Hepatite E: diagnóstico serológico em hepatites de etiologia desconhecida

Introdução A infeção por VHE tem maior incidência nos países em desenvolvimento, nomeadamente no sudoeste asiático, como por exemplo a Índia e a China, surgindo nos restantes países como casos importados. Recentemente foram descritos casos de hepatite E em países desenvolvidos sem que estivesse presente o principal fator de risco, viagens recentes a zonas endémicas, sugerindo a existência de reservatórios do VHE nestes países. O crescente número de casos de VHE autóctone alerta para um potencial problema de saúde pública em áreas não endémicas para este agente, no qual Portugal se encontra incluído. Este trabalho teve como objetivo a análise retrospetiva (2000/2011) de infeção por VHE em casos de hepatite de etiologia desconhecida. Material e Métodos Entre Janeiro de 2000 e Dezembro de 2011, foram recebidos no Instituto Nacional de Saúde Dr. Ricardo Jorge, 241 amostras de soro de indivíduos com diagnóstico de hepatite de etiologia desconhecida, nos quais foi realizada a pesquisa de anticorpos VHE (IgG/IgM), por ensaio imunoenzimático. Resultados De entre as amostras estudadas, 12.9% (n=31) revelaram a presença de VHE IgM (infeção aguda/recente), 8.3% (n=20) foram positivos apenas para VHE IgG (infeção antiga/convalescença) e 78.8% (n=190) não apresentaram anticorpos VHE. A distribuição de resultados positivos para anticorpos VHE (IgG/IgM) foi a seguinte: n=1 entre 2000 e 2005; n=2 em 2006; n=6 em 2007; n=9 em 2008, 2009 e 2010; n=15 em 2011. Conclusões A relevância da infeção por VHE, como possível causa de hepatite, é evidenciada pelo facto de 51 indivíduos (21.2%) apresentarem anticorpos VHE, dos quais 31 (12.9%) revelaram a presença de VHE IgM, resultado compatível com infeção aguda ou recente. O aumento gradual do número de pedidos, para deteção de anticorpos VHE, bem como de resultados positivos, poderá ser o reflexo não só do aumento real de número de infeções, mas também de uma maior sensibilização dos clínicos para a existência de casos de infeção por VHE, em Portugal. Não foi possível determinar se os casos de infeção encontrados seriam importados ou autóctones, por ausência de informação, evidenciando a necessidade de uma melhor colaboração entre os clínicos e o laboratório, de forma a conhecer o padrão epidemiológico da hepatite E, em Portugal

SARS-CoV-2 introductions and early dynamics of the epidemic in Portugal

Genomic surveillance of SARS-CoV-2 in Portugal was rapidly implemented by the National Institute of Health in the early stages of the COVID-19 epidemic, in collaboration with more than 50 laboratories distributed nationwide. Methods By applying recent phylodynamic models that allow integration of individual-based travel history, we reconstructed and characterized the spatio-temporal dynamics of SARSCoV-2 introductions and early dissemination in Portugal. Results We detected at least 277 independent SARS-CoV-2 introductions, mostly from European countries (namely the United Kingdom, Spain, France, Italy, and Switzerland), which were consistent with the countries with the highest connectivity with Portugal. Although most introductions were estimated to have occurred during early March 2020, it is likely that SARS-CoV-2 was silently circulating in Portugal throughout February, before the first cases were confirmed. Conclusions Here we conclude that the earlier implementation of measures could have minimized the number of introductions and subsequent virus expansion in Portugal. This study lays the foundation for genomic epidemiology of SARS-CoV-2 in Portugal, and highlights the need for systematic and geographically-representative genomic surveillance.We gratefully acknowledge to Sara Hill and Nuno Faria (University of Oxford) and Joshua Quick and Nick Loman (University of Birmingham) for kindly providing us with the initial sets of Artic Network primers for NGS; Rafael Mamede (MRamirez team, IMM, Lisbon) for developing and sharing a bioinformatics script for sequence curation (https://github.com/rfm-targa/BioinfUtils); Philippe Lemey (KU Leuven) for providing guidance on the implementation of the phylodynamic models; Joshua L. Cherry (National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health) for providing guidance with the subsampling strategies; and all authors, originating and submitting laboratories who have contributed genome data on GISAID (https://www.gisaid.org/) on which part of this research is based. The opinions expressed in this article are those of the authors and do not reflect the view of the National Institutes of Health, the Department of Health and Human Services, or the United States government. This study is co-funded by Fundação para a Ciência e Tecnologia and Agência de Investigação Clínica e Inovação Biomédica (234_596874175) on behalf of the Research 4 COVID-19 call. Some infrastructural resources used in this study come from the GenomePT project (POCI-01-0145-FEDER-022184), supported by COMPETE 2020 - Operational Programme for Competitiveness and Internationalisation (POCI), Lisboa Portugal Regional Operational Programme (Lisboa2020), Algarve Portugal Regional Operational Programme (CRESC Algarve2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF), and by Fundação para a Ciência e a Tecnologia (FCT).info:eu-repo/semantics/publishedVersio

Evolução de casos de transmissão VIH-1 da mãe ao filho em Portugal

Introdução: Um dos maiores sucessos no combate à infeção VIH/SIDA foi a redução das taxas de transmissão mãe-filho (TMF) em resultado da implementação de estratégias preventivas. Objetivo: Análise da evolução das taxas de TMF do VIH-1 entre 1999-2010 em crianças nascidas de mães infetadas seguidas através de um protocolo laboratorial para diagnóstico precoce da TMF implementado pelo Laboratório Nacional de Referência do VIH. Materiais e Métodos: Amostras de 2418 crianças em risco de infeção VIH-1 provenientes de 38 maternidades e hospitais do continente e ilhas foram processadas para pesquisa de DNA VIH-1. Foi também analisada informação disponível relacionada com o cumprimento (sim ou não) das medidas de prevenção da TMF preconizadas para a grávida e recém-nascido. Resultados: Entre 1999 a 2010, foram diagnosticados 69 casos de TMF do VIH-1. A taxa anual de transmissão mais elevada obtida foi de 7% em 1999 e a mais baixa de 0,5% em 2005. Foram obtidas taxas de transmissão de 2% em 2006, 1,9% em 2007, 2,2% em 2008 e em 2009, e 1,7% em 2010. Observou-se que em 87% (n=60) das crianças com diagnóstico de infeção, não foram seguidas as medidas de prevenção tendo sido encontrada uma associação estatisticamente significativa entre transmissão VIH-1 e ausência de prevenção (p <0,000001). Apesar dos benefícios comprovados da terapia anti retrovírica (TAR) na prevenção da TMF foi observado nos últimos 3 anos e numa proporção variando entre 18,1% e 14,6% dos casos, a ausência de cumprimento de TAR de prevenção. Neste grupo estão incluídos casos de gestação mal vigiada e de seroconversões VIH-1 na grávida. Conclusão: Observou-se uma evolução positiva na redução das taxas de transmissão de 1999 até 2005. Nos últimos 5 anos, as taxas de TMF do VIH-1 foram mantidas próximo dos 2%. Embora se continue a diagnosticar casos de TMF no país, existem objetivos estratégicos na saúde para eliminação desta via de transmissão. Neste contexto, seria importante implementar uma ação concertada para reduzir o número de gravidezes não vigiadas e promover nos parceiros das grávidas a realização de rastreio de anticorpos VIH no sentido de poder prevenir as seroconversões durante a gestação

Molecular Epidemiology of Hepatitis A Virus in a Group of Portuguese Citizens Living in Lisbon Area

Hepatitis A virus (HAV) is the most important cause of acute infectious hepatitis worldwide. In Portugal, due to improvements in sanitation epidemic outbreaks of HAV infection have become less frequent. This report is the first, to our knowledge that characterized HAV in Portugal. For the detection and molecular characterization of HAV cases in a group of Portuguese individuals in the Lisbon area, 31 serum samples were tested: 8 from symptomatic children from an acute hepatitis A outbreak in a Roma (Gipsies) community (2004–2005), and 22 from patients with acuteHAV from sporadic cases (2005–2006). A sample of CSF involved in a case of meningitis was also included. IgM anti-HAV detection and nested reverse transcription (RT-PCR), with primers located at the VP1-P2a region, was undertaken to detect HAV genome. In positive samples, molecular characterization was followed by phylogenetic analysis. All samples (n¼31) were positive for IgM anti-HAV. HAV RNA was found in 96.7% of cases. All isolates were classified as genotype I: 22 belonged to sub-genotype IA (73.3%), and 8 to sub-genotype IB (26.7%). All strains obtained from an acute HAV outbreak had sub-genotype IA, in which seven isolates (87.5%) had identical sequences. In HAV sporadic cases sub-genotypes IA and IB were identified, and this may reflect the co-circulation of these two subgenotypes in Portugal. Molecular epidemiology of HAV infection in this group of Portuguese appears to be similar to other European countries. HAV phylogenetic studies can provide important information for the design of appropriate public health measures

Fifteen years of a nationwide culture collection of Neisseria gonorrhoeae antimicrobial resistance in Portugal

PTGonoNet: Filipa Alegria, Ana Jacinta Piedade, Maria Beatriz Tomaz, Cristina Toscano, Mariana Pessanha, Eliana Costa, Agostinho Lira, Catarina Chaves, Ana Cristina Silva, Margarida Feijó Pinto, Manuela Ribeiro, Angélica Costa Ramos, Hugo Cruz, Maria Helena Ramos, José Melo Cristino, Maria Inês Stilwell, Carlos Marques, Mariana Garcez, Maritza Pereira, Vera Santos, Marco Amaral, Maria José Rego de Sousa, Maria Favila Menezes, Elsa Calado, Luís Dias, Florbela Pereira, Idalina Rocha, Paula Mota Vieira, Maria Alberta Faustino, Maria Carmen Iglesias, Rita Pinto, Lúcia Serpa, Adriana Coutinho, Filomena Caldeira, José Diogo, Luísa Sancho, Sandra Schafer, José Carlos Camisão, Graça Trigueiro, Alexandra Costa, Alda Campos, Alexandra Pereira, Ana Catarina Guerreiro, Gizela Santos, Mónica Cardoso, Filomena Lencastre, Luísa Frazão, Sofia Soares, Inês Figueiredo, Vitória Rodrigues, Eugénio Corrêa, Rui Campainha, Maria Rosário Barros, Sofia Botelho Moniz.Neisseria gonorrhoeae antimicrobial resistance (AMR) and gonorrhea disease burden remain major public health concerns worldwide. To contribute to the supranational demands to monitor and manage the spread of antimicrobial-resistant N. gonorrhoeae, the Portuguese NIH promoted the creation of the National Laboratory Network for Neisseria gonorrhoeae Collection (PTGonoNet). The present study reports the N. gonorrhoeae major AMR trends observed from 2003 up to 2018. All isolates described in the present study constitute the opportunistic ongoing N. gonorrhoeae isolate collection supported by the National Reference Laboratory for Sexually Transmitted Infections of the Portuguese NIH, enrolling strains isolated in 35 different public and private laboratories. Minimum inhibitory concentrations were determined using E-tests for azithromycin, benzylpenicillin, cefixime, ceftriaxone, ciprofloxacin, gentamicin, spectinomycin and tetracycline. Molecular typing was determined using NG-MAST. AMR data of 2596 country-spread isolates show that 87.67% of all N. gonorrhoeae isolates presented decreased susceptibility to at least one antimicrobial. A continuous decreased susceptibility and resistance to penicillin, tetracycline and ciprofloxacin can be observed along the years. However, no decreased susceptibility to cephalosporins was observed until 2018, while for azithromycin, this was always low. The most common observed NG-MAST genogroups were G1407, G7445, G225, G2, and G1034. This study evidences the advantages of a nationwide collection of isolates and of centralized AMR testing to respond to supranational (EURO-GASP) requirements while providing unprecedented data on AMR in the context of 15 years of surveillance.M. Pinto was supported by the Portuguese Science and Technology Foundation (FCT) through grant SFRH/BD/109264/2015.info:eu-repo/semantics/publishedVersio

Hepatitis C in a Mobile Low-Threshold Methadone Program

Introduction: Data on the epidemiology of hepatitis C among individuals who use drugs in low-threshold settings are lacking, although crucial to assess the burden of disease and aid in the design of treatment strategies. Objective: The aim of this study was to characterize the epidemiology and disease related to hepatitis C in a population attending a low-threshold methadone program. Materials and methods: A cross-sectional study in the population attending the Mobile Low-Threshold Methadone Program in Lisbon, Portugal, was carried out. The survey included assessment of risk factors for infection with hepatitis C virus (HCV) and liver disease, HCV serology and RNA detection, HCV genotyping, and liver disease staging. Results: A total of 825 participants were enrolled, 81.3% men, mean age 44.5 years. Injecting drug use (IDU) was reported by 58.4% – among these, 28.2% were people who inject drugs. Excessive drinking and HIV coinfection were reported by 33.4 and 15.9%, respectively. Among participants with active infection, 16.9% were followed up in hospital consultation. The overall seroprevalence for HCV was 67.6% (94.2% in IDU, 30.0% in non-IDU, 97.1% in people who inject drugs, and 75.6% in excessive drinkers). Among seropositives for HCV, active infection was present in 68.4%. Among individuals with active infection, the most common genotypes were 1a (45.3%) and 3a (28.7%), whereas 30% had severe liver fibrosis or cirrhosis. Age 45 years or older, HCV genotype 3, and coinfection with HIV were significant predictors of cirrhosis. Conclusion: This population has a high burden of hepatitis C and several characteristics that favor dissemination of infection. Healthcare strategies are urgently needed to address hepatitis C in this setting.info:eu-repo/semantics/publishedVersio

CMV and HCV infections in HIV/non-HIV mothers and newborns: prevalence, frequency and risk factors

Abstract publicado em: ESCV2011-Program Book / European Society of Clinical Virology, p. 73. Disponível em: http://escv.ivdnews.net/public/show_abstract/1126The incidence of HIV infections in gestational age is an important Public Health issue as are concerns about co-infection with opportunistic viruses, such as CMV/HCV. Several authors refer higher ratios of congenital CMV infection in children born to HIV infected mother than in uninfected. In the case of HCV, perinatal transmission increases in cases of mothers co-infected with HIV. Aims:To study CMV/HCV infection/co-infection in HIV/non-HIV women and their newborns between 2006-2010, according to epidemiological, laboratory and clinical data; to evaluate frequency of CMV/HIV/HCV maternal-fetal transmission and analyse risk factors for infections. Methods:Plasma and/or urine of 137 HIV and 140 non-HIV women, attending a Lisbon Hospital and their 140 newborns were analysed at NIH. HIV-1 and/or HIV-2 proviral DNA nested-PCR was performed on HIV mothers and their newborn’s plasma. Maternal plasma was screened for CMV and HCV antibodies; RNA determination, genotyping and viral load were performed on women with HCV antibodies, their newborn’s plasma was also screened for HCV. Newborn’s urine was inoculated for CMV detection. Data analysis was performed using SPSS 17.0 and Fisher's exact test. Results:HIV1 vertical transmission was diagnosed in 3/140(2.1%) cases. CMV congenital infection was diagnosed in 4(2.9%) newborns from HIV women and no congenital CMV infection was diagnosed in newborns from non-HIV women. 2/137(1.5%) HIV women and 14/140(10.0%) non-HIV women were CMV seronegative. HCV infection was detected in 6(4.4%) HIV women; all had HCV positive viral load; different genotypes were found. One case of HCV perinatal transmission was diagnosed. No HCV antibodies were found in non-HIV women. No children were HIV/HCV or CMV/HCV coinfected but 2 were HIV/CMV coinfected. There is evidence of significant statistical associations with race/ethnicity and time of pregnancy. Conclusion:In this study HIV women had higher CMV/HCV antibody prevalence and frequency of maternal-fetal transmission than non-HIV women. 2/137 HIV seronegative newborns and 2/3 HIV newborns were CMV congenitally infected; this difference should be further studied, as the consequences of CMV/HCV infections may become increasingly serious and complex in the presence of HIV. This specific group is not representative of the Portuguese infected women, nevertheless the significant risk factors found and other risk factors studied without strong associations should be considered in larger studies