Bruce Phelps

Hepatitis C Virus Seroconversion among Young Injection Drug Users: Relationships and Risks

The present study examined reasons for the high incidence of hepatitis C virus (HCV) infection among young injection drug users (IDUs). IDUs <30 years old who tested negative for HCV antibody were enrolled in a prospective cohort. Risk factors for seroconversion were examined using time-dependent regression analyses: 48 of 195 IDUs seroconverted to HCV, for an incidence rate of 25.1/100 person-years (95% confidence interval, 18.7-32.9/100 person-years). Independent risk factors included sharing needles with an HCV-infected sex partner (borderline statistical significance, P=.11) or a person who was not a sex partner, sharing nonsterile drug-preparation equipment, pooling money with another IDU to buy drugs, and exchanging sex for money. Ubiquitous behaviors among young IDUs, such as the forming of injecting or sexual partnerships and consequent sharing of needles and drug preparation equipment, are risk factors for HCV. Interventions to reduce HCV transmission must recognize the importance of relationships on injecting risk.

Hepatitis C Virus Infection among Prisoners in the California State Correctional System

BACKGROUND Incarcerated populations are at high risk for hepatitis C virus (HCV) infection, yet prisoners are not routinely screened or treated for HCV infection. Understanding the risk factors of HCV infection among prisoners could help improve HCV interventions. METHODS Prevalence and risk of HCV infection among 469 prisoners entering California State correctional facilities were assessed using HCV antibody screening, HCV RNA measurement, and structured interviews. Multivariate logistic regression analysis was used to identify independent correlates of HCV infection. RESULTS The prevalence of HCV infection was 34.3% overall (95% confidence interval [CI], 30%-38%) and was 65.7% among those with a history of injection drug use (IDU), compared with 10.2% among those with no history of IDU (odds ratio [OR], 17.24; 95% CI, 10.52-28.25). Significant differences in HCV antibody positivity were found in association with age at first detention but not with the nature of the crime. Independent correlates of HCV infection included age, history of IDU, cumulative time of incarceration, biological sex (OR for females subjects compared with males subjects, 0.35; 95% CI, 0.13-0.96), and a history of having sex with a male IDU (OR, 4.42; 95% CI, 1.46-13.37). We identified significant differences in risk factors between male and female subjects--notably, that the risk of HCV infection was significantly elevated among female non-IDUs who reported having sexual partners with a history of IDU. Among non-IDUs, correlates of HCV infection included history of receipt of blood products and cumulative years of incarceration. CONCLUSIONS HCV infection is pervasive among the California prison population, including prisoners who are non-IDUs and women with high-risk sexual behavior. These results should promote consideration of routine HCV antibody screening and behavioral interventions among incarcerated men and women.

Testing Strategy To Identify Cases of Acute Hepatitis C Virus (HCV) Infection and To Project HCV Incidence Rates

ABSTRACT Surveillance for hepatitis C virus (HCV) is limited by the challenge of differentiating between acute and chronic infections. In this study, we evaluate a cross-sectional testing strategy that identifies individuals with acute HCV infection and we estimate HCV incidence. Anti-HCV-negative persons from four populations with various risks, i.e., blood donors, Veterans Administration (VA) patients, young injection drug users (IDU), and older IDU, were screened for HCV RNA by minipool or individual sample nucleic acid testing (NAT). The number of detected viremic seronegative infections was combined with the duration of the preseroconversion NAT-positive window period (derived from analysis of frequent serial samples from plasma donors followed from NAT detection to seroconversion) to estimate annual HCV incidence rates. Projected incidence rates were compared to observed incidence rates. Projected HCV incidence rates per 100 person-years were 0.0042 (95% confidence interval [95% CI], 0.0025 to 0.007) for blood donors, 0.86 (95% CI, 0.02 to 0.71) for VA patients, 39.8 (95% CI, 25.9 to 53.7) for young IDU, and 53.7 (95% CI, 23.4 to 108.8) for older IDU. Projected rates were most similar to observed incidence rates for young IDU (33.4; 95% CI, 28.0 to 39.9). This study demonstrates the value of applying a cross-sectional screening strategy to detect acute HCV infections and to estimate HCV incidence.

Characterization of prion protein (PrP)-derived peptides that discriminate full-length PrPsc from PrPc

On our initial discovery that prion protein (PrP)-derived peptides were capable of capturing the pathogenic prion protein (PrPSc), we have been interested in how these peptides interact with PrPSc. After screening peptides from the entire human PrP sequence, we found two peptides (PrP19–30 and PrP100–111) capable of binding full-length PrPSc in plasma, a medium containing a complex mixture of other proteins including a vast excess of the normal prion protein (PrPC). The limit of detection for captured PrPSc was calculated to be 8 amol from a ≈105-fold dilution of 10% (wt/vol) human variant Creutzfeldt–Jakob disease brain homogenate, with >3,800-fold binding specificity to PrPSc over PrPC. Through extensive analyses, we show that positively charged amino acids play an important, but not exclusive, role in the interaction between the peptides and PrPSc. Neither hydrophobic nor polar interactions appear to correlate with binding activity. The peptide–PrPSc interaction was not sequence-specific, but amino acid composition affected binding. Binding occurs through a conformational domain that is only present in PrPSc, is species-independent, and is not affected by proteinase K digestion. These and other findings suggest a mechanism by which cationic domains of PrPC may play a role in the recruitment of PrPC to PrPSc.

Analytical and clinical sensitivity of West Nile virus RNA screening and supplemental assays available in 2003.

BACKGROUND: Transfusion‐transmitted West Nile virus (WNV) infections were first reported in 2002, which led to rapid development of investigational nucleic acid amplification tests (NAT). A study was conducted to evaluate sensitivities of WNV screening and supplemental NAT assays first employed in 2003.

Impact of HCV 3.0 EIA relative to HCV 2.0 EIA on blood‐donor screening

BACKGROUND:  In 1996, the Ortho HCV Version 3.0 ELISA Test System (HCV 3.0 EIA) was licensed in the United States for donor screening but was neither mandated nor universally implemented. Data from two studies comparing the differential performance of HCV 3.0 EIA and HCV 2.0 EIA are presented. The first study evaluated the differential performance in a cross‐section of screened whole‐blood donors after implementation of HCV 3.0 EIA; the second study evaluated the differential performance of HCV 3.0 EIA in plasma donors acutely infected with HCV, identified during routine Abbott HCV 2.0 EIA and HCV NAT (using Roche Ampliscreen plate assay) donor screening.

The course of hepatitis C viraemia in transfusion recipients prior to availability of antiviral therapy.

Summary.  Knowing the likely distribution of intervals from hepatitis C infection to first RNA‐negativity is important in deciding about therapeutic intervention. Prospectively collected sera and data from the Transfusion‐transmitted Viruses Study (1974–1980) provide specific dates of infection and pattern of alanine aminotransferase (ALT) elevations. We examined frequency, timing and correlates of spontaneous resolution for 94 acutely infected transfusion recipients followed for a median of 9.5 months. Later, follow‐up sera (>10 years) were available for 27 of the 94 cases from a Veterans Administration (VA) Study (1989–1990). Twenty‐five (27%) of the 94 cases were classified as probably resolved during the episode itself. First RNA negativity occurred at 6–50 weeks (median, 19.5 weeks) after infection, and 5–43 weeks (median, 11 weeks) after ALT elevation. Thirteen of the 25 cases remained RNA‐negative subsequently; 12 others had 1–6 RNA‐positive sera intercalated between first and last RNA‐negative results. RNA negativity, therefore, began variably and was interrupted in 12 cases of 25 (48%) by transient RNA‐positive sera. Five of these 25 patients who were RNA‐negative in the last study specimen had late, Veterans Administration Study follow‐up; none showed viraemia. Of the remaining 69 transfusion transmitted virus study recipients, whose last serum was RNA‐positive, two cleared viraemia after the last study serum but before late follow‐up. Eleven (16%) had 23 intercalated RNA‐negative sera before last positivity. RNA status, therefore, needs monitoring for many months before judging the spontaneous outcome as transient negativity may occur. Resolution was significantly more common in women and symptomatic cases; it was not associated with viral load in the infectious donation, HCV genotype, or the recipient’s age.

HCV viral load in anti-HCV-reactive donors and infectivity for their recipients.

BACKGROUND:  An attempt has been made to determine the minimum level of HCV nucleic acid in donors associated with infection of recipients. This is important for considerations about assay sensitivity, use of minipool versus single‐donation testing, and continued use of serologic testing.

Assessment of the Target-Capture PCR Hepatitis B Virus (HBV) DNA Quantitative Assay and Comparison with Commercial HBV DNA Quantitative Assays

ABSTRACT Recent clinical studies suggest that hepatitis B virus (HBV) load and genotype may be independent predictors of responses to antiviral therapies. However, it is difficult for clinicians to accurately determine viral loads in patient samples because results—both the values and the units of measure—can vary greatly among different tests. Accordingly, the World Health Organization (WHO) has produced the first international standard for HBV DNA for nucleic acid amplification technology (NAT) assays. In the present study, we describe the performance of the target-capture PCR HBV DNA quantitative assay for the quantitation of HBV DNA in clinical samples and reference panels. The range of quantitation was between 50 and 1010 IU/ml. The sensitivity and accuracy of the target-capture PCR assay were demonstrated by using the HBV panel from Quality Control for Medical Diagnostics (QCMD) and the WHO HBV DNA standard. The target-capture PCR assay quantitated the six genotype A members of the QCMD panel and dilutions of the WHO HBV DNA standard within an accuracy of 74 to 142%. Compared to current serological methods, the assay offers window period reductions of 19 days prior to HBV surface antigen and 26 days prior to HBV e antigen detection. The target-capture PCR assay was also compared with four commercially available NAT assays, and the various units of measure were standardized with respect to the international units of the WHO HBV DNA standard. The target-capture PCR assay is a sensitive, accurate, high-throughput, rapid, and reproducible assay for the determination of HBV loads.

Fluctuation of HCV viral load before seroconversion in a healthy volunteer blood donor.

BACKGROUND: Newly implemented NAT has been shown to be able to effectively identify HCV‐positive blood donated during the preseroconversion period.