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2.
Medicine (Baltimore) ; 98(51): e18334, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31860986

RESUMEN

The aim of this study was to evaluate the effectiveness of hospital-based hepatitis C epidemic surveillance initiated by China's CDC STD/AIDS (National Center for AIDS/STD Control and Prevention of Chinese Center for Disease Control and Prevention) Prevention and Control Center in 2017.A total of 104,666 anti-hepatitis C virus (HCV) and 633 HCV-RNA detection records in our hospital from 2014 to 2017 were used to analyze the anti-HCV and HCV-RNA detection rates and positive rates in patients before and after implementation of epidemic surveillance.We found that the estimated HCV positive rate was 0.395% in all patients, and this rate increased to 0.533% after the pilot research. The positive rates of anti-HCV were significantly enhanced, although certain differences were observed among different departments. Significant increase of positive rate of HCV-RNA was only found in the inpatients from nonsurgical departments. Eighty-one cases were diagnosed after this pilot research, exceeding the 70 total cases in the previous 3 years. Most cases were diagnosed by nonsurgical departments; the upward trend of the cases diagnosed by surgical departments cannot be ignored.Our study indicates expanding anti-HCV and HCV-RNA detection in the target populations in hospitals is a useful strategy for finding more occult HCV infection. In addition, our results provide useful pilot data of the seroepidemiology of Hepatitis C for the special populations in hospitals, which will provide valuable information for public health research.


Asunto(s)
Hepatitis C/diagnóstico , Hepatitis C/epidemiología , Vigilancia de la Población , Anticuerpos/sangre , China/epidemiología , Hepacivirus/genética , Hepacivirus/inmunología , Humanos , Inmunoglobulina G/inmunología , Pacientes Internos , Pacientes Ambulatorios , Proyectos Piloto , ARN Viral/sangre , Estudios Seroepidemiológicos
3.
BMC Infect Dis ; 19(1): 932, 2019 Nov 05.
Artículo en Inglés | MEDLINE | ID: mdl-31690267

RESUMEN

BACKGROUND: Although DAAs hold promise to significantly reduce rates of chronic HCV infections, its eradication still requires development of an effective vaccine. Prolonged T cell responses and cross neutralizing antibodies are ideal for vaccination against the infection. We aimed to design and synthesize a 6 multi epitope peptide vaccine candidate and provide evidence for production of extended cellular and neutralizing Abs in mice. METHODS: Six peptides derived from conserved epitopes in E1, E2 (n = 2),NS4B, NS5A and NS5B were designed, synthesized in a multiple antigenic peptide (MAP) form and administered w/o adjuvant to BALB/c mice as HCVp6-MAP at doses ranging from 800 ng to 16 µg. Humoral responses to structural epitopes were assayed by ELISA at different times after injection. ELISpot assay was used to evaluate IFN É£ producing CD4+/ CD8+ T- lymphocytes at extended durations i.e. > 20 weeks. Viral neutralization by mice sera was tested for genotypes 2a (JFH1) and a chimeric 2a/4a virus (ED43/JFH1) in HCVcc culture. RESULTS: HCVp6-MAP confers potent viral neutralization and specific cellular responses at > 1600 ng/ animal for at least 20 weeks. CONCLUSION: We report on a promising anti HCV vaccine for future studies on permissive hosts and in clinical trials.


Asunto(s)
Anticuerpos Neutralizantes/sangre , Epítopos/inmunología , Hepacivirus/inmunología , Anticuerpos contra la Hepatitis C/sangre , Inmunidad Celular , Péptidos/inmunología , Secuencia de Aminoácidos , Animales , Linfocitos T CD4-Positivos/citología , Linfocitos T CD4-Positivos/metabolismo , Linfocitos T CD8-positivos/citología , Linfocitos T CD8-positivos/metabolismo , Línea Celular , Genotipo , Hepacivirus/genética , Humanos , Interferón gamma/metabolismo , Ratones , Ratones Endogámicos BALB C , Péptidos/síntesis química , Vacunas de Subunidad/inmunología
4.
BMC Infect Dis ; 19(1): 896, 2019 Oct 28.
Artículo en Inglés | MEDLINE | ID: mdl-31660879

RESUMEN

BACKGROUND: The advent of effective direct-acting antivirals (DAAs), has prompted an assessment of the French Hepatitis C virus (HCV) screening strategy, which historically targeted high-risk groups. One of the options put forward is the implementation of combined (i.e., simultaneous) HCV, Hepatitis B virus (HBV) and HIV screening for all adults at least once during their lifetime ("universal combined screening"). However, recent national survey-based data are lacking to guide decision-making regarding which new strategy to implement. Accordingly, we aimed to provide updated data for both chronic hepatitis C (CHC) and B (CHB) prevalence and for HCV and HBV screening history, using data from the BaroTest and 2016 Health Barometer (2016-HB) studies, respectively. METHODS: 2016-HB was a national cross-sectional phone based health survey conducted in 2016 among 20,032 randomly selected individuals from the general population in mainland France. BaroTest was a virological sub-study nested in 2016-HB. Data collected for BaroTest were based on home blood self-sampling on dried blood spots (DBS). RESULTS: From 6945 analyzed DBS, chronic hepatitis C (CHC) and B (CHB) prevalence was estimated at 0.30% (95% Confidence Interval (CI): 0.13-0.70) and 0.30% (95% CI: 0.13-0.70), respectively. The proportion of individuals aware of their status was estimated at 80.6% (95% CI: 44.2-95.6) for CHC and 17.5% (95% CI: 4.9-46.4) for CHB. Universal combined screening would involve testing between 32.6 and 85.3% of 15-75 year olds according to whether we consider only individuals not previously tested for any of the three viruses, or also those already tested for one or two of the viruses. CONCLUSIONS: Our data are essential to guide decision-making regarding which new HCV screening recommendation to implement in France. They also highlight that efforts are still needed to achieve the WHO's targets for eliminating these diseases. Home blood self-sampling may prove to be a useful tool for screening and epidemiological studies.


Asunto(s)
Pruebas con Sangre Seca , Hepatitis B/sangre , Hepatitis B/epidemiología , Hepatitis C Crónica/sangre , Hepatitis C Crónica/epidemiología , Tamizaje Masivo/métodos , Adolescente , Adulto , Anciano , Anticuerpos Antivirales/sangre , Concienciación , Estudios Transversales , Femenino , Francia/epidemiología , Infecciones por VIH/epidemiología , Hepacivirus/inmunología , Hepatitis B/psicología , Virus de la Hepatitis B/inmunología , Hepatitis C Crónica/psicología , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Adulto Joven
5.
Rev Soc Bras Med Trop ; 52: e20190202, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31596352

RESUMEN

INTRODUCTION: The prevalence of hepatitis C virus (HCV) infection is affected by demographic, virological, clinical, and lifestyle-related factors and varies in different regions in Brazil or worldwide. The present study aimed to clarify the epidemiological patterns of HCV infection in the interior region of Brazil. METHODS: This study was conducted in the Southern Triangle Macro-region of the state of Minas Gerais, Brazil, according to the guidelines of the National Program for the Prevention and Control of Viral Hepatitis. The participants answered a structured questionnaire on social and epidemiological factors. Immunochromatographic rapid tests were used for the qualitative detection of antibodies against HCV in whole blood (Alere HCV® Code 02FK10) in adult subjects by a free-standing method. RESULTS: Of 24,085 tested individuals, 184 (0.76%) were anti-HCV positive. The majority of anti-HCV-positive individuals were born between 1951 and 1980 (n=146 [79.3%]), with 68 women and 116 men. Identified risk factors included syringe and/or needle sharing (p = 0.003), being in prison (p = 0.004), and having tattoos or piercings (p = 0.005) and were significantly associated with the decade of birth. CONCLUSIONS: The study shows the importance of testing populations at risk for HCV infection, including incarcerated individuals, those with tattoos or piercings, those who share or have shared syringes or needles, and those in high-risk birth cohorts (1950s, 1960s, and 1970s) in the Southern Triangle Macro-region.


Asunto(s)
Hepacivirus/inmunología , Anticuerpos contra la Hepatitis C/sangre , Hepatitis C/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Brasil/epidemiología , Estudios Transversales , Monitoreo Epidemiológico , Femenino , Hepatitis C/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Factores de Riesgo , Adulto Joven
6.
Transplant Proc ; 51(9): 2856-2859, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31606186

RESUMEN

In order to bridge the gap between available organs and patients needing transplants, donor selection criteria for donors are increasingly being extended; the possibility of using organs from nonstandard risk donors has been introduced in many countries. This clearly poses considerable ethical issues that should be analyzed and taken into consideration by the competent bodies and institutions. In this article, we illustrate the Italian situation regarding the possibility of using organs from anti-hepatitis C virus (HCV) and HCV RNA-positive donors (anti-HCV+ve) in negative recipients (healthy subjects who have never come into contact with the hepatitis C virus) in light of the availability of new direct-acting antiviral drugs (DAAs) for hepatitis C treatment. We discuss the motivations behind the both favorable opinions of the Ethics Committee of the Italian National Institute of Health (Istituto Superiore di Sanità) and the Italian National Bioethics Committee (Comitato Nazionale per la Bioetica) discussing the main implications from an ethical point of view.


Asunto(s)
Selección de Donante/normas , Hepatitis C , Donantes de Tejidos/provisión & distribución , Trasplantes/provisión & distribución , Trasplantes/virología , Antivirales/uso terapéutico , Hepacivirus/inmunología , Hepatitis C/prevención & control , Humanos , Italia
7.
BMC Med ; 17(1): 175, 2019 09 18.
Artículo en Inglés | MEDLINE | ID: mdl-31530275

RESUMEN

BACKGROUND: The introduction of highly effective direct-acting antiviral (DAA) therapy for hepatitis C has led to calls to eliminate it as a public health threat through treatment-as-prevention. Recent studies suggest it is possible to develop a vaccine to prevent hepatitis C. Using a mathematical model, we examined the potential impact of a hepatitis C vaccine on the feasibility and cost of achieving the global WHO elimination target of an 80% reduction in incidence by 2030 in the era of DAA treatment. METHODS: The model was calibrated to 167 countries and included two population groups (people who inject drugs (PWID) and the general community), features of the care cascade, and the coverage of health systems to deliver services. Projections were made for 2018-2030. RESULTS: The optimal incidence reduction strategy was to implement test and treat programmes among PWID, and in settings with high levels of community transmission undertake screening and treatment of the general population. With a vaccine available, the optimal strategy was to include vaccination within test and treat programmes, in addition to vaccinating adolescents in settings with high levels of community transmission. Of the 167 countries modelled, between 0 and 48 could achieve an 80% reduction in incidence without a vaccine. This increased to 15-113 countries if a 75% efficacious vaccine with a 10-year duration of protection were available. If a vaccination course cost US$200, vaccine use reduced the cost of elimination for 66 countries (40%) by an aggregate of US$7.4 (US$6.6-8.2) billion. For a US$50 per course vaccine, this increased to a US$9.8 (US$8.7-10.8) billion cost reduction across 78 countries (47%). CONCLUSIONS: These findings strongly support the case for hepatitis C vaccine development as an urgent public health need, to ensure hepatitis C elimination is achievable and at substantially reduced costs for a majority of countries.


Asunto(s)
Erradicación de la Enfermedad , Hepacivirus/inmunología , Hepatitis C/prevención & control , Modelos Teóricos , Vacunación , Vacunas contra Hepatitis Viral/uso terapéutico , Antivirales/economía , Antivirales/uso terapéutico , Erradicación de la Enfermedad/economía , Erradicación de la Enfermedad/organización & administración , Erradicación de la Enfermedad/normas , Erradicación de la Enfermedad/estadística & datos numéricos , Hepatitis C/economía , Hepatitis C/epidemiología , Hepatitis C Crónica/economía , Hepatitis C Crónica/epidemiología , Hepatitis C Crónica/prevención & control , Humanos , Incidencia , Salud Pública/economía , Salud Pública/métodos , Abuso de Sustancias por Vía Intravenosa/economía , Abuso de Sustancias por Vía Intravenosa/epidemiología , Abuso de Sustancias por Vía Intravenosa/virología , Vacunación/normas , Cobertura de Vacunación/economía , Cobertura de Vacunación/organización & administración , Vacunas contra Hepatitis Viral/economía
8.
PLoS Pathog ; 15(8): e1007949, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-31374104

RESUMEN

Host encounters with viruses lead to an innate immune response that must be rapid and broadly targeted but also tightly regulated to avoid the detrimental effects of unregulated interferon expression. Viral stimulation of host negative regulatory mechanisms is an alternate method of suppressing the host innate immune response. We examined three key mediators of the innate immune response: NF-KB, STAT1 and STAT2 during HCV infection in order to investigate the paradoxical induction of an innate immune response by HCV despite a multitude of mechanisms combating the host response. During infection, we find that all three are repressed only in HCV infected cells but not in uninfected bystander cells, both in vivo in chimeric mouse livers and in cultured Huh7.5 cells after IFNα treatment. We show here that HCV and Flaviviruses suppress the innate immune response by upregulation of PDLIM2, independent of the host interferon response. We show PDLIM2 is an E3 ubiquitin ligase that also acts to stimulate nuclear degradation of STAT2. Interferon dependent relocalization of STAT1/2 to the nucleus leads to PDLIM2 ubiquitination of STAT2 but not STAT1 and the proteasome-dependent degradation of STAT2, predominantly within the nucleus. CRISPR/Cas9 knockout of PDLIM2 results in increased levels of STAT2 following IFNα treatment, retention of STAT2 within the nucleus of HCV infected cells after IFNα stimulation, increased interferon response, and increased resistance to infection by several flaviviruses, indicating that PDLIM2 is a global regulator of the interferon response.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/fisiología , Infecciones por Flavivirus/inmunología , Flavivirus/inmunología , Hepacivirus/inmunología , Hepatitis C/inmunología , Inmunidad Innata/inmunología , Proteínas con Dominio LIM/fisiología , Factor de Transcripción STAT2/metabolismo , Animales , Antivirales/farmacología , Flavivirus/efectos de los fármacos , Infecciones por Flavivirus/tratamiento farmacológico , Infecciones por Flavivirus/virología , Hepacivirus/efectos de los fármacos , Hepatitis C/tratamiento farmacológico , Hepatitis C/virología , Humanos , Inmunidad Innata/efectos de los fármacos , Interferón-alfa/farmacología , Proteínas con Dominio LIM/genética , Proteínas con Dominio LIM/metabolismo , Ratones , Ratones Noqueados , Proteínas de Microfilamentos/genética , Proteínas de Microfilamentos/metabolismo , FN-kappa B , Factor de Transcripción STAT2/genética , Transducción de Señal
9.
BMC Public Health ; 19(1): 1038, 2019 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-31375104

RESUMEN

BACKGROUND: Age cohort screening for hepatitis C virus (HCV) might be an effective strategy if the majority of undiagnosed cases are concentrated in a particular age group. The objective of this study was to determine HCV prevalence in different age cohorts of the general population in the Central European part of Russia and second, to assess feasibility of HCV antigen testing for community screening programs. METHODS: Sera from 2027 volunteers were tested for anti-HCV (Architect Anti-HCV, Abbott Laboratories). All anti-HCV reactive samples were confirmed in an immunoblot and tested for HCV Ag (ARCHITECT HCV Ag, Abbott Laboratories), HCV RNA and HCV viral load. RESULTS: Out of 31 individuals with anti-HCV reactive result, 22 (71%) were confirmed by immunoblot, six were false positives and three were indeterminate. Active infection was observed in 73% of anti-HCV confirmed positives. Five out of 16 individuals had low HCV-RNA levels (< 10,000 IU/mL) and one of those had a very low level (594 IU/mL). Agreement between HCV Ag and HCV RNA was 100%. Total anti-HCV and active HCV infection rates were 1.09% (22/2027) and 0.79% (16/2027), respectively. The peak rates were observed in people 60 years or older (anti-HCV: 2.84% [95% CI: 1.66-4.74%], 13/319; HCV RNA/HCV Ag: 2.23% [95% CI: 1.20-4.00%], 10/319). CONCLUSIONS: Overall HCV prevalence is low, except in people 60 years or older. The latter should be considered as a target group for HCV screening. The high agreement between HCV RNA and HCV Ag suggests the utility of HCV Ag testing to confirm active infection in screening programs.


Asunto(s)
Servicios de Salud Comunitaria , Hepatitis C/epidemiología , Tamizaje Masivo/métodos , Adolescente , Adulto , Anciano , Niño , Preescolar , Femenino , Hepacivirus/genética , Hepacivirus/inmunología , Hepacivirus/aislamiento & purificación , Hepatitis C/sangre , Antígenos de la Hepatitis C/sangre , Humanos , Lactante , Masculino , Persona de Mediana Edad , Prevalencia , ARN Viral/sangre , Federación de Rusia/epidemiología , Adulto Joven
10.
J Immunoassay Immunochem ; 40(5): 528-539, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31378189

RESUMEN

Introduction: Hepatitis C virus (HCV) infects about 0.5% to 2.3% of the world population with most of the cases occurring in developing countries. It is primarily transmitted through transfusion of blood and blood products. There exists dearth of information on burden and circulation of HCV and their attendant health challenges in Nigeria. This study was therefore designed to determine the seroprevalence rate and risk of HCV transmission among blood donors in Lagos State Nigeria. Methodology: Blood samples were collected between January 2002 and December 2006 from 3,002 consenting (Male = 2,922; Female = 80; Age range = 18-63; Median age = 32 years) donors in five selected public hospitals' blood donation centers between 2002 and 2006. Sera was tested for anti-HCV by ELISA technique. Demographic and other relevant information were obtained by a semi-structured questionnaire to assess risk factors for HCV transmission. Results: This study found an overall rate of 3.1% for anti-HCV among the blood donors sampled. Highest rate of 6.0% for HCV was found among participants age ranged ≥50 years and lowest in the age group 40-49 years. Prevalence of HCV was higher in female (6.3%) than in male (3.0%) and was 0.21 times less risky in female compared to their male counterparts (OR = 1.29, 95%CI 0.11-1.31). By location, MSCH had the highest HCV rate (3.9%) and lowest (2.1%) in GHOA. Sharing of sharps for tattoo/tribal markings had a statistical association (p = .0379) with HCV infection. However, no significant difference was found by gender (CI = 0.99-2.01; p = .1002), age (CI = 0.79-1.55; p = .1001) and location (p = .5326). Conclusion: The relatively high prevalence of HCV infection detected and the risk of transmission among blood donors in this study are of public health importance. Hence, the institution of appropriate measures to stem down the trend of HCV circulation among this population in Nigeria is therefore advocated.


Asunto(s)
Donantes de Sangre , Hepacivirus/inmunología , Hepacivirus/aislamiento & purificación , Hepatitis C/sangre , Hepatitis C/transmisión , Adulto , Femenino , Hepatitis C/epidemiología , Hepatitis C/virología , Humanos , Masculino , Persona de Mediana Edad , Nigeria/epidemiología , Factores de Riesgo , Estudios Seroepidemiológicos , Adulto Joven
11.
Artículo en Inglés | MEDLINE | ID: mdl-31307313

RESUMEN

A 38-year-old female with tricuspid atresia and normally related great arteries, initially palliated with Björk modified Fontan, and ultimately converted to extracardiac conduit Fontan, with a history of ventricular tachycardia and hepatitis C virus (HCV) treated with sofosbuvir/ledipasvir, was referred to our center for consideration of combined heart and liver transplantation. The patient's blood group was O with panel reactive antibodies of 52%. She consented to consideration of HCV-positive donors. Fifteen days later, an HCV-positive donor was identified, and she underwent heart transplantation with pulmonary artery reconstruction performed jointly by adult and pediatric transplant surgeons. To our knowledge, this the first time an HCV-positive donor heart has been to transplant an adult with congenital heart disease.


Asunto(s)
Cardiopatías Congénitas/cirugía , Trasplante de Corazón/métodos , Hepacivirus/inmunología , Anticuerpos contra la Hepatitis C/inmunología , Hepatitis C/virología , Donantes de Tejidos , Adulto , Femenino , Anticuerpos contra la Hepatitis C/sangre , Humanos , Receptores de Trasplantes , Carga Viral
12.
APMIS ; 127(9): 642-652, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31274210

RESUMEN

Hepatitis C virus (HCV) infection always leads to chronic hepatitis via dysregulation of host immunity. Notch signaling also modulates the response of monocytes/macrophages. Thus, we aimed to investigate the regulatory role of Notch signaling to CD14+ monocytes. Forty patients with chronic hepatitis C and twenty normal controls (NC) were enrolled. CD14+ monocytes and CD4+ T cells were purified from peripheral bloods. Notch receptors' mRNA expression in CD14+ monocytes was semi-quantified by real-time PCR. Cytokine production by CD14+ monocytes in response to γ-secretase inhibitor (GSI) was investigated by ELISA. GSI-induced CD14+ monocytes activity to HCV clearance in Huh7.5 cells and to CD4+ T cell differentiation was also assessed in direct and indirect contact co-culture system. Notch1 mRNA relative level was approximately 10-fold elevated in CD14+ monocytes from chronic hepatitis C patients when compared with NC. GSI stimulation resulted in enhanced cytokines production by CD14+ monocytes from chronic hepatitis C patients. GSI-stimulated CD14+ monocytes from chronic hepatitis C patients induced suppression of HCV RNA replication in both direct and indirect contact co-culture system of CD14+ monocytes and HCVcc-infected Huh7.5 cells, and this process was accompanied by elevation of interferon-γ production but not increased target cell death. Moreover, GSI stimulation also enhanced CD14+ monocytes-induced Th1 and Th17 cells activation, and this process required direct cell-to-cell contact. Effective antiviral therapy down-regulated Notch1 mRNA expression and promoted cytokine production by CD14+ monocytes from chronic hepatitis C. Current data revealed an important immunoregulatory property of Notch signaling to CD14+ monocytes in chronic HCV infection.


Asunto(s)
Hepatitis C Crónica/inmunología , Monocitos/inmunología , Receptor Notch1/inmunología , Transducción de Señal/inmunología , Adulto , Linfocitos T CD4-Positivos , Diferenciación Celular/inmunología , Técnicas de Cocultivo , Regulación hacia Abajo/inmunología , Femenino , Hepacivirus/inmunología , Humanos , Activación de Linfocitos/inmunología , Masculino , Persona de Mediana Edad , Células TH1/inmunología , Células Th17/inmunología , Adulto Joven
13.
Arch Virol ; 164(9): 2243-2253, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31179516

RESUMEN

This study aimed to assess the seroprevalence, viraemia and genotype distribution of hepatitis C virus (HCV) in a region in Central-West Tunisia. A door-to-door cross-sectional study was conducted on a randomly selected sample. A total of 3178 individuals aged 5 to 74 years and members of 935 families were investigated. Seroprevalence of HCV was assessed using ELISA tests. The viral load was determined by real-time RT-PCR, and HCV genotyping was conducted by amplification and sequencing in the NS5b genomic region. The global prevalence of HCV antibodies was 3.32% (95% confidence interval [CI]: 2.72-4.00). It was significantly higher in women: 4.47% vs. 2.16% in men, p = 0.001. Seroprevalence increased with age, and the highest rates were found in the 50- to 59-year-old age group (12.90%, 95% CI: 9.45-16.86), suggesting a cohort effect with very low contribution of intrafamilial transmission. Genotyping showed a predominance of subtype 1b (84.6%), with cocirculation of subtypes 2c (9.6%), 1a (1.9%), 1d (1.9%) and 2k (1.9%), similar to the previously reported genotype distribution in Tunisia and with no genetic clusters specific to the study region. These results indicate a higher endemicity of HCV infection when compared to the previously reported nationwide surveillance data. This study provides valuable data that can contribute to current strategies to eliminate hepatitis C.


Asunto(s)
Hepacivirus/aislamiento & purificación , Hepatitis C/epidemiología , Adolescente , Adulto , Anciano , Niño , Preescolar , Estudios Transversales , Femenino , Genotipo , Hepacivirus/clasificación , Hepacivirus/genética , Hepacivirus/inmunología , Hepatitis C/sangre , Hepatitis C/virología , Anticuerpos contra la Hepatitis C/sangre , Humanos , Masculino , Persona de Mediana Edad , Filogenia , Prevalencia , Estudios Seroepidemiológicos , Túnez/epidemiología , Proteínas no Estructurales Virales/genética , Proteínas no Estructurales Virales/inmunología , Adulto Joven
14.
Braz J Infect Dis ; 23(3): 173-181, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31228459

RESUMEN

BACKGROUND: The prison system in Paraná, Brazil, is experiencing serious problems related to the increasing number of prisoners. Control of hepatitis C virus (HCV) has become more intense because the incarcerated population is considered a high-risk group for contagious diseases due to the favorable conditions found in prisons for the spread of these morbidities. The objective of this study was to identify features associated with hepatitis C infection among male prisoners in correctional institutions of Paraná state, Brazil. METHODS: This was a case-control study (27 cases and 54 controls) of men incarcerated in 11 penitentiaries in Paraná, Brazil. Information was obtained through a questionnaire in a cross-sectional epidemiological survey on HCV infection during the period from May 2015 to December 2016. Eligible men were recruited after testing positive for anti-HCV antibodies. Cases and controls were selected based on serological results of enzyme-linked immunosorbent assays and were matched by age, location of the penitentiary, and time in prison. Logistic regression analysis was used to identify risk factors for HCV seropositivity. RESULTS: The main significant independent risk factor for the acquisition of HCV infection was the use of injectable drugs (OR = 4.00; 95%CI:1.41-11.35; p < 0.001). CONCLUSIONS: This study provides evidence that HCV infection is associated with drug use by this population. This information is pivotal for tailoring prevention programs and guiding specific socioeducational measures that aim to reduce or prevent HCV transmission within the prison setting.


Asunto(s)
Hepacivirus/inmunología , Anticuerpos contra la Hepatitis C/sangre , Hepatitis C/epidemiología , Prisioneros/estadística & datos numéricos , Adulto , Brasil/epidemiología , Métodos Epidemiológicos , Humanos , Masculino , Persona de Mediana Edad , Estudios Seroepidemiológicos , Factores Socioeconómicos
15.
Diagn Microbiol Infect Dis ; 95(2): 149-151, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31204109

RESUMEN

We evaluated the performance of the OraQuick® HCV Rapid Antibody Test (Orasure Technologies, Inc., Bethlehem, PA) on oral fluid specimens when used by patients for self-testing. Participants used a set of instructions, self-collected their specimens, and interpreted their result. A researcher interpreted the test simultaneously and independently. Participants' true antibody status was determined by reviewing medical records or by a venipuncture blood sample. Sensitivity, specificity, and κ statistic were calculated. The sample included 95 participants (48 male and 47 female). Sensitivity and specificity on self-collected oral fluid samples were 88.4%% (95% CI, 74.9-96.1) and 100% (95% CI, 93-100), respectively, when patients interpreted the test results. Sensitivity and specificity were 97.7% (95% CI, 88-99.9) and 98% (95% CI, 89.6-100), respectively, when trained staff interpreted the result. κ statistic was 0.89 (95% CI 0.80-0.98). The rapid HCV test kit showed good performance when used for self-testing of oral fluid specimens.


Asunto(s)
Hepacivirus/inmunología , Anticuerpos contra la Hepatitis C/análisis , Hepatitis C/diagnóstico , Inmunoensayo/métodos , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Hepacivirus/aislamiento & purificación , Hepatitis C/virología , Humanos , Masculino , Persona de Mediana Edad , Juego de Reactivos para Diagnóstico , Reproducibilidad de los Resultados , Saliva/inmunología , Saliva/virología , Autocuidado , Sensibilidad y Especificidad , Manejo de Especímenes , Adulto Joven
16.
Nature ; 571(7764): 265-269, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-31207605

RESUMEN

Cytotoxic T cells are essential mediators of protective immunity to viral infection and malignant tumours and are a key target of immunotherapy approaches. However, prolonged exposure to cognate antigens often attenuates the effector capacity of T cells and limits their therapeutic potential1-4. This process, known as T cell exhaustion or dysfunction1, is manifested by epigenetically enforced changes in gene regulation that reduce the expression of cytokines and effector molecules and upregulate the expression of inhibitory receptors such as programmed cell-death 1 (PD-1)5-8. The underlying molecular mechanisms that induce and stabilize the phenotypic and functional features of exhausted T cells remain poorly understood9-12. Here we report that the development and maintenance of populations of exhausted T cells in mice requires the thymocyte selection-associated high mobility group box (TOX) protein13-15. TOX is induced by high antigen stimulation of the T cell receptor and correlates with the presence of an exhausted phenotype during chronic infections with lymphocytic choriomeningitis virus in mice and hepatitis C virus in humans. Removal of its DNA-binding domain reduces the expression of PD-1 at the mRNA and protein level, augments the production of cytokines and results in a more polyfunctional T cell phenotype. T cells with this deletion initially mediate increased effector function and cause more severe immunopathology, but ultimately undergo a massive decline in their quantity, notably among the subset of TCF-1+ self-renewing T cells. Altogether, we show that TOX is a critical factor for the normal progression of T cell dysfunction and the maintenance of exhausted T cells during chronic infection, and provide a link between the suppression of effector function intrinsic to CD8 T cells and protection against immunopathology.


Asunto(s)
Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/patología , Hepatitis C Crónica/inmunología , Hepatitis C Crónica/virología , Proteínas del Grupo de Alta Movilidad/metabolismo , Proteínas de Homeodominio/metabolismo , Coriomeningitis Linfocítica/inmunología , Coriomeningitis Linfocítica/virología , Animales , Proliferación Celular , Enfermedad Crónica , Citocinas/inmunología , Citocinas/metabolismo , Epigénesis Genética , Femenino , Regulación de la Expresión Génica/inmunología , Hepacivirus/inmunología , Factor Nuclear 1-alfa del Hepatocito/metabolismo , Humanos , Memoria Inmunológica , Virus de la Coriomeningitis Linfocítica/inmunología , Masculino , Ratones , Fenotipo , Timocitos/citología , Timocitos/inmunología , Transcripción Genética
17.
Nat Commun ; 10(1): 2073, 2019 05 06.
Artículo en Inglés | MEDLINE | ID: mdl-31061402

RESUMEN

Isolation of broadly neutralizing human monoclonal antibodies (HmAbs) targeting the E2 glycoprotein of Hepatitis C virus (HCV) has sparked hope for effective vaccine development. Nonetheless, escape mutations have been reported. Ideally, a potent vaccine should elicit HmAbs that target regions of E2 that are most difficult to escape. Here, aimed at addressing this challenge, we develop a predictive in-silico evolutionary model for E2 that identifies one such region, a specific antigenic domain, making it an attractive target for a robust antibody response. Specific broadly neutralizing HmAbs that appear difficult to escape from are also identified. By providing a framework for identifying vulnerable regions of E2 and for assessing the potency of specific antibodies, our results can aid the rational design of an effective prophylactic HCV vaccine.


Asunto(s)
Anticuerpos Monoclonales/inmunología , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , Hepacivirus/inmunología , Hepatitis C/inmunología , Proteínas del Envoltorio Viral/inmunología , Simulación por Computador , Diseño de Drogas , Mapeo Epitopo/métodos , Epítopos/genética , Epítopos/inmunología , Evolución Molecular , Hepacivirus/genética , Hepatitis C/prevención & control , Hepatitis C/virología , Humanos , Modelos Biológicos , Proteínas del Envoltorio Viral/genética , Vacunas contra Hepatitis Viral/inmunología
18.
Mol Immunol ; 111: 152-161, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-31054409

RESUMEN

Despite successful anti-viral (DAAs) treatment of Hepatitis C virus (HCV) infection, recent data indicated the need for an effective vaccine. Preexisting anti-vector immunity is an obstacle for application of live vectors for antigen delivery and development of effective T-cell based HCV vaccines. Herein, we report construction of recombinant Leishmania tarentolae, a lizard (non-human) parasite, expressing an HCV polytope DNA, PT-NT(gp96), encoding for several immunogenic HCV epitopes and evaluation of its immunogenicity in three different prime/boost immunization groups (G) of BALB/c mice. Homologous prime/boost immunization by L.tarentolae-PT-NT(gp96) either with or without CpG (G1 and G2 respectively) and heterologous immunization with a PT-NT(gp96) encoding-pCDNA plasmid followed by L.tarentolae-PT-NT (G3) was undertaken. Immune responses were measured three and nine weeks (W) post immunization. Splenocytes (cultured with antigen-stimulant) of mice in G1 showed the highest percentage of specific CTL-cytolytic activity compared to G2 and G3 at both short (W3:70.98% versus 41.29% and 13.12%) and long (W9: 50% versus 24.5% and 20%) term periods, accompanied with high levels of secreted IFN-γ. Comparison of IFN-γ, IL-4, IL-17 and TNF-α cytokines levels obtained from the supernatant of antigen-stimulated splenocytes as well as antibodies level (as IgG1/IgG2a ratio; obtained from sera of immunized mice) indicated higher Th1 oriented responses for G1, G2 groups and balanced Th1-Th17 for G3. Results indicated the potential of L.tarentolae (+CpG), as a non-pathogenic live vaccine vector, for delivery and enhancement of immune responses against HCV-polytope antigens.


Asunto(s)
Hepacivirus/inmunología , Hepatitis C/inmunología , Leishmania/inmunología , Células TH1/inmunología , Vacunas de ADN/inmunología , Animales , Citocinas/inmunología , ADN/inmunología , Inmunización/métodos , Ratones , Ratones Endogámicos BALB C , Células Th17/inmunología , Vacunación/métodos
19.
PLoS Pathog ; 15(5): e1007772, 2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-31100098

RESUMEN

Cumulative evidence supports a role for neutralizing antibodies contributing to spontaneous viral clearance during acute hepatitis C virus (HCV) infection. Information on the timing and specificity of the B cell response associated with clearance is crucial to inform vaccine design. From an individual who cleared three sequential HCV infections with genotypes 1b, 1a and 3a strains, respectively, we employed peripheral B cells to isolate and characterize neutralizing human monoclonal antibodies (HMAbs) to HCV after the genotype 1 infections. The majority of isolated antibodies, designated as HMAbs 212, target conformational epitopes on the envelope glycoprotein E2 and bound broadly to genotype 1-6 E1E2 proteins. Further, some of these antibodies showed neutralization potential against cultured genotype 1-6 viruses. Competition studies with defined broadly neutralizing HCV HMAbs to epitopes in distinct clusters, designated antigenic domains B, C, D and E, revealed that the selected HMAbs compete with B, C and D HMAbs, previously isolated from subjects with chronic HCV infections. Epitope mapping studies revealed domain B and C specificity of these HMAbs 212. Sequential serum samples from the studied subject inhibited the binding of HMAbs 212 to autologous E2 and blocked a representative domain D HMAb. The specificity of this antibody response appears similar to that observed during chronic infection, suggesting that the timing and affinity maturation of the antibody response are the critical determinants in successful and repeated viral clearance. While additional studies should be performed for individuals with clearance or persistence of HCV, our results define epitope determinants for antibody E2 targeting with important implications for the development of a B cell vaccine.


Asunto(s)
Anticuerpos Neutralizantes/inmunología , Diseño de Drogas , Hepacivirus/inmunología , Anticuerpos contra la Hepatitis C/inmunología , Hepatitis C/prevención & control , Proteínas del Envoltorio Viral/inmunología , Vacunas contra Hepatitis Viral/inmunología , Adulto , Secuencia de Aminoácidos , Anticuerpos Monoclonales/inmunología , Mapeo Epitopo , Genotipo , Hepatitis C/inmunología , Hepatitis C/virología , Humanos , Masculino , Pruebas de Neutralización , Estudios Prospectivos , Homología de Secuencia , Adulto Joven
20.
Arch Virol ; 164(8): 2083-2090, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31134354

RESUMEN

Although a few studies have been done on transmissible blood-borne viral infections in high-risk groups, little attention has been given to assessing the infection status of the general population in Afghanistan. To investigate the epidemiological status in the general population, we tested the serological markers of hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis delta virus (HDV), human immunodeficiency virus 1 (HIV-1) and human T-cell leukemia virus (HTLV) infections. In total, 492 samples were selected randomly from Nangarhar, Herat, Mazar-e Sharif, Kandahar, and Kabul from subjects between 25 and 70 years old. The samples were tested for the presence of HBsAg, anti-HBs, anti-HBc, anti-HDV, anti-HCV, anti-HIV-1 and anti-HTLV I/II antibodies using chemiluminescent immunoassays on Abbott Architect automated platforms. In addition, 220 HBsAg-positive samples identified among 5897 samples from the general population of the same regions of Afghanistan were included in the study and tested for both HBsAg and anti-HDV to investigate HDV prevalence in the country. Viral loads of HBV, HCV and HDV were determined in all seropositive samples using Ampliprep/Cobas TaqMan HBV, HCV, Test Roche (CA, USA), and an in-house method, respectively. Out of 492 samples, 31 (6.3%), 136 (27.6%) and 149 (30.3%) were found to be positive for HBsAg, anti-HBs and anti-HBc, respectively. Anti-HDV positivity was detected in five (2.1%) out of 234 HBsAg-positive samples (including 14 of the randomly selected samples that were not among the 220 previously identified as HBsAg positive). Only eight out of 492 (1.6%) subjects were positive for anti-HCV antibodies. Seven out of 489 (1.4%) were positive for anti-HIV-1 antibodies, and three out of 466 cases (0.6%) were positive for anti-HTLV I/II antibodies. These results suggest that Afghanistan is an intermediate endemic region for HBV, HDV and HCV infection. The prevalence of HIV-1 seems to be significantly higher than the global prevalence and that of the eastern Mediterranean region. In addition, the HTLV I/II screening results suggest that these viruses should be monitored in Afghanistan to confirm the trend observed in the current study.


Asunto(s)
Virosis/epidemiología , Adulto , Afganistán/epidemiología , ADN Viral/genética , Femenino , Infecciones por VIH/epidemiología , Infecciones por VIH/inmunología , VIH-1/inmunología , Hepacivirus/inmunología , Anticuerpos Antihepatitis/inmunología , Hepatitis B/epidemiología , Hepatitis B/inmunología , Anticuerpos contra la Hepatitis B/inmunología , Antígenos de Superficie de la Hepatitis B/inmunología , Virus de la Hepatitis B/inmunología , Hepatitis C/epidemiología , Hepatitis C/inmunología , Anticuerpos contra la Hepatitis C/inmunología , Hepatitis D/epidemiología , Hepatitis D/inmunología , Virus de la Hepatitis Delta/inmunología , Humanos , Masculino , Persona de Mediana Edad , Carga Viral/métodos , Virosis/inmunología
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