueadora da atividade endógena de fosfatase alcalina e persistiu mesmo com a omissão das sondas. O uso de controles negativos permitiu revelar atividade endógena de biotina nuclear em epitélio glandular da decídua, responsável por reações falso positivas em sistemas de detecção estreptavidina-biotina (StrepABC). Os resultados obtidos neste estudo fortemente recomendam que a detecção de ADN por hibridização in situ em endométrio gestacional seja feita com outro sistema de detecção que não o StrepABC.

Biotin-labeled probe was used in an in situ hybridisation assay to localize virus infection in formalin-fixed, paraffin embedded tissues taken from eleven abortion cases. Probes for human cytomegalovirus (HCMV), human Parvovirus B19 (B19) and human adenovirus type 2 (HAd2), were labeled with biotin-11-dUTP by nick-translation reaction. Streptavidin-alkaline-phosphatase (SAP) was used to detect biotin, followed by 4-nitroblue tetrazolium/5-bromo-4-chloro-3-indolyl phosphate (NBT/BCIP) solution. Positive reaction was observed in nucleus of glandular ephitelium cells of decidua either in positive or in negative control at first and second gestational trimester. The reaction was not inhibited with blocking solution for alkaline phosphatase endogenous activity and it persisted even with probes omission. The use of adequate negative control permitted to reveal the presence of nuclear biotin in glandular epithelium of decidua, responsible for false positivity in detection systems involving streptavidin biotin system (StrepABC). The stained cells resembled to cytophatic effect due to herpesvirus, which could induce further misinterpretation. The results obtained in this study strongly recommend that DNA detection by in situ hybridisation reaction in gestational endometrium should be done without using StrepABC system.

OBJETIVO: Comparar a reatogenicidade de três vacinas contra a febre amarela (FA) das sub-cepas WHO-17D e 17DD (diferentes lotes-semente), e placebo. MÉTODOS: Foram recrutados 1.087 adultos elegíveis para vacinação contra FA no Rio de Janeiro, RJ, Brasil. Vacinas produzidas por Bio-Manguinhos, Fiocruz (Rio de Janeiro, RJ) foram administradas ("dia zero") seguindo procedimentos adaptados para alocação randômica em blocos e "cega" para o tipo de vacina. Eventos adversos pós-vacinação foram registrados em questionários e diários preenchidos pelos participantes. Enzimas hepáticas foram medidas nos dias 0, 4-20 e 30 do estudo. A viremia foi medida nos dias 4-20. A resposta imune foi verificada em testes sorológicos nos dias 0 e 30. RESULTADOS: Os participantes eram predominantemente homens jovens. A taxa de soroconversão foi superior a 98% no grupo soronegativo antes da vacinação. Comparado ao placebo, a diferença de risco de eventos adversos locais variou de 0,9% a 2,5%, e de 3,5% a 7,4% para eventos adversos sistêmicos nos grupos vacinados. A diferença de risco desses eventos com assistência médica e/ou falta ao trabalho variou de 2,0% a 4,5%. Viremia foi detectada em 3% a 6% dos vacinados até 10 dias após a vacinação. As variações nos níveis de enzimas hepáticas pós-vacinação foram semelhantes nos grupos vacinados e placebo. CONCLUSÕES: Foi demonstrada pela primeira vez a semelhança do perfil de reatogenicidade das vacinas contra FA das cepas 17D e 17DD, comparados entre si e com placebo. As variações das enzimas hepáticas constituem evidência contra o potencial de viscerotropismo do vírus vacinal.

OBJECTIVE: To compare the reactogenicity of three yellow fever (YF) vaccines from WHO-17D and Brazilian 17DD substrains (different seed-lots) and placebo. METHODS: The study involved 1,087 adults eligible for YF vaccine in Rio de Janeiro, Brazil. Vaccines produced by Bio-Manguinhos, Fiocruz (Rio de Janeiro, Brazil) were administered ("day 0") following standardized procedures adapted to allow blinding and blocked randomization of participants to coded vaccine types. Adverse events after immunization were ascertained in an interview and in diary forms filled in by each participant. Liver enzymes were measured on days 0, 4-20 and 30 of the study. Viremia levels were measured on days 4 to 20 of follow-up. The immune response was verified through serologic tests. RESULTS: Participants were mostly young males. The seroconversion rate was above 98% among those seronegative before immunization. Compared to placebo, the excess risk of any local adverse events ranged from 0.9% to 2.5%, whereas for any systemic adverse events it ranged from 3.5% to 7.4% across vaccine groups. The excess risk of events leading to search for medical care or to interruption of work activities ranged from 2% to 4.5%. Viremia was detected in 3%-6% of vaccinees up to 10 days after vaccination. Variations in liver enzyme levels after vaccination were similar in placebo and vaccine recipients. CONCLUSIONS: The frequency of adverse events post-immunization against YF, accounting for the background occurrence of nonspecific signs and symptoms, was shown for the first time to be similar for vaccines from 17D and 17DD substrains. The data also provided evidence against viscerotropism of vaccine virus.

OBJETIVO: Comparar a reatogenicidade de três vacinas contra a febre amarela (FA) das sub-cepas WHO-17D e 17DD (diferentes lotes-semente), e placebo. MÉTODOS: Foram recrutados 1.087 adultos elegíveis para vacinação contra FA no Rio de Janeiro, RJ, Brasil. Vacinas produzidas por Bio-Manguinhos, Fiocruz (Rio de Janeiro, RJ) foram administradas ("dia zero") seguindo procedimentos adaptados para alocação randômica em blocos e "cega" para o tipo de vacina. Eventos adversos pós-vacinação foram registrados em questionários e diários preenchidos pelos participantes. Enzimas hepáticas foram medidas nos dias 0, 4-20 e 30 do estudo. A viremia foi medida nos dias 4-20. A resposta imune foi verificada em testes sorológicos nos dias 0 e 30. RESULTADOS: Os participantes eram predominantemente homens jovens. A taxa de soroconversão foi superior a 98% no grupo soronegativo antes da vacinação. Comparado ao placebo, a diferença de risco de eventos adversos locais variou de 0,9% a 2,5%, e de 3,5% a 7,4% para eventos adversos sistêmicos nos grupos vacinados. A diferença de risco desses eventos com assistência médica e/ou falta ao trabalho variou de 2,0% a 4,5%. Viremia foi detectada em 3% a 6% dos vacinados até 10 dias após a vacinação. As variações nos níveis de enzimas hepáticas pós-vacinação foram semelhantes nos grupos vacinados e placebo. CONCLUSÕES: Foi demonstrada pela primeira vez a semelhança do perfil de reatogenicidade das vacinas contra FA das cepas 17D e 17DD, comparados entre si e com placebo. As variações das enzimas hepáticas constituem evidência contra o potencial de viscerotropismo do vírus vacinal.

OBJECTIVE: To compare the reactogenicity of three yellow fever (YF) vaccines from WHO-17D and Brazilian 17DD substrains (different seed-lots) and placebo. METHODS: The study involved 1,087 adults eligible for YF vaccine in Rio de Janeiro, Brazil. Vaccines produced by Bio-Manguinhos, Fiocruz (Rio de Janeiro, Brazil) were administered ("day 0") following standardized procedures adapted to allow blinding and blocked randomization of participants to coded vaccine types. Adverse events after immunization were ascertained in an interview and in diary forms filled in by each participant. Liver enzymes were measured on days 0, 4-20 and 30 of the study. Viremia levels were measured on days 4 to 20 of follow-up. The immune response was verified through serologic tests. RESULTS: Participants were mostly young males. The seroconversion rate was above 98% among those seronegative before immunization. Compared to placebo, the excess risk of any local adverse events ranged from 0.9% to 2.5%, whereas for any systemic adverse events it ranged from 3.5% to 7.4% across vaccine groups. The excess risk of events leading to search for medical care or to interruption of work activities ranged from 2% to 4.5%. Viremia was detected in 3%-6% of vaccinees up to 10 days after vaccination. Variations in liver enzyme levels after vaccination were similar in placebo and vaccine recipients. CONCLUSIONS: The frequency of adverse events post-immunization against YF, accounting for the background occurrence of nonspecific signs and symptoms, was shown for the first time to be similar for vaccines from 17D and 17DD substrains. The data also provided evidence against viscerotropism of vaccine virus.

OBJETIVO: descrever a etiologia, evolução e prevalência de hidropisia fetal em coorte de gestantes em 10 anos de acompanhamento (1992 a 2002), em uma maternidade terciária. MÉTODOS: estudo retrospectivo foi realizado em pacientes referidas para a maternidade do Instituto Fernandes Figueira com o diagnóstico de hidropisia fetal, detectado pelo exame de ultra-sonografia, durante o período compreendido entre 1992 e 2002. Os casos foram selecionados quanto à etiologia (imune ou não-imune), sendo comparados quanto à evolução, procedimentos invasivos realizados e sobrevivência. A análise das variáveis foi realizada por meio do programa Epi-Info 6.0, sendo considerado valor de significância estatística um valor de p<0,05. RESULTADOS: durante o período de estudo, 80 gestantes foram atendidas com diagnóstico inicial de hidropisia fetal. A freqüência de hidropisia nesta população foi de 1 para 157 nascidos vivos. Isoimunização Rh (grupo imune - GI) foi diagnosticada em 13 casos (16,2%), restando portanto 67 casos (83,8%) considerados como devidos a causas não imunes (grupo não imune - GNI). As causas mais comuns de hidropisia fetal não imune são: idiopáticas (40,2%), genéticas (20,8%), infecciosas (20,7%) e cardiopatia fetal (7,4%). Foi encontrada diferença em relação à idade materna do grupo imune (média = 32,8 anos) quando comparada com o grupo não imune (média=28,7) (p=0,03), porém a idade gestacional ao nascimento foi similar em ambos os grupo, (média de 33,6 semanas no grupo imune e de 33,1 semanas no grupo não imune (p=0,66). Amniocentese e transfusão sanguínea in utero foram realizadas com maior freqüência no grupo imune (p<0,001) e a letalidade perinatal encontrada foi de 53,8% no grupo imune e 68,6% no grupo não imune (p=0,47). A pesquisa complementar de anticorpos IgG anti-parvovírus B19 foi realizada em 41 dos 67 casos de hidropisia fetal não imune e somente 16 apresentaram resultado positivo. CONCLUSÃO: a etiologia não imune foi a forma mais comum de apresentação de hidropisia fetal em nossa casuística. A letalidade perinatal desta entidade continua elevada e uma proporção significativa de casos não teve causa identificada. A utilização da análise do cariótipo fetal e do diagnóstico específico para parvovírus B19 pode aumentar a identificação causal de hidropisia fetal não imune classificada como idiopática.

PURPOSE: to describe etiology, evolution and prevalence of hydrops fetalis in a cohort of pregnant women during a period of ten years (1992 to 2002) in a tertiary maternity. METHODS: a retrospective study was carried out in patients referred to the maternity of the Fernandes Figueira Institute, with diagnosis of hydrops fetalis, detected by ultrasonography, during the period from 1992 to 2002. The cases were selected according to etiology (immune or nonimmune) and evolution, performed invasive procedures and survival were compared between both groups. Analysis of variables was performed by Epi-Info 6.0 and a p value less than 0.05 was considered to be statistical significant. RESULTS: in ten years of follow-up, 80 patients with an initial diagnosis of hydrops were attended. The frequency of hydrops in this population was 1 in 157 live births. Rh immunization (immune group) was detected in 13 cases (16.2%), and for 67 cases (83.8%) nonimmune causes (nonimmune group) were considered. Major causes of nonimmune hydrops fetalis were idiopathic (40.2%), genetic (20.8%), infectious diseases (20.7%), and cardiopathy (7.4%). A difference was found in relation to maternal age in the immune group (mean = 32.8 years) when compared with the nonimmune group (mean = 28.7 years) (p=0.03), but gestational age at delivery was similar in both groups (mean = 33.6 weeks in the immune group and 33.1 weeks in the nonimmune group) (p=0.66). Amniocentesis and blood transfusion in utero were carried out more frequently in the immune group (p<0.001) and perinatal mortality was 53.8% in the immune group and 68.6% in the nonimmune group (p=0.47). Complementary research of IgG anti-parvovirus B19 antibodies was carried out in 41 of 67 cases of nonimmune hydrops, with 16 being positive for the presence of anti-B19 IgG antibodies. CONCLUSION: nonimmune etiology was the most common form of presentation of hydrops fetalis in our study. Perinatal mortality of this entity is still high and a substantial number of cases had no identified cause. Characterization of fetal karyotype and performance of specific parvovirus B19 serology could increase causal identification of nonimmune hydrops classified as idiopathic.

OBJETIVO: Comparar a imunogenicidade de três vacinas contra febre amarela ) das subcepas WHO-17D e 17DD brasileira (diferentes lotes-semente). MÉTODOS: Trata-se de ensaio de equivalência envolvendo 1.087 adultos no Rio de Janeiro, RJ. As vacinas foram produzidas em Bio-Manguinhos, Fiocruz (Rio de Janeiro, Brasil) e foram administradas seguindo procedimentos adaptados para randomização em blocos, com tipos de vacinas codificados ("duplo-cego"). Anticorpos neutralizantes contra febre amarela foram dosados antes e depois da vacinação. Definiu-se equivalência como diferença nas taxas de soroconversão não superior a cinco pontos percentuais, e razão de títulos médios geométricos superior (TMG) a 0,67. RESULTADOS: As taxas de soroconversão foram iguais ou maiores do que 98% nos participantes previamente soronegativos. Na coorte completa (incluindo os previamente soropositivos) a soroconversão foi igual ou superior a 90%. As diferenças na soroconversão variaram de -0,05% a -3,02% entre os grupos de comparação. A intensidade da resposta imune também foi semelhante nos grupos: 14,5 UI/mL a 18,6 UI/mL. As razões de TMG variaram de 0,78 a 0,93. Considerando o grupo placebo, as vacinas explicaram 93% da soroconversão. Viremia foi detectada entre os dias três e sete em 2,7% dos participantes vacinados. CONCLUSÕES: A equivalência na imunogenicidade das vacinas contra a febre amarela das subcepas 17D e 17DD foi demonstrada pela primeira vez em ensaio clínico randomizado, duplo-cego, controlado com placebo. O estudo completou o processo de validação clínica do novo lote-semente de vacina, além de ampliar as bases para utilização da vacina brasileira em outros países e de trazer alternativas de subcepas para o produtor da vacina no Brasil.

OBJECTIVE: To compare the immunogenicity of three yellow fever vaccines from WHO-17D and Brazilian 17DD substrains (different seed-lots). METHODS: An equivalence trial was carried out involving 1,087 adults in Rio de Janeiro. Vaccines produced by Bio-Manguinhos, Fiocruz (Rio de Janeiro, Brazil) were administered following standardized procedures adapted to allow blocked randomized allocation of participants to coded vaccine types (double-blind). Neutralizing yellow fever antibody titters were compared in pre- and post-immunization serum samples. Equivalence was defined as a difference of no more than five percentage points in seroconversion rates, and ratio between Geometric Mean Titters (GMT) higher than 0.67. RESULTS: Seroconversion rates were 98% or higher among subjects previously seronegative, and 90% or more of the total cohort of vaccinees, including those previously seropositive. Differences in seroconversion ranged from -0.05% to -3.02%. The intensity of the immune response was also very similar across vaccines: 14.5 to 18.6 IU/mL. GMT ratios ranged from 0.78 to 0.93. Taking the placebo group into account, the vaccines explained 93% of seroconversion. Viremia was detected in 2.7% of vaccinated subjects from Day 3 to Day 7. CONCLUSIONS: The equivalent immunogenicity of yellow fever vaccines from the 17D and 17DD substrains was demonstrated for the first time in placebo-controlled double-blind randomized trial. The study completed the clinical validation process of a new vaccine seed-lot, provided evidence for use of alternative attenuated virus substrains in vaccine production for a major manufacturer, and for the utilization of the 17DD vaccine in other countries.

OBJETIVO: Comparar a imunogenicidade de três vacinas contra febre amarela ) das subcepas WHO-17D e 17DD brasileira (diferentes lotes-semente). MÉTODOS: Trata-se de ensaio de equivalência envolvendo 1.087 adultos no Rio de Janeiro, RJ. As vacinas foram produzidas em Bio-Manguinhos, Fiocruz (Rio de Janeiro, Brasil) e foram administradas seguindo procedimentos adaptados para randomização em blocos, com tipos de vacinas codificados ("duplo-cego"). Anticorpos neutralizantes contra febre amarela foram dosados antes e depois da vacinação. Definiu-se equivalência como diferença nas taxas de soroconversão não superior a cinco pontos percentuais, e razão de títulos médios geométricos superior (TMG) a 0,67. RESULTADOS: As taxas de soroconversão foram iguais ou maiores do que 98% nos participantes previamente soronegativos. Na coorte completa (incluindo os previamente soropositivos) a soroconversão foi igual ou superior a 90%. As diferenças na soroconversão variaram de -0,05% a -3,02% entre os grupos de comparação. A intensidade da resposta imune também foi semelhante nos grupos: 14,5 UI/mL a 18,6 UI/mL. As razões de TMG variaram de 0,78 a 0,93. Considerando o grupo placebo, as vacinas explicaram 93% da soroconversão. Viremia foi detectada entre os dias três e sete em 2,7% dos participantes vacinados. CONCLUSÕES: A equivalência na imunogenicidade das vacinas contra a febre amarela das subcepas 17D e 17DD foi demonstrada pela primeira vez em ensaio clínico randomizado, duplo-cego, controlado com placebo. O estudo completou o processo de validação clínica do novo lote-semente de vacina, além de ampliar as bases para utilização da vacina brasileira em outros países e de trazer alternativas de subcepas para o produtor da vacina no Brasil.

OBJECTIVE: To compare the immunogenicity of three yellow fever vaccines from WHO-17D and Brazilian 17DD substrains (different seed-lots). METHODS: An equivalence trial was carried out involving 1,087 adults in Rio de Janeiro. Vaccines produced by Bio-Manguinhos, Fiocruz (Rio de Janeiro, Brazil) were administered following standardized procedures adapted to allow blocked randomized allocation of participants to coded vaccine types (double-blind). Neutralizing yellow fever antibody titters were compared in pre- and post-immunization serum samples. Equivalence was defined as a difference of no more than five percentage points in seroconversion rates, and ratio between Geometric Mean Titters (GMT) higher than 0.67. RESULTS: Seroconversion rates were 98% or higher among subjects previously seronegative, and 90% or more of the total cohort of vaccinees, including those previously seropositive. Differences in seroconversion ranged from -0.05% to -3.02%. The intensity of the immune response was also very similar across vaccines: 14.5 to 18.6 IU/mL. GMT ratios ranged from 0.78 to 0.93. Taking the placebo group into account, the vaccines explained 93% of seroconversion. Viremia was detected in 2.7% of vaccinated subjects from Day 3 to Day 7. CONCLUSIONS: The equivalent immunogenicity of yellow fever vaccines from the 17D and 17DD substrains was demonstrated for the first time in placebo-controlled double-blind randomized trial. The study completed the clinical validation process of a new vaccine seed-lot, provided evidence for use of alternative attenuated virus substrains in vaccine production for a major manufacturer, and for the utilization of the 17DD vaccine in other countries.

Erythrovirus B19 infection is usually benign but may have serious consequences in patients with hemolytic anemia (transient aplastic crisis), immunodeficiency (in whom persistent infection can lead to chronic bone marrow failure with anemia), or who are in the first or second trimester of gestation (spontaneous abortion, hydrops fetalis, and fetal death). Being non-enveloped, B19 resists most inactivation methods and can be transmitted by transfusion. B19 is difficult to cultivate and native virus is usually obtained from viremic blood. As specific antibodies may be absent, and there is no reliable immunological method for antigen detection, hybridization or polymerase chain reaction are needed for detecting viremia. A rapid method, gel hemagglutination (Diamed ID-Parvovirus B19 Antigen Test), can disclose highly viremic donations, whose elimination lessens the viral burden in pooled blood products and may even render them non-infectious. In order to obtain native antigen and to determine the frequency of viremic donors, we applied this test to blood donors in a period of high viral activity in our community. Positive or indeterminate results were re-tested by dot-blot hybridization. We tested 472 donors in 1998 and 831 ones in 1999. One viremic donor was found in 1999. We suggest that in periods of high community viral activity the gel hemagglutination test may be useful in avoiding highly viremic blood being added to plasma pools or directly transfused to patients under risk.

O parvovírus B19 replica-se em precursores eritróides. Não há geralmente manifestações hematológicas aparentes. Entretanto, nas altas taxas de reposição de eritrócitos, como as que ocorrem na anemia falciforme ou no feto, a infecção pode resultar, respectivamente, em aplasia transitória e hidropisia fetal. Em pacientes com AIDS, a infecção persistente pode resultar em anemia crônica. Já num paciente HIV-positivo sem AIDS, a infecção evolui como uma doença exantemática leve. Duas descrições exemplificam estas diferentes modalidades de apresentação clínica. Na primeira, um paciente com AIDS apresentou aplasia medular que respondeu a imunoglobulina. Na segunda, um paciente HIV-positivo sem AIDS apresentou um exantema morbiliforme, que cedeu sem tratamento. Diagnosticar a anemia crônica por B19 diminui as preocupações infundadas sobre anemia por drogas, evita que o paciente seja submetido a manobras diagnósticas invasivas, e impede que o paciente dissemine a infecção. Em pacientes com AIDS acometidos de aplasia eritrocítica pura, está indicada a pesquisa de DNA do parvovírus B19 no soro ou na medula óssea.

Human parvovirus B19 replicates in erythrocyte precursors. Usually, there are no apparent hematological manifestations. However, in individuals with high erythrocyte turnover, as in patients with sickle-cell disease and in the fetus, the infection may lead to severe transient aplasia and hydrops fetalis, respectively. In AIDS patients, persistent infection may result in chronic anemia. By contrast, in HIV-positive patients without AIDS the infection evolves as a mild exanthematous disease. Two clinical descriptions exemplify these forms of presentation. In the first, an AIDS patient presented with bone marrow failure that responded to immunoglobulin. In the second, an HIV-positive patient without AIDS had a morbilliform rash, and needed no treatment. Knowing that an AIDS patient has chronic B19 anemia lessens concern about drug anemia; protects the patient from invasive diagnostic maneuvers; and prevents the patient from disseminating the infection. In AIDS patients with pure red cell aplasia, a search for parvovirus B19 DNA in the serum or in the bone marrow is warranted.

This study was designed to analyse the clinical and epidemiological data from human parvovirus B19 cases in a six-year study of rash diseases conduct in an urban area in Brazil (Niterói city area, State of Rio de Janeiro). A total of 673 patients with acute rash diseases were seen at two primary health care units and at a general hospital. A clotted blood sample was collected from all subjects at the time of consultation. Forty-nine per cent (330 cases) of the patients were negative for dengue, rubella and measles IgM or for low avidity IgG to HHV-6. Of these 330, 105 (31.8%) were identified as IgM positive to parvovirus B19 by using an antibody capture EIA. During the study period, three distinct peaks of parvovirus infection were detected, suggesting that the disease appears to cycle in approximately 4-5 years. B19 infection was characterized by variable combinations of fever, flu-like symptoms, arthropathy, and gastrointestinal symptoms. Frequency of fever and arthropathy was substantially higher in adults, 75% [chi2 (1 D.F.) = 11.39, p = 0.0007] and 62.5% [chi2 (1 D.F.) = 29.89, p = 0.0000], respectively. "Slapped-cheek" appearance and reticular or lace-like rash were seen in only 30.1% of the children. No adult presented this typical rash. The lack of the typical rash pattern in a large proportion of parvovirus B19 and the similarity of clinical manifestations to other rash diseases, specially to rubella, highlight the difficulty of diagnosing B19 infection on clinical grounds alone.

Human parvovirus B19 infection can cause erythema infectiosum (EI) and several other clinical presentations. Central nervous system (CNS) involvement is rare, and only a few reports of encephalitis and aseptic meningitis have been published. Here, we describe 2 cases of B19 infection in a family presenting different clinical features. A 30 year old female with a 7-day history of headache, malaise, myalgias, joint pains, and rash was seen. Physical examination revealed a maculopapular rash on the patient's body, and arthritis of the hands. She completely recovered in 1 week. Two days before, her 6 year old son had been admitted to a clinic with a 1-day history of fever, headache, abdominal pain and vomiting. On admission, he was alert, and physical examination revealed neck stiffness, Kerning and Brudzinski signs, and a petechial rash on his trunk and extremities. Cerebrospinal fluid analysis was normal. He completely recovered in 5 days. Acute and convalescent sera of both patients were positive for specific IgM antibody to B19. Human parvovirus B19 should be considered in the differential diagnosis of aseptic meningitis, particularly during outbreaks of erythema infectiosum. The disease may mimic meningococcemia and bacterial meningitis.

Amostras fecais de cães com gastrenterite, até 6 meses de idade, foram testadas para a presença do parvovírus canino (CPV-2) pela reação de hemaglutinação (HA) e confirmadas pela reação de inibição da hemaglutinação (HI). Quarenta das 79 amostras, recebidas no período de abril de 1995 a junho de 1997, foram consideradas positivas. Aproximadamente 70% destas amostras foram obtidas de animais entre 2 e 4 meses de idade, época em que o risco de contraírem a infecção pelo CPV-2 é alto apesar da vacinação. Nenhuma variação sazonal da infecção pelo parvovírus canino pôde ser observada, e um estudo retrospectivo realizado na PolVet - UFF mostrou que em um período de 6 anos (1991-97), casos de gastrenterite ocorreram durante todos os anos em Niterói, sem uma sazonalidade definida.

Fecal samples from puppies with gastroenteritis less than 7 months old were examined for canine parvovirus infection (CPV-2) by hemagglutination (HA) and subsequent hemagglutination-inhibition (HI) tests. Forty of the 79 samples collected from April 1995 to June 1997 were found to be positive. About 70% of these samples were from 2 to 4 months old puppies, age in which they are at increased risk of developing CPV-2 infection, despite of vaccination. No seasonal distribution of canine parvovirus cases was found and it was supported by the results of a retrospective study realized at PolVet-UFF, which showed that gastroenteritis cases occurred throughout the year, for a six-year period (1991-97) in Niterói, Rio de Janeiro.