RESUMO
Acute hepatitis B related to injection drug use is often caused by HBV-D3, a subgenotype that probably was introduced in Western Europe in the 1960s. The aim of this study was to describe genetic change over time in injection drug use-related HBV-D3 in one geographic area. Fourteen complete genomes and partial genomic regions of 17 HBV strains of subgenotype D3 causing acute (n = 30) or chronic (n = 1) hepatitis B at different time points between 1975 and 2009 were investigated. The 14 complete genomes clustered in phylogenetic trees on a sub-branch of HBV-D3 along with a few published sequences with high bootstrap values. In contrast, the phylogenetic tree topology based on nucleotides coding for surface antigen or core was uncertain with bootstrap values below 70% or lower. Variation of nucleotides coding for amino acids 125, 136, and 143 in the a determinant of HBsAg was however linked to complete genome phylogeny, indicating that these codons might be useful as markers for clades. The results show that knowledge about circulating strains is critical for the interpretation of molecular epidemiology investigations. The low degree of genetic change over time of HBV-D3 in the studied groups suggests that outbreaks of acute hepatitis B in injection drug users might originate from a limited number of individuals with chronic infection. Classification based on core or S region phylogeny obtained poor support from bootstrap values, but the presence of clade-specific amino acid substitutions suggests that the S region may be useful for subgenomic molecular epidemiology of HBV.
Assuntos
Variação Genética , Vírus da Hepatite B/classificação , Vírus da Hepatite B/genética , Hepatite B/epidemiologia , Hepatite B/virologia , Abuso de Substâncias por Via Intravenosa/complicações , Adolescente , Adulto , Análise por Conglomerados , DNA Viral/química , DNA Viral/genética , Feminino , Genótipo , Vírus da Hepatite B/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Epidemiologia Molecular , Dados de Sequência Molecular , Filogenia , Análise de Sequência de DNA , Suécia/epidemiologia , Adulto JovemRESUMO
BACKGROUND: Infection caused by Streptococcus pneumoniae is the leading cause of mortality in children worldwide. The aim of this study was to determine if a noted increase in non-susceptibility to penicillin among pneumococcal clinical isolates from young children reflected a similar increase in healthy children. METHODS: During 2004-2005, before the conjugate pneumococcal vaccine was introduced in Sweden, 663 healthy children (13-24 months of age) attending 17 child health centres in Gothenburg, Sweden, were cultured for bacteria in the nasopharynx. Social factors were identified through a parental questionnaire. Pneumococcal serotypes and antibiotic resistance rates were determined. Antibiotic resistance was also monitored in 162 simultaneously obtained nasopharyngeal pneumococci isolated from clinical samples. RESULTS: The healthy children frequently carried pneumococci (45%), Moraxella catarrhalis (54%), and Haemophilus influenzae (22%). The carriage rates for all these pathogens were higher in children attending day care centres compared to children staying at home (p < 0.001). The dominating pneumococcal serotypes were 6B, 19F, 23F, and 6A. Non-susceptibility to penicillin was low (4.0%) and only exceeded by that to trimethoprim-sulfamethoxazole (9.8%). Both rates were higher in the clinical isolates (9.3% and 16.7%, respectively; p < 0.05). No relationships to geographic area, day care attendance, recent antibiotic use, or travel abroad were shown for any specific serotype or for the presence of penicillin-non-susceptible pneumococci in the healthy children. CONCLUSIONS: Pneumococcal resistance rates in the healthy child population were low and did not reflect the higher rates noted at the laboratory in clinical samples obtained before and during the study.
Assuntos
Portador Sadio/microbiologia , Penicilinas/farmacologia , Infecções Pneumocócicas/microbiologia , Streptococcus pneumoniae/efeitos dos fármacos , Antibacterianos/farmacologia , Portador Sadio/epidemiologia , Pré-Escolar , Farmacorresistência Bacteriana , Feminino , Humanos , Lactente , Masculino , Testes de Sensibilidade Microbiana , Nasofaringe/microbiologia , Infecções Pneumocócicas/epidemiologia , Reprodutibilidade dos Testes , Streptococcus pneumoniae/isolamento & purificação , Inquéritos e Questionários , Suécia/epidemiologiaRESUMO
BACKGROUND: Following the discovery of the hepatitis C virus (HCV) in 1989, screening of all blood donors for antibodies became mandatory in Sweden as of 1 January 1992. METHODS: Serum samples were collected from patients who had received a blood transfusion in the period prior to 1992 in western Sweden. The prevalence of HCV infection was assessed by antibody screening. RESULTS: Of 13,573 screening serologies, 124 patients (0.9%) had antibodies against HCV; 113 (0.8%) had detectable HCV RNA indicating an ongoing infection. Ninety-one (73%) were female, of whom 32 had been transfused in conjunction with childbirth. A review of the 32 liver biopsy reports available showed that 2 patients had cirrhosis and an additional 9 patients had periportal or septal fibrosis. CONCLUSION: A considerable portion of screened patients had an ongoing HCV infection and were eligible for antiviral treatment. Look-back screening for HCV among recipients of blood transfusions prior to 1992 is meaningful and should include women transfused in childbirth.
Assuntos
Anticorpos Anti-Hepatite C/sangue , Hepatite C/diagnóstico , Hepatite C/epidemiologia , Reação Transfusional , Adulto , Idoso , Feminino , Humanos , Masculino , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Estudos Soroepidemiológicos , Testes Sorológicos , Suécia/epidemiologiaRESUMO
The main goal for treatment of chronic hepatitis B is to prevent complications such as liver cirrhosis or hepatocellular carcinoma. Knowledge from population studies of the long-term risk of chronic HBV infection, as well as the recent introduction of pegylated interferon and additional nucleoside analogues has changed the therapeutic situation. Recently, a Swedish expert panel convened to update the national recommendations for treatment. The panel recommends treatment for patients with active HBV infection causing protracted liver inflammation or significant liver fibrosis, verified by liver histology. In general, pegylated interferon alpha-2a is recommended as first-line treatment, in particular for HBeAg-positive patients with HBV genotypes A or B. Among nucleoside analogues, entecavir is the first choice and adefovir or tenofovir can be used as alternatives. Lamivudine monotherapy is not recommended due to the high risk of resistance development. Combinations of nucleoside analogues such as tenofovir and lamivudine or emtricitabine are alternatives for patients with non-response or infection with resistant variants, or as first choice for patients with advanced liver disease. Nucleoside analogue treatment should be monitored to detect primary non-response and virological breakthrough. Special recommendations are given for HBV/HIV coinfected patients, immunosuppressed patients, children, and for treatment before and after liver transplantation. The present guideline is translated from Swedish, where it is published on the MPA and RAV websites (www.mpa.se and www.rav.nu.se) including 7 separate papers based on thorough literature search. The complete reference list can be received from the Medical Products Agency upon request.
Assuntos
Antivirais/uso terapêutico , Hepatite B Crônica/tratamento farmacológico , Adenina/análogos & derivados , Adenina/uso terapêutico , Carcinoma Hepatocelular/prevenção & controle , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Quimioterapia Combinada , Emtricitabina , Guanina/análogos & derivados , Guanina/uso terapêutico , Infecções por HIV/complicações , Hepatite B Crônica/complicações , Humanos , Hospedeiro Imunocomprometido , Interferon alfa-2 , Interferon-alfa/uso terapêutico , Lamivudina/uso terapêutico , Cirrose Hepática/prevenção & controle , Transplante de Fígado , Organofosfonatos/uso terapêutico , Polietilenoglicóis/uso terapêutico , Proteínas Recombinantes , Suécia , TenofovirAssuntos
Antibacterianos/administração & dosagem , Otite Média/tratamento farmacológico , Doença Aguda , Criança , Pré-Escolar , Consenso , Farmacorresistência Bacteriana , Uso de Medicamentos , Medicina Baseada em Evidências , Fidelidade a Diretrizes , Humanos , Mastoidite/tratamento farmacológico , Guias de Prática Clínica como AssuntoRESUMO
A large community outbreak of norovirus (NV) gastrointestinal infection occurred in Västra Götaland County, Sweden in August 2004, following attendance at recreational lakes. A frequency age-matched case control study was undertaken of persons who had attended these lakes to identify risk factors. 163 cases and 329 controls were included. Analysis indicates that having water in the mouth while swimming (OR=4.7; 95% CI 1.1-20.2), attendance at the main swimming area at Delsjön Lake (OR=25.5; 95% CI 2.5-263.8), taking water home from a fresh water spring near Delsjön lake (OR=17.3; 95% CI 2.7-110.7) and swimming less than 20 m from shore (OR=13.4; 95% CI 2.0-90.2) were significant risk factors. The probable vehicle was local contamination of the lake water (especially at the main swimming area). The source of contamination could not be determined.
Assuntos
Infecções por Caliciviridae/epidemiologia , Surtos de Doenças , Água Doce/virologia , Gastroenterite/epidemiologia , Norovirus , Natação , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Gastroenterite/virologia , Inquéritos Epidemiológicos , Humanos , Lactente , Masculino , Recreação , Fatores de Risco , Suécia/epidemiologiaRESUMO
Beta-haemolytic group A streptococci (GAS) is a common cause of sore throat, usually spread person-to-person. Outbreaks related to infected food have more seldom been reported. The bacteria may originate from the throat or from wounds on the hands of persons handling the food. An outbreak in Sätila, Sweden, in April/May 2003 involving 153 individuals who fell ill after eating contaminated 'sandwich-layer cakes' was investigated in a descriptive, retrospective cohort study. Questionnaires were distributed, one immediately after the outbreak and one 3 months later. The average attack rate was 72%. 143 individuals sought medical care and 137 were treated with antibiotics. 76 individuals were ill for more than 4 days. GAS isolates of identical T-type were obtained from the throats of the patients, wounds on the caterer's fingers and also from the cakes. PFGE banding patterns of 14 representative isolates were identical, as well as the emm-sequence type, emm 89, of 3 chosen isolates. The study shows that GAS from a small wound on a finger can cause illness in a large number of individuals. To prevent further outbreaks, it is important to increase public awareness of this type of transmission.
Assuntos
Surtos de Doenças , Manipulação de Alimentos/métodos , Doenças Transmitidas por Alimentos/etiologia , Faringite/epidemiologia , Infecções Estreptocócicas/epidemiologia , Streptococcus pyogenes/isolamento & purificação , Estudos de Coortes , Eletroforese em Gel de Campo Pulsado , Microbiologia de Alimentos , Humanos , Faringite/tratamento farmacológico , Faringite/microbiologia , Estudos Retrospectivos , Infecções Estreptocócicas/tratamento farmacológico , Infecções Estreptocócicas/transmissão , Suécia/epidemiologiaRESUMO
Hepatitis B virus (HBV) is a major cause worldwide of liver disease, including hepatocellular carcinoma. There are eight known genotypes (A-H), of which genotype A has been divided into two subtypes: A2, prevalent in Europe, and A1, which is prevalent in sub-Saharan Africa, but also occurs in southern Asia. In this study, which includes 14 new complete genomes of non-European genotype A HBV, it was found that West African strains seem to constitute a new subgroup, A3. The high degree of genetic diversity within Africa indicates that genotype A originates from Africa. Based on a 2 % genetic distance between Asian and Somali sequences, it seems that the A1 subtype has spread from East Africa to southern Asia during the last 1000-2000 years. Moreover, it is proposed here that the A2 subtype originates from southern Africa and was imported to Europe around 500 years ago or later. The finding of T-1809/1812 close to the precore start codon and T-1862 and A-1888 in the precore region in HBV e antigen-positive children with signs of a mimimal immune response indicates that these substitutions are stable variants, rather than mutations emerging during infection in individual carriers.
Assuntos
Genoma Viral , Vírus da Hepatite B/genética , Hepatite B/virologia , Adolescente , Adulto , África , Ásia , Criança , Variação Genética , Humanos , Dados de Sequência Molecular , FilogeniaRESUMO
Further knowledge about factors predicting response to interferon treatment for chronic hepatitis B in children is required, in particular as the benefits of therapy are uncertain. In the present study, baseline characteristics were related to virological and histological responses in 27 children given interferon-alpha for 24 weeks after steroid priming. HBe seroconversion was seen in 8 of 27 HBeAg positive patients and was accompanied by a sustained virological response (SR), with a median 4.1 log HBV DNA reduction. Pretreatment viraemia level was the only baseline parameter associated with SR. After 12 weeks of IFN (mid-treatment), viraemia was significantly reduced in all patients, with a median of 3.0 (range 0.6-5.2) log decline in SR compared with 0.6 (range -0.5-3.6) log decline in non-sustained responders (NSR). HBV DNA levels below 1 million copies/ml at week 12 predicted sustained response with a positive predictive value of 75% and a negative predictive value of 89%. During the latter half of the IFN treatment HBV DNA tended to increase by a mean of 0.4-0.5 log for all patient groups. Flares during IFN treatment were rare or mild as measured by ALT. Pretreatment anti-HBc IgM was associated with liver damage but not with response. Histological inflammation scores were improved in SR. Thus, pretreatment HBV DNA levels were associated with IFN response, and the virological response at week 12 predicts SR and may be useful in the decision to continue or modify therapy.
Assuntos
Antivirais/uso terapêutico , DNA Viral/efeitos dos fármacos , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Adolescente , Antivirais/efeitos adversos , Criança , Pré-Escolar , DNA Viral/sangue , Feminino , Hepatite B Crônica/enzimologia , Hepatite B Crônica/patologia , Humanos , Interferon-alfa/efeitos adversos , Masculino , Neutropenia/induzido quimicamente , Valor Preditivo dos TestesAssuntos
Surtos de Doenças/estatística & dados numéricos , Infecções por Escherichia coli/epidemiologia , Escherichia coli O157/isolamento & purificação , Contaminação de Alimentos/estatística & dados numéricos , Doenças Transmitidas por Alimentos/epidemiologia , Gastroenterite/epidemiologia , Lactuca/microbiologia , Estudos de Casos e Controles , Comércio , Infecções por Escherichia coli/microbiologia , Feminino , Doenças Transmitidas por Alimentos/microbiologia , Gastroenterite/microbiologia , Humanos , Incidência , Masculino , Vigilância da População , Medição de Risco/métodos , Fatores de Risco , Suécia/epidemiologiaRESUMO
Little is known about how pregnancy influences viremia levels in women with chronic hepatitis B virus infection. In this study, we first retrospectively analysed changes in HBV DNA levels during and after 55 pregnancies in HBsAg-positive women, of whom 9 were HBeAg-positive. Secondly, HBV DNA levels in 3 HBeAg-positive mothers whose babies became chronic HBV carriers, were compared with levels in 18 mothers whose babies were not infected by HBV. We found that HBV DNA ranged from 10(8.1) to 10(9.5) copies/mL in HBeAg-positive, and from undetectable (< 100) to 10(6.8) copies/mL in HBeAg-negative mothers. HBV DNA increased by a mean of 0.4 log late in pregnancy or early post partum; in 4 out of 16 HBeAg negative mothers by > 1 log during pregnancy. Post partum ALT increased in both HBeAg-positive and negative women. HBV DNA was 10(9.4)-10(10.4) copies/mL in 3 HBeAg-positive mothers whose babies were, as compared to < 100-10(10.4) copies/mL in 18 whose babies were not, vertically infected. Although the majority of HBeAg-negative women had low and relatively stable HBV DNA during pregnancy, viremia was also relatively high in some HBeAg-negative mothers, and both viremia and ALT increased significantly late in pregnancy or shortly after delivery. Vertical transmission was only seen in HBeAg-positive mothers with very high levels of viremia. The value of measuring HBV DNA in the pregnant woman to modify immunoprophylaxis to her infant needs further study.
Assuntos
Vírus da Hepatite B/isolamento & purificação , Hepatite B/transmissão , Transmissão Vertical de Doenças Infecciosas/estatística & dados numéricos , Complicações Infecciosas na Gravidez/virologia , Resultado da Gravidez , Estudos de Coortes , DNA Viral/análise , Feminino , Seguimentos , Hepatite B/diagnóstico , Hepatite B/epidemiologia , Antígenos E da Hepatite B/análise , Humanos , Incidência , Recém-Nascido , Masculino , Reação em Cadeia da Polimerase/métodos , Período Pós-Parto , Gravidez , Complicações Infecciosas na Gravidez/diagnóstico , Probabilidade , Estudos Retrospectivos , Medição de Risco , Estatísticas não Paramétricas , Suécia/epidemiologiaRESUMO
BACKGROUND: Despite high viral load, children with chronic hepatitis B virus (HBV) infection may lack significant biochemical signs of liver dysfunction. Failure to develop abnormal liver chemistriesis is probably due to immunologic hyporeactivity. Despite the absence of biochemical abnormalities in these patients, there is still a risk for long-term complications. The pathogenic importance of viral load and genetic variability is less well studied in children than in adults. METHODS: We evaluated viremia levels, genotypes, and mutations related to histologic evidence of liver damage in 71 HBV carriers, aged 2 to 18 years, all of non-Swedish origin. RESULTS: None of the of 22 children who were hepatitis B e antigen (HBeAg) negative had severe liver disease or had HBV DNA levels greater than 10 copies/mL (mean 10 ); 3 (14%) of them had increased alanine aminotransferase (ALT). The 49 HBeAg-positive children had a mean HBV DNA level of 10 copies/mL, and increased ALT was seen in 28 (55%). Core promoter mutations (at nt 1764) or precore mutations (at codon 1, 2, or 28) were rare; they were seen in four and one HBeAg-positive children, and in four and nine HBeAg-negative children, respectively, without association to liver damage. C-1858 was associated with more liver inflammation. Genotype did not significantly influence liver damage. Children with horizontal transmission had a faster rate of seroconversion and more inflammation of the liver. CONCLUSIONS: Severe HBeAg-negative hepatitis with high HBV DNA levels and mutations in the core promoter or precore regions seems to be less common in children than in adults. C-1858 strains may be more pathogenic, but this requires further study. Epidemiologic factors influence the course of infection.