Fine-mapping of genetic loci driving spontaneous clearance of hepatitis C virus infection.

Approximately three quarters of acute hepatitis C (HCV) infections evolve to a chronic state, while one quarter are spontaneously cleared. Genetic predispositions strongly contribute to the development of chronicity. We have conducted a genome-wide association study to identify genomic variants underlying HCV spontaneous clearance using ImmunoChip in European and African ancestries.

West Nile virus nucleic acid persistence in whole blood months after clearance in plasma: implication for transfusion and transplantation safety.

Background: Previous reports of West Nile virus (WNV) RNA persistence in blood compartments have raised concerns around the remaining risk of WNV transfusion transmission. This study characterized the dynamics of WNV viremia in blood compartments in a longitudinal cohort of 54 WNV-infected blood donors.

Study Design And Methods: Blood samples were collected throughout the year after WNV RNA-positive blood donation (index) and characterized for WNV immunoglobulin (Ig)M and IgG antibodies and for WNV RNA by real-time reverse transcription-polymerase chain reaction.

Comparison of Hepatitis C Virus RNA and antibody detection in dried blood spots and plasma specimens.

Background: Current diagnostic tests for Hepatitis C Virus (HCV) involve phlebotomy and serologic testing for HCV antibodies (anti-HCV) and RNA, which are not always feasible. Dried blood spots (DBS) present a minimally invasive sampling method and are suitable for sample collection, storage and testing.

Objectives: To assess the utility of DBS in HCV detection, we evaluated the sensitivity and specificity of DBS for anti-HCV and HCV RNA detection compared to plasma specimens.

Development of a contemporary globally diverse HIV viral panel by the EQAPOL program.

The significant diversity among HIV-1 variants poses serious challenges for vaccine development and for developing sensitive assays for screening, surveillance, diagnosis, and clinical management. Recognizing a need to develop a panel of HIV representing the current genetic and geographic diversity NIH/NIAID contracted the External Quality Assurance Program Oversight Laboratory (EQAPOL) to isolate, characterize and establish panels of HIV-1 strains representing global diverse subtypes and circulating recombinant forms (CRFs), and to make them available to the research community. HIV-positive plasma specimens and previously established isolates were collected through a variety of collaborations with a preference for samples from acutely/recently infected persons.

Human leukocyte antigen B*57 does not fully explain hepatitis C clearance in HIV controllers.

Objective: HIV controllers demonstrate high rates of spontaneous clearance of hepatitis C virus (HCV) infection. The objective of this study was to evaluate the role of human leukocyte antigen (HLA) B*57 and other genetic polymorphisms on HCV clearance in HIV controllers.

Design: This is a prospective cohort study.

Genome-wide association study of spontaneous resolution of hepatitis C virus infection: data from multiple cohorts.

Unlabelled: Chinese translation

Background: Hepatitis C virus (HCV) infections occur worldwide and either spontaneously resolve or persist and markedly increase the person's lifetime risk for cirrhosis and hepatocellular carcinoma. Although HCV persistence occurs more often in persons of African ancestry and persons with genetic variants near interleukin-28B (IL-28B), the genetic basis is not well-understood.

Objective: To evaluate the host genetic basis for spontaneous resolution of HCV infection.

Frequent longitudinal sampling of hepatitis C virus infection in injection drug users reveals intermittently detectable viremia and reinfection.

Background: Detection of hepatitis C virus (HCV) reinfection and intercalation (ie, intermittent recurrent bouts of viremia with homologous virus interspersed with aviremic periods) requires extensive and frequent evaluation and viral sequencing.

Methods: HCV infection outcomes were studied prospectively in active injection drug users with recurrent HCV RNA-positive tests after serial negative results. HCV viremia and viral sequences (Core/E1) were assessed from monthly blood samples.

Distinct roles of trauma and transfusion in induction of immune modulation after injury.

Background: Trauma and transfusion can both alter immunity, and while transfusions are common among traumatically injured patients, few studies have examined their combined effects on immunity.

Study Design And Methods: We tracked the plasma levels of 41 immunomodulatory proteins in 56 trauma patients from time of injury up to 1 year later. In addition, a murine model was developed to distinguish between the effects of transfusion and underlying injury and blood loss.

Epidemiologic and laboratory findings from 3 years of testing United States blood donors for Trypanosoma cruzi.

Background: At most blood centers in the United States routine testing of donations for Trypanosoma cruzi using an enzyme-linked immunosorbent assay (ELISA) is followed by supplemental testing by radioimmunoprecipitation assay (RIPA). The objective of this study was to report the results of routine testing and risk factor data from allogeneic blood donors.

Study Design And Methods: T.

Genetic diversity of recently acquired and prevalent HIV, hepatitis B virus, and hepatitis C virus infections in US blood donors.

Background: Genetic variations of human immunodeficiency virus (HIV), hepatitis C virus (HCV), and hepatitis B virus (HBV) can affect diagnostic assays and therapeutic interventions. Recent changes in prevalence of subtypes/genotypes and drug/immune-escape variants were characterized by comparing recently infected vs more remotely infected blood donors.

Methods: Infected donors were identified among approximately 34 million US blood donations, 2006-2009; incident infections were defined as having no or low antiviral antibody titers.

Iron deficiency in blood donors: the REDS-II Donor Iron Status Evaluation (RISE) study.

Background: Blood donors are at risk of iron deficiency. We evaluated the effects of blood donation intensity on iron and hemoglobin (Hb) in a prospective study.

Study Design And Methods: Four cohorts of frequent and first-time or reactivated (FT/RA) blood donors (no donation in 2 years), female and male, totaling 2425, were characterized and followed as they donated blood frequently.

Failure to confirm XMRV/MLVs in the blood of patients with chronic fatigue syndrome: a multi-laboratory study.

Murine leukemia viruses (MLVs), including xenotropic-MLV-related virus (XMRV), have been controversially linked to chronic fatigue syndrome (CFS). To explore this issue in greater depth, we compiled coded replicate samples of blood from 15 subjects previously reported to be XMRV/MLV-positive (14 with CFS) and from 15 healthy donors previously determined to be negative for the viruses. These samples were distributed in a blinded fashion to nine laboratories, which performed assays designed to detect XMRV/MLV nucleic acid, virus replication, and antibody.

Association between HLA class I and class II alleles and the outcome of West Nile virus infection: an exploratory study.

Background: West Nile virus (WNV) infection is asymptomatic in most individuals, with a minority developing symptoms ranging from WNV fever to serious neuroinvasive disease. This study investigated the impact of host HLA on the outcome of WNV disease.

Methods: A cohort of 210 non-Hispanic mostly white WNV(+) subjects from Canada and the U.

Relative distribution of West Nile virus RNA in blood compartments: implications for blood donor nucleic acid amplification technology screening.

Background: Despite implementation of targeted individual-donor nucleic acid test (NAT) screening of blood donors for West Nile virus (WNV), three "breakthrough" WNV transfusion transmission cases were reported (2004-2008), suggesting that current plasma-based assays are unable to detect all WNV-infectious donations. A 2007 report found that 19 of 20 red blood cell components from WNV-infected donors contained 1 log higher viral load than plasma components. This study's aim was to further establish the value of screening whole blood relative to plasma for WNV RNA by generating differential viral loads on paired samples derived from blood screening tubes.

Patient-care practices associated with an increased prevalence of hepatitis C virus infection among chronic hemodialysis patients.

Objective: To identify patient-care practices related to an increased prevalence of hepatitis C virus (HCV) infection among chronic hemodialysis patients.

Design: Survey.

Setting: Chronic hemodialysis facilities in the United States.

Distribution of parvovirus B19 DNA in blood compartments and persistence of virus in blood donors.

Background: Because the receptor for parvovirus B19 (B19V) is on red blood cells (RBCs), we investigated B19V distribution in blood by in vitro spiking experiments and evaluated viral compartmentalization and persistence in natural infection.

Study Design And Methods: Two whole blood (WB) protocols (ultracentrifugation and a rapid RBC lysis and removal protocol) were evaluated using quantitative real-time polymerase chain reaction. WB was spiked with known concentrations of B19V and recovery in various blood fractions was determined.

Induction of CXCR3- and CCR5-associated chemokines during acute hepatitis C virus infection.

Background & Aims: Characterization of inflammatory mediators, such as chemokines, during acute hepatitis C virus (HCV) infection might shed some light on viral clearance mechanisms.

Methods: Plasma levels of CXCR3 (CXCL9-11)- and CCR5 (CCL3-4)-associated chemokines, ALT, and HCV RNA were measured in nine injection drug users (median 26 samples/patient) before and during 10 acute (eight primary and two secondary) HCV infections. Using functional data analysis, we estimated smooth long-term trends in chemokine expression levels to obtain the magnitude and timing of overall changes.

Host genetic basis for hepatitis C virus clearance: a role for blood collection centers.

Purpose Of Review: Host genetic factors influencing hepatitis C virus (HCV) transmission outcomes are incompletely defined. However, vast differences observed in rates of spontaneous clearance between individuals infected with the same parental HCV strain strongly indicate a role for genetic determinants in the host immune response to HCV. This review discusses genetic association studies, particularly those published in the last year, that show gene linkages with spontaneous and treatment-induced HCV clearance.

A case-control study of factors associated with resolution of hepatitis C viremia in former blood donors (CME).

Background: Nucleic acid testing (NAT) is performed on blood collected in the United States allowing for the classification of hepatitis C virus (HCV) antibody-positive donors into resolved and chronic hepatitis C infections. We report a case-control study of factors associated with HCV resolution.

Study Design And Methods: Blood donors with resolved (HCV antibody positive, RNA negative defined as "cases") or chronic (HCV antibody positive, RNA positive defined as "controls") based on their index donation HCV test results were enrolled.

Large-scale candidate gene analysis of spontaneous clearance of hepatitis C virus.

Human genetic variation is a determinant of recovery from acute hepatitis C virus (HCV) infection; however, to date, single-nucleotide polymorphisms (SNPs) in only a limited number of genes have been studied with respect to HCV clearance. We determined whether SNPs in 112 selected immune response genes are important for HCV clearance, by genotyping 1536 SNPs in a cohort of 343 persons with natural HCV clearance and 547 persons with HCV persistence. PLINK (version 1.

Tregs control the development of symptomatic West Nile virus infection in humans and mice.

West Nile virus (WNV) causes asymptomatic infection in most humans, but for undefined reasons, approximately 20% of immunocompetent individuals develop West Nile fever, a potentially debilitating febrile illness, and approximately 1% develop neuroinvasive disease syndromes. Notably, since its emergence in 1999, WNV has become the leading cause of epidemic viral encephalitis in North America. We hypothesized that CD4+ Tregs might be differentially regulated in subjects with symptomatic compared with those with asymptomatic WNV infection.

Acute hepatitis C virus infection in young adult injection drug users: a prospective study of incident infection, resolution, and reinfection.

Background: Hepatitis C virus (HCV) infection, clearance, and reinfection are best studied in injection drug users (IDUs), who have the highest incidence of HCV and are likely to represent most infections.

Methods: A prospective cohort of HCV-negative young IDUs was followed up from January 2000 to September 2007, to identify acute and incident HCV and prospectively study infection outcomes.

Results: Among 1,191 young IDUs screened, 731 (61.