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1.
Nature ; 586(7831): 776-778, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32408337

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first detected in Wuhan in December 2019 and caused coronavirus disease 2019 (COVID-19)1,2. In 2003, the closely related SARS-CoV had been detected in domestic cats and a dog3. However, little is known about the susceptibility of domestic pet mammals to SARS-CoV-2. Here, using PCR with reverse transcription, serology, sequencing the viral genome and virus isolation, we show that 2 out of 15 dogs from households with confirmed human cases of COVID-19 in Hong Kong were found to be infected with SARS-CoV-2. SARS-CoV-2 RNA was detected in five nasal swabs collected over a 13-day period from a 17-year-old neutered male Pomeranian. A 2.5-year-old male German shepherd was positive for SARS-CoV-2 RNA on two occasions and virus was isolated from nasal and oral swabs. Antibody responses were detected in both dogs using plaque-reduction-neutralization assays. Viral genetic sequences of viruses from the two dogs were identical to the virus detected in the respective human cases. The dogs remained asymptomatic during quarantine. The evidence suggests that these are instances of human-to-animal transmission of SARS-CoV-2. It is unclear whether infected dogs can transmit the virus to other animals or back to humans.


Assuntos
Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/transmissão , Infecções por Coronavirus/veterinária , Doenças do Cão/transmissão , Doenças do Cão/virologia , Pandemias/veterinária , Pneumonia Viral/transmissão , Pneumonia Viral/veterinária , Zoonoses/transmissão , Zoonoses/virologia , Enzima de Conversão de Angiotensina 2 , Animais , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Betacoronavirus/genética , COVID-19 , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Cães , Feminino , Hong Kong/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Peptidil Dipeptidase A/metabolismo , Filogenia , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Receptores Virais/metabolismo , SARS-CoV-2 , Fatores de Tempo
2.
Virol J ; 21(1): 153, 2024 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-38972989

RESUMO

Wild waterfowl serve as a reservoir of some astroviruses. Fecal samples from wild waterfowl collected at Hong Kong's Marshes were tested using pan-astrovirus reverse transcription-PCR. Positive samples underwent subsequent host identification using DNA barcoding. Based on deduced partial sequences, noteworthy samples from three astrovirus groups (mammalian, avian and unclassified astroviruses) were further analyzed by next-generation sequencing. One sample of Avastrovirus 4 clade, MP22-196, had a nearly complete genome identified. The results of ORF2 phylogenetic analysis and genetic distance analysis indicate that Avastrovirus 4 is classified as a distinct subclade within Avastrovirus. MP22-196 has typical astrovirus genome characteristics. The unique characteristics and potential differences of this genome, compared to other avian astrovirus sequences, involve the identification of a modified sgRNA sequence situated near the ORF2 start codon, which precedes the ORF1b stop codon. Additionally, the 3' UTR of MP22-196 is shorter than other avian astroviruses. This study expands our understanding of the Avastrovirus 4 clade.


Assuntos
Infecções por Astroviridae , Aves , Fezes , Variação Genética , Genoma Viral , Filogenia , Animais , Hong Kong , Aves/virologia , Fezes/virologia , Infecções por Astroviridae/veterinária , Infecções por Astroviridae/virologia , Animais Selvagens/virologia , Doenças das Aves/virologia , Sequenciamento de Nucleotídeos em Larga Escala , Avastrovirus/genética , Avastrovirus/classificação , Avastrovirus/isolamento & purificação , RNA Viral/genética , Fases de Leitura Aberta , Astroviridae/genética , Astroviridae/isolamento & purificação , Astroviridae/classificação
3.
Lancet ; 399(10329): 1070-1078, 2022 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-35279259

RESUMO

BACKGROUND: Transmission of SARS-CoV-2 from humans to other mammals, including pet animals, has been reported. However, with the exception of farmed mink, there is no previous evidence that these infected animals can infect humans, resulting in sustained human-to-human transmission. Following a confirmed SARS-CoV-2 infection of a pet shop worker, animals in the shop and the warehouse supplying it were tested for evidence of SARS-CoV-2 infection. METHODS: In this case study, viral swabs and blood samples were collected from animals in a pet shop and its corresponding warehouse in Hong Kong. Nasal swab or saliva samples from human COVID-19 patients epidemiologically linked to the pet shop and from subsequent local cases confirmed to be infected by SARS-CoV-2 delta variant were collected. Oral swabs were tested by quantitative RT-PCR (RT-qPCR) for SARS-CoV-2 and blood samples were serologically tested by a surrogate virus neutralisation test and plaque reduction neutralisation test. The SARS-CoV-2 RT-qPCR positive samples were sequenced by next generation viral full genome sequencing using the ISeq sequencing platform (Illumina), and the viral genomes were phylogenetically analysed. FINDINGS: Eight (50%) of 16 individually tested Syrian hamsters in the pet shop and seven (58%) of 12 Syrian hamsters in the corresponding warehouse were positive for SARS-CoV-2 infection in RT-qPCR or serological tests. None of the dwarf hamsters (n=75), rabbits (n=246), guinea pigs (n=66), chinchillas (n=116), and mice (n=2) were confirmed positive for SARS-CoV-2 in RT-qPCR tests. SARS-CoV-2 viral genomes deduced from human and hamster cases in this incident all belong to the delta variant of concern (AY.127) that had not been circulating locally before this outbreak. The viral genomes obtained from hamsters were phylogenetically related with some sequence heterogeneity. Phylogenetic dating suggests infection in these hamsters occurred around Oct 14, 2021 (95% CI Sept 15 to Nov 9, 2021). Multiple zoonotic transmission events to humans were detected, leading to onward human-to-human transmission. INTERPRETATION: Pet hamsters can be naturally infected with SARS-CoV-2. The virus can circulate among hamsters and lead to human infections. Both genetic and epidemiological results strongly suggest that there was more than one hamster-to-human transmission event in this study. This incident also led to onward human transmission. Importation of SARS-CoV-2-infected hamsters was a likely source of this outbreak. FUNDING: US National Institutes of Health, Research Grants Council of Hong Kong, Food and Health Bureau, and InnoHK.


Assuntos
COVID-19/veterinária , Cricetinae/virologia , SARS-CoV-2 , Zoonoses Virais/transmissão , Adulto , Animais , COVID-19/epidemiologia , COVID-19/transmissão , Teste de Ácido Nucleico para COVID-19 , Criança , Surtos de Doenças , Feminino , Hong Kong/epidemiologia , Humanos , Masculino , Animais de Estimação/virologia , Filogenia
4.
Emerg Infect Dis ; 28(10): 2009-2015, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36037827

RESUMO

Zoonotic and pandemic influenza continue to pose threats to global public health. Pandemics arise when novel influenza A viruses, derived in whole or in part from animal or avian influenza viruses, adapt to transmit efficiently in a human population that has little population immunity to contain its onward transmission. Viruses of previous pandemic concern, such as influenza A(H7N9), arose from influenza A(H9N2) viruses established in domestic poultry acquiring a hemagglutinin and neuraminidase from influenza A viruses of aquatic waterfowl. We report a novel influenza A(H3N8) virus in chicken that has emerged in a similar manner and that has been recently reported to cause zoonotic disease. Although they are H3 subtype, these avian viruses are antigenically distant from contemporary human influenza A(H3N2) viruses, and there is little cross-reactive immunity in the human population. It is essential to heighten surveillance for these avian A(H3N8) viruses in poultry and in humans.


Assuntos
Vírus da Influenza A Subtipo H3N8 , Subtipo H7N9 do Vírus da Influenza A , Vírus da Influenza A Subtipo H9N2 , Influenza Aviária , Influenza Humana , Animais , Galinhas , China/epidemiologia , Hemaglutininas , Hong Kong/epidemiologia , Humanos , Vírus da Influenza A Subtipo H3N2/genética , Subtipo H7N9 do Vírus da Influenza A/genética , Vírus da Influenza A Subtipo H9N2/genética , Influenza Humana/epidemiologia , Neuraminidase/genética , Filogenia , Aves Domésticas
5.
J Clin Microbiol ; 59(2)2021 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-33139421

RESUMO

Surrogate neutralization assays for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that can be done without biosafety level 3 containment and in multiple species are desirable. We evaluate a recently developed surrogate virus neutralization test (sVNT) in comparison to 90% plaque reduction neutralization tests (PRNT90) in human, canine, cat, and hamster sera. With PRNT90 as the reference, sVNT had sensitivity of 98.9% and specificity of 98.8%. Using a panel of immune sera corresponding to other coronaviruses, we confirm the lack of cross-reactivity to other coronaviruses in SARS-CoV-2 sVNT and PRNT90, except for cross-reactivity to SARS-CoV-1 in sVNT.


Assuntos
Teste Sorológico para COVID-19/métodos , COVID-19/diagnóstico , Testes de Neutralização/métodos , SARS-CoV-2/isolamento & purificação , Animais , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , COVID-19/sangue , COVID-19/patologia , Gatos , Cricetinae , Reações Cruzadas , Cães , Feminino , Humanos , Soros Imunes/imunologia , Masculino , Testes de Neutralização/normas , SARS-CoV-2/imunologia , Sensibilidade e Especificidade
6.
Emerg Infect Dis ; 26(12): 3071-3074, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32938527

RESUMO

We tested 50 cats from coronavirus disease households or close contacts in Hong Kong, China, for severe acute respiratory syndrome coronavirus 2 RNA in respiratory and fecal samples. We found 6 cases of apparent human-to-feline transmission involving healthy cats. Virus genomes sequenced from 1 cat and its owner were identical.


Assuntos
COVID-19/veterinária , Gatos , Animais de Estimação , Animais , COVID-19/transmissão , Características da Família , Hong Kong , Humanos , Pandemias , Quarentena , SARS-CoV-2/genética , Zoonoses Virais
7.
J Viral Hepat ; 23 Suppl 1: 1-12, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26809941

RESUMO

In the WHO-EURO region, around 28 million people are currently living with chronic viral hepatitis, and 120,000 people die every year because of it. Lack of awareness and understanding combined with the social stigma and discrimination exacerbate barriers related to access to prevention, diagnosis and treatment services for those most in need. In addition, the persisting economic crisis has impacted on public health spending, thus posing challenges on the sustainable investment in promotion, primary and secondary prevention, diagnosis and treatment of viral hepatitis across European countries. The Hepatitis B and C Public Policy Association in cooperation with the Hellenic Center for Disease Prevention and Control together with 10 partner organizations discussed at the Athens High Level Meeting held in June 2014 recent policy developments, persisting and emerging challenges related to the prevention and management of viral hepatitis and the need for a de minimis framework of urgent priorities for action, reflected in a Call to Action (Appendix S1). The discussion confirmed that persisting barriers do not allow the full realisation of the public health potential of diagnosing and preventing hepatitis B and C, treating hepatitis B and curing hepatitis C. Such barriers are related to (a) lack of evidence-based knowledge of hepatitis B and C, (b) limited access to prevention, diagnosis and treatment services with poor patient pathways, (c) declining resources and (d) the presence of social stigma and discrimination. The discussion also confirmed the emerging importance of fiscal constraints on the ability of policymakers to adequately address viral hepatitis challenges, particularly through increasing coverage of newer therapies. In Europe, it is critical that public policy bodies urgently agree on a conceptual framework for addressing the existing and emerging barriers to managing viral hepatitis. Such a framework would ensure all health systems share a common understanding of definitions and indicators and look to integrate their responses to manage policy spillovers in the most cost-effective manner, while forging wide partnerships to sustainably and successfully address viral hepatitis.


Assuntos
Política de Saúde , Hepatite B/diagnóstico , Hepatite B/terapia , Hepatite C/diagnóstico , Hepatite C/terapia , Europa (Continente) , Prática Clínica Baseada em Evidências , Acessibilidade aos Serviços de Saúde , Hepatite B/prevenção & controle , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/prevenção & controle , Hepatite B Crônica/terapia , Hepatite C/prevenção & controle , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/prevenção & controle , Hepatite C Crônica/terapia , Humanos , Discriminação Social , Estigma Social
8.
Metab Brain Dis ; 29(3): 625-34, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24615429

RESUMO

Neuro-psychiatric and cognitive disorders are frequent in patients with chronic hepatitis C (CHC) virus (HCV) infection which adversely impact quality of life, antiviral treatment adherence and outcome. HCV has neurotrophic properties and affects lipid metabolism, essential for cognitive function. We evaluated the relationship of lipid profiles with depression and anxiety symptoms and the effects of 12-weeks of therapy with fluvastatin and omega-3 ethyl esters (n-3 PUFA) in a randomised pilot study of CHC prior non-responders. Participants (n = 60) had fasting lipid profiles and assessment of depression and anxiety symptoms using the Hospital Anxiety and Depression Scale (HADS) questionnaire at each study visit. At screening 26/60 (43 %) had HADS-A score ≥8 and 13/60 (22 %) had HADS-D scores ≥8. Depressed patients had significantly lower apolipoprotein-E concentrations (30 mg/l vs 39 mg/l, P = 0.029) than those without depression and a tendency toward lower total cholesterol (3.8 vs 4.4 mmol/l, P = 0.053). 3 patients discontinued lipid-modifying treatment because of worsening depression. However, there was a small but significant improvement in anxiety symptoms after 12-weeks of high-dose (2-4 g daily) n-3 PUFA. In conclusion, depression in CHC is associated with plasma apoE deficiency. We postulate that apoE deficiency disrupts blood brain barrier integrity to promote HCV infection of the CNS. High-dose n-PUFAs may alleviate anxiety in some CHC patients but the use of lipid lowering therapy must be balanced against risks of worsening depression.


Assuntos
Apolipoproteínas E/sangue , Depressão/sangue , Depressão/psicologia , Hepatite C Crônica/sangue , Hepatite C Crônica/psicologia , Adulto , Ansiedade/sangue , Ansiedade/tratamento farmacológico , Ansiedade/psicologia , Colesterol/sangue , Depressão/tratamento farmacológico , Ácidos Graxos Monoinsaturados/uso terapêutico , Feminino , Fluvastatina , Hepatite C Crônica/complicações , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Indóis/uso terapêutico , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Resultado do Tratamento
9.
J Viral Hepat ; 19(2): e89-96, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22239531

RESUMO

Patients with chronic hepatitis C infection may exhibit neuropsychological symptoms and cognitive impairment. Post-mortem studies of hepatitis C virus HCV quasispecies and replicative intermediates indicate that the brain might act as a separate compartment for viral replication and microglia may be the locus for infection and subsequent neuroinflammatory activity. We sought to use two independent in vivo imaging techniques to determine evidence of neuroinflammation in patients with histologically mild chronic hepatitis C. Using positron emission tomography (PET) with a ligand for microglial/brain macrophage activation, (11)C-(R)-PK11195 (PK11195) and cerebral proton magnetic resonance spectroscopy, we determined whether there was evidence of neuroinflammation in a pilot study of 11 patients with biopsy-proven mild chronic hepatitis C, compared to healthy volunteers. Patients were characterized by cognitive testing and the fatigue impact scale to assess for CNS impairment. PK11195 binding potential was significantly increased in the caudate nucleus of patients, compared to normal controls (P = 0.03). The caudate and thalamic binding potential were more significantly increased in six patients with genotype 1 infection (P = 0.007) and positively correlated with viraemia (r = 0.77, P = 0.005). Basal ganglia myo-inositol/creatine and choline/creatine ratios were also significantly elevated in patients with chronic hepatitis C compared to normal controls (P = 0.0004 and P = 0.01, respectively). Using PET, we demonstrated evidence of microglial activation, which positively correlated with HCV viraemia and altered cerebral metabolism in the brains of patients with mild hepatitis C. This provides further in vivo evidence for a neurotropic role for HCV.


Assuntos
Encéfalo/imunologia , Encéfalo/patologia , Hepatite C Crônica/imunologia , Hepatite C Crônica/patologia , Microglia/imunologia , Adulto , Idoso , Encéfalo/diagnóstico por imagem , Encéfalo/virologia , Feminino , Humanos , Espectroscopia de Ressonância Magnética , Masculino , Microglia/virologia , Pessoa de Meia-Idade , Radiografia
10.
J Viral Hepat ; 18(10): e530-4, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21914073

RESUMO

We compared in vivo hepatic (31) P magnetic resonance spectroscopy ((31) P MRS) and hepatic vein transit times (HVTT) using contrast-enhanced ultrasound with a microbubble agent to assess the severity of hepatitis C virus (HCV)-related liver disease. Forty-six patients with biopsy-proven HCV-related liver disease and nine healthy volunteers had (31) P MRS and HVTT performed on the same day. (31) P MR spectra were obtained at 1.5 T. Peak areas were calculated for metabolites, including phosphomonoesters (PME) and phosphodiesters (PDE). Patients also had the microbubble ultrasound contrast agent, Levovist (2 g), injected into an antecubital vein, and time-intensity Doppler ultrasound signals of the right and middle hepatic veins were measured. The HVTT was calculated as the time from injection to a sustained rise in Doppler signal 10% greater than baseline. The shortest times were used for analysis. Based on Ishak histological scoring, there were 15 patients with mild hepatitis, 20 with moderate/severe hepatitis and 11 with cirrhosis. With increasing severity of disease, the PME/PDE ratio was steadily elevated, while the HVTT showed a monotonic decrease. Both imaging modalities could separate patients with cirrhosis from the mild and moderate/severe hepatitis groups. No statistical difference was observed in the accuracy of each test to denote mild, moderate/severe hepatitis and cirrhosis (Fisher's exact test P =1.00). (31) P MRS and HVTT show much promise as noninvasive imaging tests for assessing the severity of chronic liver disease. Both are equally effective and highly sensitive in detecting cirrhosis.


Assuntos
Hepatite C/diagnóstico , Hepatite C/patologia , Fígado/patologia , Espectroscopia de Ressonância Magnética/métodos , Ultrassonografia/métodos , Adulto , Idoso , Feminino , Humanos , Masculino , Microbolhas , Pessoa de Meia-Idade , Isótopos de Fósforo/metabolismo , Sensibilidade e Especificidade , Índice de Gravidade de Doença
11.
J Viral Hepat ; 18 Suppl 1: 1-16, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21824223

RESUMO

Worldwide, the hepatitis B virus (HBV) and the hepatitis C virus (HCV) cause, respectively, 600,000 and 350,000 deaths each year. Viral hepatitis is the leading cause of cirrhosis and liver cancer, which in turn ranks as the third cause of cancer death worldwide. Within the WHO European region, approximately 14 million people are chronically infected with HBV, and nine million people are chronically infected with HCV. Lack of reliable epidemiological data on HBV and HCV is one of the biggest hurdles to advancing policy. Risk groups such as migrants and injecting drug users (IDU) tend to be under-represented in existing prevalence studies; thus, targeted surveillance is urgently needed to correctly estimate the burden of HBV and HCV. The most effective means of prevention against HBV is vaccination, and most European Union (EU) countries have universal vaccination programmes. For both HBV and HCV, screening of individuals who present a high risk of contracting the virus is critical given the asymptomatic, and thereby silent, nature of disease. Screening of migrants and IDUs has been shown to be effective and potentially cost-effective. There have been significant advances in the treatment of HCV and HBV in recent years, but health care professionals remain poorly aware of treatment options. Greater professional training is needed on the management of hepatitis including the treatment of liver cancer to encourage adherence to guidelines and offer patients the best possible outcomes. Viral hepatitis knows no borders. EU Member States, guided by the EU, need to work in a concerted manner to implement lasting, effective policies and programmes and make tackling viral hepatitis a public health priority.


Assuntos
Hepatite B/epidemiologia , Hepatite B/prevenção & controle , Hepatite C/epidemiologia , Hepatite C/prevenção & controle , Europa (Continente)/epidemiologia , Hepatite B/complicações , Hepatite B/mortalidade , Hepatite C/complicações , Hepatite C/mortalidade , Humanos , Cirrose Hepática/epidemiologia , Cirrose Hepática/prevenção & controle , Cirrose Hepática/virologia , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/prevenção & controle , Neoplasias Hepáticas/virologia , Programas de Rastreamento/métodos , Vigilância da População/métodos , Vacinação/estatística & dados numéricos
12.
Nat Med ; 1(4): 374-5, 1995 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-7585070

RESUMO

Severe malaria is a major cause of childhood mortality in sub-Saharan Africa but the factors predisposing children to severe forms of malaria have not been fully elucidated. In a case-control study of over 1,200 Gambian children hepatitis B virus carriage was significantly increased amongst cases of severe malaria compared to matched controls. We suggest that this association may relate to impaired clearance of liver stage parasites in the presence of the reduced level of HLA class I antigen expression on hepatocytes infected by hepatitis B virus. If this association is causal and viral carriage predisposes to severe malaria, widespread vaccination against hepatitis B virus may reduce mortality from severe malaria.


Assuntos
Portador Sadio , Antígenos de Superfície da Hepatite B/sangue , Vírus da Hepatite B/imunologia , Hepatite B/complicações , Malária Cerebral/complicações , Malária Falciparum/complicações , Animais , Portador Sadio/epidemiologia , Portador Sadio/imunologia , Estudos de Casos e Controles , Criança , Pré-Escolar , Ensaio de Imunoadsorção Enzimática , Gâmbia/epidemiologia , Hepatite B/epidemiologia , Hepatite B/imunologia , Humanos , Fígado/parasitologia , Fígado/virologia , Malária Cerebral/epidemiologia , Malária Cerebral/imunologia , Malária Falciparum/epidemiologia , Malária Falciparum/imunologia , Razão de Chances , Plasmodium falciparum/fisiologia , Prevalência
13.
J Viral Hepat ; 17(11): 778-83, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20002308

RESUMO

Microbubble measurement of hepatic vein transit times (HVTT) may have the potential to assess severity of hepatitis C virus (HCV)-related liver disease, where there is a shorter HVTT with more severe disease. We investigated the utility of this test as a marker of response to antiviral treatment. Thirty-seven patients with biopsy-proven HCV-related disease undergoing antiviral treatment were studied. All had baseline scans and then repeat scans 6 months after the end of treatment. HVTT using Levovist were obtained from the right and middle hepatic veins, and the shorter time was used for analysis. The aspartate aminotransferase to platelet ratio index (APRI) scores were calculated retrospectively. There were seven patients with mild hepatitis, 23 with moderate/severe hepatitis and seven with cirrhosis. The mean baseline HVTT in responders ± SE increased from 27.3 ± 2.29 s to 33.5 ± 2.8 s posttreatment (P = 0.01). In the 10 nonresponders, the HVTT remained the same; 43.3 ± 9 s baseline compared to 44 ± 7.8 s posttreatment (P = 0.84). This trend was also seen with the APRI score where in responders, the mean score decreased from 1.1 ± 0.2 to 0.74 ± 1 (P = 0.03) and in nonresponders, the score remained unchanged; 0.88 ± 0.2 compared to 0.84 ± 0.2 (P = 0.31). HVTT measurement lengthened, while APRI scores decreased in patients who responded to antiviral treatment while both remained the same, shortened (HVTT) or increased (APRI), respectively, in patients who were nonresponders. These results are encouraging and indicate that these tests could be potentially used as markers of response to treatment and could obviate the need for serial biopsies in antiviral future treatment studies.


Assuntos
Antivirais/farmacocinética , Meios de Contraste/farmacocinética , Monitoramento de Medicamentos/métodos , Veias Hepáticas/diagnóstico por imagem , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/patologia , Microbolhas , Adulto , Idoso , Aspartato Aminotransferases/sangue , Feminino , Seguimentos , Hepatite C Crônica/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Radiografia , Fatores de Tempo , Resultado do Tratamento
14.
J Viral Hepat ; 17(8): 537-45, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19804501

RESUMO

Combinations of noninvasive markers may improve discrimination of chronic liver disease severity. The aims of this study were to compare four validated serum and ultrasound-based markers of hepatic disease severity head-to-head with liver biopsy and to assess optimal combinations with consideration of cost. A total of 67 patients with biopsy-proven chronic hepatitis C underwent all four techniques on the same visit [aspartate aminotransferase (AST) to platelet ratio index (APRI); Enhanced Liver Fibrosis (ELF) panel; transient elastography (TE) and ultrasound microbubble hepatic transit times (HTT)]. Markers were combined according to increasing financial cost and ordinal regression used to determine contributions. APRI, ELF, TE and HTT predicted cirrhosis with diagnostic accuracy of 86%, 91%, 90% and 83% respectively. ELF and TE were the most reliable tests with an intra-class correlation of 0.94 each. Either ELF or TE significantly enhanced the prediction of fibrosis stage when combined with APRI, but when combined together, did not improve the model further. Addition of third or fourth markers did not significantly improve prediction of fibrosis. Combination of APRI with either ELF or TE effectively predicts fibrosis stage, but combinations of three or more tests lead to redundancy of information and increased cost.


Assuntos
Aspartato Aminotransferases/sangue , Meios de Contraste/farmacologia , Técnicas de Imagem por Elasticidade/métodos , Hepatite C Crônica/patologia , Cirrose Hepática/patologia , Adolescente , Adulto , Idoso , Aspartato Aminotransferases/economia , Técnicas de Imagem por Elasticidade/economia , Hepatite C Crônica/sangue , Hepatite C Crônica/diagnóstico por imagem , Humanos , Cirrose Hepática/sangue , Cirrose Hepática/diagnóstico por imagem , Pessoa de Meia-Idade , Contagem de Plaquetas/economia , Contagem de Plaquetas/métodos , Curva ROC , Análise de Regressão , Reprodutibilidade dos Testes , Adulto Jovem
15.
J Viral Hepat ; 17(5): 327-35, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20002307

RESUMO

The prevalence of hepatitis B and hepatitis C in immigrant communities is unknown. Immigrants from south Asia are common in England and elsewhere, and the burden of viral hepatitis in these communities is unknown. We aimed to determine the prevalence of viral hepatitis in immigrants from south Asia living in England, and we therefore undertook a community-based testing project in such people at five sites in England. A total of 4998 people attending community centres were screened for viral hepatitis using oral fluid testing. The overall prevalence of anti-hepatitis C virus (HCV) in people of south Asian origin was 1.6% but varied by country of birth being 0.4%, 0.2%, 0.6% and 2.7% in people of this ethnic group born in the UK, India, Bangladesh and Pakistan, respectively. The prevalence of hepatitis B surface antigen was 1.2%-0.2%, 0.1%, 1.5% and 1.8% in people of this ethnic group born in the UK, India, Bangladesh and Pakistan, respectively. Analysis of risk factors for HCV infection shows that people from the Pakistani Punjab and those who have immigrated recently are at increased risk of infection. Our study suggests that migrants from Pakistan are at highest risk of viral hepatitis, with those from India at low risk. As prevalence varies both by country and region of origin and over time, the prevalence in migrant communities living in western countries cannot be easily predicted from studies in the country of origin.


Assuntos
Emigrantes e Imigrantes , Hepatite B Crônica/etnologia , Hepatite C Crônica/etnologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Ásia , Criança , Pré-Escolar , Inglaterra/epidemiologia , Feminino , Antígenos de Superfície da Hepatite B/análise , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/epidemiologia , Anticorpos Anti-Hepatite C/análise , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/epidemiologia , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Saliva/química , Adulto Jovem
17.
J Clin Invest ; 90(6): 2543-7, 1992 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-1281839

RESUMO

A previous study (Carman, W. F., A. R. Zanetti, P. Karayiannis, J. A. Waters, G. Manzillo, E. Tanzi, A. J. Zuckerman, and H. C. Thomas. 1990. Lancet. 336:325-329) demonstrated a variant hepatitis B surface antigen (HBsAg) in a vaccinated child born to a hepatitis B virus-infected mother. A substitution of arginine for glycine at amino acid 145 in HBsAg was observed. In this study the effect of this substitution on the common "a" determinant of this protein, against which protective immunity is directed, is investigated. Using recombinant HBsAg with and without the amino acid substitution, the binding of monoclonal antibodies that recognize different epitopes of the "a" determinant, was shown to be destroyed by the presence of arginine at amino acid 145. In convalescent and vaccinee sera, antibody binding to HBsAg was not inhibited by the variant HBsAg. Immunization with the variant HBsAg, although eliciting a high titer antibody that recognized the variant, produced a low titer of antibody recognizing the native protein. Studies in mice demonstrate that the immunogenicity of the variant protein is also substantially altered. The data presented here demonstrate that this variant evades the known protective anti-HBs response and lends support to the suggestion that this mutation arose as the result of immune pressure.


Assuntos
Anticorpos Anti-Hepatite B/imunologia , Antígenos de Superfície da Hepatite B/imunologia , Vacinas contra Hepatite B/imunologia , Animais , Formação de Anticorpos , Epitopos , Feminino , Hepatite B/imunologia , Antígenos de Superfície da Hepatite B/química , Antígenos de Superfície da Hepatite B/genética , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Mutação Puntual , Gravidez , Complicações Infecciosas na Gravidez , Relação Estrutura-Atividade , Vacinação
18.
Microb Drug Resist ; 12(2): 145-8, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16922633

RESUMO

A study was conducted to evaluate the occurrence of extended-spectrum beta-lactamases (ESBLs)-producing Escherichia coli from fecal samples of healthy food animals in Hong Kong. Rectal or cloacal swabs were obtained from cattle, pigs, chicken, ducks, geese, and pigeons in slaughterhouses or wholesale markets over a 5- month period in 2002. Antibiotic-containing medium was used for selective isolation of potentially ESBL-producing E. coli. Of 734 samples analyzed, six (2%) from pigs, three (3.1%) from cattle, and one (3%) from pigeons had E. coli strains with the ESBL phenotype. The ESBL content for the 10 isolates include CTXM- 3 (n = 4), CTX-M-13 (n = 3), CTX-M-14 (n = 2), and CTX-M-24 (n = 1). In five isolates, the bla (CTX-M) gene was encoded on transferable plasmids (60 or 90 kb), and the gene was found to transfer to E. coli (J53 or JP995) with frequencies of 10(7) to 10(3) per donor cells. The ten isolates had five distinct pulsotypes with some clonal spread. However, the isolates from the different kinds of animals were not clonally related. These findings imply that bacteria of animal origins may serve as reservoirs of some ESBL genes.


Assuntos
Animais Domésticos/microbiologia , Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla/genética , Escherichia coli/efeitos dos fármacos , Microbiologia de Alimentos , beta-Lactamases/genética , Animais , Bovinos , Escherichia coli/genética , Escherichia coli/metabolismo , Genes Bacterianos , Hong Kong/epidemiologia , Aves Domésticas , Suínos , beta-Lactamases/biossíntese
19.
Health Technol Assess ; 10(21): 1-113, iii, 2006 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-16750059

RESUMO

OBJECTIVES: To determine whether combined therapy with interferon-alpha and ribavirin was more effective and cost-effective than no treatment for patients with mild chronic hepatitis C. DESIGN: A multicentre, randomised, controlled, non-blinded trial assessed the efficacy of combination therapy. A Markov model used these efficacy data combined with data on transition probabilities, costs and health-related quality of life (HRQoL) to assess the lifetime cost-effectiveness of the intervention. SETTING: A multicentre NHS setting. PARTICIPANTS: Treatment-naive, adult patients with histologically mild chronic hepatitis C (Ishak necroinflammatory scores <4 and fibrosis scores <3 on liver biopsy). INTERVENTIONS: Patients were randomised to receive interferon-alpha and ribavirin for 48 weeks or no treatment (control). MAIN OUTCOME MEASURES: The primary outcome measure was the proportion of patients having a sustained virological response (SVR), measured at 6 months after cessation of therapy. Secondary outcome measures were: the ability of early phase kinetics to predict the eventual outcome of treating mild disease; HRQoL measured using the Short Form 36 and EuroQol (5 Dimensions) questionnaires, and the cost per quality-adjusted life-year (QALY) of interferon-alpha and ribavirin for mild disease compared with no treatment. RESULTS: In the treatment group, 32 out of 98 patients (33%) achieved an SVR. Patients infected with genotype 1 had a lower SVR than those infected with genotype non-1 (18% versus 49%, p = 0.02). No patients who failed to achieve a 2-log drop in viral load at 12 weeks achieved an SVR. HRQoL fell during treatment and rose with treatment cessation. For patients having an SVR there were modest improvements in HRQoL at 6 months post-treatment. The mean cost per QALY gained was 4535 pounds sterling for 40-year-old patients with genotype non-1 and 25,188 pounds sterling for patients with genotype 1. For patients with genotype 1 aged 65, providing interferon-alpha and ribavirin for mild disease led to fewer QALYs gained, and a mean cost per QALY of 53,017 pounds sterling. The model using efficacy estimates from the literature, showed that the cost per QALY gained from providing pegylated interferon alpha-2b and ribavirin at a mild stage rather than a moderate stage was 7821 pounds sterling for patients with genotype non-1 and 28,409 pounds sterling for patients with genotype 1. CONCLUSIONS: Based on the evidence collected in this study, interferon-alpha and ribavirin treatment for mild chronic hepatitis C patients is in general cost-effective at the 30,000 pounds sterling per QALY threshold previously used by policy-makers in the NHS. For patients with chronic hepatitis C aged 65 or over with genotype 1, antiviral treatment at a mild stage does not appear cost-effective. Further research is required on the cost-effectiveness of pegylated interferon and ribavirin, in particular the intervention's long-term impact on HRQoL and health service costs requires further evaluation. Further research is also needed to develop predictive tests, based on pharmacogenomics, that can identify those cases most likely to respond to antiviral therapy. Liver biopsy before treatment no longer appears justified apart from for older patients (aged 65 or over) with genotype 1. However, further research should monitor the impact this strategy would have on costs and outcomes.


Assuntos
Antivirais/economia , Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/economia , Interferon-alfa/uso terapêutico , Ribavirina/economia , Ribavirina/uso terapêutico , Adulto , Análise de Variância , Efeitos Psicossociais da Doença , Análise Custo-Benefício , Quimioterapia Combinada , Feminino , Genótipo , Hepacivirus/efeitos dos fármacos , Hepacivirus/genética , Humanos , Interferon alfa-2 , Masculino , Polietilenoglicóis , Qualidade de Vida , Anos de Vida Ajustados por Qualidade de Vida , Proteínas Recombinantes , Inquéritos e Questionários , Resultado do Tratamento , Reino Unido , Carga Viral
20.
AIDS ; 2(5): 391-3, 1988 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-3146270

RESUMO

Five HIV p24 antigen (p24Ag)-positive patients received alpha interferon during trials of therapy for hepatitis B. Four of these showed marked falls in p24Ag during treatment. One of the two patients who became p24Ag-negative [corrected] developed anti-p24 antibodies (anti-p24). Five out of nine p24Ag-negative HIV-antibody-positive patients showed a rise in anti-p24 titres during interferon therapy, whereas only two out of six untreated controls showed a similar rise. This study provides evidence that alpha interferon has anti-HIV activity in vivo.


Assuntos
Anticorpos Anti-HIV/biossíntese , Soropositividade para HIV/terapia , Hepatite B/terapia , Interferon Tipo I/uso terapêutico , Adulto , Ensaios Clínicos como Assunto , Antígenos HIV/análise , Proteína do Núcleo p24 do HIV , Soropositividade para HIV/complicações , Hepatite B/complicações , Hepatite B/imunologia , Humanos , Pessoa de Meia-Idade , Distribuição Aleatória , Proteínas dos Retroviridae/imunologia
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