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. Participants. Equal-probability 2-stage cluster sampling was used to select 87 facilities from all Medicare-approved providers treating 30–150 patients; 53 facilities and 2,933 of 3,680 eligible patients agreed to participate. Methods. Patients were tested for HCV antibody and HCV RNA. Data on patient-care practices were collected using direct observation. Results. The overall prevalence of HCV infection was 9.9% (95% confidence interval [CI], 8.2%–11.6%); only 2 of 294 HCV-positive patients were detected solely by HCV RNA testing. After adjusting for non-dialysis-related HCV risk factors, patient-care practices independently associated with a higher prevalence of HCV infection included reusing priming receptacles without disinfection (odds ratio [OR], 2.3 [95% CI, 1.4–3.9]), handling blood specimens adjacent to medications and clean supplies (OR, 2.2 [95% CI, 1.3–3.6]), and using mobile carts to deliver injectable medications (OR, 1.7 [95% CI, 1.0–2.8]). Independently related facility covariates were at least 10% patient HCV infection prevalence (OR, 3.0 [95% CI, 1.8–5.2]), patient-to-staff ratio of at least 7: 1 (OR, 2.4 [95% CI, 1.4–4.1]), and treatment duration of at least 2 years (OR, 2.4 [95% CI, 1.3–4.4]). Conclusions. This study provides the first epidemiologic evidence of associations between specific patient-care practices and higher HCV infection prevalence among hemodialysis patients. Staff should review practices to ensure that hemodialysis-specific infection control practices are being implemented, especially handling clean and contaminated items in separate areas, reusing items only if disinfected, and prohibiting mobile medication and clean supply carts within treatment areas

A New Model to Produce Infectious Hepatitis C Virus without the Replication Requirement

Numerous constraints significantly hamper the experimental study of hepatitis C virus (HCV). Robust replication in cell culture occurs with only a few strains, and is invariably accompanied by adaptive mutations that impair in vivo infectivity/replication. This problem complicates the production and study of authentic HCV, including the most prevalent and clinically important genotype 1 (subtypes 1a and 1b). Here we describe a novel cell culture approach to generate infectious HCV virions without the HCV replication requirement and the associated cell-adaptive mutations. The system is based on our finding that the intracellular environment generated by a West-Nile virus (WNV) subgenomic replicon rendered a mammalian cell line permissive for assembly and release of infectious HCV particles, wherein the HCV RNA with correct 5′ and 3′ termini was produced in the cytoplasm by a plasmid-driven dual bacteriophage RNA polymerase-based transcription/amplification system. The released particles preferentially contained the HCV-based RNA compared to the WNV subgenomic RNA. Several variations of this system are described with different HCV-based RNAs: (i) HCV bicistronic particles (HCVbp) containing RNA encoding the HCV structural genes upstream of a cell-adapted subgenomic replicon, (ii) HCV reporter particles (HCVrp) containing RNA encoding the bacteriophage SP6 RNA polymerase in place of HCV nonstructural genes, and (iii) HCV wild-type particles (HCVwt) containing unmodified RNA genomes of diverse genotypes (1a, strain H77; 1b, strain Con1; 2a, strain JFH-1). Infectivity was assessed based on the signals generated by the HCV RNA molecules introduced into the cytoplasm of target cells upon virus entry, i.e. HCV RNA replication and protein production for HCVbp in Huh-7.5 cells as well as for HCVwt in HepG2-CD81 cells and human liver slices, and SP6 RNA polymerase-driven firefly luciferase for HCVrp in target cells displaying candidate HCV surface receptors. HCV infectivity was inhibited by pre-incubation of the particles with anti-HCV antibodies and by a treatment of the target cells with leukocyte interferon plus ribavirin. The production of authentic infectious HCV particles of virtually any genotype without the adaptive mutations associated with in vitro HCV replication represents a new paradigm to decipher the requirements for HCV assembly, release, and entry, amenable to analyses of wild type and genetically modified viruses of the most clinically significant HCV genotypes

Heterosexual Transmission of Hepatitis B and Implications for Vaccine Prevention Strategies

Since 1985, cases of hepatitis B virus infection attributable to heterosexual activity have increased by 38%, whereas those attributable to homosexual activity have declined by 62%, Heterosexual activity now accounts for 26% of cases and has replaced homosexual activity in importance as a risk factor for hepatitis B. For heterosexuals, the number of recent (ie, in the preceding four to six months) and lifetime sex partners, as well as a history of other sexually transmitted diseases (eg. syphilis) appear to be significantly associated with increased hepatitis B virus infection. Of equal concern is the rising number of cases among parenteral drug users in the United States and some minority groups, including blacks, Hispanics and Asians. Hepatitis B prevention by administering hepatitis B vaccine to high risk groups before exposure to infection has not been successful, and at least 30% of hepatitis B cases in the United States have no identifiable risk factors. Thus, participation in the current programs which target only high risk groups is not possible. The ideal immunization strategy is integration of hepatitis B vaccine in to the routine childhood immunization schedule

Chapter 3, Hepatitis A: 3 --1 Chapter 3: Hepatitis A

ronic liver disease. II. Background In the United States, large nationwide epidemics have occurred approximately every 10 years, with the last increase in cases in 1995. 2 However, even between these epidemics, disease rates are relatively high and many communities experience periodic epidemics. Until recently, hepatitis A was one of the most frequently reported vaccine-preventable diseases in the U.S. with 20,000--30,000 cases reported to the NNDSS. In 2000, 13,397 hepatitis A cases were reported for a rate of 4.87 cases per 100,000 population. This is the lowest rate of disease ever reported in the U.S. and represents, after correcting for underreporting and asymptomatic infections, an estimated 57,000 cases and 143,000 infections, respectively. This remarkable decline in cases could be the result of vaccination of children, begun in selected areas in 1996. Based on testing from the Third National Health and Nutrition Examination Survey (NHANES III) survey conducted during 1988--