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A Leucemia Linfocítica Crônica (LLC) é uma doença linfoproliferativa considerada a doença mais comum nos idosos no mundo ocidental. A citogenética é uma importante ferramenta prognóstica que demonstra as principais alterações cromossômicas predizendo o curso clínico da doença, a sobrevida do paciente e auxilia na escolha do tratamento. O vírus Epstein-Barr (EBV) é um γ ubíquo-herpesvírus que infecta mais de 90% da população mundial. A relação entre EBV e o curso clínico de pacientes com LLC é desconhecida. O objetivo desse trabalho é investigar a infecção do EBV em pacientes portadores de LLC. Foi realizado um estudo transversal de 46 pacientes sob diagnóstico de LLC e tratamento efetivado nos períodos de 2017 a 2019. Os dados foram obtidos pela revisão de prontuários médicos e registrados via formulário eletrônico com aspectos demográficos, clínicos, parâmetros hematológicos e perfil citogenético. Para a detecção do EBV foi utilizado o teste de reação em cadeia da polimerase (PCR). O DNA viral foi extraído com auxílio do kit “QIAamp DNA Mini” (QIAGEN) e submetido à reação de PCR, utilizando o kit comercial Ludwig Biotec, tendo como alvo o gene EBNA-3C. Observou-se que o sinal clínico mais frequente foi esplenomegalia e a linfocitose a alteração laboratorial de mau prognóstico. As alterações citogenéticas foram encontradas em 36,6% da população estuda e 16,67% foram de mau prognóstico (deleção 11q, 17p e tp53). Foram detectados 43,47% dos pacientes com DNA viral do EBV. Ocorrendo um aumento estatístico significativo de complicações e comorbidade e evoluções a óbito nos pacientes EBV positivo (p

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.

Interleukin-6 have been recognized as a major role player in COVID-19 severity, being an important regulator of cytokine storm. Hence, the evaluation of the influence of polymorphisms in key genes of IL-6 pathway, namely IL6, IL6R and IL6ST, may provide valuable prognostic/predictive biomarkers on COVID-19. The present cross-sectional study genotyped three Single Nucleotide Polymorphisms - SNPs (rs1800795, rs2228145 and rs7730934) at IL6, IL6R and IL6ST genes, respectively, in 227 COVID-19 patients (132 hospitalized and 95 non-hospitalized). Genotype frequencies were compared between these groups. As control group, published data on gene and genotype frequencies was gathered from published studies from before the pandemic started. Our major results point to an association of IL6 C allele with COVID-19 severity. Moreover, IL-6 plasmatic levels were higher among IL6 CC genotype carriers. Additionally, the frequency of symptoms was higher at IL6 CC and IL6R CC genotypes. In conclusion the data suggest an important role of IL6 C allele and IL6R CC genotype on COVID-19 severity, in agreement with indirect evidences from literature about association of these genotypes with mortality rates, pneumonia, heightening of protein plasmatic levels proinflammatory driven effects.

IntroductionImmune 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 MethodsTreatment-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.ResultsOf 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.ConclusionsThe 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.

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.

Female sex workers (FSWs) represent a high vulnerability group for the acquisition of sexual and parenteral infections such as hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. The present study aimed to determine the prevalence of serological markers and risk factors associated with exposure to HBV and HCV among FSWs in the state of Para, Brazil. A cross-sectional study using principles of the time location sampling (TLS) method was conducted in four cities (Belem, Braganca, Barcarena, and Augusto Correa) of the state of Para, from 2005 to 2006. In total, 365 FSWs were interviewed using a standardized questionnaire. Blood samples were collected and tested for serological markers of exposure to HBV and HCV using an enzyme immunoassay. The overall prevalence of exposure to HBV and HCV was 36.7% and 7.7%, respectively. The prevalence of surface antigen of HBV was 3.0%. The prevalence of anti-HBc and anti-HBc+ anti-HBs antibodies were 6.3% and 27.4%. Very few (4.7%) FSWs had vaccine immunity against HBV (anti-HBs antibodies only). The prevalence of anti-HCV antibodies was 7.7%. Low monthly income, drug usage, and unprotected sex were some of the social characteristics associated with exposure to the viruses using different analysis. The seroprevalence of HBV and HCV infections among FSWs in four cities of the state of Para is high when compared to the general population of Brazil, but similar to those found in FSWs in other nondeveloped countries. The prevalence of HBV was higher in Belem, while the prevalence of HCV was higher in the other three cities, highlighting the importance of establishing control and prevention programs to reduce the risk of acquiring these viruses in Para.

Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. P?s-gradua??o em Virologia. Ananindeua, PA, Brasil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil / Universidade Estadual do Par?. Resid?ncia M?dica. Bel?m, PA, Brazil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Laborat?rio de Rotav?rus. Ananindeua, PA, Brasil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Laborat?rio de Rotav?rus. Ananindeua, PA, Brasil / Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. P?s-gradua??o em Virologia. Ananindeua, PA, Brasil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Ananindeua, PA, Brasil / Universidade Federal do Par?. N?cleo de Medicina Tropical. Bel?m, PA, Brazil / Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. P?s-gradua??o em Virologia. Ananindeua, PA, Brasil. 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 Bel?m, 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.

The COVID-19 pandemic in Brazil has demonstrated an important public health impact, as has been observed in the world. In Brazil, the Amazon Region contributed with a large number of cases of COVID-19, especially in the beginning of the circulation of SARS-CoV-2 in the country. Thus, we describe the epidemiological profile of COVID-19 and the genetic diversity of SARS-CoV-2 strains circulating in the Amazon Region. We observe an extensive spread of virus in this Brazilian site. The data on sex, age and symptoms presented by the investigated individuals were similar to what has been observed worldwide. The genomic analysis of the viruses revealed important amino acid changes, including the D614G and the I33T in Spike and ORF6 proteins, respectively. The latter found in strains originating in Brazil. The phylogenetic analyzes demonstrated the circulation of the lineages B.1 and B.1.1, whose circulation in Brazil has already been previous reported. Our data reveals molecular epidemiology of SARS-CoV-2 in the Amazon Region. These findings also reinforce the importance of continuous genomic surveillance this virus with the aim of providing accurate and updated data to understand and map the transmission network of this agent in order to subsidize operational decisions in public health.

Background: Two types of Epstein Barr virus (EBV1/EBV2) have been shown to infect humans by causing infectious mononucleosis, their genome being very similar, except for regions of the EBNA genes. This study aimed to describe the EBV genotypes in cases of infectious mononucleosis in the metropolitan region of Belém, Brazil, from 2005 to 2016. Methods: A total of 8.295 suspected cases with symptoms/signs of infectious mononucleosis (MI) were investigated by doctors of infectious diseases at the Evandro Chagas Institute Health Care Service from January 2005 to December 2016. In 3.0% (251/8.295) of the cases were positive by enzymatic immunoassay were submitted to PCR for EBNA3C region to detect the types of EBV. Biochemical testing involving aspartate aminotransferase, alanine aminotransferase and gamma-glutamyl transferase were realized. Results: The identification of EBV types by PCR was verified in 30.3% (76/251) of individuals, being 71.1% (54/76) classified as EBV1, 17.1% (13/76) as EBV2 and 11.8% (9/76) as EBV1+EBV2. The number of women infected with EBV1 was higher (61.1% - 33/54) than for men (38.9% - 21/54), most were over 14 years old (66.7%-36/54). The main symptoms/clinical signs observed in EBV1 infection were: cervical lymphadenopathy (64.8%-35/54), fever (63%-34/54), headache (20.3%-11/54), arthralgia (20.3%-11/54) and exanthema (18.5%-10/54). In EBV2 infection, it was also detected in all age groups, with the exception of two groups, with an average age of 24 years. The presence of fever in 76.9% (10/13) with an average duration of 18 days and lymphadenopathy in 53.8 (7/13) were the most relevant signs/symptoms in EBV2. In contrast, EBV1+EBV2 co-infection was more frequent in the £5 year age group, affecting 20.0% (2/10). Women presented 66.7% (6/9) more positive cases. The symptoms involving EBV1+EBV2 co-infection were more related to fever (66.7%-6/9) and cervical lymphadenopathy (55.6% -5/9). The average of enzymatic values according to type of EBV was statistically significant (p

Background: Two types of Epstein Barr virus (EBV1 and 2) have been shown to infect humans. This study aimed to detect the types of EBV that cause infectious mononucleosis and correlate these viral types with clinical parameters in the metropolitan region of Belém from 2005 to 2016.Methods: A total of 76 cases of infectious mononucleosis (IM) were processed at the Instituto Evandro Chagas, Ananindeua, Brazil. PCR was used to analyze the EBNA 3C region for the recognition of EBV types. Biochemical testing (aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT) was performed by the COBAS INTEGRA clinical biochemistry PLUS 400 / ROCHE automatic analyzer. The data were evaluated using the Statistical Package for Social Science - SPSS 17.0 and GraphPadPrism 7.0 for Windows.Results: EBV1 infection was observed in 71.1% (54/76) of individuals, among whom those > 14 years constituted 66.7% (36/54); the average age was 23 years, and the number of women infected was higher (61.1% [33/54]) than that of men 38.9%[21/54]). The symptoms/clinical signs observed in infection by EBV1 were cervical lymphadenopathy in 64.8% (35/54), fever in 63% (34/54), headache and arthralgia in 20.3% (11/54), and exanthema in 18.5% (10/54). Infection by EBV2 was observed in only 17.1% (13/76) of cases. Coinfections by EBV1 and EBV2, most frequently showing symptoms of fever and cervical lymphadenopathy, occurred in 66.7% (6/9) and 55.6% (5/9) of individuals. Alterations to AST were confirmed in 14.8% (8/54), EBV2 of cases in 7.7% (1/13) in EBV1 infection. Conclusions: EBV1 was predominant in 71% of clinical cases of infectious mononucleosis. The correlation of biochemical parameters in infection by EBV1, EBV2, and coinfections by EBV1/2 revealed a statistically significant difference in mean changes of EBV1 in individuals older than 14 years.

El lupus eritematoso sistemico (LES) es una enfermedad autoinmune cronica, cuyo desarrollo puede estar asociado a la infeccion por virus, como el virus de Epstein-Barr (VEB), parvovirus B19 y virus linfotropico de celulas T humanas (HTLV). Durante el periodo de junio a setiembre de 2014, se realizo un estudio transversal, incluyendo a 85 pacientes oriundos del Hospital Jean Bitar en la Ciudad de Belem, Estado de Para, Brasil. Se hizo el estudio de anticuerpos especificos contra los agentes virales estudiados, ademas de investigar la presencia del genoma para EBV y HTLV. Se evaluaron tambien, variables clinicas y epidemiologicas. La mayoria de los pacientes era de mujeres, con un promedio de edad de 30 anos y se declararon blancos. Para VEB, se detecto una positividad de 37,6% para IgM, 98,8% para IgG y 2,4% por PCR, con cuantificaciones de 85.028 y 298 copias del genoma/mL de plasma. Para B19, la positividad para IgM fue 0% y para IgG 67,1%. No hubo deteccion serologica o por PCR de HTLV. Se verifico una relacion estadisticamente significante entre la positividad para IgM anti VEB y pacientes mas jovenes. Este hallazgo puede estar relacionado con la mayor eficiencia en la produccion de esa inmunoglobulina en las infecciones primarias agudas, que ocurren generalmente en individuos infantes o adultos jovenes. Adicionalmente, el resultado de IgG anti B19 fue asociado a la edad avanzada de los pacientes, probablemente por un tiempo mayor de exposicion al virus aliado a la persistencia de este marcador luego del contacto. La presencia de los marcadores no estuvo asociada a las variables clinicas y epidemiologicas. Sin embargo, el porcentual de positividad para el marcador de infeccion aguda por VEB puede sugerir que haya una implicacion del virus con el LES