Sociobehavioral Risk Factors and Clinical Implications of Late Presentation Among People Living with HIV in the Brazilian Amazon Region.

This study aimed to analyze the prevalence, sociobehavioral factors and clinical-laboratory consequences of late presentation among people living with HIV (PLHIV) in the Brazilian Amazon region. In total, 402 HIV + individuals treated at reference units in Belém city (Pará, Brazil) between 2018 and 2019 were evaluated. Late presentation was defined as a first-collection LTCD4+ count below 350 cells/µL. Sociodemographic, behavioral and clinical data were obtained from questionnaires or medical records. Th1, Th2 and Th17 cytokine profiles were evaluated by flow cytometry. Longitudinal data on viral load, T lymphocytes, and antiretroviral therapy administration were obtained from control and logistic databases. Approximately 52.73% of the participants were late presenters and sought medical care 7-12 + months after their primary HIV diagnosis. Sociobehavioral factors associated with late presentation included illicit drug use for more than 5 years, polyamory, no alcohol consumption, homosexuality, and sexual inactiveness after HIV diagnosis. Clinically, late presentation was associated with coinfection rate; polysymptomatology; high IFN-É£, IL-6 and IL-10 levels; nonresponse to antiretroviral therapy; and virological failure- and tuberculosis coinfection-motivated changes to therapy. In summary, the prevalence of late presentation in Pará in the Brazilian Amazon region is high. Delays in seeking specialized care after a primary HIV diagnosis cause medium/long-term changes in the life expectancy and health of PLHIV.

DRB1 locus alleles of HLA class II are associated with modulation of the immune response in different serological profiles of HIV-1/Epstein-Barr virus coinfection in the Brazilian Amazon region.

Background: Epstein-Barr virus (EBV) infection involves distinct clinical and serological profiles. We evaluated the frequency of alleles of locus DRB1 of HLA class II in different serological profiles of EBV infection among HIV-1 infected patients. Methods: We recruited 19 patients with primary infection, 90 with serological transition and 467 with past infection by EBV, HIV-1 co-infection was 100% in primary infection and approximately 70% in other serological profiles. EBV viral load was quantified by real-time PCR, T lymphocyte quantification and cytokine level analysis were performed by flow cytometry, and HLA locus genotyping was performed by PCR-SSO. Results: The DRB1*09 allele was associated with primary infection (p: 0.0477), and carriers of the allele showed changes in EBV viral load (p: 0.0485), CD8(+) T lymphocyte counts (p: 0.0206), double-positive T lymphocyte counts (p: 0.0093), IL-4 levels (p: 0.0464) and TNF levels (p: 0.0161). This allele was also frequent in HIV-coinfected individuals (p: 0.0023) and was related to the log10 HIV viral load (p: 0.0176) and CD8(+) T lymphocyte count (p: 0.0285). In primary infection, the log10 HIV viral load was high (p: 0.0060) and directly proportional to the EBV viral load (p: 0.0412). The DRB1*03 allele correlated with serological transition (p: 0.0477), EBV viral load (p: 0.0015), CD4(+) T lymphocyte count (p: 0.0112), CD8(+) T lymphocyte count (p: 0.0260), double-negative T lymphocyte count (p: 0.0540), IL-4 levels (p: 0.0478) and IL-6 levels (p: 0.0175). In the serological transition group, the log10 HIV viral load was high (p: 0.0060), but it was not associated with the EBV viral load (p: 0.1214). Past infection was related to the DRB1*16 allele (p: 0.0477), with carriers displaying IgG levels (p: 0.0020), CD4(+) T lymphocyte counts (p: 0.0116) and suggestive CD8(+) T count alterations (p: 0.0602). The DRB01*16 allele was also common in HIV-1 patients with past EBV infection (p: 0.0192); however, the allele was not associated with clinical markers of HIV-1 infection. Conclusion: Our results suggest that HLA class II alleles may be associated with the modulation of the serological profiles of the immune response to Epstein-Barr virus infection in patients coinfected with HIV-1.

Manejo de saúde mental na atenção primária: relato de experiência com ferramentas de abordagem familiar / Management of mental health in primary care: an experience report with family approach tools / Manejo de la salud mental en atención primaria: informe de experiencia con herramientas de abordaje familiar

Quando atuamos no nível da Atenção Primária, nas Equipes de Saúde da Família, o vínculo com a população e com os atendidos é essencial para o desenvolvimento do trabalho de cuidado. Conhecendo o território, é possível uma aproximação e um fazer consistente com as ferramentas adequadas, que visem à melhoria da população adscrita e do núcleo familiar. Assim, este trabalho tem como objetivo relatar um caso de acompanhamento de uma família cadastrada em uma Equipe de Saúde da Família do Município de Montes Claros, MG, utilizando-se as seguintes ferramentas de abordagem familiar: Genograma, Ecomapa, Ciclo de Vida, F.I.R.O. e P.R.A.C.T.I.C.E. Elas permitiram o aprofundamento na dinâmica familiar, em seu histórico de saúde e convivência social, possibilitando a proposição de uma intervenção adequada. A coleta de dados foi feita em entrevistas nas visitas domiciliares realizadas pelos profissionais. As propostas de intervenção foram feitas por meio da conferência familiar realizada com seus membros. As ferramentas de abordagem familiar possibilitaram que a equipe interviesse de acordo com a realidade da família em questão, gerando um cuidado em saúde em uma perspectiva ampliada.

In work at Primary Care level with Family Health Strategies, the bond with the served population and families is essential to develop care work. Knowing the territory makes it possible to approach and act consistently with the appropriate tools to improve the enrolled population and family nuclei. Thus, this study aims to report a case study of a family registered with a family health team in the municipality of Montes Claros, MG, using the following family approach tools: Genogram, Ecomapa, Life Cycle, F.I.R.O., and P.R.A.C.T.I.C.E. The use of these tools made it possible to delve deeper into family dynamics, their health history, and social coexistence, making it possible to propose an appropriate intervention. Data were collected by interviews during home visits carried out by professionals. Intervention proposals were made by family conferences held with family members. Family approach tools enabled the family health team to act, intervening according to the reality of the family in question and enabling health care from a broader perspective.

Cuando trabajamos en el nivel de atención primaria, en equipos de Estrategias de Salud Familiar, el vínculo con la población y las familias atendidas es fundamental para el desarrollo del trabajo de asistencia. El conocimiento del territorio permite abordar y actuar coherentemente con las herramientas adecuadas, encaminadas a mejorar la población asignada y el núcleo familiar. Así, este trabajo tiene como objetivo describir un estudio de caso de una familia registrada en un equipo de salud familiar en la ciudad de Montes Claros, Minas Gerais (Brasil), utilizando las siguientes herramientas de abordaje familiar: Genograma, Ecomapa, Ciclo de Vida, F.I.R.O. y P.R.A.C.T.I.C.E. El uso de estas herramientas permitió profundizar en la dinámica familiar, su historia de salud y convivencia social, lo que posibilitó proponer una intervención adecuada. La recolección de datos se realizó por entrevistas durante visitas domiciliarias realizadas por profesionales. Las propuestas de intervención se realizaron por conferencias familiares realizadas con los familiares. Las herramientas del abordaje familiar permitieron al equipo de salud familiar actuar interviniendo de acuerdo con la realidad de la familia en cuestión y posibilitando la atención de la salud desde una perspectiva más amplia.

Impact of Epstein-Barr virus co-infection on natural acquired Plasmodium vivax antibody response.

BACKGROUND: The simultaneous infection of Plasmodium falciparum and Epstein-Barr virus (EBV) could promote the development of the aggressive endemic Burkitt's Lymphoma (eBL) in children living in P. falciparum holoendemic areas. While it is well-established that eBL is not related to other human malaria parasites, the impact of EBV infection on the generation of human malaria immunity remains largely unexplored. Considering that this highly prevalent herpesvirus establishes a lifelong persistent infection on B-cells with possible influence on malaria immunity, we hypothesized that EBV co-infection could have impact on the naturally acquired antibody responses to P. vivax, the most widespread human malaria parasite. METHODOLOGY/PRINCIPAL FINDINGS: The study design involved three cross-sectional surveys at six-month intervals (baseline, 6 and 12 months) among long-term P. vivax exposed individuals living in the Amazon rainforest. The approach focused on a group of malaria-exposed individuals whose EBV-DNA (amplification of balf-5 gene) was persistently detected in the peripheral blood (PersVDNA, n = 27), and an age-matched malaria-exposed group whose EBV-DNA could never be detected during the follow-up (NegVDNA, n = 29). During the follow-up period, the serological detection of EBV antibodies to lytic/ latent viral antigens showed that IgG antibodies to viral capsid antigen (VCA-p18) were significantly different between groups (PersVDNA > NegVDNA). A panel of blood-stage P. vivax antigens covering a wide range of immunogenicity confirmed that in general PersVDNA group showed low levels of antibodies as compared with NegVDNA. Interestingly, more significant differences were observed to a novel DBPII immunogen, named DEKnull-2, which has been associated with long-term neutralizing antibody response. Differences between groups were less pronounced with blood-stage antigens (such as MSP1-19) whose levels can fluctuate according to malaria transmission. CONCLUSIONS/SIGNIFICANCE: In a proof-of-concept study we provide evidence that a persistent detection of EBV-DNA in peripheral blood of adults in a P. vivax semi-immune population may impact the long-term immune response to major malaria vaccine candidates.

HLA-B*13, B*35 and B*39 Alleles Are Closely Associated With the Lack of Response to ART in HIV Infection: A Cohort Study in a Population of Northern Brazil.

Introduction: Immune reconstitution failure after HIV treatment is a multifactorial phenomenon that may also be associated with a single polymorphism of human leukocyte antigen (HLA); however, few reports include patients from the Brazilian Amazon. Our objective was to evaluate the association of the immunogenic profile of the "classical" HLA-I and HLA-II loci with treatment nonresponse in a regional cohort monitored over 24 months since HIV diagnosis. Materials and Methods: Treatment-free participants from reference centers in the state of Pará, Brazil, were enrolled. Infection screening was performed using enzyme immunoassays (Murex AG/AB Combination DiaSorin, UK) and confirmed by immunoblots (Bio-Manguinhos, FIOCRUZ). Plasma viral load was quantified by real-time PCR (ABBOTT, Chicago, Illinois, USA). CD4+/CD8+ T lymphocyte quantification was performed by immunophenotyping and flow cytometry (BD Biosciences, San Jose, CA, USA). Infection was monitored via test and logistics platforms (SISCEL and SICLOM). Therapeutic response failure was inferred based on CD4+ T lymphocyte quantification after 1 year of therapy. Loci A, B and DRB1 were genotyped using PCR-SSO (One Lambda Inc., Canoga Park, CA, USA). Statistical tests were applied using GENEPOP, GraphPad Prism 8.4.3 and BioEstat 5.3. Results: Of the 270 patients monitored, 134 responded to treatment (CD4+ ≥ 500 cells/µL), and 136 did not respond to treatment (CD4+ < 500 cells/µL). The allele frequencies of the loci were similar to heterogeneous populations. The allelic profile of locus B was statistically associated with treatment nonresponse, and the B*13, B*35 and B*39 alleles had the greatest probabilistic influence. The B*13 allele had the highest risk of treatment nonresponse, and carriers of the allele had a detectable viral load and a CD4+ T lymphocyte count less than 400 cells/µL with up to 2 years of therapy. The B*13 allele was associated with a switch in treatment regimens, preferably to efavirenz (EFZ)-based regimens, and among those who switched regimens, half had a history of coinfection with tuberculosis. Conclusions: The allelic variants of the B locus are more associated with non-response to therapy in people living with HIV (PLHIV) from a heterogeneous population in the Brazilian Amazon.

Epstein-Barr Virus (EBV) Genotypes Associated with the Immunopathological Profile of People Living with HIV-1: Immunological Aspects of Primary EBV Infection.

BACKGROUND: The aim of the present study was to evaluate the immunological profile of adult HIV-1+ patients coinfected with primary Epstein-Barr virus (EBV) infection who were free of antiretroviral drugs and inhabitants of the Brazilian Amazon region. MATERIALS AND METHODS: Primary EBV infection was screened by the semiquantitative detection of IgM and IgG anti-VCA. Genotypes were determined by conventional PCR. EBV and HIV viral load (VL) were quantified by real-time PCR. Cytokine dosage and cell quantification were performed by cytometry. RESULTS: Only HIV-1+ individuals had primary EBV infection (7.12%). The EBV-1 genotype was the most prevalent (47.37%). The VL of HIV-1 was lower in the HIV/EBV-2 group. CD4+ T lymphocytes were inversely proportional to the VL of EBV in HIV/EBV-1/2 multi-infected patients. The HIV/EBV-2 group had the lowest cytokine levels, especially IFN-γ and IL-4. Different correlations were proposed for each coinfection. The late search for specific care related to HIV infection directly affected the cytokine profile and the number of CD8+ T lymphocytes. Symptoms were associated with the increase in VL of both viruses and cytokine profile. CONCLUSIONS: Different immunological profiles were associated with EBV genotypes in primary infection, with EBV-2 being more frequent in patients with low levels of HIV viral load. With late infection monitoring and consequent delay in the initiation of HAART, clinical changes and effects on the maintenance of the immune response were observed.

Detection of Epstein-Barr virus in gastric adenocarcinoma: qPCR and FISH comparison.

EBV-associated gastric cancer accounts for about 10% of all gastric carcinomas worldwide. We aimed to verify the prevalence of EBV in gastric adenocarcinoma samples using FISH and qPCR and comparing the results obtained by both techniques. Gastric cancer samples from 191 cases were analyzed. The FISH assay was performed to detect small EBV RNAs (EBER1) and qPCR was performed to detect the EBV-EBNA-1 gene region. Cohen's kappa index and the chi-square test were used to compare the methodologies and investigate correlations with the clinical-pathological data of the gastric adenocarcinoma patients. Most of the patients were men, and the average age was 60 years. The intestinal subtype cancer presented more aggressive stages with 90% of patients having a reactive FISH for EBV (EBV+), although the virus infection frequency in epithelial gastric tissue was only 1%. No positive association with clinicopathological features and EBV+ was found by FISH. Using qPCR analysis, the percentage of positive samples was lower (52.4%), and a positive association was found in samples from older patients (> 60 years). Interestingly, 71 qPCR-negative cases were detected by FISH in the presence of non-epithelial cells and in 10 qPCR-positive cases with no evidence of EBV according to FISH. The concordance between the two techniques was low, with only 57.6%. FISH is more informative for associating the gastric carcinoma with EBV positivity in tumor/epithelial cells; however, qPCR can provide relevant information regarding the progression and characteristics of neoplasia.

Epidemiological risk factors associated with primary infection by Epstein-Barr virus in HIV-1-positive subjects in the Brazilian Amazon region.

To identify the prevalence and risk factors for primary Epstein-Barr virus (EBV) infection in human immunodeficiency virus (HIV)-1-positive adult treatment-naïve patients between January 2018 and December 2019 in a state of the Brazilian Amazon region. A total of 268 HIV-1 positive patients and 65 blood donors participated in the study. Epidemiological data were obtained from medical records and through a designed questionnaire. EBV infection was screened by the semiquantitative detection of anti-viral capsid antigen (VCA) EBV IgM and IgG, followed by molecular detection of the EBNA-3C gene. The plasma viral loads of HIV-1 and EBV were quantified using a commercial kit. The prevalence of primary coinfection was 7.12%. The associated risk factors were education level, family income, history of illicit drug use and sexually transmitted infections, homosexual contact and condom nonuse. Approximately 58.5% had late initiation of highly active antiretroviral therapy, which influenced the risk of HIV-EBV 1/2 multiple infection (odds ratio (OR): 4.76; 95% CI 1.51-15.04) and symptom development (p = 0.004). HIV viral load was associated with patient age (OR: 2.04; 95% CI 2.01-2.07; p = 0.026) and duration of illicit drug use (OR: 1.57; 95% CI 1.12-2.22; p = 0.0548). EBV viral load was associated with younger age (OR: 0.82; 95% CI 0.79-1.03; p = 0.0579). The replication of both viruses was associated with symptom development (HIV = OR: 2.06; 95% CI 1.22-3.50; p = 0.0073; EBV = OR: 8.81; 95% CI 1-10; p = 0.0447). The prevalence of HIV/EBV coinfection was lower than that observed in other studies, and social vulnerability and promiscuous sexual behavior were associated risk factors. A long time of HIV-1 infection, without therapy, influenced the risk of coinfection and disease progression. The viral loads of both viruses may be associated with some epidemiological aspects of the population.

Genotypes of Epstein-Barr virus (EBV1/EBV2) in individuals with infectious mononucleosis in the metropolitan area of Belém, Brazil, between 2005 and 2016.

Two types of Epstein Barr virus (EBV1/EBV2) have been shown to infect humans. Although their genomes are similar, the regions containing the EBNA genes differ. This study aimed to characterize the EBV genotypes of infectious mononucleosis (IM) cases in the metropolitan region of Belém, Brazil, from 2005 to 2016. A total of 8295 suspected cases with symptoms/signs of IM were investigated by infectious disease physicians at Evandro Chagas Institute, Health Care Service, from January 2005 to December 2016. Out of the total, 1645 (19.8%) samples had positive results for EBV by enzyme immunoassay and 251 (15.3%) were submitted to polymerase chain reaction (PCR) technique, using the EBNA3C region, in order to determine the type of EBV. Biochemical testing involving aspartate aminotransferase, alanine aminotransferase and gamma-glutamyl transferase were also performed. EBV type was identified by PCR in 30.3% (76/251) of individuals; of those, 71.1% (54/76) were classified as EBV1, 17.1% (13/76) as EBV2, and 11.8% (9/76) as EBV1 + EBV2. The main symptoms/signs observed with EBV1 infection were cervical lymphadenopathy (64.8%, 35/54), fever (63%, 34/54), headache (20.4%, 11/54), arthralgia (20.4%, 11/54), and exanthema (18.5%, 10/54). EBV2 infection was detected in all but two age groups, with an average age of 24 years. The most common signs/symptoms of EBV2 were fever (76.9%, 10/13), average duration of 18 days, and lymphadenopathy (69.2%, 9/13). In contrast, EBV1 + EBV2 coinfections were more frequent in those aged five years or less (20.0%, 2/10). The symptoms of EBV1 + EBV2 coinfection included fever (66.7%, 6/9), and cervical lymphadenopathy and headache (33.3%, 3/9) each. The mean values of hepatic enzymes according to type of EBV was significantly different (p < 0.05) in those EBV1 infected over 14 years of age. Thus, this pioneering study, using molecular methods, identified the EBV genotypes in 30.3% of the samples, with circulation of EBV1, EBV2, and EBV1 + EBV2 co-infection in cases of infectious mononucleosis in the northern region of Brazil.

Potential role of dengue virus, chikungunya virus and Zika virus in neurological diseases.

This study showed that laboratory markers of recent infection by dengue, Zika or chikungunya arboviruses were detected in the biological samples of approximately one-third of patients with encephalitis, myelitis, encephalomyelitis or Guillain-Barré syndrome, in a surveillance programme in Piauí state, Brazil, between 2015-2016. Fever and myalgia had been associated with these cases. Since in non-tropical countries most infections or parainfectious diseases associated with the nervous system are attributed to herpesviruses, enteroviruses, and Campylobacter jejuni, the present findings indicate that in tropical countries, arboviruses may now play a more important role and reinforce the need for their surveillance and systematic investigation in the tropics.

Encephalitis associated with Zika virus infection and reactivation of the varicella-zoster virus in a Brazilian child.

We report a case of encephalitis associated with Zika virus infection and reactivation of varicella-zoster virus in the central nervous system of a Brazilian child. This case raises the possibility that reactivation of the latent varicella-zoster virus may be a mechanism of neurological impairment induced by acquired Zika virus infection.

Encephalitis associated with Zika virus infection and reactivation of the varicella-zoster virus in a Brazilian child

Abstract We report a case of encephalitis associated with Zika virus infection and reactivation of varicella-zoster virus in the central nervous system of a Brazilian child. This case raises the possibility that reactivation of the latent varicella-zoster virus may be a mechanism of neurological impairment induced by acquired Zika virus infection.

Potential role of dengue virus, chikungunya virus and Zika virus in neurological diseases

This study showed that laboratory markers of recent infection by dengue, Zika or chikungunya arboviruses were detected in the biological samples of approximately one-third of patients with encephalitis, myelitis, encephalomyelitis or Guillain-Barré syndrome, in a surveillance programme in Piauí state, Brazil, between 2015-2016. Fever and myalgia had been associated with these cases. Since in non-tropical countries most infections or parainfectious diseases associated with the nervous system are attributed to herpesviruses, enteroviruses, and Campylobacter jejuni, the present findings indicate that in tropical countries, arboviruses may now play a more important role and reinforce the need for their surveillance and systematic investigation in the tropics.

Persistência do baculovírus anticarsia após diferentes regimes pluviométricos / Velvet-bean nucleopolyhedrovirus persistence after different rainfall intensities

A persistência do vírus da lagarta-da-soja AgMNPV, produzido de forma bruta (maceração de lagartas) e liofilizada (produto comercial), foi avaliada após a aplicação em plantas de soja seguida de diferentes regimes pluviométricos (0; 10; 20; 30mm) na intensidade de 30mm.hora-1. Essas precipitações foram simuladas com microaspersores, em casa-de-vegetação. Após a simulação, a soja foi oferecida às lagartas zero, três, seis e nove dias após a aplicação (DAP). As plantas, durante esse período, foram mantidas em casa-de-vegetação, protegidas da chuva. O experimento foi conduzido em delineamento inteiramente casualizado em condições controladas (UR 70±10%, 25±2°C, fotofase de 14h), em esquema fatorial 4 (intensidades de precipitações pluviométricas) x 2 (formulações de vírus, bruta e liofilizada) com quatro repetições, com 30 lagartas cada. Os resultados comprovam que precipitações até 30mm, em 60 minutos, não reduzem a mortalidade das lagartas, causada por AgMNPV em ambas as formas de produção, quando a oferta das folhas às lagartas ocorre no mesmo dia da aplicação. As formas de preparo do AgMNPV influenciaram na persistência do vírus aos seis DAP. Nesta avaliação, a taxa de mortalidade foi superior a 90%, quando o produto bruto foi aplicado e inferior a 50% para o produto liofilizado. Esses resultados indicam que a eficiência de AgMNPV não é afetada por chuvas de até 30mm em uma hora, para ambas as formas de preparo do AgMNPV. Entretanto, ao longo dos dias, o método de preparo bruto apresenta-se mais eficiente, devido à maior persistência sobre a área foliar da soja após a lavagem pela água.

The persistence of the velvet-bean nucleopolyhedrovirus (AgMNPV) produced raw (macerated caterpillars) and lyophilized (commercial product) was evaluated after spraying in soybean plants followed by different simulated rainfall rates (0; 10; 20; 30mm) at 30mm hour-1 rate. Rainfall was simulated in greenhouse through micro sprinkler irrigation. After simulated rainfall, soybean leaves were offered to caterpillar in laboratory conditions at zero, three, six and nine days after spraying (DAS). Soybean plants were kept in greenhouse protected from rainfall. Trial was carried out in complete randomized design, under controlled conditions (RH 70%±10%, 25±2°C, 14h photophase) in a factorial 4 (rainfall rates) x2 (formulations, raw and lyophilized) with four replicates of 30 caterpillars. Results indicate that rainfall rates up to 30mm, in 60 minutes, do not decrease caterpillar mortality caused by AgMNPV regarding to both tested baculovirus formulations, raw and lyophilized virus, when leaves were offered to caterpillars at zero DAS. However, virus production (raw or lyophilized) impacted its persistence. Six DAS, mortality rate was higher than 90% when the virus was applied raw and lower than 50% when it was applied lyophilized. These results suggest that both raw and lyophilized AgMNPV efficacy is not impaired by 30-mm rainfalls at 30mm hour-1 rate. However, raw virus was more efficient in a long term evaluation since it had longer persistence on soybean leaves after being water washed.

Identificação do gene EBER1 e EBNA1 do vírus de Epstein Barr (EBV) em tecidos de pacientes com doença de Hodgkin na região Norte do Brasil / Identification of gene EBER1 and EBNA 1 of Epstein Barr virus (EBV) in tissues of patients with Hodgkin’s disease in Northern Brazil

O vírus de Epstein Barr (EBV) é o agente causador da mononucle¬ose infecciosa e está associado a várias desordens proliferativas malignas tais como: linfoma de Burkitt, linfoma de Hodgkin e lin¬fomas não Hodgkin. Objetivo: detectar o genoma do EBV mediante a identificação dos genes EBER1 e EBNA1 em casos de doença de Hodgkin. Métodos: um total de 65 casos de linfomas diagnosti¬cados no Hospital Ophir Loyola no período de 1996 e 2005 foram analisados no Instituto Evandro Chagas, Ananindeua, Brasil. Todos os espécimes parafinizados foram analisados por hibridização in situ (gene EBER1) e PCR em tempo real (EBNA1). Resultados: do total, 64,6% (42/65) dos pacientes eram do sexo masculino e 35,4% (23/65) do sexo feminino. O EBV foi identificado por HIS nas células Reed Sternberg e variantes em 76,9% (50/65) dos casos com idade média de 28,3 anos (variação 2-84 anos). Os subtipos histológicos de casos EBV-positivos foram os seguintes: esclerose nodular em 50% (25/50), celularidade mista em 28% (14/50), depleção linfocitária em 14% (7/50) e predominância linfocitária em 8% (4/50). O DNA do EBV foi detectado em 53% (26/49) dos casos de doença de Hodgkin com um coeficiente de regressão para a curva padrão de 0,99. Conclusão: este estudo foi a primeira descrição do vírus de Epstein Barr em casos de linfoma de Hodgkin na Amazônia Brasileira, reforçando a hipótese de que o EBV seja um co-fator no processo de transformação neoplásica em conjunto com a predisposição genética e imunidade do paciente

Introduction: EBV is the causative agent of infectious mononucleosis and is associated with several malignant proliferative disorders such as Burkitt’s lymphoma, Hodgkin’s lymphoma, some B and T cell non-Hodgkin’s lymphomas. Objective: The main objective of the study was to determine the prevalence of EBER 1 gene and EBNA1 gene in cases of Hodgkin’s disease. Material and Methods: A total of 65 cases of lymphomas diagnosed between 1996 and 2005 were obtained from “Instituto Ofir Loyola” and analyzed at the “Instituto Evandro Chagas” Ananindeua, Brazil. The EBV antigens using EBER 1 probe in situ hybridization (HIS) and real time quantitative PCR. Results: From the total obtained, 64.6% (42/65) were male and 35.4% (23/65) female. EBV was identified in the Reed- Sternberg cells and variants in 76.9% (50/65) of Hodgkin’s disease cases, the median age were 28.3 years (range 2-84). The histologic subtypes of EBV-positive cases were as follows: nodular sclerosis in 50% (25/50), mixed cellularity in 28% (14/50), lymphocyte depletion in 14% (7/50) and lymphocyte predominance in 8% (4/50). We detected EBV DNA in 53% (26/49) with a coefficient of regression for the standard curve of a minimum of 0.99. Conclusion: These results were the first demonstration of the role of Epstein Barr virus in cases of Hodgkin diseases in northern Brazil and are consistent with the hypothesis that the presence of EBV during neoplasic transformation could be an additional cofactor acting together with both genetic predisposition and immunity of the patient

Segurança, imunogenicidade e eficácia protetora de duas doses da vacina RIX4414 contendo rotavírus atenuado de origem humana / Safety, immunogenicity, and protective efficacy of two doses of RIX4414 live attenuated human rotavirus vaccine in healthy Brazilian infants

OBJETIVO: Determinar a segurança, imunogenicidade e eficácia de duas doses da vacina contra o rotavírus em lactentes brasileiros saudáveis. MÉTODOS: Foi realizado um estudo randomizado, multicêntrico, duplo-cego e controlado por placebo no Brasil, México e Venezuela. Os lactentes receberam duas doses orais de vacina ou placebo aos 2 e 4 meses de idade, juntamente com as imunizações de rotina, exceto a vacina oral contra poliomielite (VOP). O presente estudo relata apenas os resultados obtidos em Belém, Brasil, onde o número de indivíduos por grupo e os títulos da vacina viral foram os seguintes: 194 (104,7 unidades formadoras de focos - UFF), 196 (10(5,2) UFF), 194 (10(5,8) UFF) e 194 (placebo). A resposta de anticorpos anti-rotavírus (anti-RV) foi avaliada em 307 indivíduos. A gravidade clínica dos episódios de gastroenterite (GE) foi determinada através de um escore com 20 pontos, onde um valor > 11 foi considerado como GE grave. RESULTADOS: As taxas de sintomas gerais solicitados foram semelhantes tanto nos indivíduos que receberam a vacina como naqueles a quem se administrou placebo. Aos 2 meses após a segunda dose, ocorreu resposta em termos de IgA sérica para RV em 54,7 a 74,4 por cento dos vacinados. Não houve interferência na imunogenicidade das vacinas de rotina. A eficácia da vacina contra qualquer gastroenterite por rotavírus (GERV) foi de 63,5 por cento (IC95 por cento 20,8-84,4) para a maior concentração (10(5,8) UFF). A eficácia foi de 81,5 por cento (IC95 por cento 44,5-95,4) contra GERV grave. Em sua maior concentração (10(5,8) UFF), a RIX4414 conferiu uma proteção de 79,8 por cento (IC95 por cento 26,4-96,3) contra GERV grave causada pela amostra G9. CONCLUSÕES: A RIX4414 foi altamente imunogênica com baixa reatogenicidade, e não interferiu na resposta sérica à difteria, tétano, coqueluche, hepatite B e antígenos Hib. Duas doses da RIX4414 conferiram proteção significativa contra a GE grave causada pelo RV.

OBJECTIVE: To determine the safety, immunogenicity and efficacy of two doses of rotavirus vaccine in healthy Brazilian infants. METHODS: A randomized, multicenter, double-blind, placebo-controlled trial was conducted in Brazil, Mexico and Venezuela. Infants received two oral doses of vaccine or placebo at 2 and 4 months of age, concurrently with routine immunizations, except for oral poliomyelitis vaccine (OPV). This paper reports results from Belém, Brazil, where the number of subjects per group and the viral vaccine titers were: 194 (10(4.7) focus forming units - FFU), 196 (10(5.2) FFU), 194 (10(5.8) FFU) and 194 (placebo). Anti-rotavirus (anti-RV) antibody response was assessed in 307 subjects. Clinical severity of gastroenteritis episodes was measured using a 20-point scoring system with a score of > 11 defined as severe GE. RESULTS: The rates of solicited general symptoms were similar in vaccine and placebo recipients. At 2 months after the second dose, a serum IgA response to RV occurred in 54.7 to 74.4 percent of vaccinees. No interference was seen in the immunogenicity of routine vaccines. Vaccine efficacy against any rotavirus gastroenteritis (RVGE) was 63.5 percent (95 percentCI 20.8-84.4) for the highest concentration (10(5.8) FFU). Efficacy was 81.5 percent (95 percentCI 44.5-95.4) against severe RVGE. At its highest concentration (10(5.8) FFU), RIX4414 provided 79.8 percent (95 percentCI 26.4-96.3) protection against severe RVGE by G9 strain. CONCLUSIONS: RIX4414 was highly immunogenic with a low reactogenicity profile and did not interfere with seroresponse to diptheria, tetanus, pertussis, hepatitis B and Hib antigens. Two doses of RIX4414 provided significant protection against severe GE caused by RV.

Safety, immunogenicity, and protective efficacy of two doses of RIX4414 live attenuated human rotavirus vaccine in healthy infants.

OBJECTIVE: To determine the safety, immunogenicity and efficacy of two doses of rotavirus vaccine in healthy Brazilian infants. METHODS: A randomized, multicenter, double-blind, placebo-controlled trial was conducted in Brazil, Mexico and Venezuela. Infants received two oral doses of vaccine or placebo at 2 and 4 months of age, concurrently with routine immunizations, except for oral poliomyelitis vaccine (OPV). This paper reports results from Belém, Brazil, where the number of subjects per group and the viral vaccine titers were: 194 (10(4.7) focus forming units - FFU), 196 (10(5.2) FFU), 194 (10(5.8) FFU) and 194 (placebo). Anti-rotavirus (anti-RV) antibody response was assessed in 307 subjects. Clinical severity of gastroenteritis episodes was measured using a 20-point scoring system with a score of >or= 11 defined as severe GE. RESULTS: The rates of solicited general symptoms were similar in vaccine and placebo recipients. At 2 months after the second dose, a serum IgA response to RV occurred in 54.7 to 74.4% of vaccinees. No interference was seen in the immunogenicity of routine vaccines. Vaccine efficacy against any rotavirus gastroenteritis (RVGE) was 63.5% (95%CI 20.8-84.4) for the highest concentration (10(5.8) FFU). Efficacy was 81.5% (95%CI 44.5-95.4) against severe RVGE. At its highest concentration (10(5.8) FFU), RIX4414 provided 79.8% (95%CI 26.4-96.3) protection against severe RVGE by G9 strain. CONCLUSIONS: RIX4414 was highly immunogenic with a low reactogenicity profile and did not interfere with seroresponse to diphtheria, tetanus, pertussis, hepatitis B and Hib antigens. Two doses of RIX4414 provided significant protection against severe GE caused by RV.

Prevalence of human astrovirus genotypes associated with acute gastroenteritis among children in Belém, Brazil.

Worldwide human astroviruses (HAstV) have increasingly been recognized as causative agents of viral gastroenteritis, mainly in infants and young children. The aim of this study was to assess the epidemiology and genotype diversity of HAstVs detected in children who participated in a trial in Belém, Brazil with the rhesus human reassortant rotavirus vaccine tetravalent (RRV-TV). From April/1990 to August/1992, 624 diarrheic stool samples were tested by enzyme immunoassay (EIA) for HAstV, with a positive rate of 4.0%. Reverse transcription-polymerase chain reaction (RT-PCR) was done in 129 samples (25 positive and 104 with twice the optical density (OD) value of negative control by EIA) being 33 positive. The overall positivity yielded by both methods was 5.4% (34/624). Genotyping of the 33 positive samples was done by type-specific RT-PCR and confirmed by sequence analysis. Phylogenetic analysis was performed using a 348-bp fragment of the ORF2 region of the capsid gene. HAstV-1 was the most prevalent, accounting for 45.5% of the isolates, followed by HAstV-2 (27.3%), HAstV-3 (12.1%), HAstV-4 (12.1%), and HAstV-6 (3.0%). The monthly distribution showed that HAstV-1 was predominant in the first year of study (May/1990 to May/1991) with highest prevalence in January/1991. HAstV-2 was predominant from July to November/1991 and HAstV-4 from September to October/1990. At 24 months of age, 30.6% of children had been infected by HAstV. The clinical symptoms registered during HAstV associated-diarrhea were usually mild. These data highlight the circulation of the different HAstV genotypes in Belém during the study period.

Prevalência de IgG do vírus varicela-zoster (VVZ) em indígenas da tribo Araweté, em altamira, Pará, de janeiro-fevereiro de 2001 / Prevalence of IgG of the varicela zoster vírus (VZV)

Objetivo: determinar a prevalência de anticorpos IgG para o vírus da varicela-zoster (VVZ) em indivíduos da comunidade indígena Araweté, Altamira, Pará, Brasil. Método: foram testadas 357 amostras de soros de indivíduos residentes na comunidade indígena Araweté, coletadas em janeiro e fevereiro de 2001, após um surti grave causado por esse vírus. Utilizou-se o procedimento imunoenzimático (ELISA) "Kit" da "Clark LaboratorieisTM" (Jamestown-NY-EUA) na pesquisa de anticorpos IgG para o VVZ. Resultados: as 357 amostra. analisadas mostraram taxa de 83,2% (297/357) de positividade. O sexo feminino foi mais acometido que o masculino, com 88,0% (162/184) e 78,0% (135/173), respectivamente, resultando diferença estatisticamente significativa, p= 0,017. A freqüência de soropositividade até os 20 anos de idade foi de 64,0% (190/297) Conclusão: aproximadamente 17% do total de indivíduos pesquisados, ainda não apresentam imunidade contra o VVZ. Os autores recomendam a necessidade de vacinação de rotina contra varicela na população suscetível afim de conferir proteção contra doença severa em comunidades não imunes.

Objective: the aim of the study was to determine the prevalence of anti- VZV antibodies of immunoglobulin G class (lgG) among remote indian communities living in the central-west region of Pará state, in the municipality of Allamira. Method: serum samples were collected in January 2000 from the Araweté Indians group afier the notification of in outbreak of chickenpox starty with 12 cases. VZV-IgG antibodies were measured by enzyme-linked immunosorbent assay (ELISA), using a commercial kit (Clark LaboratoriesTM, Jamestown-NY-USA). Results: of the 357 tested, 297 (83%) were IgG-positive, of which 45,3% (135/297) were from male indians and 54,7% (162/297) from females individuals. Rates of seropositivity up to 20 years of age was 64,0% (190/297). In addition, frequencies of seropositivity were consistently higher in females than in males (p=0,0I7). Conclusion: about 17% of the total of searched individuals, still they do not present immunity against the VZV. The need for routine vaccination against varicella of susceptible population is recommended, in order to confer protection against severe disease among these non-immune communities.