RESUMEN
OBJECTIVE: To stop transmission of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections in association with myocardial perfusion imaging (MPI) at a cardiology clinic. DESIGN: Outbreak investigation and quasispecies analysis of HCV hypervariable region 1 genome. SETTING: Outpatient cardiology clinic. PATIENTS: Patients undergoing MPI. METHODS: Case patients met definitions for HBV or HCV infection. Cases were identified through surveillance registry cross-matching against clinic records and serological screening. Observations of clinic practices were performed. RESULTS: During 2012-2014, 7 cases of HCV and 4 cases of HBV occurred in 4 distinct clusters among patients at a cardiology clinic. Among 3 case patients with HCV infection who had MPI on June 25, 2014, 2 had 98.48% genetic identity of HCV RNA. Among 4 case patients with HCV infection who had MPI on March 13, 2014, 3 had 96.96%-99.24% molecular identity of HCV RNA. Also, 2 clusters of 2 patients each with HBV infection had MPI on March 7, 2012, and December 4, 2014. Clinic staff reused saline vials for >1 patient. No infection control breaches were identified at the compounding pharmacy that supplied the clinic. Patients seen in clinic through March 27, 2015, were encouraged to seek testing for HBV, HCV, and human immunodeficiency virus. The clinic switched to all single-dose medications and single-use intravenous flushes on March 27, 2015, and no further cases were identified. CONCLUSIONS: This prolonged healthcare-associated outbreak of HBV and HCV was most likely related to breaches in injection safety. Providers should follow injection safety guidelines in all practice settings.
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Cardiología , Infección Hospitalaria , Hepatitis B , Hepatitis C , Infección Hospitalaria/epidemiología , Brotes de Enfermedades , Hepacivirus/genética , Hepatitis B/epidemiología , Virus de la Hepatitis B , Humanos , West VirginiaRESUMEN
Beginning in 2013, multiple local government areas (LGAs) in Borno and Yobe in northeast Nigeria and other parts of the Lake Chad basin experienced a violent insurgency that resulted in substantial numbers of isolated and displaced people. Northeast Nigeria represents the last known reservoir country of wild poliovirus (WPV) transmission in Africa, with detection of paralytic cases caused by serotype 1 WPV in 2016 in Borno and serotype 3 WPV in late 2012. Parts of Borno and Yobe are also problematic areas for transmission of serotype 2 circulating vaccine-derived polioviruses, and they continue to face challenges associated with conflict and inadequate health services in security-compromised areas that limit both immunization and surveillance activities. We model poliovirus transmission of all three serotypes for Borno and Yobe using a deterministic differential equation-based model that includes four subpopulations to account for limitations in access to immunization services and dynamic restrictions in population mixing. We find that accessibility issues and insufficient immunization allow for prolonged poliovirus transmission and potential undetected paralytic cases, although as of the end of 2019, including responsive program activities in the modeling suggest die out of indigenous serotypes 1 and 3 WPVs prior to 2020. Specifically, recent and current efforts to access isolated populations and provide oral poliovirus vaccine continue to reduce the risks of sustained and undetected transmission, although some uncertainty remains. Continued improvement in immunization and surveillance in the isolated subpopulations should minimize these risks. Stochastic modeling can build on this analysis to characterize the implications for undetected transmission and confidence about no circulation.
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Poliomielitis/transmisión , Poliomielitis/virología , Poliovirus , Medición de Riesgo/métodos , Niño , Preescolar , Brotes de Enfermedades/prevención & control , Humanos , Programas de Inmunización , Lactante , Nigeria/epidemiología , Vacuna Antipolio de Virus Inactivados , Vacuna Antipolio Oral , Vacunas contra Poliovirus , VacunaciónRESUMEN
In this study, the prevalence rate, associated risk factors and genetic diversity of hepatitis C virus (HCV) infection were determined among people who use crack from an international drug trafficking route in Central-West, Brazil. Blood samples were collected from 700 users of crack from Campo Grande and two border cities of Mato Grosso do Sul State and tested for HCV infection using serological and molecular testing methodologies. Anti-HCV was detected in 31/700 (4.5%, 95% CI: 2.9-6.0%) and HCV RNA in 26/31 (83.9%) of anti-HCV positive samples. Phylogenetic analysis of three HCV sub-genomic regions (5'UTR, NS5B and HVR-1) revealed the circulation of 1a (73.9%), 1b (8.7%) and 3a (17.4%) genotypes. Next-generation sequencing and phylogenetic analysis of intra-host viral populations of HCV HVR-1 showed a significant variation in intra-host genetic diversity among infected individuals, with 58.8% composed of more than one sub-population. Bayesian analysis estimated that the most recent common HCV ancestor for strains identified here was introduced to this region after 1975 following expansion of intravenous drug use in Brazil. Multivariate analyses showed that only 'ever having injected drugs' was independently associated with HCV infection. These results indicate an increasing spread of multiple HCV strains requiring public health intervention, such as harm reduction, testing services and treatment among crack users in this important border region of Central Brazil.
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Cocaína Crack , Tráfico de Drogas/estadística & datos numéricos , Hepacivirus/genética , Anticuerpos contra la Hepatitis C/sangre , Hepatitis C/epidemiología , ARN Viral/genética , Abuso de Sustancias por Vía Intravenosa/sangre , Adulto , Brasil/epidemiología , Estudios Transversales , Femenino , Variación Genética , Genotipo , Humanos , Masculino , Epidemiología Molecular , Filogenia , Prevalencia , Abuso de Sustancias por Vía Intravenosa/epidemiología , Adulto JovenRESUMEN
The number of wild poliovirus (WPV) cases in Nigeria decreased from 1,122 in 2006 to six WPV type 1 (WPV1) in 2014 (1). During August 2014-July 2016, no WPV cases were detected; during August-September 2016, four cases were reported in Borno State. An insurgency in northeastern Nigeria had resulted in 468,800 children aged <5 years deprived of health services in Borno by 2016. Military activities in mid-2016 freed isolated families to travel to camps, where the four WPV1 cases were detected. Oral poliovirus vaccine (OPV) campaigns were intensified during August 2016-December 2017; since October 2016, no WPV has been detected (2). Vaccination activities in insurgent-held areas are conducted by security forces; however, 60,000 unvaccinated children remain in unreached settlements. Since 2018, circulating vaccine-derived poliovirus type 2 (cVDPV2) has emerged and spread from Nigeria to Niger and Cameroon; outbreak responses to date have not interrupted transmission. This report describes progress in Nigeria polio eradication activities during January 2018-May 2019 and updates the previous report (2). Interruption of cVDPV2 transmission in Nigeria will need increased efforts to improve campaign quality and include insurgent-held areas. Progress in surveillance and immunization activities will continue to be reviewed, potentially allowing certification of interruption of WPV transmission in Africa in 2020.
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Erradicación de la Enfermedad , Brotes de Enfermedades/prevención & control , Poliomielitis/prevención & control , Vigilancia de la Población , Adolescente , Niño , Preescolar , Brotes de Enfermedades/estadística & datos numéricos , Humanos , Programas de Inmunización , Lactante , Nigeria/epidemiología , Poliomielitis/epidemiología , Poliovirus/genética , Poliovirus/aislamiento & purificación , Vacunas contra Poliovirus/administración & dosificación , Evaluación de Programas y Proyectos de Salud , Serogrupo , ViolenciaRESUMEN
BACKGROUND: A high prevalence (92.3%) of hepatitis C virus (HCV) co-infection among HIV patients identified during a large HIV outbreak associated with injection of oxymorphone in Indiana prompted genetic analysis of HCV strains. METHODS: Molecular epidemiological analysis of HCV-positive samples included genotyping, sampling intra-host HVR1 variants by next-generation sequencing (NGS) and constructing transmission networks using Global Hepatitis Outbreak and Surveillance Technology (GHOST). FINDINGS: Results from the 492 samples indicate predominance of HCV genotypes 1a (72.2%) and 3a (20.4%), and existence of 2 major endemic NS5B clusters involving 49.8% of the sequenced strains. Among 76 HIV co-infected patients, 60.5% segregated into 2 endemic clusters. NGS analyses of 281 cases identified 826,917 unique HVR1 sequences and 51 cases of mixed subtype/genotype infections. GHOST mapped 23 transmission clusters. One large cluster (nâ¯=â¯130) included 50 cases infected with ≥2 subtypes/genotypes and 43 cases co-infected with HIV. Rapid strain replacement and superinfection with different strains were found among 7 of 12 cases who were followed up. INTERPRETATION: GHOST enabled mapping of HCV transmission networks among persons who inject drugs (PWID). Findings of numerous transmission clusters, mixed-genotype infections and rapid succession of infections with different HCV strains indicate a high rate of HCV spread. Co-localization of HIV co-infected patients in the major HCV clusters suggests that HIV dissemination was enabled by existing HCV transmission networks that likely perpetuated HCV in the community for years. Identification of transmission networks is an important step to guiding efficient public health interventions for preventing and interrupting HCV and HIV transmission among PWID. FUND: US Centers for Disease Control and Prevention, and US state and local public health departments.
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Coinfección , Brotes de Enfermedades , Hepatitis C , Oximorfona , Población Rural , Abuso de Sustancias por Vía Intravenosa/epidemiología , Adulto , Coinfección/epidemiología , Coinfección/transmisión , Femenino , Infecciones por VIH/epidemiología , Infecciones por VIH/transmisión , Hepatitis C/epidemiología , Hepatitis C/transmisión , Humanos , Indiana/epidemiología , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Hepatitis B e antigen (HBeAg) is considered an indicator of high hepatitis B virus (HBV) replication. Performance characteristics of commercially available HBeAg assays have not been determined, thus it is unknown whether lack of HBeAg detection is because of test sensitivity or HBV basal core promoter and precore mutations. OBJECTIVES: We studied the correlation between HBeAg reactivity with HBV DNA levels in three commercially available HBeAg assays using 335 HBsAg and HBV DNA positive serum/plasma samples. STUDY DESIGN: Diagnostic sensitivity was determined by serial dilutions of a WHO HBeAg standard. The limit of HBeAg detection estimated through regression was 1 IU/mL (Centaur), 97 IU/mL (DiaSorin) and 129 IU/mL (Vitros). Of these 335 samples, enough sample volume remained in 253 samples for head-to-head comparison of the assays. RESULTS: 81 (32%), 41 (16%) and 36 (14%) of the samples were HBeAg positive by the Centaur, DiaSorin and Vitros assays, respectively. Compared to the FDA-approved Centaur assay the specificity of the other two assays was 98%, while sensitivity was 47% for the DiaSorin assay and 41% for the Vitros assay. Significant association was found between HBeAg positive samples and HBV DNA levels >20,000 IU/mL; 31% of HBeAg negative samples (Centaur) had HBV DNA levels >20,000 IU/mL, 26% of HBeAg positive samples had HBV DNA levels <20,000 IU/mL and 5 HBeAg positive samples had HBV DNA levels <2000 IU/mL. CONCLUSION: Discordance was seen between these HBeAg assays, indicating reliance on HBeAg alone as a marker of high HBV replication can be misleading. Detection and quantification of HBV DNA remains the accurate and reliable marker of HBV replication.
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Antígenos e de la Hepatitis B/sangre , Virus de la Hepatitis B/inmunología , Hepatitis B/diagnóstico , Inmunoensayo/métodos , Inmunoensayo/normas , Pruebas Serológicas/normas , ADN Viral/sangre , Femenino , Hepatitis B/sangre , Antígenos de Superficie de la Hepatitis B/sangre , Virus de la Hepatitis B/genética , Virus de la Hepatitis B/aislamiento & purificación , Humanos , Límite de Detección , MasculinoRESUMEN
Nearly three decades after the World Health Assembly launched the Global Polio Eradication Initiative in 1988, four of the six World Health Organization (WHO) regions have been certified polio-free (1). Nigeria is one of three countries, including Pakistan and Afghanistan, where wild poliovirus (WPV) transmission has never been interrupted. In September 2015, after >1 year without any reported WPV cases, Nigeria was removed from WHO's list of countries with endemic WPV transmission (2); however, during August and September 2016, four type 1 WPV (WPV1) cases were reported from Borno State, a state in northeastern Nigeria experiencing a violent insurgency (3). The Nigerian government, in collaboration with partners, launched a large-scale coordinated response to the outbreak (3). This report describes progress in polio eradication activities in Nigeria during January-December 2017 and updates previous reports (3-5). No WPV cases have been reported in Nigeria since September 2016; the latest case had onset of paralysis on August 21, 2016 (3). However, polio surveillance has not been feasible in insurgent-controlled areas of Borno State. Implementation of new strategies has helped mitigate the challenges of reaching and vaccinating children living in security-compromised areas, and other strategies are planned. Despite these initiatives, however, approximately 130,000-210,000 (28%-45%) of the estimated 469,000 eligible children living in inaccessible areas in 2016 have not been vaccinated. Sustained efforts to optimize surveillance and improve immunization coverage, especially among children in inaccessible areas, are needed.
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Erradicación de la Enfermedad , Poliomielitis/prevención & control , Vacunas contra Poliovirus/administración & dosificación , Vigilancia de la Población , Adolescente , Niño , Preescolar , Humanos , Programas de Inmunización , Lactante , Nigeria/epidemiología , Poliomielitis/epidemiología , Poliovirus/aislamiento & purificación , Vacunas contra Poliovirus/efectos adversos , Medidas de SeguridadRESUMEN
Despite the significant public health problems associated with hepatitis B virus (HBV) in sub-Saharan Africa, many countries in this region do not have systematic HBV surveillance or genetic information on HBV circulating locally. Here, we report on the genetic characterization of 772 HBV strains from Tanzania. Phylogenetic analysis of the S-gene sequences showed prevalence of HBV genotype A (HBV/A, n=671, 86.9â%), followed by genotypes D (HBV/D, n=95, 12.3â%) and E (HBV/E, n=6, 0.8â%). All HBV/A sequences were further classified into subtype A1, while the HBV/D sequences were assigned to a new cluster. Among the Tanzanian sequences, 84â% of HBV/A1 and 94â% of HBV/D were unique. The Tanzanian and global HBV/A1 sequences were compared and were completely intermixed in the phylogenetic tree, with the Tanzanian sequences frequently generating long terminal branches, indicating a long history of HBV/A1 infections in the country. The time to the most recent common ancestor was estimated to be 188 years ago [95â% highest posterior density (HPD): 132 to 265 years] for HBV/A1 and 127 years ago (95â% HPD: 79 to 192 years) for HBV/D. The Bayesian skyline plot showed that the number of transmissions 'exploded' exponentially between 1960-1970 for HBV/A1 and 1970-1990 for HBV/D, with the effective population of HBV/A1 having expanded twice as much as that of HBV/D. The data suggest that Tanzania is at least a part of the geographic origin of the HBV/A1 subtype. A recent increase in the transmission rate and significant HBV genetic diversity should be taken into consideration when devising public health interventions to control HBV infections in Tanzania.
RESUMEN
A cloned stable cell line, HepG2-HBVE6, was established following transfection of HepG2 cells with a retroviral plasmid into which a 1.1-fold genomic construct of hepatitis B virus (HBV) belonging to genotype E (HBV/E) was inserted. The cell line retains the entire HBV/E insert, and produces episomal HBV DNA. It expresses HBV pregenomic, preS1 and preS2/S transcripts, and sheds hepatitis B surface and e antigens as well as structures resembling HBV-subviral and Dane particles. The HepG2-HBVE6 cell line, in permitting recapitulation of the HBV life cycle, may be used for studying viral characteristics, therapeutic and preventative outcomes and for preparing reagents specific to HBV genotype E.
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Genotipo , Virus de la Hepatitis B/fisiología , Replicación Viral , Línea Celular , Virus de la Hepatitis B/genética , Hepatocitos/virología , HumanosRESUMEN
Outbreaks of hepatitis C virus (HCV) infections can occur among hemodialysis patients when recommended infection control practices are not followed (1). On January 30, 2014, a dialysis clinic in Tennessee identified acute HCV in a patient (patient A) during routine screening and reported it to the Tennessee Department of Health. Patient A had enrolled in the dialysis clinic in March 2010 and had annually tested negative for HCV (including a last HCV test on December 19, 2012), until testing positive for HCV antibodies (anti-HCV) on December 18, 2013 (confirmed by a positive HCV nucleic acid amplification test). Patient A reported no behavioral risk factors, but did have multiple health care exposures.
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Brotes de Enfermedades , Hepatitis C/epidemiología , Hepatitis C/transmisión , Diálisis Renal/efectos adversos , Instituciones de Atención Ambulatoria , Anticuerpos Antivirales/aislamiento & purificación , Hepacivirus/genética , Hepacivirus/inmunología , Hepacivirus/aislamiento & purificación , Humanos , Control de Infecciones/normas , Tennessee/epidemiologíaRESUMEN
Hepatitis C is a major public health problem in the United States and worldwide. Outbreaks of hepatitis C virus (HCV) infections are associated with unsafe injection practices, drug diversion, and other exposures to blood and are difficult to detect and investigate. Here, we developed and validated a simple approach for molecular detection of HCV transmissions in outbreak settings. We obtained sequences from the HCV hypervariable region 1 (HVR1), using end-point limiting-dilution (EPLD) technique, from 127 cases involved in 32 epidemiologically defined HCV outbreaks and 193 individuals with unrelated HCV strains. We compared several types of genetic distances and calculated a threshold, using minimal Hamming distances, that identifies transmission clusters in all tested outbreaks with 100% accuracy. The approach was also validated on sequences obtained using next-generation sequencing from HCV strains recovered from 239 individuals, and findings showed the same accuracy as that for EPLD. On average, the nucleotide diversity of the intrahost population was 6.2 times greater in the source case than in any incident case, allowing the correct detection of transmission direction in 8 outbreaks for which source cases were known. A simple and accurate distance-based approach developed here for detecting HCV transmissions streamlines molecular investigation of outbreaks, thus improving the public health capacity for rapid and effective control of hepatitis C.
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Brotes de Enfermedades , Ligamiento Genético , Hepacivirus/genética , Hepacivirus/aislamiento & purificación , Hepatitis C/transmisión , Hepatitis C/virología , Análisis por Conglomerados , Variación Genética , Genotipo , Hepatitis C/epidemiología , Humanos , Reproducibilidad de los ResultadosRESUMEN
BACKGROUND In November and December 2012, 6 patients at a hemodialysis clinic were given a diagnosis of new hepatitis C virus (HCV) infection. OBJECTIVE To investigate the outbreak to identify risk factors for transmission. METHODS A case patient was defined as a patient who was HCV-antibody negative on clinic admission but subsequently was found to be HCV-antibody positive from January 1, 2008, through April 30, 2013. Patient charts were reviewed to identify and describe case patients. The hypervariable region 1 of HCV from infected patients was tested to assess viral genetic relatedness. Infection control practices were evaluated via observations. A forensic chemiluminescent agent was used to identify blood contamination on environmental surfaces after cleaning. RESULTS Eighteen case patients were identified at the clinic from January 1, 2008, through April 30, 2013, resulting in an estimated 16.7% attack rate. Analysis of HCV quasispecies identified 4 separate clusters of transmission involving 11 case patients. The case patients and previously infected patients in each cluster were treated in neighboring dialysis stations during the same shift, or at the same dialysis station on 2 consecutive shifts. Lapses in infection control were identified. Visible and invisible blood was identified on multiple surfaces at the clinic. CONCLUSIONS Epidemiologic and laboratory data confirmed transmission of HCV among numerous patients at the dialysis clinic over 6 years. Infection control breaches were likely responsible. This outbreak highlights the importance of rigorous adherence to recommended infection control practices in dialysis settings.
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Infección Hospitalaria/epidemiología , Infección Hospitalaria/transmisión , Hepatitis C/epidemiología , Hepatitis C/transmisión , Diálisis Renal/efectos adversos , Adulto , Anciano , Anciano de 80 o más Años , Instituciones de Atención Ambulatoria , Infección Hospitalaria/prevención & control , Infección Hospitalaria/virología , Brotes de Enfermedades/prevención & control , Contaminación de Equipos , Femenino , Hepacivirus/genética , Hepacivirus/aislamiento & purificación , Hepatitis C/sangre , Hepatitis C/prevención & control , Humanos , Control de Infecciones/métodos , Luminiscencia , Masculino , Registros Médicos , Persona de Mediana Edad , Philadelphia/epidemiología , Reacción en Cadena en Tiempo Real de la Polimerasa , Factores de RiesgoRESUMEN
Globally, hepatitis C Virus (HCV) infection is responsible for a large proportion of persons with liver disease, including cancer. The infection is highly prevalent in sub-Saharan Africa. West Africa was identified as a geographic origin of two HCV genotypes. However, little is known about the genetic composition of HCV populations in many countries of the region. Using conventional and next-generation sequencing (NGS), we identified and genetically characterized 65 HCV strains circulating among HCV-positive blood donors in Kumasi, Ghana. Phylogenetic analysis using consensus sequences derived from 3 genomic regions of the HCV genome, 5'-untranslated region, hypervariable region 1 (HVR1) and NS5B gene, consistently classified the HCV variants (n = 65) into genotypes 1 (HCV-1, 15%) and genotype 2 (HCV-2, 85%). The Ghanaian and West African HCV-2 NS5B sequences were found completely intermixed in the phylogenetic tree, indicating a substantial genetic heterogeneity of HCV-2 in Ghana. Analysis of HVR1 sequences from intra-host HCV variants obtained by NGS showed that three donors were infected with >1 HCV strain, including infections with 2 genotypes. Two other donors share an HCV strain, indicating HCV transmission between them. The HCV-2 strain sampled from one donor was replaced with another HCV-2 strain after only 2 months of observation, indicating rapid strain switching. Bayesian analysis estimated that the HCV-2 strains in Ghana were expanding since the 16th century. The blood donors in Kumasi, Ghana, are infected with a very heterogeneous HCV population of HCV-1 and HCV-2, with HCV-2 being prevalent. The detection of three cases of co- or super-infections and transmission linkage between 2 cases suggests frequent opportunities for HCV exposure among the blood donors and is consistent with the reported high HCV prevalence. The conditions for effective HCV-2 transmission existed for ~ 3-4 centuries, indicating a long epidemic history of HCV-2 in Ghana.
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Hepacivirus/genética , Hepatitis C/virología , Adulto , Epidemias , Evolución Molecular , Genes Virales , Variación Genética , Genotipo , Ghana/epidemiología , Hepatitis C/epidemiología , Hepatitis C/transmisión , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Masculino , Tipificación Molecular , Filogenia , Análisis de Secuencia de ADNRESUMEN
Hepatitis C virus (HCV) is classified into seven genotypes based on genetic diversity, and most genotypes have been found in Africa. Infections with HCV genotype 2 (HCV2) are most prevalent in West Africa and it was suggested that HCV2 originated in West Africa. To better understand the evolutionary epidemiology of HCV2 in Africa, we examined new NS5B sequences of HCV2 strains obtained from Côte d'Ivoire, Ghana and Nigeria sequenced at the Centers for Disease Control and Prevention with those available from West, North and Central Africa. Bayesian phylogeographic analysis using a discrete trait model showed that Ghana was the most likely geographical region for the origin of HCV2. Spread of HCV2 from Ghana did not appear to be through diffusion to adjacent countries along the coast. Rather, it was transmitted from Ghana to many distant countries in Africa, suggesting that certain routes of geographical dissemination were historically more efficient than mere proximity and that the HCV2 epidemic history in West Africa is extremely complex.
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Hepacivirus/genética , Hepacivirus/aislamiento & purificación , Hepatitis C/virología , África Occidental/epidemiología , Variación Genética , Genotipo , Hepacivirus/clasificación , Hepatitis C/epidemiología , Humanos , Datos de Secuencia Molecular , FilogeniaRESUMEN
BACKGROUND: Sub-Saharan Africa (SSA) has one of the highest global hepatitis C virus (HCV) prevalence estimates. However, reports that suggest high rates of serologic false positives and low levels of viremia have led to uncertainty regarding the burden of active infection in this region. Additionally, little is known about the predominant transmission risk factors in SSA. METHODS: We prospectively recalled 363 past blood donors (180 who were rapid screen assay [RSA] positive and 183 who were RSA negative at time of donation) to identify the level of active infection and risk factors for infection at a teaching hospital in Kumasi, Ghana. Participants had repeat blood testing and were administered a questionnaire on risk factors. RESULTS: The frequency of HCV active infection ranged from 74.4% to 88% depending on the criteria used to define serologically positive cases. Individuals with active disease had biochemical evidence of liver inflammation and median viral loads of 5.7 log copies/mL. Individuals from the northern and upper regions of Ghana had greater risks of infection compared with participants from other areas. Additional risk factors included traditional circumcision, home birth, tribal scarring, and hepatitis B virus coinfection. CONCLUSIONS: Viremic infection was common among serologically confirmed cases. Attention to testing algorithms is needed in order to define the true HCV burden in SSA. These data also suggest that several transmission modes are likely contributing to the current HCV epidemic in Ghana and that the distribution of these practices may result in substantial regional variation in prevalence.
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Transmisión de Enfermedad Infecciosa , Hepatitis C/epidemiología , Hepatitis C/transmisión , Adulto , Donantes de Sangre , Femenino , Ghana/epidemiología , Humanos , Masculino , Prevalencia , Estudios Prospectivos , Factores de Riesgo , Encuestas y CuestionariosRESUMEN
Dried blood spots (DBS) expedite the collection, storage and shipping of blood samples, thereby facilitating large-scale serologic studies. We evaluated the sensitivity of anti-HCV IgG testing and HCV-RNA quantitation using freshly prepared and stored DBS derived from HCV-infected patients. Protocols for elution were optimized using DBS prepared from plasma of 52 HCV-infected persons and 51 uninfected persons (control DBS), then applied to DBS from 33 chronic hepatitis C patients that had been stored at -20°C for 5 years (stored DBS). Control and stored DBS, and their corresponding plasma, were processed for anti-HCV IgG testing using the VITROS chemiluminescence assay (CIA) and the HCV 3.0 enzyme immunoassay (EIA) (Ortho-Clinical Diagnostics), and for HCV RNA quantitation by quantitative (q) RT-PCR. HCV genotyping was conducted by nucleotide sequencing. The sensitivity of CIA and EIA in control DBS was 92% and 90%, respectively, compared to 100% and 97%, respectively, in stored DBS. The sensitivity of HCV RNA detection was 88% in control DBS, compared to 36% in stored DBS. Specificity was 100% for all the assays in both control and stored DBS. Genotypes 1, 2 and 3 were detected in 16 (62%), 6 (23.1%), and 4 (15.3%) samples, respectively. Sequences generated from DBS and their corresponding plasma samples were identical. Whereas the sensitivity of anti-HCV IgG detection in stored DBS was equivalent to that in recently prepared DBS, the sensitivity of HCV RNA detection was markedly lower in stored DBS compared to recently prepared DBS. Stored DBS may be reliably used for anti-HCV detection but for HCV-RNA-based testing freshly prepared DBS is preferable to stored DBS.
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Sangre/virología , Desecación/métodos , Hepacivirus/aislamiento & purificación , Anticuerpos contra la Hepatitis C/sangre , Inmunoglobulina G/sangre , ARN Viral/sangre , Manejo de Especímenes/métodos , Genotipo , Hepacivirus/clasificación , Hepacivirus/genética , Hepacivirus/inmunología , Hepatitis C/diagnóstico , Humanos , Inmunoensayo , Reacción en Cadena en Tiempo Real de la Polimerasa , Sensibilidad y Especificidad , Análisis de Secuencia de ADNRESUMEN
Hepatitis C virus (HCV) genotype 3a accounts for â¼80% of HCV infections in Pakistan, where â¼10 million people are HCV-infected. Here, we report analysis of the genetic heterogeneity of HCV NS3 and NS5b subgenomic regions from genotype 3a variants obtained from Pakistan. Phylogenetic analyses showed that Pakistani genotype 3a variants were as genetically diverse as global variants, with extensive intermixing. Bayesian estimates showed that the most recent ancestor for genotype 3a in Pakistan was last extant in â¼1896-1914 C.E. (range: 1851-1932). This genotype experienced a population expansion starting from â¼1905 to â¼1970 after which the effective population leveled. Death/birth models suggest that HCV 3a has reached saturating diversity with decreasing turnover rate and positive extinction. Taken together, these observations are consistent with a long and complex history of HCV 3a infection in Pakistan.
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Variación Genética , Hepacivirus/genética , Hepatitis C/virología , Teorema de Bayes , Evolución Molecular , Genotipo , Hepatitis C/epidemiología , Humanos , Pakistán/epidemiología , Filogenia , Proteínas no Estructurales ViralesRESUMEN
BACKGROUND: Next-generation sequencing (NGS) allows for sampling numerous viral variants from infected patients. This provides a novel opportunity to represent and study the mutational landscape of Hepatitis C Virus (HCV) within a single host. RESULTS: Intra-host variants of the HCV E1/E2 region were extensively sampled from 58 chronically infected patients. After NGS error correction, the average number of reads and variants obtained from each sample were 3202 and 464, respectively. The distance between each pair of variants was calculated and networks were created for each patient, where each node is a variant and two nodes are connected by a link if the nucleotide distance between them is 1. The work focused on large components having > 5% of all reads, which in average account for 93.7% of all reads found in a patient. CONCLUSIONS: Most intra-host variants are organized into distinct single-mutation components that are: well separated from each other, represent genetic distances between viral variants, robust to sampling, reproducible and likely seeded during transmission events. Facilitated by NGS, large components offer a novel evolutionary framework for genetic analysis of intra-host viral populations and understanding transmission, immune escape and drug resistance.
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Variación Genética , Hepacivirus/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Mutación , Simulación por Computador , Genotipo , Hepatitis C/transmisión , Humanos , Compartición de Agujas , ARN Viral/genética , Análisis de Secuencia de ADNRESUMEN
BACKGROUND: Four patients were hospitalized July 2011 with Pseudomonas aeruginosa bloodstream infection (BSI), 2 of whom also had Klebsiella pneumoniae BSI. All 4 patients had an indwelling port and received infusion services at the same outpatient oncology center. METHODS: Cases were defined by blood or port cultures positive for K pneumoniae or P aeruginosa among patients receiving infusion services at the oncology clinic during July 5-20, 2011. Pulsed-field gel electrophoresis (PFGE) was performed on available isolates. Interviews with staff and onsite investigations identified lapses of infection control practices. Owing to concerns over long-standing deficits, living patients who had been seen at the clinic between January 2008 and July 2011 were notified for viral blood-borne pathogen (BBP) testing; genetic relatedness was determined by molecular testing. RESULTS: Fourteen cases (17%) were identified among 84 active clinic patients, 12 of which involved symptoms of a BSI. One other patient had a respiratory culture positive for P aeruginosa but died before blood cultures were obtained. Available isolates were indistinguishable by PFGE. Multiple injection safety lapses were identified, including overt syringe reuse among patients and reuse of syringes to access shared medications. Available BBP results did not demonstrate iatrogenic viral infection in 331 of 623 notified patients (53%). CONCLUSIONS: Improper preparation and handling of injectable medications likely caused the outbreak. Increased infection control oversight of oncology clinics is critical to prevent similar outbreaks.