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1.
Support Care Cancer ; 29(1): 97-105, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32314052

RESUMO

BACKGROUND: Optimal hepatitis C virus (HCV) screening strategies for cancer patients have not been established. We compared the performance of selective HCV screening strategies. METHODS: We surveyed patients presenting for first systemic anticancer therapy during 2013-2014 for HCV risk factors. We estimated the prevalence of positivity for HCV antibody (anti-HCV) and examined factors associated with anti-HCV status using Fisher's exact test or Student's t test. Sensitivity was calculated for screening patients born during 1945-1965, patients with ≥ 1 other risk factor, or both cohorts ("combined screening"). RESULTS: We enrolled 2122 participants. Median age was 59 years (range, 18-91); 1138 participants were women. Race/ethnicity distribution was white non-Hispanic, 76% (n = 1616); Hispanic, 11% (n = 233); black non-Hispanic, 8% (n = 160); Asian, 4% (n = 78); and other, 2% (n = 35). Primary cancer distribution was non-liver solid tumor, 78% (n = 1664); hematologic cancer, 20% (n = 422); and liver cancer, 1% (n = 28). Prevalence of anti-HCV was 1.93% (95% CI, 1.39%-2.61%). Over 28% of patients with detectable HCV RNA were unaware of infection. Factors significantly associated with anti-HCV positivity included less than a bachelor's degree, birth in 1945-1965, chronic liver disease, injection drug use, and blood transfusion or organ transplant before 1992. A total of 1315 participants (62%), including 39 of 41 with anti-HCV, reported ≥ 1 risk factor. Sensitivity was 80% (95% CI, 65-91%) for birth-cohort-based, 68% (95% CI, 52-82%) for other-risk-factor-based, and 95% (95% 83-99%) for combined screening. CONCLUSION: Combined screening still missed 5% of patients with anti-HCV. These findings favor universal HCV screening to identify all HCV-infected cancer patients.


Assuntos
Hepacivirus/imunologia , Anticorpos Anti-Hepatite C/sangue , Hepatite C/diagnóstico , Neoplasias Hepáticas/tratamento farmacológico , Programas de Rastreamento/métodos , Adolescente , Adulto , Afro-Americanos/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Grupo com Ancestrais do Continente Europeu/estatística & dados numéricos , Feminino , Hepatite C/etnologia , Hispano-Americanos/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , RNA Viral/sangue , Fatores de Risco , Adulto Jovem
2.
PLoS Comput Biol ; 16(12): e1008451, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33347439

RESUMO

Simulations of tissue-specific effects of primary acute viral infections like COVID-19 are essential for understanding disease outcomes and optimizing therapies. Such simulations need to support continuous updating in response to rapid advances in understanding of infection mechanisms, and parallel development of components by multiple groups. We present an open-source platform for multiscale spatiotemporal simulation of an epithelial tissue, viral infection, cellular immune response and tissue damage, specifically designed to be modular and extensible to support continuous updating and parallel development. The base simulation of a simplified patch of epithelial tissue and immune response exhibits distinct patterns of infection dynamics from widespread infection, to recurrence, to clearance. Slower viral internalization and faster immune-cell recruitment slow infection and promote containment. Because antiviral drugs can have side effects and show reduced clinical effectiveness when given later during infection, we studied the effects on progression of treatment potency and time-of-first treatment after infection. In simulations, even a low potency therapy with a drug which reduces the replication rate of viral RNA greatly decreases the total tissue damage and virus burden when given near the beginning of infection. Many combinations of dosage and treatment time lead to stochastic outcomes, with some simulation replicas showing clearance or control (treatment success), while others show rapid infection of all epithelial cells (treatment failure). Thus, while a high potency therapy usually is less effective when given later, treatments at late times are occasionally effective. We illustrate how to extend the platform to model specific virus types (e.g., hepatitis C) and add additional cellular mechanisms (tissue recovery and variable cell susceptibility to infection), using our software modules and publicly-available software repository.


Assuntos
Biologia Computacional/métodos , Epitélio , Modelos Imunológicos , Viroses , Antivirais/uso terapêutico , Simulação por Computador , Epitélio/imunologia , Epitélio/virologia , Hepacivirus/imunologia , Hepatite C/tratamento farmacológico , Hepatite C/imunologia , Humanos , Viroses/tratamento farmacológico , Viroses/imunologia
3.
BMC Infect Dis ; 20(1): 851, 2020 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-33198672

RESUMO

BACKGROUND: HIV, HBV and HCV infections continue to represent major health concerns, especially among key at-risk populations such as men who have sex with men (MSM), people who inject drugs (PWIDs), transgender women (TGW) and sex workers (SW). The objective of the ANRS-CUBE study was to evaluate the acceptability of a healthcare, community-based strategy offering a triple rapid HIV-HBV-HCV testing, and HBV vaccination, targeted at three priority groups (MSM, PWIDs and TGW/SWs), in three community centers, in the Paris area. METHODS: This longitudinal multicentric non-randomized study included all adult volunteers attending one of the three specialized community centers in Paris, between July 2014 and December 2015. HIV, HBV and HCV status and acceptability of HBV vaccination were evaluated. RESULTS: A total of 3662, MSM, 80 PWIDs and 72 TGW/SW were recruited in the three centers respectively. Acceptability of rapid tests was 98.5% in MSM and 14.9% in TGW/SWs, but could not be estimated in PWIDs since the number of users attending and the number of proposals were not recorded. User acceptability of HBV vaccination was weak, only 17.9% of the eligible MSM (neither vaccinated, nor infected) agreed to receive the first dose, 12.2% two doses, 5.9% had a complete vaccination. User acceptability of HBV vaccination was greater in PWIDs and TGW/SWs, but decreased for the last doses (66.7 and 53.3% respectively received a first dose, 24.4 and 26.7% a second dose and 6.7 and 0% a third dose). Fifty-three participants (49 MSM and 4 PWIDs) were discovered HIV positive, more than half with a recent infection. All but two HIV positive participants were linked to appropriate care in less than one month. CONCLUSIONS: Rapid HIV-HCV-HBV screening showed a very high level of acceptability among MSM. Efforts need to be made to improve immediate acceptability for HBV vaccination, especially among MSM, and follow-up doses compliance. Our results show the important role of community centers in reaching targets, often fragile, populations, while also suggesting the need to reinforce on-site human support in terms of testing and vaccination, especially when addressing PWIDs.


Assuntos
Infecções por HIV/diagnóstico , HIV-1/imunologia , HIV-2/imunologia , Hepacivirus/imunologia , Vírus da Hepatite B/imunologia , Hepatite B Crônica/diagnóstico , Hepatite C Crônica/diagnóstico , Vacinação , Vacinas Virais/imunologia , Adolescente , Adulto , Serviços de Saúde Comunitária , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , Hepatite B Crônica/epidemiologia , Hepatite B Crônica/virologia , Hepatite C Crônica/epidemiologia , Hepatite C Crônica/virologia , Homossexualidade Masculina , Humanos , Estudos Longitudinais , Masculino , Programas de Rastreamento/métodos , Paris/epidemiologia , Projetos Piloto , Estudos Prospectivos , Fatores de Risco , Testes Sorológicos , Profissionais do Sexo , Minorias Sexuais e de Gênero , Abuso de Substâncias por Via Intravenosa , Pessoas Transgênero , Adulto Jovem
4.
J Prim Care Community Health ; 11: 2150132720969554, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33225792

RESUMO

INTRODUCTION: Coronavirus disease 2019 (COVID-19) has led to unprecedented modifications to healthcare delivery in the U.S. To preserve resources in preparation for a COVID-19 surge, Boston Medical Center (BMC) implemented workflows to decrease ambulatory in-person visits effective March 16th, 2020. Telemedicine was incorporated into clinical workflows and much preventive care, including Hepatitis C (HCV) testing, was not routinely performed. OBJECTIVE: To explore the impact that the COVID-19 rapid restructuring response has had on HCV testing and identification hospital-wide and in ambulatory settings. METHODS: BMC utilizes reflex confirmatory testing for HCV. When a sample is HCV Ab positive, it is automatically reflexed for confirmatory RNA and genotype testing. HCV test results for patients were collected daily. We compared unique patient tests for 3.5 month periods before and after March 16th, 2020. Descriptive statistics showed total tests and total new HCV RNA+ before versus after, both hospital-wide and in ambulatory clinics alone. Mean daily tests completed were compared. RESULTS: Hospital-wide, total HCV testing decreased by 49.6%, and new HCV+ patient identification decreased by 42.1%. In ambulatory clinics, testing decreased by 71.9%, and new HCV+ identification decreased by 63.3%. Hospital-wide, mean daily tests decreased by 22.9 tests per day (95% CI: 17.9-28.0, P < .001), and mean daily new HCV+ identification decreased by 0.36 (95% CI: 0.20-0.53, P < .001). In ambulatory clinics, mean daily tests decreased by 22.1 tests per day (95% CI: 17.5-26.7, P < .001) and mean daily HCV+ decreased by 1.40 (95% CI: 1.03-1.76, P < .001). CONCLUSION: The COVID-19 systematic emergency response led to decreased HCV testing and identification, and in this regard telemedicine acts as a barrier to HCV care. Other public health initiatives must be monitored in the context of telemedicine workflows. Continued monitoring of HCV screening trends is vital, and adaptive approaches to work toward the goal of HCV elimination are needed.


Assuntos
Instituições de Assistência Ambulatorial , Assistência à Saúde , Hepatite C/diagnóstico , Programas de Rastreamento , Pandemias , Telemedicina , Adolescente , Adulto , Idoso , Anticorpos Antivirais/sangue , Boston , Coronavirus , Assistência à Saúde/métodos , Assistência à Saúde/organização & administração , Emergências , Feminino , Acesso aos Serviços de Saúde , Hepacivirus/genética , Hepacivirus/imunologia , Hepatite C/virologia , Hospitais , Humanos , Masculino , Programas de Rastreamento/métodos , Programas de Rastreamento/estatística & dados numéricos , Pessoa de Meia-Idade , RNA Viral , Adulto Jovem
5.
Sci Rep ; 10(1): 16261, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-33004836

RESUMO

There is a large unmet need for a prophylactic hepatitis C virus (HCV) vaccine to control the ongoing epidemic with this deadly pathogen. Many antiviral vaccines employ whole viruses as antigens. For HCV, this approach became feasible following the development of infectious cell culture systems for virus production. However, the lack of efficient downstream processes (DSP) for HCV purification poses a roadblock for the development of a whole virus vaccine. Using cell culture-derived genotype 1a HCV we developed a scalable and efficient DSP train, employing commonly used clarification and ultrafiltration techniques, followed by two membrane-based chromatography steps. For virus capture, steric exclusion chromatography using cellulose membranes was established, resulting in a virtually complete virus recovery with > 99% protein and 84% DNA depletion. Virus polishing was achieved by sulphated cellulose membrane adsorbers with ~ 50% virus recovery and > 99% protein and 90% DNA depletion. Additional nuclease digestion resulted in 99% overall DNA depletion with final DNA concentrations of 2 ng/mL. Process results were comparable for cell culture-derived HCV of another major genotype (5a). This study provides proof-of-concept for establishment of an efficient and economically attractive DSP with potential application for production of an inactivated whole virus vaccine against HCV for human use.


Assuntos
Hepacivirus/imunologia , Vacinas contra Hepatite Viral/imunologia , Cromatografia em Gel , Hepacivirus/genética , Humanos , Ultrafiltração , Vacinas de Produtos Inativados , Vacinas contra Hepatite Viral/genética , Vacinas contra Hepatite Viral/isolamento & purificação
6.
BMC Infect Dis ; 20(1): 742, 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33036558

RESUMO

BACKGROUND: The surge of methamphetamine use has been a complicating factor compounding the steeply increasing number of drug overdose deaths in the U.S. Infection from blood-borne viruses including hepatitis B virus (HBV), hepatitis C virus (HCV) and HIV, related to methamphetamine use continue to grow. This study aims to examine the risk factors associated with HBV, HCV and HIV among people who used methamphetamine. METHODS: People who ever used methamphetamine were identified from five National Health and Nutrition Examination Survey (NHANES) cohorts, 2007 to 2016. The outcome was either positive or negative for blood-borne viruses as identified from laboratory tests. Weighted statistics for the combined ten years of data were calculated by multiplying the weighted variable for laboratory measurements by 0.2. We examined the association of sexual activities (sexual partners, sexual identity), drug use behaviors (poly-drug use, injection drug use, frequency of drug use, age started using methamphetamine), demographics, and socio-economic status with blood-borne viruses using bivariate and multivariable logistic regression models. RESULTS: There were 1132 participants representing approximately 11,996,319 persons who ever used methamphetamine in the U.S. Blood-borne viruses' positive rate was 13.0 per 100,000. Multivariable logistic regression analyses showed significant associations of blood-borne infections with age 40-49 years (vs. age 20-29 years, adjusted odds ratio 4.77, 95% CI 1.11-20.55), age 50-59 years (vs. age 20-29 years, 10.25, 2.40-43.82), living within poverty index 1-1.9 (vs. poverty index > = 2, 2.55; 1.19-5.49), living below the poverty threshold (vs. poverty index > = 2, 2.55; 1.11-5.86), having lower than high school education (vs. equal or higher than high school education, 3.13; 1.51-6.46), sexual identity as other than heterosexual (vs. heterosexual, 5.60; 1.72-18.28), using methamphetamine and heroin and cocaine (vs. using methamphetamine alone, 4.24; 1.06-16.92), injection drug use (vs. no injection drug use, 3.15; 1.61-6.16), and started using methamphetamine at age above 25 (vs. started using methamphetamine at age between 10 and 17, 2.09; 1.01-4.35). CONCLUSIONS: Among people who use methamphetamine, those who use polysubstance, or who inject substances, are in urgent need for vaccination and interventions to avoid further harm from blood borne infections.


Assuntos
Infecções por HIV/epidemiologia , HIV-1/imunologia , HIV-2/imunologia , Hepacivirus/imunologia , Vírus da Hepatite B/imunologia , Hepatite B/epidemiologia , Hepatite C/epidemiologia , Metanfetamina , Abuso de Substâncias por Via Intravenosa , Adulto , Estudos de Coortes , Estudos Transversais , Feminino , Infecções por HIV/virologia , Hepatite B/virologia , Hepatite C/virologia , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais , Razão de Chances , Fatores de Risco , Assunção de Riscos , Testes Sorológicos , Comportamento Sexual , Parceiros Sexuais , Adulto Jovem
7.
J Virol ; 94(22)2020 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-32878891

RESUMO

An effective vaccine for hepatitis C virus (HCV) is a major unmet need, and it requires an antigen that elicits immune responses to key conserved epitopes. Based on structures of antibodies targeting HCV envelope glycoprotein E2, we designed immunogens to modulate the structure and dynamics of E2 and favor induction of broadly neutralizing antibodies (bNAbs) in the context of a vaccine. These designs include a point mutation in a key conserved antigenic site to stabilize its conformation, as well as redesigns of an immunogenic region to add a new N-glycosylation site and mask it from antibody binding. Designs were experimentally characterized for binding to a panel of human monoclonal antibodies (HMAbs) and the coreceptor CD81 to confirm preservation of epitope structure and preferred antigenicity profile. Selected E2 designs were tested for immunogenicity in mice, with and without hypervariable region 1, which is an immunogenic region associated with viral escape. One of these designs showed improvement in polyclonal immune serum binding to HCV pseudoparticles and neutralization of isolates associated with antibody resistance. These results indicate that antigen optimization through structure-based design of the envelope glycoproteins is a promising route to an effective vaccine for HCV.IMPORTANCE Hepatitis C virus infects approximately 1% of the world's population, and no vaccine is currently available. Due to the high variability of HCV and its ability to actively escape the immune response, a goal of HCV vaccine design is to induce neutralizing antibodies that target conserved epitopes. Here, we performed structure-based design of several epitopes of the HCV E2 envelope glycoprotein to engineer its antigenic properties. Designs were tested in vitro and in vivo, demonstrating alteration of the E2 antigenic profile in several cases, and one design led to improvement of cross-neutralization of heterologous viruses. This represents a proof of concept that rational engineering of HCV envelope glycoproteins can be used to modulate E2 antigenicity and optimize a vaccine for this challenging viral target.


Assuntos
Hepacivirus/genética , Hepacivirus/imunologia , Proteínas do Envelope Viral/química , Proteínas do Envelope Viral/imunologia , Animais , Anticorpos Monoclonais/imunologia , Anticorpos Neutralizantes/imunologia , Formação de Anticorpos , Antígenos Virais/química , Antígenos Virais/genética , Antígenos Virais/imunologia , Linhagem Celular , Epitopos/química , Epitopos/imunologia , Feminino , Células HEK293 , Hepatite C/imunologia , Hepatite C/virologia , Anticorpos Anti-Hepatite C/sangue , Anticorpos Anti-Hepatite C/imunologia , Humanos , Imunogenicidade da Vacina , Camundongos , Modelos Moleculares , Testes de Neutralização , Conformação Proteica , Proteínas do Envelope Viral/genética , Vacinas contra Hepatite Viral/imunologia
8.
APMIS ; 128(11): 593-602, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32870528

RESUMO

Induction of broad Th1 cellular immune responses and cytokines is crucial characteristics for vaccines against intracellular infections such as hepatitis C virus (HCV). Plants (especially oilseed tissues) and plant-immunomodulators (like oil bodies) offer cost-effective and scalable possibilities for the production of immunologically relevant and safe vaccine antigens and adjuvants, respectively. Herein, we provide data of the murine immunization by transgenic canola oilseed-derived HCV core protein (HCVcp) soluble extract (TSE) and Escherichia coli- derived rHCVcp in combination with Canola oil bodies (oil) compared to that of the Freund's (FA) adjuvant. Mice immunized by TSE+ oil developed both strong humeral (IgG) and Th1-biased cellular responses, manifested by high levels of IFN-γ and lower IgG1/IgG2a ratio and IL-4 secretion. Results of the intracellular cytokine staining indicated that TSE+ oil immunization in mice triggered both CD4+ and CD8+ T cells to release IFN-γ, while CD4+ cells were mostly triggered when FA was used. Analyses by qRT-PCR indicated that a combination of rHCVcp/TSE with oil body induced high levels of IL-10 cytokines compared to that of the FA adjuvant. These characteristics are important properties for the design of an HCV vaccine candidate and indicate the potential of Canola-derived antigen and oil bodies in addressing these concerns.


Assuntos
Hepacivirus/efeitos dos fármacos , Hepatite C Crônica/prevenção & controle , Proteínas Recombinantes/administração & dosagem , Células Th1/efeitos dos fármacos , Proteínas do Core Viral/administração & dosagem , Vacinas contra Hepatite Viral/administração & dosagem , Adjuvantes Imunológicos/administração & dosagem , Adjuvantes Imunológicos/química , Animais , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/virologia , Escherichia coli/genética , Escherichia coli/metabolismo , Feminino , Hepacivirus/imunologia , Hepacivirus/patogenicidade , Hepatite C Crônica/imunologia , Hepatite C Crônica/patologia , Hepatite C Crônica/virologia , Imunidade Celular/efeitos dos fármacos , Imunoglobulina G/biossíntese , Interferon gama/biossíntese , Interferon gama/imunologia , Interleucina-10/biossíntese , Interleucina-10/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Óleo de Brassica napus/administração & dosagem , Óleo de Brassica napus/química , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/imunologia , Células Th1/imunologia , Células Th1/virologia , Proteínas do Core Viral/biossíntese , Proteínas do Core Viral/imunologia , Vacinas contra Hepatite Viral/biossíntese
9.
BMC Infect Dis ; 20(1): 664, 2020 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-32907538

RESUMO

BACKGROUND: Hepatitis C virus (HCV) infection and type 2 diabetes mellitus (T2DM) are two major public health problems associated with increasing complications and mortality rates worldwide. The objective of this study is to evaluate the prevalence of hepatitis C virus (HCV) infection in diabetic patients and to investigate the influence of several epidemiological and clinical factors on HCV infection. METHOD: A total number of one hundred and eighty diabetic patients were recruited for this study. Consented subjects made up of 71(39.4%) males and 109(60.56%) females were recruited for the study. While one-Hundred (100) Non-Diabetics (Controls) were also recruited for the study. Structured questionnaires were administered to the consented participants to obtain relevant data. Sera samples were assayed for antibodies to HCV using an enzyme linked immunosorbent assay [Inteco Diagnostic Limited]. ELISA technique. RESULT: Overall prevalence of HCV infection among diabetes patients assayed was 13.3% out of which 8(11.3%) was obtained from the male subjects compared to 16 (14.7%) seropositivity recorded among the females (P = 0.511; P > 0.05). Considering age distribution, Subjects aged 41-50 years recorded, 9 (22.5%) positivity (P = 0.238; P > 0.05).Considering educational status of subjects screened, 22 (14.9%) positivity was rescored among subjects who have attained tertiary status of education.(P = 0.574;P > 0.05).Risk factors considered showed that, 7 (18.9%) seropositive subject were alcoholic consumers(P value = 0.2621;P > 0.05) while 5 (8.9%) recorded history of sharing sharp objects P = 0.2427;P > 0.05). CONCLUSION: Our study shows a slightly higher prevalence of hepatitis C infection in type 2 diabetics. This call for urgent routine screening exercise among diabetic patients for HCV infection. This study also emphasizes the need for public enlightenment on the association between HCV infection and T2DM, to avert possible complications among diabetic patients.


Assuntos
Diabetes Mellitus Tipo 2/epidemiologia , Hepacivirus/imunologia , Hepatite C/epidemiologia , Centros de Atenção Terciária , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Comorbidade , Ensaio de Imunoadsorção Enzimática , Feminino , Hepatite C/virologia , Anticorpos Anti-Hepatite C/sangue , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Nigéria/epidemiologia , Prevalência , Fatores de Risco , Inquéritos e Questionários , Adulto Jovem
10.
BMC Infect Dis ; 20(1): 655, 2020 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-32894072

RESUMO

BACKGROUND: People who use drugs including people who inject drugs (PWUD/ID), sex workers (SWs) and men who have sex with men (MSM) are at increased risk of HIV and viral hepatitis infection. Limited epidemiological data on the infections exists in key populations (KPs) in South Africa. We investigated the prevalence of hepatitis B (HBV), hepatitis C (HCV) and HIV and selected risk factors among these KPs to inform effective responses. METHODS: We used convenience sampling to recruit a targeted 3500 KPs accessing HIV-related health services across Cape Town (SWs, MSM, PWUD/ID), Durban (SWs, PWUD/ID), Pietermaritzburg (SWs), Mthatha (SWs), Port Elizabeth (SWs), Johannesburg (MSM) and Pretoria (MSM and PWUD/ID) into a cross-sectional survey. An interviewer questionnaire to assess socio-demographic characteristics, drug use and sexual risk practices, was administered. HBV surface antigen (HBsAg); HCV antibody, viral load and genotype, and HIV antibody, was tested. RESULTS: Among the 3439 people included in the study (1528 SWs, 746 MSM, 1165 PWUD/ID) the median age was 29 years, most participants were black African (60%), and 24% reported homelessness. 82% reported substance use in the last month, including alcohol (46%) and heroin (33%). 75% were sexually active in the previous month, with condom use at last sex at 74%. HIV prevalence was 37% (highest among SWs at 47%), HBsAg prevalence 4% (similar across KPs) and HCV prevalence was 16% (highest among PWUD/ID at 46%). CONCLUSIONS: HBV, HCV and HIV pose a health burden for KPs in South Africa. While HIV is key for all included KPs, HCV is of particular importance to PWUD/ID. For KPs, HBV vaccination and behavioural change interventions that support consistent condom and lubricant access and use are needed. Coverage of opioid substitution therapy and needle and syringe services, and access to HCV treatment for PWUD/ID need to be expanded.


Assuntos
Infecções por HIV/epidemiologia , HIV/imunologia , Hepacivirus/genética , Hepacivirus/imunologia , Vírus da Hepatite B/imunologia , Hepatite B/epidemiologia , Hepatite C/epidemiologia , Adulto , Estudos Transversais , Feminino , Genótipo , Anticorpos Anti-HIV/sangue , Infecções por HIV/tratamento farmacológico , Infecções por HIV/etiologia , Infecções por HIV/prevenção & controle , Hepatite B/etiologia , Antígenos de Superfície da Hepatite B/sangue , Hepatite C/etiologia , Anticorpos Anti-Hepatite C/sangue , Homossexualidade Masculina , Humanos , Masculino , Prevalência , Estudos Prospectivos , Fatores de Risco , Profissionais do Sexo , Minorias Sexuais e de Gênero , África do Sul/epidemiologia , Abuso de Substâncias por Via Intravenosa/complicações , Carga Viral , Adulto Jovem
11.
Sci Rep ; 10(1): 15290, 2020 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-32943718

RESUMO

Autophagy, a degradation system, works to maintain cellular homeostasis. However, as the impact of Hepatitis C virus (HCV) infection on hepatocyte autophagy and its effect on HCV replication remain unclear, we examined them. HCV infection suppressed late-stage autophagy and increased Rubicon. siRNA-mediated knockdown of Rubicon promoted autophagy in HCV-infected cells. In Huh-7 cells harbouring the HCV replicon, Rubicon knockdown downregulated the expression of type 1 interferon (IFN)-related genes and upregulated HCV replication. Rubicon overexpression or administration of bafilomycin A1 or chloroquine, an inhibitor of late-stage autophagy, suppressed autophagy and activated the type 1 IFN pathway. On the other hand, Atg7 knockout suppressed early-stage autophagy and did not activate the type 1 IFN pathway. In livers of humanized liver chimeric mice, HCV infection increased Rubicon and enhanced type 1 IFN signalling. Elimination of HCV in the mice reduced the increase in Rubicon due to HCV infection. The expression levels of Rubicon and IFN-stimulated genes in chronic hepatitis C patients were higher than those in non-B, non-C hepatitis patients. HCV infection increased Rubicon and suppressed hepatocyte autophagy, leading to activation of the intracellular immune response. Rubicon induction is involved in HCV replication via activation of the intracellular immune response.


Assuntos
Proteínas Relacionadas à Autofagia/imunologia , Autofagia/imunologia , Hepacivirus/imunologia , Hepatite C Crônica/imunologia , Imunidade Inata/imunologia , Animais , Linhagem Celular Tumoral , Citoplasma/imunologia , Hepatócitos/imunologia , Interações Hospedeiro-Patógeno/imunologia , Humanos , Interferon Tipo I/imunologia , Camundongos , Replicon/imunologia , Transdução de Sinais/imunologia , Replicação Viral/imunologia
13.
BMC Infect Dis ; 20(1): 634, 2020 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-32847528

RESUMO

BACKGROUND: People who inject drugs (PWID) have increased risk of acquiring blood-transmitted chronic viral infections such as Hepatitis B (HBV), Hepatitis C (HCV) and Human Immunodeficiency Virus (HIV) as well as increased risk of acquiring bacterial infections. We aimed to identify and describe bacteraemic episodes, their recurrence rates, predictive and prognostic factors amongst hospitalised PWID. METHODS: In this retrospective cohort study, we included 257 hospitalised PWID during 2000-2006 with follow up at the Department of Infectious Diseases, Hvidovre Hospital, Denmark. Data collection included comorbidity (HBV-, HCV-, HIV-, and psychiatric comorbidities), social information (contact to an addiction treatment centre, homelessness), opioid substitution treatment (OST), treatment completion and microbiology findings. There was a 10-years follow-up regarding mortality. RESULTS: The study identified 257 patients classified as PWID. Of these, 58 (22.6%) had at least one episode of bacteraemia during their first hospital admission. Recurrence was found in 29 (50.0%) of the bacteraemia cases. Staphylococcus aureus was the dominant microorganism of both first and recurrent episodes with 24 (41.4%) and nine (31.4%) of cases, respectively. A psychiatric diagnose was significantly associated with a lower risk of bacteraemia in the multivariate analysis (OR: 0.29, [95%CI: 0.11-0.77], P = 0.01). Mortality was significantly higher in patients with bacteraemia (17.2% vs. 3.0%, P < 0.01, OR: 6.67 [95%CI: 2.33-20], P < 0.01). CONCLUSIONS: In hospitalised PWID, bacteraemia was found in 22.6% and was associated with at higher mortality. The most common microorganism of bacteraemia was S. aureus. Psychiatric comorbidity was significantly associated with a lower risk of bacteraemia.


Assuntos
Bacteriemia/epidemiologia , Infecções por HIV/epidemiologia , Hepatite B/epidemiologia , Hepatite C/epidemiologia , Transtornos Mentais/epidemiologia , Infecções Estafilocócicas/epidemiologia , Staphylococcus aureus/isolamento & purificação , Abuso de Substâncias por Via Intravenosa/complicações , Adulto , Comorbidade , Dinamarca/epidemiologia , Feminino , Seguimentos , HIV/imunologia , Hepacivirus/imunologia , Vírus da Hepatite B/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Recidiva , Estudos Retrospectivos , Abuso de Substâncias por Via Intravenosa/mortalidade
14.
Artigo em Russo | MEDLINE | ID: mdl-32827366

RESUMO

The purpose of study was to establish risk group on hepatitis C in conditionally healthy population of the Belgorod oblast. Total 2025 conditionally healthy inhabitants aged between 1 and 99 were surveyed and serum samples from them were tested. There were eight age groups: 1-14 years (12.3%), 15-19 years (13.1%), 20-29 years (12.7%), 30-39 years (12.8%), 40-49 years (12.8%), 50-59 years (11.8%), 60-69 years (8.6%) and over 70 years of age (15.7%). Overall, 44.6% of the examined persons were male. 41.3% (ranging from 6.5 to 72.1%) of respondents reported surgery in their anamnesis, 5.1% (ranging from 0.8 to 12.6%) had blood/blood products transfusion, 10.3% (ranging from 1.7 to 57.9%) ear/nose piercing and 2.96% (ranging from 0.8 to 6.6%) tattoos. There were no people who injected drugs. The piercing was significantly higher in age groups 15-19 years and 20-29 years than other age groups (p-value<0.05). The tattoos were significantly higher in group of 70 years and older than in age groups 15-19 years, 30-39 years and 40-49 years (p-value<0.05). Anti-HCV antibodies were detected using third-generation enzyme-linked immunosorbent assay ("IFA-ANTI-HCV", Nizhny Novgorod). The HCV RNA was tested with RT-PCR. The Anti-HCV was detected in 22 persons (1.1%), 77.3% out of them were older than 53 year and they were born prior to 1965. The Anti-HCV were significantly higher for the people over 70 years of age than in the age groups of 1-14 years, 15-19 years, 30-39 years and 40-49 years (p-value<0.05). The 2.65% of the examined persons were older 53 years had anti-HCV. Only 0.36% of anti-HCV were found in the young age groups of the examined persons who were born after 1965, the percentage was significantly lower than in older age groups (p-value<0.05). The 16 people had RNA-HCV and 87.5% persons were born in or before 1965. There was one person with genotype 3a (age group 30-39 years), 15 persons with genotype 1b (fourteen out of them were older 53 years and one person was in the age group 20-29 years. The study established that risk age group are inhabitants born before 1965 in Belgorod region. It can be taken into account in regional hepatitis С screening programs.


Assuntos
Anticorpos Anti-Hepatite C , Hepatite C , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Genótipo , Hepacivirus/imunologia , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Adulto Jovem
15.
PLoS One ; 15(8): e0237890, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32810190

RESUMO

INTRODUCTION: Inclusion body myositis (IBM) is an idiopathic inflammatory myopathy, characterized by unique clinical features including finger flexor and quadriceps muscle weakness and a lack of any reliable treatment. The human leukocyte antigen (HLA)-DRB1 allele and autoantibody profiles in Japanese IBM patients have not been fully elucidated. METHODS: We studied 83 Japanese IBM patients with a mean age of 69 years (49 males and 34 females) who participated in the 'Integrated Diagnosis Project for Inflammatory Myopathies' from January 2011 to September 2016. IBM was diagnosed by histological diagnosis. Various autoantibodies were screened by RNA immunoprecipitation and enzyme-linked immunosorbent assays. HLA-DRB1 genotyping was performed using polymerase chain reaction-sequence based typing. A total of 460 unrelated healthy Japanese controls were also studied. RESULTS: The allele frequencies of DRB1*01:01, DRB1*04:10, and DRB1*15:02 were significantly higher in the IBM group than in the healthy control group (Corrected P = 0.00078, 0.00038 and 0.0046). There was a weak association between the DRB1*01:01 allele and severe leg muscle weakness and muscle atrophy. While hepatitis type C virus infection and autoantibodies to cytosolic 5'-nucleotidase 1A were found in 18 and 28 patients, respectively, no significant association with HLA-DRB1 alleles was observed. CONCLUSION: Japanese IBM patients had the specific HLA-DRB1 allele and autoantibody profiles.


Assuntos
Alelos , Grupo com Ancestrais do Continente Asiático/genética , Autoanticorpos/sangue , Cadeias HLA-DRB1/genética , Cadeias HLA-DRB1/imunologia , Miosite de Corpos de Inclusão/sangue , Miosite de Corpos de Inclusão/genética , Idoso , Anticorpos Antivirais/imunologia , Feminino , Frequência do Gene/genética , Hepacivirus/imunologia , Humanos , Masculino , Miosite de Corpos de Inclusão/imunologia
16.
BMC Infect Dis ; 20(1): 485, 2020 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-32641006

RESUMO

BACKGROUND: Bhutan is committed to eliminating hepatitis B and hepatitis C, though recent baseline estimates of disease burden in the general population are unknown. In 2017, we carried out a biomarker survey in the general population to estimate the prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) biomarkers to evaluate the impact of immunization and guide further efforts. METHODS: In 2017, a cross-sectional, population-based, three-stage cluster survey was undertaken of the general population (1-17 and 20+ years of age). We visited households, collected blood specimens and administered a standard questionnaire. Specimens were collected for hepatitis B surface antigen (HBsAg) and hepatitis C virus antibody (anti-HCV) testing. We calculated prevalence of infection and selected characteristics, along with confidence intervals (CIs). RESULTS: Of 1372 individuals approached, 1358 (99%) participated. Of those, 1321 (97%) had a specimen tested for HBsAg, and among 1173 enrolled individuals 5 years of age or older, 1150 (98%) individuals were tested for anti-HCV. The prevalence of HBsAg was 2.0% in 775 persons 20 years of age or older (95% CI: 1.0-4.0) and 0.5% in 546 persons 1-17 years of age (95% CI: 0.1-1.8). The prevalence of anti-HCV was 0.3% (95% CI: 0.1-0.8) among persons ≥5 years. CONCLUSIONS: Universal hepatitis B immunization of infants has resulted in a low prevalence of chronic HBV infection in persons 1-17 years of age and the prevalence of anti-HCV is low among persons aged ≥5 years. Efforts should continue to reach high coverage of the timely birth dose along with completion of the hepatitis B vaccine series. To reduce the chronic liver disease burden among adults, HBV and HCV testing and treatment as indicated might be restricted to pregnant women, blood donors, individuals with chronic liver diseases, and other groups with history of high-risk exposures.


Assuntos
Hepacivirus/imunologia , Vírus da Hepatite B/imunologia , Hepatite B Crônica/epidemiologia , Hepatite B Crônica/prevenção & controle , Hepatite C/epidemiologia , Hepatite C/prevenção & controle , Vacinação , Adolescente , Adulto , Butão/epidemiologia , Biomarcadores/sangue , Criança , Pré-Escolar , Análise por Conglomerados , Estudos Transversais , Feminino , Antígenos de Superfície da Hepatite B/sangue , Hepatite B Crônica/sangue , Hepatite B Crônica/transmissão , Hepatite C/sangue , Hepatite C/transmissão , Anticorpos Anti-Hepatite C/sangue , Humanos , Lactente , Transmissão Vertical de Doença Infecciosa/prevenção & controle , Masculino , Prevalência , Inquéritos e Questionários , Adulto Jovem
17.
Anticancer Res ; 40(7): 3983-3990, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32620641

RESUMO

BACKGROUND/AIM: Few studies have studied micro hepatic vein invasion in hepatocellular carcinoma (HCC). We explored the correlation between hepatic vein invasion and hepatitis B/C virus infection. PATIENTS AND METHODS: Between April 2000 and February 2018, 869 patients underwent liver resection for HCC at a single center. The patients were divided into two groups: those with micro hepatic vein invasion (VV+) and those without (VV-). The clinical data, overall survival (OS) and correlations with the presence of hepatitis B and C viruses were investigated. RESULTS: There were 817 VV- patients and 43 VV+ patients. OS was 66.2 months for VV- patients and 9.9 months for VV+ patients (p=0.0010). VV+ patients had significantly higher levels of serum HBV DNA (p=0.016). CONCLUSION: HCC patients with micro hepatic vein invasion showed significantly shorter OS. A higher level of HBV DNA appears to be a risk factor for micro hepatic vein invasion.


Assuntos
Carcinoma Hepatocelular/patologia , Veias Hepáticas/patologia , Neoplasias Hepáticas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos Virais/sangue , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/virologia , DNA Viral/sangue , Feminino , Hepacivirus/genética , Hepacivirus/imunologia , Hepatite B/patologia , Hepatite B/virologia , Vírus da Hepatite B/genética , Vírus da Hepatite B/imunologia , Hepatite C/patologia , Hepatite C/virologia , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Adulto Jovem
18.
BMC Infect Dis ; 20(1): 529, 2020 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-32698841

RESUMO

BACKGROUND: The risk of viral hepatitis among healthcare students (HCSs) is greater than that among the general population. Therefore, this study was conducted to investigate the seroprevalence of the hepatitis A virus (HAV), hepatitis B virus (HBV) and hepatitis C virus (HCV) among first-year HCSs at a university in Turkey and as a secondary objective, to determine the factors associated with HAV and HBV seropositivity. METHODS: This cross-sectional study was performed in first-year HCSs in Izmir, western Turkey. Data were collected using a self-administered questionnaire including items on sociodemographic characteristics, medical history, and hygiene. A total of 650 HCSs were tested for the HAV, HBV and HCV markers. Categorical variables were compared using the chi-square test. The association between independent variables and anti-HAV seropositivity and anti-HBs seropositivity was assessed by multinomial logistic regression analysis. RESULTS: The overall frequency of total anti-HAV seropositivity was 34.9%. HBsAg, total anti-HBc and anti-HBs seropositivity were found in 0.3, 1.2 and 93.7% of samples, respectively. All of the HCSs were negative for anti-HCV. Total anti-HAV seropositivity was found to be 1.73 times higher in those ≥21 years old, and it was 1.61 times higher in those who perceived their economic status to be average and 2.75 times higher in those who perceived their economic status to be low. Total anti-HAV seropositivity was found to be 4.37 times higher in those who lived in provinces with intermediate human development index levels. Total anti-HBs seropositivity was found to be 2.48 times higher in those ≤20 years old, and it was 2.13 times higher in those who perceived their economic status to be average. CONCLUSIONS: Approximately two out of three HCSs were susceptible to HAV infection. Since HCSs are at high risk for HAV infection, they should be vaccinated before medical clerkships begin. Our results indicate that there is a high prevalence of anti-HBs seropositivity among HCSs. This result may be largely attributed to the implementation of a successful vaccination program in Turkey since 1998.


Assuntos
Hepacivirus/imunologia , Vírus da Hepatite A/imunologia , Hepatite A/epidemiologia , Vírus da Hepatite B/imunologia , Hepatite B/epidemiologia , Hepatite C/epidemiologia , Estudantes de Medicina , Adolescente , Adulto , Estudos Transversais , Feminino , Hepatite A/sangue , Hepatite A/virologia , Hepatite B/sangue , Hepatite B/virologia , Anticorpos Anti-Hepatite B/sangue , Antígenos de Superfície da Hepatite B/sangue , Hepatite C/sangue , Hepatite C/virologia , Humanos , Programas de Imunização , Masculino , Prevalência , Autorrelato , Estudos Soroepidemiológicos , Turquia/epidemiologia , Adulto Jovem
19.
PLoS One ; 15(7): e0223087, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32692782

RESUMO

Both Human T-lymphotropic virus type 1 (HTLV-1) and hepatitis C virus (HCV) are endemic in Brazil. In Salvador, the capital of the state of Bahia, 2% and 1.5% of the general population is infected with HTLV-1 or HCV. This study aimed to estimate the prevalence and the distribution of HTLV/HCV coinfection in Bahia. This cross-sectional study was conducted at the Central Laboratory of Public Health for the state of Bahia (LACEN-BA). All samples in the LACEN database submitted to serological testing for anti-HCV (chemiluminescence) and anti-HTLV-1/2 (chemiluminescence/ELISA and Western blot) from 2004 to 2013 were included. Infection rate was expressed as the number of infected individuals per 100,000 inhabitants in a given municipality; municipalities were grouped by microregion for further analysis. A total of 120,192 samples originating from 358 of the 417 municipalities in Bahia (85.8%) were evaluated. The overall HCV coinfection rate in HTLV-positive was 14.31% [2.8 (ranging from 0.4 to 8.0) per 100,000 inhabitants.] Twenty-one (5%) of the municipalities reported at least one case of HTLV/HCV coinfection. Most cases (87%) were concentrated in three microregions (Salvador: 79%, Ilhéus/Itabuna: 5%, Porto Seguro: 3%). Coinfection occurred more frequently in males (51%) with a mean age of 59 [(IQR): 46-59] years. HTLV/HCV coinfection in the state of Bahia was more frequently found among males living in the microregions of Salvador, Ilhéus/Itabuna and Porto Seguro, all of which are known to be endemic for HTLV infection.


Assuntos
Coinfecção/epidemiologia , Infecções por HTLV-I/epidemiologia , Hepatite C/epidemiologia , Adulto , Anticorpos Antivirais/sangue , Brasil/epidemiologia , Coinfecção/diagnóstico , Feminino , Genótipo , Infecções por HTLV-I/diagnóstico , Hepacivirus/genética , Hepacivirus/imunologia , Hepatite C/diagnóstico , Anticorpos Anti-Hepatite C/sangue , Vírus Linfotrópico T Tipo 1 Humano/genética , Vírus Linfotrópico T Tipo 1 Humano/imunologia , Humanos , Masculino , Prevalência , Estudos Retrospectivos
20.
Sci Rep ; 10(1): 10388, 2020 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-32587314

RESUMO

Chronic viral hepatitis C (CHC) and its complications have a negative effect on patient's quality of life. We evaluated the impact of a successful interferon-free treatment on the quality of life of patients with obesity and metabolic disorders in the context of immunological disturbances. Twenty overweight or obese (BMI > 25) patients with CHC were tested before the therapy and after a successful treatment regimen. After the therapy, patient's emotional well-being improved (p = 0.02), while physical well-being remained unchanged. There was a decrease of patient's liver fibrosis and an increase of steatosis along with body mass. Among HCV-infected individuals, the expression of toll-like receptor 3 (TLR3) on lymphocytes was higher than in the control group (p = 0.03), but it decreased (p = 0.001) after the treatment. There was also a decrease of the intensity of immunofluorescence of FoxP3+ after the treatment (p = 0.04). Our study showed an improvement in mental aspects of patient's quality of life after the treatment. Unfortunately, probably due to rapid immunological changes, patient's BMI, serum cholesterol levels and hepatic steatosis have a tendency to increase and may lead to cardiovascular and other complications, like hepatocellular carcinoma.


Assuntos
Antivirais/uso terapêutico , Hepacivirus/imunologia , Hepatite C Crônica/imunologia , Doenças Metabólicas/fisiopatologia , Neoplasias/tratamento farmacológico , Obesidade/fisiopatologia , Qualidade de Vida , Adulto , Idoso , Índice de Massa Corporal , Estudos de Casos e Controles , Feminino , Seguimentos , Hepacivirus/efeitos dos fármacos , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/epidemiologia , Hepatite C Crônica/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/patologia , Prognóstico , Adulto Jovem
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