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Biomedical subjects

S L Stramer

Publications and source records attributed to S L Stramer.

At least 19 recordsLinked to original sources
PubMed2007

Antibodies to a novel antigen in acute hepatitis C virus infections.

BACKGROUND: Conformational viral proteins potentially play an important role in the immunobiology of acute hepatitis C virus (HCV) infection and may enable earlier antibody detection. MATERIALS AND METHODS: HCV RNA was detected using nucleic acid testing. Early antibody production was evaluated using three enzyme immunoassays (EIAs) containing antigenic proteins not present in licensed EIAs. Respectively, these contained: (1) multiple-epitope fusion antigen (MEFA) 7.1-NS3/4a, (2) F and Core, and (3) E1/E2 proteins. NS3/4a is a conformational antigen retaining protease and helicase enzymatic activities. MEFA 7.1 contains the linear epitopes used in licenced EIAs, including the latest EIA-3.0, in combination with genotype 1-3 specific epitopes. Forty-two RNA positive, EIA-3.0 negative samples, including two persistently serosilent cases, were used to evaluate these research EIAs. As controls, 54 EIA-3.0 negative/RNA negative and three HCV RNA+/antibody positive specimens were included. RESULTS: Only the MEFA 7.1-NS3/4a EIA was positive in seven (17%) of the 42 HCV RNA + specimens, in all three EIA-3.0 positive controls but in none of 54 EIA-3.0 negative/HCV RNA negative controls. Notably, six of the seven (86%) specimens had evidence of active hepatitis (ALT > 210 IU/l). The two serosilent cases were research EIA negative. CONCLUSION: A novel EIA with conformational and linear epitopes detected HCV antibodies in 17% of viraemic specimens missed by the standard reference EIA-3.0. Our research EIA appears to detect HCV antibodies closer to the initiation of acute hepatitis. Given that the average RNA-positive, antibody-negative window period is 56.4 days, this 17% yield would translate into a 10-day earlier detection of antibodies.

Blood Donors↗
PubMed2006

Self-reported symptoms associated with West Nile virus infection in RNA-positive blood donors.

BACKGROUND: In 2003, West Nile virus (WNV) nucleic acid amplification testing (NAT) was implemented to detect potentially infected donors. Of more than 5.3 million donations screened prospectively by the American Red Cross during the epidemic periods of 2003 and 2004, 974 were NAT-reactive and 519 confirmed-positive. A subset of both the confirmed-positive and the false-positive groups was assessed for demographic characteristics, symptoms, and symptom reporting relative to date of donation. STUDY DESIGN AND METHODS: All donors with initial WNV NAT-reactive results were invited to participate in a study that included a demographic, symptom, and date-of-symptom questionnaire. WNV confirmed-positive cases were compared to false-positive controls for comparison of frequency of symptom reporting before, on the day of, and after donation. RESULTS: Enrolled cases and controls were similar in all characteristics except cases were more likely to live in rural areas. Symptoms were reported by 61 percent of cases versus 20 percent of controls, with 74 percent of symptoms reported by cases within the 14 days after donation. The frequency of headache and fever reported together in the 7 days before donation was not significantly different between cases and controls; only the individual frequencies of headache, eye pain, and new rash during this time were significantly different. The most commonly reported symptoms, after adjustment for symptom reporting by controls, were headache, new rash, and generalized weakness; these symptoms were reported by 25 percent of cases. CONCLUSIONS: The demographic characteristics of infected donors reflected the rural nature of the 2003 to 2004 WNV epidemics. This study suggests that asking donors about predonation headache and fever had no detectable contribution to blood safety.

Blood Donors↗
PubMed2006

Effectiveness of human T-lymphotropic virus (HTLV) recipient tracing (lookback) and the current HTLV-I and -II confirmatory algorithm, 1999 to 2004.

BACKGROUND: This study reports on the efficacy of an investigational human T-lymphotropic virus (HTLV)-I and -II lookback program in the context of differing confirmatory testing algorithms. STUDY DESIGN AND METHODS: The results of testing approximately 35 million donations for anti-HTLV-I and -II were evaluated for two recent periods reflecting the use of two different confirmatory algorithms. The number of seroconverting donors was established for the entire period, and the results of lookback on their prior donations were investigated. RESULTS: The dual enzyme immunoassay (EIA) strategy was used throughout both study periods and resulted in a 57 to 76 percent reduction in the number of samples requiring confirmatory testing. From May 2000 to February 2002, a total of 9138 samples were repeatedly reactive by the primary screening test; of the concordant EIA-reactive samples, 461 (12%) were confirmed by Western blot, whereas 3083 (79%) were indeterminate. From March 2002 to December 2004, a total of 21,291 samples were repeatedly reactive; of the concordant EIA-reactive samples, 1099 (22%) were confirmed by the State of California's reference laboratory and only 273 (5%) were equivocal. Overall, 38 or 1 in 921,000 donations were from a seroconverting donor with 32 prior donations within the lookback period. Of those 32, components from only 11 were transfused to recipients who survived; of these, 4 were tested and all were nonreactive for HTLV-I and -II antibodies. CONCLUSION: Use of creative algorithms can increase the efficacy of anti-HTLV-I and -II confirmatory testing and reduce the number of indeterminate results. Currently, lookback for HTLV-I and -II has a very low yield, and its public health benefit is questionable.

Algorithms↗
PubMed2005

Performance of ORTHO HCV core antigen and trak-C assays for detection of viraemia in pre-seroconversion plasma and whole blood donors.

OBJECTIVE: Logistics and cost of nucleic acid amplification testing (NAT) screening preclude its current use in many developing countries. Development of hepatitis C virus (HCV) core antigen assays offer an alternative to NAT. We evaluated two specimen populations to assess the sensitivity, relative to NAT, of the HCV core antigen (HCVcAg) ELISA (enzyme-linked immunosorbent assay) test system and the trak-C assay: (1) plasma donor HCV NAT-conversion panels and (2) cross-sectional whole blood donor NAT yield specimens. METHODS: Differential sensitivities among NAT (NGI; Chiron/Gen-Probe) and both HCVcAg assays (Ortho-Clinical Diagnostics, Rochester, NY) were evaluated using: (1) 102 serial ramp-up phase specimens from 37 plasma donor NAT-conversion panels (Alpha Therapeutic/BioClinical Partners); and (2) 42 cross-sectional whole blood donor NAT yield specimens (confirmed RNA positive, antibody negative) plus 54 NAT false-positive specimens (American Red Cross). RESULTS: Viral load among the plasma donor NAT-conversion panels at the cutoffs for HCVcAg and trak-C assays were 32 000 copies/ml (95% confidence interval [CI] 8000-120 000) and 8000 copies/ml (95% CI: 2200-28 000), respectively. The mean (95% CI) difference in window period reduction compared to routine mini-pool NAT screening (estimated sensitivity 100 copies/ml) was delayed 5.2 days (2.2-7.6 days) for HCVcAg assay and 3.8 days (2.1-5.5 days) for the trak-C assay. Among the 42 NAT yield specimens, the HCVcAg assay detected 31 (74%) as core antigen-positive while the trak-C assay detected 37 (88%) as core antigen-positive. Viral loads for the five specimens not detected by the trak-C HCVcAg assay ranged from 100 to 7770 copies/ml. All 54 NAT false-positive specimens were non-reactive on both HCV core antigen assays. CONCLUSION: These data indicate that the trak-C assay has sensitivity approaching routine mini-pool NAT screening for the detection of seronegative HCV infection. In the absence of routine NAT screening for early HCV infection, the use of an HCV core antigen assay should be considered.

Blood Donors↗
PubMed2004

Risk factors for HCV infection among blood donors confirmed to be positive for the presence of HCV RNA and not reactive for the presence of anti-HCV.

BACKGROUND: In 1999, NAT of blood donations was implemented to detect "window-period" infections. Blood donors who have confirmed NAT results positive for the presence of HCV in the absence of anti-HCV are likely to have been recently infected. Of over 26.8 million donations tested between March 3, 1999, and March 31, 2003, 810 were HCV-reactive by NAT. A subset of these donors was assessed for recent exposure risk. STUDY DESIGN AND METHODS: All anti-HCV- blood donors with reactive, unconfirmed HCV NAT results were invited to participate in a study that included an extensive demographic and risk questionnaire. Confirmed HCV+ cases were compared to HCV- (falsely positive) controls for histories of potential risk factors during the 6 months before donation. RESULTS: Recent injection drug use (IDU) was independently associated with HCV infection (29.2% vs. 0% of cases vs. controls, p < 0.001). In addition, likely sources were identified for three other cases (4.6%), including occupational exposure, sexual contact with an HCV-infected partner (who was an IDU), and perinatal exposure, none of which was known to the donors at the time of donation. Incarceration was independently associated with HCV infection among the group not reporting IDU and after removal of the three donors with likely sources of risk (14.6% vs. 1.3% of cases vs. controls, p < 0.001). CONCLUSIONS: A likely risk, primarily IDU, was found for 43 percent of HCV+ donors whose infections were identified solely by NAT. Because the maximum efficiency of the donor history questions may have been reached, NAT will continue to be an important measure to interdict recently infected blood donors.

Adolescent↗
PubMed2003

The cost-effectiveness of NAT for HIV, HCV, and HBV in whole-blood donations.

BACKGROUND: The risk of viral infection associated with blood transfusion is lower than ever before because of aggressive screening and testing practices. NAT technology has lowered that risk even further but at an additional cost to the health-care system. STUDY DESIGN AND METHODS: Marginal cost-effectiveness of NAT for HIV, HCV, and HBV in whole-blood donations was calculated with a previously published Markov decision model. This model was updated with disease incidence data from all 2001 American Red Cross whole-blood donations as well as window-period data from the Retrovirus Epidemiology Donor Study (REDS). RESULTS: Whole-blood donation NAT for HIV and HCV is expected to cost between 155 US dollars million (minipool NAT) and 428 million US dollars(single-donation NAT) per year in the US and avert 4 to 7 HIV infections and 56 to 59 HCV infections. Adding HBV NAT would be expected to avert 9 to 37 HBV infections at an additional cost of between 39 million US dollars and 130 million US dollars per year. Overall, NAT would cost between 4.7 million US dollars and 11.2 million US dollars per quality-adjusted life-year saved. Discontinuing HIV p24 antigen and HBc testing would offset this somewhat. CONCLUSIONS: The cost-effectiveness of whole-blood NAT is poor. The testing cost would need to decrease significantly to bring the cost-effectiveness in line with most other accepted medical practices.

Blood Donors↗
PubMed2002

US NAT yield: where are we after 2 years?

The US blood supply has been tested for human immunodeficiency virus-1 (HIV-1) and hepatitis C virus (HCV) using nucleic acid amplification testing (NAT) of pools of small number of samples since early 1999. Since the implementation of NAT under an investigational new drug (IND) application, the results for the yield and false positivity have been remarkably consistent for greater than 2 years of testing even among multiple programmes using two different test methodologies and manufacturers: Gen-Probe/Chiron transcription-mediated amplification (TMA) and Roche polymerase chain reaction. All programmes in the US and Canada use NAT as a criterion for cellular as well as frozen product release. The focus of this paper is to provide an update of the programmes in the US and Canada, provide data in support of p24 antigen replacement by HIV-1 NAT and discuss the projections of residual risk of HIV, HCV and hepatitis B virus (HBV) following NAT and the associated cost/benefit.

Antigens, Viral↗
PubMed2002

Current prevalence and incidence of infectious disease markers and estimated window-period risk in the American Red Cross blood donor population.

BACKGROUND: There has been continuing progress in measures to reduce the risk of transfusion-transmitted infection, including introduction of serologic tests of increased sensitivity and the recent implementation of investigational NAT in small pools of samples. STUDY DESIGN AND METHODS: Data relating to all blood donations to the American Red Cross have been consolidated into a single database. The prevalence of confirmed-positive test results for HBsAg, HCV, HIV, and HTLV were evaluated for each year for first-time donors from 1995 through 2001. Incidence rates for these infections were evaluated among repeat donors having at least two donations in a 2-year period. The frequencies of HIV-1 RNA- and HCV RNA-positive, seronegative donations were assessed for first-time and repeat donations. The relationship risk = (window period) x (incidence) was used to assess residual risk among repeat donations and to evaluate the incidence of HCV and HIV infection among first-time donors. RESULTS: During the study period, prevalence rates for all markers declined significantly over time: in 2001, the rates per 100,000 were 75.6 for HBsAg, 299 for HCV, 9.7 for HIV, and 9.6 for HTLV; the corresponding incidence rates (/100,000 person-years) were 1.267, 1.889, 1.554, and 0.239, respectively. Estimates of residual risk in donations from repeat donors (after NAT) for HCV and HIV were 1 per 1,935,000 and 1 per 2,135,000, respectively. However, incidence rates for these agents are approximately two times greater among first-time donors. For both HCV and HIV, NAT yield was concordant with that predicted by current window-period models. CONCLUSION: These data cover about half of all the whole blood collected in the United States. They suggest increasing improvement in transfusion safety and clearly define the benefit of pooled NAT.

Biomarkers↗
PubMed2002

NAT update: where are we today?

The US blood supply has been tested for HIV-1 and HCV using Nucleic Acid Amplification Testing (NAT) of small pools since early in 1999. Since the implementation of NAT under an investigational new drug (IND) application, the results for yield and false positivity have been amazingly consistent for greater than two years of testing even among multiple programmes using two different test methodologies and manufacturers: Gen-Probe/Chiron transcription-mediated amplification (TMA) and Roche PCR. All programmes in the US and Canada use NAT as a criterion for cellular as well as frozen product release. The focus of this manuscript is to provide an update of the programmes in the US and Canada, provide data in support of p24 antigen replacement by HIV-1 NAT, and discuss the projections of residual risk of HIV, HCV and HBV following NAT and the associated cost/benefit.

Blood↗
PubMed2000

Lookback on donors who are repeatedly reactive on first-generation hepatitis C virus assays:justification and rational implementation.

BACKGROUND: The purpose of this study was to explore strategies to minimize the number of unwarranted consignee notifications resulting from hepatitis C virus (HCV) first-generation (single-antigen) enzyme immunoassay (EIA 1.0) targeted lookback. STUDY DESIGN AND METHOD: The four blood centers participating in this study contributed data on 3753 HCV EIA 1.0-repeatably reactive (RR) donations. The analysis focused on 1) statistical evaluation of HCV EIA 1.0 signal-to-cutoff (S/CO) ratios versus HCV second-generation recombinant immunoblot assay (RIBA 2.0) interpretation from all participating blood centers and 2) RNA testing using transcription-mediated amplification on all HCV EIA 1.0 RR/RIBA 2. 0-positive or -indeterminate specimens and a subset of RIBA 2. 0-negative donations for which specimens were available. RESULTS: Analysis of HCV EIA 1.0 S/CO ratios versus RIBA 2.0 indicated that 1180 (89%) of 1326 RIBA 2.0-positive specimens had an S/CO ratio >2. 5, while 146 (11%) had a ratio </=2.5. In contrast, of 2253 RIBA 2. 0-negative specimens, 299 (13%) had an S/CO ratio >2.5, while 1954 (87%) had a ratio </=2.5. Of 248 HCV EIA 1.0-RR/RIBA 2.0-positive samples with stored specimens available for additional testing, 198 (80%) were HCV RNA positive; 15 (7.5%) of these specimens had an S/CO ratio </=2.5, while 183 (92%) had a ratio >2.5. HCV RNA was detected in only 2 (1.5%) of 137 HCV EIA 1.0-RR/RIBA 2.0-negative specimens: 1 of these 2 specimens had an S/CO >2.5, while the other had an S/CO </=2.5. CONCLUSION: A highly significant (<0.0001) correlation was found between the S/CO ratio on HCV EIA 1.0- and RIBA 2.0-positive or -negative results. An S/CO ratio >2.5 yielded an 89- percent sensitivity for RIBA 2.0-positive specimens, and donations with an S/CO ratio >2.5 had a 75-percent probability of being RIBA 2.0 positive. A policy recommendation to use the S/CO ratio to triage lookback would prevent unwarranted notification of 87 percent of recipients of blood from RIBA 2.0-negative donors and would result in a failure to notify only 5 to 10 percent of recipients potentially exposed to infectious units.

Blood Donors↗
PubMed2000

Performance of second- and third-generation RIBAs for confirmation of third-generation HCV EIA-reactive blood donations. Retrovirus Epidemiology Donor Study.

BACKGROUND: Licensure of an enhanced HCV screening assay (HCV 3.0 EIA) without concurrent licensure of a complementary supplemental assay (i.e., RIBA HCV 3.0 strip immunoblot assay [RIBA-3]) decoupled screening and supplemental testing. In March 1998, the FDA Center for Biologics Evaluation and Research (CBER) recommended the use of RIBA-3 on RIBA HCV 2.0 strip immunoblot assay (RIBA-2)-indeterminate units screened with HCV EIA 3.0. STUDY DESIGN AND METHODS: The sensitivity of RIBA-2 and RIBA-3 was compared in tests on HCV 3.0 EIA-repeatably reactive (RR) units identified immediately after the implementation of HCV 3.0 EIA screening. Two protocols were evaluated: parallel testing of HCV 3.0 EIA-RR units by RIBA-2 and RIBA-3 and reflex testing of HCV 3.0 EIA-RR and RIBA-3-confirmed-positive units by RIBA-2. All specimens with discordant RIBA-2 and RIBA-3 results and a representative sampling with concordant RIBA results were tested by PCR. RESULTS: In the parallel testing protocol, 99,777 donations were screened, with 245 HCV 3.0 EIA-RR specimens included in the study. Of 166 RIBA-2-positive samples, 165 tested positive in RIBA-3 (1 sample reacted to the control superoxide dismutase antigen in RIBA-3). Thirty-two (74%) of 43 RIBA-2-indeterminate specimens and 4 (11%) of 36 RIBA-2-negative specimens tested positive in RIBA-3. HCV RNA was identified in 5 (16%) of 32 RIBA-2-indeterminate/RIBA-3-positive donations, as well as in 26 (70%) of 37 concordant RIBA-2/RIBA-3-positive donations. In the reflex testing protocol, 292,459 donations were screened, with 709 HCV 3.0 EIA-RR specimens included in the study. RIBA-3 testing yielded 517 (73%) positive specimens, of which 50 (9.7%) tested indeterminate and 15 (2.9%) tested negative in RIBA-2. Among the RIBA-discordant specimens, 10 (20%) RIBA-2-indeterminate specimens and 1 (7%) RIBA-2-negative specimens tested positive in PCR; in comparison, 60 (77%) of 78 concordant RIBA-2/RIBA-3-positive units tested positive in PCR. CONCLUSIONS: RIBA-3 is significantly more sensitive than RIBA-2 in testing of HCV 3.0 EIA-screened donations. During the review process of this manuscript, the FDA licensed the RIBA-3 test.

Blood Donors↗