RESUMO
The chewing of the leaves of Catha edulis (khat) has been implicated in the development of liver disease, but no controlled observations have been undertaken. The objective of the present study was to determine whether khat chewing is associated with development of chronic liver disease (CLD). A case-control study was conducted at two public hospitals in Harar, Ethiopia, between April 2015 and April 2016. A consecutive sample of 150 adult hospital attendees with CLD were included as cases, and 300 adult hospital attendees without clinical or laboratory evidence of CLD were included as controls. Khat consumption was quantified in "khat years"; 1 khat year was defined as daily use of 200 g of fresh khat for 1 year. A logistic regression model was used to control for confounders. There was a significant association between chewing khat and the risk for developing CLD (crude odds ratio, 2.64; 95% confidence interval [CI], 1.56-4.58). In men, this risk, following adjustment for age, alcohol use, and chronic hepatitis B/C infection, increased with increasing khat exposure; thus, compared to never users the adjusted odds ratios were for low khat exposure 3.58 (95% CI 1.05-12.21), moderate khat exposure 5.90 (95% CI 1.79-19.44), and high khat exposure 13.03 (95% CI 3.61-47.02). The findings were robust in a post hoc sensitivity analysis in which individuals with identifiable risk factors for CLD were excluded. CONCLUSION: A significant association was observed between chewing khat and the risk for developing CLD, and in men the association was strong and dose-dependent, suggesting a causal relationship; as the prevalence of khat chewing is increasing worldwide, these findings have major public health implications. (Hepatology 2018;68:248-257).
Assuntos
Catha/toxicidade , Hepatopatias/epidemiologia , Adulto , Estudos de Casos e Controles , Doença Crônica/epidemiologia , Etiópia/epidemiologia , Feminino , Humanos , Hepatopatias/etiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto JovemRESUMO
BACKGROUND: Hepatitis B virus (HBV) infection remains a serious global health challenge. The widespread distribution of HBV is highlighted by multiple HBV genotypes associated with different geographical origin and transmission patterns, as well as, clinical outcomes. Investigating population HBV genotype composition and origin is therefore highly warranted. METHODS: In this molecular epidemiological study we analysed 1157 HBV S-gene sequences collected from patients in Norway, primarily in the period 2004-2011, and linked them to epidemiological data from the Norwegian surveillance system for communicable diseases. RESULTS: Of the patients with reported country of infection (n = 909), 10% (n = 93) were infected in Norway, but the majority (n = 816; 90%) stated that they became infected outside of Norway. Of the patients infected outside of Norway, most became infected in Southeast and East Asia (n = 465; 51%) and Central, West, and North Africa (n = 254; 28%). The distribution of HBV genotypes in Norway is dominated by genotype D (32%) followed by genotype A (22%), B and C (18 and 18%, respectively), and E (7%). Genotype B, C and E were phylogenetically categorized by a majority of sequences originating from distinct geographical regions, either Asia or Africa, whereas genotype A and D originated from multiple geographic regions. However, within genotype A and D, our molecular epidemiology analysis indicated a geographical clustering of sequences depending on their geographical origin. CONCLUSIONS: The majority of HBV patients in Norway became infected outside of Norway and were represented by most common genotypes. Patients stated to have been infected in Norway were found primarily within genotype A and D, and were phylogenetically characterized by both small local clusters and interspersed sequences that clustered with non-Norwegian sequences, indicating that a proportion of the patients assumed to have been infected in Norway likely became infected outside of Norway although assumed the contrary.
Assuntos
Vírus da Hepatite B/genética , Hepatite B/diagnóstico , DNA Viral/genética , DNA Viral/isolamento & purificação , DNA Viral/metabolismo , Emigrantes e Imigrantes , Feminino , Genótipo , Hepatite B/epidemiologia , Hepatite B/virologia , Vírus da Hepatite B/classificação , Vírus da Hepatite B/isolamento & purificação , Humanos , Masculino , Noruega/epidemiologia , FilogeniaRESUMO
IntroductionSequence-based typing of hepatitis A virus (HAV) is important for outbreak detection, investigation and surveillance. In 2013, sequencing was central to resolving a large European Union (EU)-wide outbreak related to frozen berries. However, as the sequenced HAV genome regions were only partly comparable between countries, results were not always conclusive.AimThe objective was to gather information on HAV surveillance and sequencing in EU/European Economic Area (EEA) countries to find ways to harmonise their procedures, for improvement of cross-border outbreak responses.MethodsIn 2014, the European Centre for Disease Prevention and Control (ECDC) conducted a survey on HAV surveillance practices in EU/EEA countries. The survey enquired whether a referral system for confirming primary diagnostics of hepatitis A existed as well as a central collection/storage of hepatitis A cases' samples for typing. Questions on HAV sequencing procedures were also asked. Based on the results, an expert consultation proposed harmonised procedures for cross-border outbreak response, in particular regarding sequencing. In 2016, a follow-up survey assessed uptake of suggested methods.ResultsOf 31 EU/EEA countries, 23 (2014) and 27 (2016) participated. Numbers of countries with central collection and storage of HAV positive samples and of those performing sequencing increased from 12 to 15 and 12 to 14 respectively in 2016, with all countries typing an overlapping fragment of 218 nt. However, variation existed in the sequenced genomic regions and their lengths.ConclusionsWhile HAV sequences in EU/EEA countries are comparable for surveillance, collaboration in sharing and comparing these can be further strengthened.
Assuntos
Surtos de Doenças/prevenção & controle , Vírus da Hepatite A/isolamento & purificação , Hepatite A/diagnóstico , Tipagem Molecular/métodos , Vigilância da População/métodos , Sequenciamento Completo do Genoma/métodos , Europa (Continente)/epidemiologia , União Europeia , Hepatite A/epidemiologia , Vírus da Hepatite A/genética , Humanos , RNA Viral/análise , Análise de Sequência de DNARESUMO
BACKGROUND: The World Health Organization has set an ambitious goal of eliminating viral hepatitis as a major public health threat by 2030. However, in sub-Saharan Africa, antiviral treatment of chronic hepatitis B (CHB) is virtually unavailable. Herein, we present the 1-year results of a pilot CHB treatment program in Ethiopia. METHODS: At a public hospital in Addis Ababa, CHB patients were treated with tenofovir disoproxil fumarate based on simplified eligibility criteria. Baseline assessment included liver function tests, viral markers, and transient elastography (Fibroscan). Changes in laboratory markers were analyzed using Wilcoxon signed-rank tests. Adherence to therapy was measured by pharmacy refill data. RESULTS: Out of 1303 patients, 328 (25.2%) fulfilled the treatment criteria and 254 (19.5%) had started tenofovir disoproxil fumarate therapy prior to September 1, 2016. Of the patients who started therapy, 30 (11.8%) died within the first year of follow-up (28 of whom had decompensated cirrhosis), 9 (3.5%) self-stopped treatment, 7 (2.8%) were lost to follow-up, and 4 (1.6%) were transferred out. In patients who completed 12 months of treatment, the median Fibroscan value declined from 12.8 to 10.4 kPa (p < 0.001), 172 of 202 (85.1%) patients with available pharmacy refill data had taken ≥ 95% of their tablets, and 161 of 189 (85.2%) patients with viral load results had suppressed viremia. Virologic failure (≥ 69 IU/mL) at 12 months was associated with high baseline HBV viral load (> 1,000,000 IU/mL; adjusted OR 2.41; 95% CI 1.04-5.55) and suboptimal adherence (< 95%; adjusted OR 3.43, 95% CI 1.33-8.88). CONCLUSIONS: This pilot program demonstrated that antiviral therapy of CHB can be realized in Ethiopia with good clinical and virologic response. Early mortality was high in patients with decompensated cirrhosis, underscoring the need for earlier detection of hepatitis B virus infection and timely initiation of treatment, prior to the development of irreversible complications, in sub-Saharan Africa. TRIAL REGISTRATION: NCT02344498 (ClinicalTrials.gov identifier). Registered 16 January 2015.
Assuntos
Antivirais/uso terapêutico , Hepatite B Crônica/tratamento farmacológico , Tenofovir/uso terapêutico , Adolescente , Adulto , Biomarcadores , Etiópia , Feminino , Seguimentos , Hepatite B Crônica/complicações , Humanos , Cirrose Hepática/mortalidade , Cirrose Hepática/virologia , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Cooperação e Adesão ao Tratamento , Resultado do Tratamento , Carga Viral/efeitos dos fármacos , Adulto JovemRESUMO
BACKGROUND & AIMS: Hepatitis D virus (HDV) infection is associated with a more severe outcome in patients with chronic hepatitis B (CHB); however, little is known about the presence of HDV in sub-Saharan Africa. We aimed to determine the prevalence of HDV infection, as well as its clinical, biological and virological characteristics, in a large CHB cohort in Ethiopia. METHODS: In total, 1267 HIV-negative CHB patients at St. Paul's Hospital Millennium Medical College in Addis Ababa were screened for anti-HDV antibodies using ELISA assays. Confirmed positive samples were further tested for HDV RNA using a consensus commercial real-time RT-PCR assay. HDV genotypes were also determined for RNA-positive samples by nucleotide sequencing followed by phylogenetic analyses. Demographical, clinical and biological data from patients were recorded and compared based on HDV RNA results. RESULTS: Most patients (n = 748, 59.0%) were men, and the median age was 31 years (interquartile range 26-40). Anti-HDV antibodies were detected in 19 individuals (1.5%), 12 of whom were HDV RNA-positive with a viral load ranging from <2 to >8 log 10 IU/mL. All strains were genotype 1. HDV RNA-positive patients were more likely to have significant liver fibrosis (63.6% vs 24.7%, P = .007) and cirrhosis (45.5% vs 16.4%, P = .024). CONCLUSIONS: HDV infection is rare in Ethiopia but is associated with more advanced liver fibrosis.
Assuntos
Coinfecção/virologia , Hepatite B Crônica/complicações , Hepatite D/epidemiologia , Vírus Delta da Hepatite/genética , Cirrose Hepática/virologia , Adolescente , Adulto , Estudos de Coortes , Coinfecção/mortalidade , Ensaio de Imunoadsorção Enzimática , Etiópia/epidemiologia , Feminino , Anticorpos Anti-Hepatite/sangue , Hepatite D/mortalidade , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Filogenia , Reação em Cadeia da Polimerase em Tempo Real , Carga Viral , Adulto JovemRESUMO
BACKGROUND: Hepatitis B virus (HBV) infection is assumed to be the major cause of chronic liver disease (CLD) in sub-Saharan Africa. The contribution of other aetiological causes of CLD is less well documented and hence opportunities to modulate other potential risk factors are being lost. The aims of this study were to explore the aetiological spectrum of CLD in eastern Ethiopia and to identify plausible underlying risk factors for its development. METHODS: A cross-sectional study was undertaken between April 2015 and April 2016 in two public hospitals in Harar, eastern Ethiopia. The study population comprised of consenting adults with clinical and radiological evidence of chronic liver disease. The baseline evaluation included: (i) a semi-structured interview designed to obtain information about the ingestion of alcohol, herbal medicines and local recreational drugs such as khat (Catha edulis); (ii) clinical examination; (iii) extensive laboratory testing; and, (iv) abdominal ultrasonography. RESULTS: One-hundred-and-fifty patients with CLD (men 72.0%; median age 30 [interquartile range 25-40] years) were included. CLD was attributed to chronic HBV infection in 55 (36.7%) individuals; other aetiological agents were identified in a further 12 (8.0%). No aetiological factors were identified in the remaining 83 (55.3%) patients. The overall prevalence of daily khat use was 78.0%, while alcohol abuse, defined as > 20 g/day in women and > 30 g/day in men, was rare (2.0%). Histological features of toxic liver injury were observed in a subset of patients with unexplained liver injury who underwent liver biopsy. CONCLUSION: The aetiology of CLD in eastern Ethiopia is largely unexplained. The widespread use of khat in the region, together with histopathological findings indicating toxic liver injury, suggests an association which warrants further investigation.
Assuntos
Hepatopatias/epidemiologia , Hepatopatias/etiologia , Lesão Pulmonar Aguda/patologia , Adulto , Alcoolismo/complicações , Biópsia , Catha , Doença Crônica , Estudos Transversais , Etiópia/epidemiologia , Feminino , Humanos , Fígado/patologia , Hepatopatias/diagnóstico , Hepatopatias/patologia , Masculino , Prevalência , Fatores de Risco , Transtornos Relacionados ao Uso de Substâncias/complicaçõesRESUMO
BACKGROUND: HBsAg immune-escape mutations can favor HBV-transmission also in vaccinated individuals, promote immunosuppression-driven HBV-reactivation, and increase fitness of drug-resistant strains. Stop-codons can enhance HBV oncogenic-properties. Furthermore, as a consequence of the overlapping structure of HBV genome, some immune-escape mutations or stop-codons in HBsAg can derive from drug-resistance mutations in RT. This study is aimed at gaining insight in prevalence and characteristics of immune-associated escape mutations, and stop-codons in HBsAg in chronically HBV-infected patients experiencing nucleos(t)ide analogues (NA) in Europe. METHODS: This study analyzed 828 chronically HBV-infected European patients exposed to ≥ 1 NA, with detectable HBV-DNA and with an available HBsAg-sequence. The immune-associated escape mutations and the NA-induced immune-escape mutations sI195M, sI196S, and sE164D (resulting from drug-resistance mutation rtM204 V, rtM204I, and rtV173L) were retrieved from literature and examined. Mutations were defined as an aminoacid substitution with respect to a genotype A or D reference sequence. RESULTS: At least one immune-associated escape mutation was detected in 22.1% of patients with rising temporal-trend. By multivariable-analysis, genotype-D correlated with higher selection of ≥ 1 immune-associated escape mutation (OR[95%CI]:2.20[1.32-3.67], P = 0.002). In genotype-D, the presence of ≥ 1 immune-associated escape mutations was significantly higher in drug-exposed patients with drug-resistant strains than with wild-type virus (29.5% vs 20.3% P = 0.012). Result confirmed by analysing drug-naïve patients (29.5% vs 21.2%, P = 0.032). Strong correlation was observed between sP120T and rtM204I/V (P < 0.001), and their co-presence determined an increased HBV-DNA. At least one NA-induced immune-escape mutation occurred in 28.6% of patients, and their selection correlated with genotype-A (OR[95%CI]:2.03[1.32-3.10],P = 0.001). Finally, stop-codons are present in 8.4% of patients also at HBsAg-positions 172 and 182, described to enhance viral oncogenic-properties. CONCLUSIONS: Immune-escape mutations and stop-codons develop in a large fraction of NA-exposed patients from Europe. This may represent a potential threat for horizontal and vertical HBV transmission also to vaccinated persons, and fuel drug-resistance emergence.
Assuntos
Antivirais/uso terapêutico , Códon de Terminação , Antígenos de Superfície da Hepatite B/genética , Vírus da Hepatite B/genética , Hepatite B Crônica/imunologia , Mutação , Adulto , Substituição de Aminoácidos , Europa (Continente) , Feminino , Genótipo , Antígenos de Superfície da Hepatite B/imunologia , Vírus da Hepatite B/imunologia , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/virologia , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Background: Evidence has shown that Hepatitis E virus (HEV) genotype 3 is autochthonous in industrialized countries due to zoonotic transmission through direct contact or consumption of raw or undercooked meat from domestic swine or wild boar. As there is lack of data on seroprevalence of HEV in the general Portuguese population, a wide survey was conducted as part of the HEPeCONTROL project (60DT2), under EEA grants funding. Methods: Sera from a representative sample of the Portuguese population (n = 1656) at different geographic locations (30 territorial units), and age (0-99 years) were collected between July 2015 and February 2016. The sera were tested for the presence of anti-HEV IgG and IgM by EIA using one of the two most commonly used commercial immunoassays in Europe. Results: The overall HEV IgG seroprevalence was found to be 16.3% increasing with age (P < 0.05) from 0.6% in the 0-9 years group to 30.1% in people older than 70 years. The seroprevalence also varied geographically with generally higher seropositivities (25-30%) in the most rural areas of Portugal. However, the geographical differences were not statistically significant (P > 0.05). Out of 1656 samples, 8 were positive for anti-HEV IgM indicating current of recent HEV infection but no significant differences were found concerning age groups, regions and sex. Conclusions: The present nation-wide survey provides insight in the epidemiology of HEV in Portugal and confirms that HEV is endemic in the Portuguese population.
Assuntos
Biomarcadores/sangue , Anticorpos Anti-Hepatite/sangue , Vírus da Hepatite E/isolamento & purificação , Hepatite E/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Vigilância da População , Portugal/epidemiologia , Estudos Soroepidemiológicos , Adulto JovemRESUMO
BACKGROUND: Treatment for chronic hepatitis B (CHB) is virtually absent in sub-Saharan Africa. Here we present early experiences from a pilot program for treatment of CHB in Ethiopia. METHODS: Adults (≥18 years) with CHB were included in a cohort study at St. Paul's Hospital Millennium Medical College, Addis Ababa, from February 2015. The baseline assessment included liver function tests, viral markers and transient elastography (Fibroscan 402, Echosense, France). Logistic regression models were used to identify predictors of fibrosis. Tenofovir disoproxil fumarate (TDF) was initiated based on the European Association for the Study of the Liver (EASL) criteria, with some modifications. The initial 300 patients underwent a more comprehensive evaluation and are presented here. RESULTS: One-hundred-and-thirty-eight patients (46.0%) were women and median age was 30 years (interquartile range 26-40). Co-infections were rare: four patients (1.3%) were anti-HCV positive, 11 (3.7%) were anti-HDV positive, whereas 5 (1.7%) had HIV-infection. The majority were hepatitis B e-antigen (HBeAg) negative (n = 262; 90.7%) and had a normal (≤40 U/L) alanine aminotransferase (ALT) (n = 245; 83.1%). Of 268 patients with a valid Fibroscan result, 79 (29.5%) had significant fibrosis (>7.9 kPa). Independent predictors of fibrosis were male sex, age > 35 years and viral load >20,000 IU/ml. In total, 74 patients (24.7%) started TDF therapy, of whom 46 (62.2%) had cirrhosis. CONCLUSIONS: The majority were HBeAg negative and had normal ALT. However, one quarter of the patients were in need of antiviral treatment, underscoring the need to scale up CHB treatment on the African continent. TRIAL REGISTRATION: NCT02344498 ( ClinicalTrials.gov identifier). Registered 16 January 2015.
Assuntos
Antivirais/uso terapêutico , Hepatite B Crônica/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/virologia , Adulto , Alanina Transaminase/sangue , Biomarcadores , Estudos de Coortes , Coinfecção/tratamento farmacológico , Etiópia , Feminino , Antígenos E da Hepatite B/sangue , Hepatite B Crônica/sangue , Hepatite B Crônica/complicações , Humanos , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/virologia , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Gravidez , Complicações Infecciosas na Gravidez/tratamento farmacológico , Tenofovir/uso terapêutico , Carga Viral , Adulto JovemRESUMO
BACKGROUND: European guidelines recommend treatment of chronic hepatitis B virus infection (CHB) with the nucleos(t)ide analogs (NAs) entecavir or tenofovir. However, many European CHB patients have been exposed to other NAs, which are associated with therapy failure and resistance. The CAPRE study was performed to gain insight in prevalence and characteristics of NA resistance in Europe. METHODS: A survey was performed on genotypic resistance testing results acquired during routine monitoring of CHB patients with detectable serum hepatitis B virus DNA in European tertiary referral centers. RESULTS: Data from 1568 patients were included. The majority (73.8%) were exposed to lamivudine monotherapy. Drug-resistant strains were detected in 52.7%. The most frequently encountered primary mutation was M204V/I (48.7%), followed by A181T/V (3.8%) and N236T (2.6%). In patients exposed to entecavir (n = 102), full resistance was present in 35.3%. Independent risk factors for resistance were age, viral load, and lamivudine exposure (P < .001). CONCLUSIONS: These findings support resistance testing in cases of apparent NA therapy failure. This survey highlights the impact of exposure to lamivudine and adefovir on development of drug resistance and cross-resistance. Continued use of these NAs needs to be reconsidered at a pan-European level.
Assuntos
Antivirais/farmacologia , Farmacorresistência Viral/genética , Vírus da Hepatite B/efeitos dos fármacos , Vírus da Hepatite B/genética , Hepatite B Crônica/epidemiologia , Hepatite B Crônica/virologia , Adulto , Antivirais/uso terapêutico , Estudos Transversais , Feminino , Genótipo , Hepatite B Crônica/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , PrevalênciaRESUMO
BACKGROUND & AIMS: On-going risk behaviour can lead to hepatitis C virus (HCV) reinfection following successful treatment. We aimed to assess the incidence of persistent HCV reinfection in a population of people who inject drugs (PWID) who had achieved sustained virological response (SVR) seven years earlier. METHODS: In 2004-2006 we conducted a multicentre treatment trial comprising HCV genotype 2 or 3 patients in Sweden, Norway and Denmark (NORTH-C). Six months of abstinence from injecting drug use (IDU) was required before treatment. All Norwegian patients who had obtained SVR (n=161) were eligible for participation in this long-term follow-up study assessing virological and behavioural characteristics. RESULTS: Follow-up data were available in 138 of 161 (86%) individuals. Persistent reinfection was identified in 10 of 94 (11%) individuals with a history of IDU prior to treatment (incidence rate 1.7/100 person-years (PY); 95% CI 0.8-3.1) and in 10 of 37 (27%) individuals who had relapsed to IDU after treatment (incidence rate 4.9/100 PY; 95% CI 2.3-8.9). Although relapse to IDU perfectly predicted reinfection, no baseline factor was associated with reinfection. Relapse to IDU was associated with age <30 years (vs. ⩾40 years) at treatment (adjusted odds ratio [aOR] 7.03; 95% CI 1.78-27.8) and low education level (aOR 3.64; 95% CI 1.44-9.18). CONCLUSIONS: Over time, persistent HCV reinfection was common among individuals who had relapsed to IDU after treatment. Reinfection should be systematically addressed and prevented when providing HCV care for PWID.
Assuntos
Antivirais/uso terapêutico , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , RNA Viral/genética , Resposta Viral Sustentada , Carga Viral/efeitos dos fármacos , Adulto , Dinamarca/epidemiologia , Feminino , Seguimentos , Hepatite C Crônica/epidemiologia , Hepatite C Crônica/virologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Noruega/epidemiologia , Razão de Chances , Recidiva , Estudos Retrospectivos , Fatores de Risco , Suécia/epidemiologiaRESUMO
BACKGROUND: The discovery of autochthonous hepatitis E in industrialized countries has changed the understanding of hepatitis E virus (HEV) infection in these regions, now known to be mainly due to zoonotic transmission of genotype 3. The foodborne route of transmission via consumption of contaminated meat from HEV infected pigs is well documented as well as the direct occupational exposure to animal reservoirs. Accumulating evidence also points to an emerging potential threat to blood safety after the identification of viremic blood donors and the documentation of HEV-contaminated blood or blood products. Moreover, the origin of several iatrogenic cases remains unclear and porcine-derived pharmaceutic products have been suspected as a cause. Severe morbidity following HEV infection in patients receiving immunosuppressive therapy and in those with severe immunodeficiency from other causes has been recently recognized as a serious consequence of this infection in industrialized countries. In Portugal no large-scale HEV seroprevalence study has been undertaken, no professional risk groups have been identified, and the risk of blood donation from HEV silent infected donors is unknown. The present paper describes seroepidemiological and molecular approaches to answer these questions. METHODS/DESIGN: To address these issues a study protocol was designed that will approach: i) the seroprevalence of HEV among the Portuguese general population; ii) HEV infection among butchers and slaughterhouse workers (occupational risk); iii) the silent HEV infection in Portuguese blood donors (HEV transfusion-associated risk); iv) the potential HEV contamination of porcine-derived pharmaceutical products. Commercial enzyme immunoassays and real-time/conventional RT-PCR assays will be used. DISCUSSION: This study is the first evaluation of the seroepidemiological status to HEV infection of the Portuguese population, the first to potentially identify professional risk groups, and to evaluate the safety of blood and blood products and porcine-derived pharmaceutics in Portugal. It will generate valuable data applicable for preventive and control measures against HEV infection (e.g., introduction of systematic screening of blood donors, control of blood products or porcine derived pharmaceutical products), thus helping to manage the burden of this viral disease.
Assuntos
Vírus da Hepatite E/fisiologia , Hepatite E/epidemiologia , Doenças Profissionais/epidemiologia , Animais , Anticorpos Antivirais/sangue , Doadores de Sangue , Segurança do Sangue , Protocolos Clínicos , Genótipo , Hepatite E/transmissão , Hepatite E/virologia , Vírus da Hepatite E/genética , Vírus da Hepatite E/isolamento & purificação , Humanos , Doenças Profissionais/imunologia , Doenças Profissionais/virologia , Portugal/epidemiologia , Saúde Pública , Reação em Cadeia da Polimerase em Tempo Real , Estudos Soroepidemiológicos , Sus scrofa , Suínos , Doenças dos Suínos/epidemiologia , Doenças dos Suínos/virologia , Reação Transfusional , Viremia/etiologiaRESUMO
In March 2014, after an increase of notifications of domestically acquired hepatitis A virus infections, an outbreak investigation was launched in Norway. Sequenced-based typing results showed that these cases were associated with a strain that was identical to one causing an ongoing multinational outbreak in Europe linked to frozen mixed berries. Thirty-three confirmed cases with the outbreak strain were notified in Norway from November 2013 to June 2014. Epidemiological evidence and trace-back investigations linked the outbreak to the consumption of a berry mix cake. Identification of the hepatitis A virus outbreak strain in berries from one of the implicated cakes confirmed the cake to be the source. Subsequently, a cluster in Germany linked to the cake was also identified.
Assuntos
Vírus da Hepatite A/isolamento & purificação , Hepatite A/virologia , Surtos de Doenças , Contaminação de Alimentos/análise , Frutas/virologia , Alemanha/epidemiologia , Hepatite A/epidemiologia , Vírus da Hepatite A/classificação , Vírus da Hepatite A/genética , Humanos , Tipagem Molecular , Noruega/epidemiologiaRESUMO
Treatment of hepatitis C among people who inject drugs (PWID) may be complicated by loss to follow-up and reinfection. We aimed to evaluate sustained virologic response (SVR) and reinfection, and to validate complete pharmacy dispensation as a proxy for cure among PWID enrolled in a trial of opportunistic HCV treatment. Data were obtained by reviewing the electronic patient files and supplemented by outreach HCV RNA testing. Reinfection was defined based on clinical, behavioral, and virological data. Intention to treat SVR ≥ 4 within 2 years after enrolment was accomplished by 59 of 98 (60% [95% CI 50-70]) during intervention conditions (opportunistic treatment) and by 57 of 102 (56% [95% CI 46-66]) during control conditions (outpatient treatment). The time to end of treatment response (ETR) or SVR ≥ 4 was shorter among intervention participants (HR 1.55 [1.08-2.22]; p = 0.016). Of participants with complete dispensation, 132 of 145 (91%) achieved ETR or SVR > 4 (OR 12.7 [95% CI 4.3-37.8]; p < 0.001). Four cases of reinfection were identified (incidence 3.8/100 PY [95% CI 1.0-9.7]). Although SVR was similar, the time to virologic cure was shorter among intervention participants. Complete dispensation is a valid correlate for cure among individuals at risk of loss to follow-up. Reinfection following successful treatment remains a concern.
Assuntos
Antivirais , Hepacivirus , Hepatite C , Reinfecção , Abuso de Substâncias por Via Intravenosa , Resposta Viral Sustentada , Humanos , Masculino , Feminino , Adulto , Abuso de Substâncias por Via Intravenosa/complicações , Pessoa de Meia-Idade , Antivirais/uso terapêutico , Hepacivirus/efeitos dos fármacos , Hepacivirus/genética , Seguimentos , Hepatite C/tratamento farmacológico , Hepatite C/virologia , Resultado do Tratamento , Hospitalização , RNA Viral/sangueRESUMO
BACKGROUND: Vaccination constitutes an attractive control measure for hepatitis E virus (HEV), a major cause of maternal and perinatal mortality globally. Analysis of pregnant participants in an effectiveness trial of the HEV vaccine HEV239 showed possible HEV239-associated fetal losses. We aimed to conduct a detailed analysis of this safety signal. METHODS: In a double-blind, cluster-randomised trial, 67 villages in Matlab, Bangladesh, were randomly allocated (1:1) to two vaccine groups, in which non-pregnant women aged 16-39 years received either HEV239 (HEV239 group) or Hepa-B (a hepatitis B vaccine; control group). We implemented weekly surveillance for pregnancy detection, and follow-up of pregnancies once every 2 weeks, using physician-confirmed diagnoses to evaluate fetal loss outcomes (miscarriage [spontaneous abortion], stillbirth, and elective termination). Data from a parallel system of reproductive health surveillance in Matlab were used to clarify study diagnoses when necessary. Miscarriage was assessed only among participants whose first positive pregnancy test and vaccination date (for whichever dose was closest to the date of last menstrual period [LMP]) were before 20 weeks' gestation. We defined the following analysis periods of interest: from 90 days before the LMP until the pregnancy outcome (the proximal period); from the LMP date until the pregnancy outcome (the pregnancy period); from 90 days before the LMP until the LMP date (90 days pre-LMP period); and from enrolment until 90 days before the LMP (the distal period). Both Poisson and Cox regression models were used to assess the associations between receipt of HEV239 and fetal loss outcomes. The trial was registered with ClinicalTrials.gov (NCT02759991). FINDINGS: Among the 19â460 non-pregnant participants enrolled in the trial, 5011 were identified as having pregnancies within 2 years following vaccination and met the criteria for analysis (2407 in the HEV239 group and 2604 in the control group). Among participants vaccinated in the proximal period and evaluated for miscarriage, miscarriage occurred in 54 (8·9%) of 607 in the HEV239 group and 32 (4·5%) of 719 in the control group (adjusted relative risk [aRR] 2·0 [95% CI 1·3-3·1], p=0·0009). Similarly, the risk of miscarriages was increased in the HEV239 group versus the control group among participants inadvertently vaccinated during pregnancy (22 [10·5%] miscarriages among 209 participants in the HEV239 group vs 14 [5·3%] of 266 in the control group; aRR 2·1 [95% CI 1·1-4·1], p=0·036) and among those vaccinated within 90 days pre-LMP (32 [8·0%] of 398 vs 18 [4·0%] of 453; 1·9 [1·1-3·2], p=0·013). No increased risk of miscarriage was observed in those who received HEV239 in the distal period (93 [5·6%] of 1647 vs 80 [4·5%] of 1773; 1·3 [0·8-1·9], p=0·295). Stillbirth and elective termination showed no increased risk among women administered HEV239 versus those administered Hepa-B in any of the analysis periods. INTERPRETATION: HEV239 given shortly before or during pregnancy was associated with an elevated risk of miscarriage. This association poses a possible safety concern for programmatic use of HEV239 in women of childbearing age. FUNDING: Research Council of Norway and Innovax.
Assuntos
Aborto Espontâneo , Hepatite E , Vacinas contra Hepatite Viral , Humanos , Feminino , Bangladesh/epidemiologia , Gravidez , Adulto , Método Duplo-Cego , Adulto Jovem , Vacinas contra Hepatite Viral/administração & dosagem , Adolescente , Hepatite E/epidemiologia , Hepatite E/prevenção & controle , Aborto Espontâneo/epidemiologia , População Rural/estatística & dados numéricos , Vírus da Hepatite E/imunologia , Morte FetalRESUMO
BACKGROUND: Hepatitis E virus (HEV) leads to high mortality in pregnant women in low-income countries. We aimed to evaluate the safety of a HEV vaccine and its effectiveness in preventing hepatitis E during pregnancy. METHODS: In this phase 4, double-blind, cluster-randomised trial, 67 villages in Matlab, Bangladesh, were randomised 1:1 to receive HEV239 (a recombinant HEV vaccine) or a control vaccine (Hepa-B, a hepatitis B vaccine), using block randomisation with random number tables and blocks of size eight, stratified by cluster population size. Eligible non-pregnant women (aged 16-39 years) were vaccinated intramuscularly on day 0, at 1 month, and at 6 months, and followed up for 2 years after the last immunisation. The primary endpoint was hepatitis E in the pregnant, per-protocol population (those who received all three doses within 2 days of the scheduled dates), while safety was a secondary endpoint, assessed in the intention-to-treat (ITT) population (participants who received at least one dose). Solicited adverse events were recorded for the first 7 days after each dose, and unsolicited events until 2 years after a participant's final dose. Pregnancy-related safety outcomes were assessed in the pregnant ITT population. This study is registered with ClinicalTrials.gov (NCT02759991). FINDINGS: Between Oct 2, 2017, and Feb 28, 2019, 19â460 participants were enrolled and received either HEV239 (9478 [48·7%] participants, 33 clusters) or Hepa-B (9982 [51·3%] participants, 34 clusters), of whom 17â937 (92·2%) participants received three doses and 17â613 (90·5%) were vaccinated according to protocol (8524 [48·4%] in the HEV239 group and 9089 [51·6%] in the control group). No pregnant participants were confirmed to have hepatitis E in either treatment group. HEV239 showed a mild safety profile, similar to Hepa-B, with no difference in the proportion of solicited adverse events between groups and no severe solicited events. Pain was the most common local symptom (1215 [12·8%] HEV239 recipients and 1218 [12·2%] Hepa-B recipients) and fever the most common systemic symptom (141 [1·5%] HEV239 recipients and 145 [1·5%] Hepa-B recipients). None of the serious adverse events or deaths were vaccine related. Among pregnant participants, the HEV239 group had a higher risk of miscarriage (136 [5·7%] of 2407 pregnant participants) compared with the control group (102 [3·9%] of 2604; adjusted odds ratio 1·54 [95% CI 1·15-2·08]). INTERPRETATION: The effectiveness of HEV239 in pregnant women remains uncertain. HEV239 was safe and well tolerated in non-pregnant women, but findings regarding miscarriage warrant further investigation. FUNDING: Research Council of Norway; Innovax.
Assuntos
Hepatite E , População Rural , Vacinas contra Hepatite Viral , Humanos , Feminino , Bangladesh/epidemiologia , Adulto , Método Duplo-Cego , Hepatite E/prevenção & controle , Hepatite E/epidemiologia , Gravidez , Adulto Jovem , Adolescente , Vacinas contra Hepatite Viral/administração & dosagem , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/efeitos adversos , Vírus da Hepatite E/imunologia , Complicações Infecciosas na Gravidez/prevenção & controleRESUMO
BACKGROUND: Infection with the hepatitis B virus can lead to chronic liver inflammation with the risk of developing cirrhosis and cancer of the liver. Increased knowledge and improved treatment of chronic hepatitis B infection in recent years mean that virological tests are increasingly used to ascertain the course of illness, status and response to treatment by the individual patient. The purpose is therefore to provide an updated overview of available diagnostics. METHOD: The article builds on a selection of original and review articles identified through a search in Medline, as well as experience of microbiological diagnostics from the national reference laboratory for the hepatitis virus in Norway. RESULTS: Detection of virus proteins and antibodies to these, as well as virus quantification and characterisation, form an important part of the assessment of hepatitis B infection, including confirmation of the chronic phase of the illness. INTERPRETATION: Proper diagnosis is based on a broad selection of different serological and virological markers. Genotype and certain mutations may affect the course of illness and the response to treatment. To prevent further transmission and offer effective treatment, it is important to identify chronic carriers, but also persons who have previously been infected with hepatitis B virus with risk of reactivation.
Assuntos
Hepatite B Crônica , Biomarcadores/sangue , DNA Viral/sangue , DNA Viral/genética , Genótipo , Anticorpos Anti-Hepatite B/sangue , Antígenos da Hepatite B/sangue , Vírus da Hepatite B/genética , Vírus da Hepatite B/imunologia , Vírus da Hepatite B/isolamento & purificação , Hepatite B Crônica/sangue , Hepatite B Crônica/genética , Hepatite B Crônica/imunologia , Hepatite B Crônica/virologia , Humanos , Mutação , Recidiva , Carga ViralRESUMO
BACKGROUND: Hepatitis E virus (HEV) is a major cause of acute viral hepatitis worldwide and it contributes to considerable maternal and neonatal mortality and morbidity in many low-income countries like Bangladesh. A three-dose regimen of a vaccine against HEV (HEV 239) has shown promising results in China. The effects and safety of this vaccine in other populations and with different dosing regimens remains uncertain. OBJECTIVES: Investigate the immune response and safety of a two-dose regimen with the HEV 239 vaccine among healthy adults. Examine the feasibility of conducting a larger HEV 239 vaccine trial in rural Bangladesh. METHODS: One-hundred healthy men and non-pregnant women 16-39 years old were randomized in a 1:1 ratio to receive two doses of either the study (HEV) or control (Hepatitis B virus, HBV) vaccine (at 0, 1 month). Blood samples were collected at day 0, day 60 and 2 years after vaccination. The primary endpoints were the proportion and severity of adverse events up to 2 months after dose one and the longitudinal shift in anti-HEV IgG levels from day 0 to day 60 and 2 years after vaccination. RESULTS: Adverse events to HEV 239 were comparable to the control vaccine, mild in severity and resolved within one to nine days. All participants in the study group seroconverted and achieved high levels of HEV IgG antibodies that remained positive for two years in all but one. A T-cell response was detected one month after HEV 239 vaccination. CONCLUSION: Our results show that two doses of the HEV 239 vaccine produces broad and likely functional immune responses against HEV that remain for at least two years. The safety profile was acceptable and a phase four study of HEV 239 in rural Bangladesh is feasible. CLINICALTRIALS: gov Identifier: NCT02759991.
Assuntos
Vírus da Hepatite E , Vacinas , Masculino , Feminino , Recém-Nascido , Humanos , Adulto , Adolescente , Adulto Jovem , Bangladesh , Projetos Piloto , Anticorpos Anti-Hepatite , Imunoglobulina G , Método Duplo-Cego , Imunogenicidade da Vacina , Anticorpos AntiviraisRESUMO
Hepatitis E virus (HEV) is the most common cause of acute viral hepatitis worldwide. In many low-income countries it causes large outbreaks and disproportionally affects pregnant women and their offspring. Surveillance studies to find effective preventive interventions are needed but are hampered by the lack of funding and infrastructure. Dried blood spots (DBS) offer an easier and more robust way to collect, transport, and store blood samples compared to plasma/serum samples, and could ease some of the barriers for such studies. In this study we optimize an HEV IgG ELISA for DBS samples and validate it on 300 paired DBS and plasma samples collected in rural areas of Bangladesh from participants in a HEV vaccine study. We demonstrate that HEV IgG in blood stored as DBS is stable for two months at up to 40 °C, and for five freeze-thaw cycles. The specificity was 97% and the overall sensitivity of the DBS assay was 81%. The sensitivity was higher in samples from vaccinated participants (100%) compared to previously infected participants (59%), reflecting a positive correlation between IgG titer and sensitivity. We found a strong correlation between DBS and plasma samples with an r2 of 0.90, but with a higher degree of difference between individual paired samples. Our study shows that DBS offers a stable alternative to plasma/serum for HEV IgG measurements and can facilitate serological studies, particularly in resource limited areas.
Assuntos
Vírus da Hepatite E , Feminino , Humanos , Gravidez , Estudos de Viabilidade , Anticorpos Anti-Hepatite , Testes Hematológicos , Imunoglobulina GRESUMO
OBJECTIVE: To improve understanding of SARS-CoV-2-transmission and prevention measures on cruise ships, we investigated a Norwegian cruise ship outbreak from July to August 2020 using a multidisciplinary approach after a rapid outbreak response launched by local and national health authorities. METHODS: We conducted a cross-sectional study among crew members using epidemiologic data and results from SARS-CoV-2 polymerase chain reaction (PCR) of nasopharynx-oropharynx samples, antibody analyses of blood samples, and whole-genome sequencing. RESULTS: We included 114 multinational crew members (71% participation), median age 36 years, and 69% male. The attack rate was 33%; 32 of 37 outbreak cases were seropositive 5-10 days after PCR. One PCR-negative participant was seropositive, suggesting a previous infection. Network-analysis showed clusters based on common exposures, including embarkation date, nationality, sharing a cabin with an infected cabin-mate (adjusted odds ratio [AOR] 3.27; 95% confidence interval [CI] 0.97-11.07, p = 0.057), and specific workplaces (mechanical operations: 9.17 [1.82-45.78], catering: 6.11 [1.83-20.38]). Breaches in testing, quarantine, and isolation practices before/during expeditions were reported. Whole-genome sequencing revealed lineage B.1.36, previously identified in Asia. Despite extensive sequencing, the continued transmission of B.1.36 in Norway was not detected. CONCLUSIONS: Our findings confirm the high risk of SARS-CoV-2-transmission on cruise ships related to workplace and cabin type and show that continued community transmission after the outbreak could be stopped by implementing immediate infection control measures at the final destination.