Predictors of HBeAg status and hepatitis B viraemia in HIV-infected patients with chronic hepatitis B in the HAART era in Brazil

<p>Abstract</p> <p>Background</p> <p>HBV-HIV co-infection is associated with an increased liver-related morbidity and mortality. However, little is known about the natural history of chronic hepatitis B in HIV-infected individuals under highly active antiretroviral therapy (HAART) receiving at least one of the two drugs that also affect HBV (TDF and LAM). Information about HBeAg status and HBV viremia in HIV/HBV co-infected patients is scarce. The objective of this study was to search for clinical and virological variables associated with HBeAg status and HBV viremia in patients of an HIV/HBV co-infected cohort.</p> <p>Methods</p> <p>A retrospective cross-sectional study was performed, of HBsAg-positive HIV-infected patients in treatment between 1994 and 2007 in two AIDS outpatient clinics located in the São Paulo metropolitan area, Brazil. The baseline data were age, sex, CD4 T+ cell count, ALT level, HIV and HBV viral load, HBV genotype, and duration of antiretroviral use. The variables associated to HBeAg status and HBV viremia were assessed using logistic regression.</p> <p>Results</p> <p>A total of 86 HBsAg patients were included in the study. Of these, 48 (56%) were using combination therapy that included lamivudine (LAM) and tenofovir (TDF), 31 (36%) were using LAM monotherapy, and 7 patients had no previous use of either one. Duration of use of TDF and LAM varied from 4 to 21 and 7 to 144 months, respectively. A total of 42 (48. 9%) patients were HBeAg positive and 44 (51. 1%) were HBeAg negative. The multivariate analysis revealed that the use of TDF for longer than 12 months was associated with undetectable HBV DNA viral load (serum HBV DNA level < 60 UI/ml) (<it>p </it>= 0. 047). HBeAg positivity was associated with HBV DNA > 60 UI/ml (p = 0. 001) and ALT levels above normality (<it>p </it>= 0. 038).</p> <p>Conclusion</p> <p>Prolonged use of TDF containing HAART is associated with undetectable HBV DNA viral load. HBeAg positivity is associated with HBV viremia and increased ALT levels.</p

Zika virus infection among symptomatic patients from two healthcare centers in Sao Paulo State, Brazil: prevalence, clinical characteristics, viral detection in body fluids and serodynamics.

Zika virus (ZIKV) clinical presentation and frequency/duration of shedding need further clarification. Symptomatic ZIKV-infected individuals identified in two hospitals in Sao Paulo State, Brazil, were investigated regarding clinical characteristics, shedding in body fluids, and serodynamics. Ninety-four of 235 symptomatic patients (Site A: 58%; Site B: 16%) had Real-Time PCR-confirmed ZIKV infection; fever, headache and gastrointestinal symptoms were less frequent, and rash was more frequent compared to ZIKV-negative patients. Real-Time PCR in serum had worse performance compared to plasma, while urine had the highest sensitivity. Shedding in genital fluids and saliva was rare. IgM positivity was the highest 28 days (24%); IgG positivity increased >14 days (96%) remaining positive in 94% of patients >28 days. ZIKV prevalence varied importantly in two neighboring cities during the same transmission season. Urine Real-Time PCR can improve diagnostic sensitivity; serum testing is less useful. Accurate serological tests are needed to improve diagnosis and surveillance

Zika virus infection among symptomatic patients from two healthcare centers in Sao Paulo State, Brazil: prevalence, clinical characteristics, viral detection in body fluids and serodynamics

Zika virus (ZIKV) clinical presentation and frequency/duration of shedding need further clarification. Symptomatic ZIKV-infected individuals identified in two hospitals in Sao Paulo State, Brazil, were investigated regarding clinical characteristics, shedding in body fluids, and serodynamics. Ninety-four of 235 symptomatic patients (Site A: 58%; Site B: 16%) had Real-Time PCR-confirmed ZIKV infection; fever, headache and gastrointestinal symptoms were less frequent, and rash was more frequent compared to ZIKV-negative patients. Real-Time PCR in serum had worse performance compared to plasma, while urine had the highest sensitivity. Shedding in genital fluids and saliva was rare. IgM positivity was the highest &lt;14 days after the symptoms onset (86%), decreasing &gt;28 days (24%); IgG positivity increased &gt;14 days (96%) remaining positive in 94% of patients &gt;28 days. ZIKV prevalence varied importantly in two neighboring cities during the same transmission season. Urine Real-Time PCR can improve diagnostic sensitivity; serum testing is less useful. Accurate serological tests are needed to improve diagnosis and surveillance

Study protocol for the multicentre cohorts of Zika virus infection in pregnant women, infants, and acute clinical cases in Latin America and the Caribbean: The ZIKAlliance consortium

Background: The European Commission (EC) Horizon 2020 (H2020)-funded ZIKAlliance Consortium designed a multicentre study including pregnant women (PW), children (CH) and natural history (NH) cohorts. Clinical sites were selected over a wide geographic range within Latin America and the Caribbean, taking into account the dynamic course of the ZIKV epidemic. Methods: Recruitment to the PW cohort will take place in antenatal care clinics. PW will be enrolled regardless of symptoms and followed over the course of pregnancy, approximately every 4 weeks. PW will be revisited at delivery (or after miscarriage/abortion) to assess birth outcomes, including microcephaly and other congenital abnormalities according to the evolving definition of congenital Zika syndrome (CZS). After birth, children will be followed for 2 years in the CH cohort. Follow-up visits are scheduled at ages 1-3, 4-6, 12, and 24 months to assess neurocognitive and developmental milestones. In addition, a NH cohort for the characterization of symptomatic rash/fever illness was designed, including follow-up to capture persisting health problems. Blood, urine, and other biological materials will be collected, and tested for ZIKV and other relevant arboviral diseases (dengue, chikungunya, yellow fever) using RT-PCR or serological methods. A virtual, decentralized biobank will be created. Reciprocal clinical monitoring has been established between partner sites. Substudies of ZIKV seroprevalence, transmissio

Encephalopathy Caused by Human Parvovirus B19 Genotype 1 Associated with <i>Haemophilus influenzae</i> Meningitis in a Newborn

Parvovirus B19 infection is associated with a wide range of clinical manifestations, from asymptomatic to severe neurological disorders. Its major clinical symptoms, fever and rash, are common to multiple viruses, and laboratory tests to detect B19 are frequently not available. Thus, the impact of B19 on public health remains unclear. We report the case of a 38-day old girl admitted to São Paulo Clinical Hospital, Brazil, with an initial diagnosis of bacterial meningitis, seizures, and acute hydrocephalus. Antibiotic therapy was maintained for one week after admission and discontinued after negative laboratory results were obtained. Nine days after symptoms onset, a cerebral spinal fluid (CSF) sample revealed persistent pleocytosis. The complete B19 complete genome was subsequently identified in her CSF by a metagenomic next-generation sequencing approach. This report highlights the possible involvement of B19 in the occurrence of acute neurological manifestations and emphasizes that its possible involvement might be better revealed by the use of metagenomic technology to detect viral agents in clinical situations of unknown or uncertain etiology

Establishment and cryptic transmission of Zika virus in Brazil and the Americas

University of Oxford. Department of Zoology, Oxford, UK / Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.University of Birmingham. Institute of Microbiology and Infection. Birmingham, UK.University of Oxford. Department of Zoology. Oxford UK.University of Oxford. Department of Zoology. Oxford, UK / Harvard Medical School. Boston, MA, USA / Boston Children's Hospital. Boston, MA, USA.University of Oxford. Department of Zoology. Oxford, UK.Fred Hutchinson Cancer Research Center. Vaccine and Infectious Disease Division. Seattle, WA, USA / University of Washington. Department of Epidemiology. Seattle, WA, USA.University of São Paulo. School of Medicine &Institute of Tropical Medicine. Department of Infectious Disease. São Paulo, SP, Brazil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.University of Oxford. Department of Statistics. Oxford, UK.University of Oxford. Department of Zoology. Oxford, UK.Institut Pasteur. Biostatistics and Integrative Biology. Mathematical Modelling of Infectious Diseases and Center of Bioinformatics. Paris, FR / Centre National de la Recherche Scientifique. Paris, FR.University of Oxford. Department of Zoology. Oxford, UK.Ministry of Health. Coordenação dos Laboratórios de Saúde. Brasília, DF, Brazil.Ministry of Health. Coordenação Geral de Vigilância e Resposta às Emergências em Saúde Pública. Brasília, DF, Brazil / Fundação Oswaldo Cruz. Center of Data and Knowledge Integration for Health. Salvador, BA, Brazil.Ministry of Health. Departamento de Vigilância das Doenças Transmissíveis. Brasilia, DF, Brazil.Ministry of Health. Coordenação Geral dos Programas de Controle e Prevenção da Malária e das Doenças Transmitidas pelo Aedes. Brasília, DF, Brazil / Pan American Health Organization (PAHO). Buenos Aires, AR.Ministry of Health. Coordenação Geral dos Programas de Controle e Prevenção da Malária e das Doenças Transmitidas pelo Aedes. Brasília, DF, Brazil / Fundação Oswaldo Cruz. Rio de Janeiro, RJ, Brazil.Ministry of Health. Coordenação Geral dos Programas de Controle e Prevenção da Malária e das Doenças Transmitidas pelo Aedes. Brasília, DF, BrazilMinistry of Health. Departamento de Vigilância das Doenças Transmissíveis. Brasilia, DF, Brazil.Ontario Institute for Cancer Research. Toronto, ON, Canada.University of Nottingham. Nottingham, UKThe Scripps Research Institute. Department of Immunology and Microbial Science. La Jolla, CA, USA.The Scripps Research Institute. Department of Immunology and Microbial Science. La Jolla, CA, USA.University of California. Departments of Laboratory Medicine and Medicine & Infectious Diseases. San Francisco, CA, USA.University of California. Departments of Laboratory Medicine and Medicine & Infectious Diseases. San Francisco, CA, USA.Instituto Mexicano del Seguro Social. División de Laboratorios de Vigilancia e Investigación Epidemiológica. Ciudad de México, MC.Instituto Mexicano del Seguro Social. División de Laboratorios de Vigilancia e Investigación Epidemiológica. Ciudad de México, MC.Universidad Nacional Autónoma de México. Instituto de Biotecnología. Cuernavaca, MC.Instituto Oswaldo Cruz. Rio de Janeiro, RJ, Brazil.Paul-Ehrlich-Institut. Langen, Germany.Laboratório Central de Saúde Pública Noel Nutels. Rio de Janeiro, RJ, Brazil.Laboratório Central de Saúde Pública Noel Nutels. Rio de Janeiro, RJ, Brazil.Laboratório Central de Saúde Pública Noel Nutels. Rio de Janeiro, RJ, Brazil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil.Fundação Oswaldo Cruz. Salvador, BA, Brazil.Laboratório Central de Saúde Pública. Natal, RN, Brazil.Laboratório Central de Saúde Pública. Natal, RN, Brazil / Universidade Potiguar. Natal, RN, Brazil.Laboratório Central de Saúde Pública. Natal, RN, Brazil / Faculdade Natalense de Ensino e Cultura. Natal, RN, Brazil.Laboratório Central de Saúde Pública. João Pessoa, PB, Brazil.Laboratório Central de Saúde Pública. João Pessoa, PB, Brazil.Laboratório Central de Saúde Pública. João Pessoa, PB, Brazil.Laboratório Central de Saúde Pública. João Pessoa, PB, Brazil.Fundação Oswaldo Cruz. Recife, PE, Brazil.Fundação Oswaldo Cruz. Recife, PE, Brazil.Fundação Oswaldo Cruz. Recife, PE, Brazil / Colorado State University. Department of Microbiology, Immunology &Pathology. Fort Collins, CO, USA.Fundação Oswaldo Cruz. Recife, PE, Brazil.Heidelberg University Hospital. Department for Infectious Diseases. Section Clinical Tropical Medicine. Heidelberg, Germany.Fundação Oswaldo Cruz. Recife, PE, Brazil.Laboratório Central de Saúde Pública. Maceió, AL, Brazil.Laboratório Central de Saúde Pública. Maceió, AL, Brazil.Laboratório Central de Saúde Pública. Maceió, AL, Brazil.Universidade Estadual de Feira de Santana. Feira de Santana, BA, Brazil.Secretaria de Saúde de Feira de Santana. Feira de Santana, BA, Brazil.Universidade Federal do Amazonas. Manaus, AM, Brazil.University of São Paulo. School of Medicine &Institute of Tropical Medicine. Department of Infectious Disease. São Paulo, SP, Brazil.University of São Paulo. School of Medicine &Institute of Tropical Medicine. Department of Infectious Disease. São Paulo, SP, Brazil.Hospital São Francisco. Ribeirão Preto, SP, Brazil.University of São Paulo. School of Medicine &Institute of Tropical Medicine. Department of Infectious Disease. São Paulo, SP, Brazil.Universidade Federal do Tocantins. Palmas, TO, Brazil.University of São Paulo. School of Medicine &Institute of Tropical Medicine. Department of Infectious Disease. São Paulo, SP, Brazil.University of Sydney. Sydney, Australia.University of Edinburgh. Institute of Evolutionary Biology. Edinburgh, UK / National Institutes of Health. Fogarty International Center. Bethesda, MD, USA.Fred Hutchinson Cancer Research Center. Vaccine and Infectious Disease Division. Seattle, WA, USA.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Ananindeua, PA, Brasil / University of Texas Medical Branch. Department of Pathology. Galveston, TX, USA.University of São Paulo. School of Medicine &Institute of Tropical Medicine. Department of Infectious Disease. São Paulo, SP, Brazil.Fundação Oswaldo Cruz. Salvador, BA, Brazil.University of Birmingham. Institute of Microbiology and Infection. Birmingham, UK.University of Oxford. Department of Zoology, Oxford, UK / Metabiota. San Francisco, CA, USA.University of São Paulo. School of Medicine &Institute of Tropical Medicine. Department of Infectious Disease. São Paulo, SP, Brazil.Fundação Oswaldo Cruz. Salvador, BA, Brazil.Fundação Oswaldo Cruz. Salvador, BA, Brazil / University of Rome Tor Vergata. Rome, Italy.Transmission of Zika virus (ZIKV) in the Americas was first confirmed in May 2015 in northeast Brazil. Brazil has had the highest number of reported ZIKV cases worldwide (more than 200,000 by 24 December 2016) and the most cases associated with microcephaly and other birth defects (2,366 confirmed by 31 December 2016). Since the initial detection of ZIKV in Brazil, more than 45 countries in the Americas have reported local ZIKV transmission, with 24 of these reporting severe ZIKV-associated disease. However, the origin and epidemic history of ZIKV in Brazil and the Americas remain poorly understood, despite the value of this information for interpreting observed trends in reported microcephaly. Here we address this issue by generating 54 complete or partial ZIKV genomes, mostly from Brazil, and reporting data generated by a mobile genomics laboratory that travelled across northeast Brazil in 2016. One sequence represents the earliest confirmed ZIKV infection in Brazil. Analyses of viral genomes with ecological and epidemiological data yield an estimate that ZIKV was present in northeast Brazil by February 2014 and is likely to have disseminated from there, nationally and internationally, before the first detection of ZIKV in the Americas. Estimated dates for the international spread of ZIKV from Brazil indicate the duration of pre-detection cryptic transmission in recipient regions. The role of northeast Brazil in the establishment of ZIKV in the Americas is further supported by geographic analysis of ZIKV transmission potential and by estimates of the basic reproduction number of the virus

Study protocol for the multicentre cohorts of Zika virus infection in pregnant women, infants, and acute clinical cases in Latin America and the Caribbean: the ZIKAlliance consortium

Background: The European Commission (EC) Horizon 2020 (H2020)-funded ZIKAlliance Consortium designed a multicentre study including pregnant women (PW), children (CH) and natural history (NH) cohorts. Clinical sites were selected over a wide geographic range within Latin America and the Caribbean, taking into account the dynamic course of the ZIKV epidemic. Methods: Recruitment to the PW cohort will take place in antenatal care clinics. PW will be enrolled regardless of symptoms and followed over the course of pregnancy, approximately every 4 weeks. PW will be revisited at delivery (or after miscarriage/abortion) to assess birth outcomes, including microcephaly and other congenital abnormalities according to the evolving definition of congenital Zika syndrome (CZS). After birth, children will be followed for 2 years in the CH cohort. Follow-up visits are scheduled at ages 1-3, 4-6, 12, and 24 months to assess neurocognitive and developmental milestones. In addition, a NH cohort for the characterization of symptomatic rash/fever illness was designed, including follow-up to capture persisting health problems. Blood, urine, and other biological materials will be collected, and tested for ZIKV and other relevant arboviral diseases (dengue, chikungunya, yellow fever) using RT-PCR or serological methods. A virtual, decentralized biobank will be created. Reciprocal clinical monitoring has been established between partner sites. Substudies of ZIKV seroprevalence, transmission clustering, disabilities and health economics, viral kinetics, the potential role of antibody enhancement, and co-infections will be linked to the cohort studies. Discussion: Results of these large cohort studies will provide better risk estimates for birth defects and other developmental abnormalities associated with ZIKV infection including possible co-factors for the variability of risk estimates between other countries and regions. Additional outcomes include incidence and transmission estimates of ZIKV during and after pregnancy, characterization of short and long-term clinical course following infection and viral kinetics of ZIKV