Biomedical subjects

Michael P Busch

Publications and source records attributed to Michael P Busch.

At least 55 records · Page 3Linked to original sources

PubMed2005

Prevalence, incidence, and residual risk of human immunodeficiency virus among community and replacement first-time blood donors in São Paulo, Brazil.

BACKGROUND: Concerted efforts have been directed toward recruitment of community rather than replacement donors in Brazil. Time trends and demographic correlates of human immunodeficiency (HIV) prevalence and incidence among first-time (FT) donors in Brazil were examined by donation type. HIV residual risk from FT-donor transfusions, and projected yield of p24 antigen and nucleic acid test (NAT) screening were estimated. STUDY DESIGN AND METHODS: HIV prevalence data and seroreactive specimens were obtained at Fundação Pró-Sangue/Hemocentro-de-São Paulo from 1995 to 2001. To estimate incidence, confirmed-positive samples from July 1998 through December 2001 were tested with a less-sensitive (detuned) enzyme immunoassay to detect recent seroconversions. Incidence data were used to estimate residual risk and p24 and NAT yield based on published window periods (WPs). RESULTS: HIV prevalence was 22 percent higher among the FT community donors than replacement donors (19.6 vs. 16.1 per 10,000; p < 0.01) and 48 percent higher among men than women (19.1 vs. 12.9; p < 0.01). In the multivariable logistic regression, both variables remained significant predictors of HIV prevalence. HIV prevalence decreased from 20.4 (1995) to 13.1 per 10,000 FT donations (2001). HIV incidence was 2.7 per 10,000 person-years. The estimated rate of infected antibody-negative donations was 14.9 per 1,000,000 units (95% confidence interval, 9.8-20.0). It was estimated that addition of p24 antigen, minipool NAT, and individual-donation NAT assays would detect 3.9 (2.0-5.8), 8.3 (5.3-11.3), and 10.8 (7.1-14.5) WP units per 1,000,000 FT donations, respectively. CONCLUSION: HIV incidence and residual transfusion risk estimates are approximately 10 times higher in Brazil FT donors compared to US and European FT donors. Community FT donors had higher HIV prevalence than replacement FT donors. The yield of p24 antigen or RNA screening will be low in Brazilian donors, but substantially higher than in US donors.

Adult↗

PubMed2005

Relative sensitivities of licensed nucleic acid amplification tests for detection of viremia in early human immunodeficiency virus and hepatitis C virus infection.

BACKGROUND: Screening donors for human immunodeficiency virus (HIV) and hepatitis C virus (HCV) RNA is primarily performed on minipools (MPs) with one of two commercial nucleic acid amplification tests (NAT; Roche Molecular Systems; or Gen-Probe/Chiron). We compared these assays with respect to detection of RNA in early HIV and HCV infection. STUDY DESIGN AND METHODS: Twelve HIV plasma donor panels (116 serial samples) and 12 HCV panels (180 serial samples) were selected to optimally represent early viremia. Initial testing was performed in singlicate or triplicate on separately coded aliquots, both neat and at dilutions corresponding to MP screening (1:16 for Gen-Probe; 1:24 for Roche); 20 additional replicates were performed when discordant results were observed. Odds ratios (ORs) comparing detection of RNA by different assays were derived with logistic regression models. Differences in window-period closure and yields of assays in MP or individual-donation (ID) format were estimated. RESULTS: Differences in detection rates between Roche and Gen-Probe NAT assays were small and only observed with samples with very-low-level viremia. ORs for detecting RNA by the Gen-Probe versus the Roche assay were significant for HIV if conducted on MPs (1.8; 95% confidence interval [CI], 1.3-2.5) but not neat (1.0; 95% CI, 0.72-1.4). Odds of detecting HCV RNA were higher if the Gen-Probe assay was conducted either neat (2.3; 95% CI, 1.6-3.2) or on MPs (4.0; 95% CI, 2.8-5.8). These differences translated to <1 day window-period closure and <or=1 infection per 20 million donations. In contrast, comparisons of ID versus MP assays were highly significant for both viruses (ORs for ID vs. MP ranged from 45.3 to 93.4), with projected yields of one to two additional infections per 10 million donations. CONCLUSIONS: Differences in sensitivities of licensed NAT assays for HIV and HCV are very small and clinically insignificant, particularly when compared to differences of MP versus ID NAT screening.

Blood Banking↗

PubMed2005

The impact of male-to-male sexual experience on risk profiles of blood donors.

BACKGROUND: Men who have had sex with men (MSM) since 1977 are permanently deferred from donating blood. Excluding only men who engaged in male-to-male sex within either the prior 12 months or 5 years has been proposed. Little is known about infectious disease risks of MSM who donate blood. STUDY DESIGN AND METHODS: Weighted analyses of data from an anonymous mail survey of blood donors were conducted to examine the characteristics of men reporting male-to-male sex during specified time periods. RESULTS: Of the 25,168 male respondents, 569 (2.4%) reported male-to-male sex, 280 (1.2%) since 1977. Compared to donors who did not report male-to-male sex, the prevalence of reactive screening test results was higher among donors who reported the practice within the past 5 years (< or =12 months odds ratio [OR] 5.3, 95% confidence interval [CI] 2.6-10.4; >12 months to 5 years, OR 7.1, 95% CI 1.2-41.7); however, no significant difference was found for donors who last practiced male-to-male sex more than 5 years ago (>5 years-after 1977, OR 1.4, 95% CI 0.7-2.6; 1977 or earlier, OR 1.6, 95% CI 0.7-3.7). The prevalence of unreported deferrable risks (UDRs) other than male-to-male sex was significantly higher for all donors who reported male-to-male sex with ORs ranging from 3.1 to 18.9 (p < or = 0.01). CONCLUSIONS: No evidence was found to support changing current policy to permit donations from men who practiced male-to-male sex within the past 5 years. For donors with a more remote history of male-to-male sex, the findings were equivocal. A better understanding of the association between male-to-male sex and other UDRs appears needed.

Blood Banks↗

PubMed2005

Dynamics of viremia in early hepatitis C virus infection.

BACKGROUND: It is important to characterize viral dynamics in early hepatitis C virus (HCV) infection to further our understanding of viral pathogenesis and the potential for secondary transmission in acute infection through blood transfusion or other routes. STUDY DESIGN AND METHODS: Serial units given by 77 source plasma donors who had evolved from HCV RNA-negative to HCV RNA-positive by nucleic acid amplification technology (NAT) screening with 512-unit pool-NAT or were followed from RNA detection to antibody conversion were tested by individual NAT and quantitative RNA assays. RESULTS: During the ramp-up phase when exponential growth occurs, HCV viral load doubled every 10.8 hours (95% confidence interval [CI], 9.9-12.0). Intermittent viremia was observed before the ramp-up phase in 37 of 50 panels with the earliest detectable viremic bleed occurring 63 days before the estimated onset of ramp-up. The plateau phase or high-titer viremic period that occurs between ramp-up and seroconversion was estimated to last 56.3 days (95% CI, 44.8-67.8). CONCLUSIONS: Intermittent low-level HCV viremia can occur as much as 2 months before the periods of exponential increase in viral load and the high-titer plateau-phase viremia that usually precede seroconversion. Animal inoculation studies are in progress to evaluate if transfusion of low-level viremic plasma can transmit HCV infection.

Blood Donors↗

PubMed2005

Utilization of follow-up specimens from viremic blood donors to assess the value of west nile virus immunoglobulin G avidity as an indicator of recent infection.

The value of West Nile virus immunoglobulin G avidity for distinguishing recent from past infection was investigated using 348 follow-up specimens from 170 viremic blood donors. Low avidity accurately indicated infection within the previous 4 months. However, due to rapid avidity maturation in some individuals, high avidity did not accurately indicate past infection.

Antibodies, Viral↗

PubMed2005

Development and persistence of West Nile virus-specific immunoglobulin M (IgM), IgA, and IgG in viremic blood donors.

West Nile Virus (WNV) antibody development and persistence were investigated in blood donors who made WNV RNA-positive (viremic) donations in 2003. Plasma samples from the index donations and follow-up serum or plasma samples were tested for WNV immunoglobulin M (IgM), IgA, and IgG by using enzyme-linked immunosorbent assays. Antibody development was investigated with 154 samples collected from 84 donors 1 to 21 days after their RNA-positive, antibody-negative, index donation. WNV IgM and IgA were first detected on day 3, and all samples collected after day 9 were WNV IgM and IgA positive; WNV IgG was first detected on day 4, and all samples collected after day 16 were positive. Antibody persistence in this donor group (index donations antibody negative) was evaluated by using 128 samples collected from 89 donors on days 22 to 440 of follow-up; 88% of samples were WNV IgM positive, 86% were WNV IgA positive, and 100% were WNV IgG positive. In linear regression analysis, trendlines for WNV IgM and IgA reached the value discriminating positive from negative results at 218 days and 232 days of follow-up, respectively. Similar WNV IgM and IgA persistence trends characterized 27 donors whose index samples were positive for WNV IgM and IgA, as well as 14 donors whose index samples were positive for WNV IgG but negative for WNV IgM. These findings show that WNV IgG emerges after WNV IgM and IgA and that both WNV IgM and IgA typically persist for at least 6 months after infection. Thus, unlike some other flavivirus infections, WNV infection is not characterized by a relatively rapid disappearance of virus-specific IgA.

Antibodies, Viral↗

PubMed2004

Persistence of primary drug resistance among recently HIV-1 infected adults.

OBJECTIVES: Primary, or transmitted, drug resistance is common among treatment naive patients recently infected with HIV-1, and impairs response to anti-retroviral therapy. We previously observed that patients with secondary resistance (developed in response to anti-retroviral treatment) who chose to stop an anti-retroviral regimen experience rapid overgrowth of drug resistant viruses by wild-type virus of higher pol replication capacity. We sought to determine if primary drug resistance would be lost at a rapid rate, and viral pol replication capacity would increase, in the absence of treatment. METHODS: We tracked drug resistance phenotype, genotype, viral pol replication capacity (single cycle recombinant assay incorporating a segment of the patient pol gene [pol RC]), plasma HIV-1 RNA, and CD4 T cell counts in the absence of treatment among patients in early HIV-1 infection. RESULTS: Six of 22 patients had evidence of primary drug resistance to at least one class of drug; three resistant to protease inhibitors, three resistant to non-nucleoside reverse transcriptase inhibitors, and four resistant to nucleoside reverse transcriptase inhibitors. All six patients maintained evidence of drug resistance for the period of observation. Among patients with baseline primary drug resistance pol RC did not increase over time. CONCLUSION: The selection environment of early infection is determined by immune pressure, and stochastic events, not viral pol replication capacity. In contrast to secondary resistant infections that are rapidly overgrown when therapy is stopped, primary drug resistance persists over time. Surveillance and clinical detection of primary resistance is feasible in the first year of infection.

Adult↗

PubMed2004

Detection of HIV-1 and HCV infections among antibody-negative blood donors by nucleic acid-amplification testing.

BACKGROUND: Testing of blood donors for human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV) RNA by means of nucleic acid amplification was introduced in the United States as an investigational screening test in mid-1999 to identify donations made during the window period before seroconversion. METHODS: We analyzed all antibody-nonreactive donations that were confirmed to be positive for HIV-1 and HCV RNA on nucleic acid-amplification testing of "minipools" (pools of 16 to 24 donations) by the main blood-collection programs in the United States during the first three years of nucleic acid screening. RESULTS: Among 37,164,054 units screened, 12 were confirmed to be positive for HIV-1 RNA--or 1 in 3.1 million donations--only 2 of which were detected by HIV-1 p24 antigen testing. For HCV, of 39,721,404 units screened, 170 were confirmed to be positive for HCV RNA, or 1 in 230,000 donations (or 1 in 270,000 on the basis of 139 donations confirmed to be positive for HCV RNA with the use of a more sensitive HCV-antibody test). The respective rates of positive HCV and HIV-1 nucleic acid-amplification tests were 3.3 and 4.1 times as high among first-time donors as among donors who gave blood repeatedly. Follow-up studies of 67 HCV RNA-positive donors demonstrated that seroconversion occurred a median of 35 days after the index donation, followed by a low rate of resolution of viremia; three cases of long-term immunologically silent HCV infection were documented. CONCLUSIONS: Minipool nucleic acid-amplification testing has helped prevent the transmission of approximately 5 HIV-1 infections and 56 HCV infections annually and has reduced the residual risk of transfusion-transmitted HIV-1 and HCV to approximately 1 in 2 million blood units.

Alanine Transaminase↗

PubMed2004

HIV RNA testing in the context of nonoccupational postexposure prophylaxis.

BACKGROUND: The specificity and positive predictive value of human immunodeficiency virus (HIV) RNA assays have not been evaluated in the setting of postexposure prophylaxis (PEP). METHODS: Plasma from subjects enrolled in a nonoccupational PEP study was tested with 2 branched-chain DNA (bDNA) assays, 2 polymerase chain reaction (PCR) assays, and a transcription-mediated amplification (TMA) assay. Assay specificity and positive predictive value were determined for subjects who remained negative for HIV antibody for >or=3 months. RESULTS: In 329 subjects examined, the lowest specificities (90.1%-93.7%) were seen for bDNA testing performed in real time. The highest specificities were seen with batched bDNA version 3.0 (99.1%), standard PCR (99.4%), ultrasensitive PCR (100%), and TMA (99.6%) testing. Only the 2 assays with the highest specificities had positive predictive values >40%. For the bDNA assays, increasing the cutoff point at which a test is called positive (e.g., from 50 copies/mL to 500 copies/mL for version 3.0) increased both specificity and positive predictive values to 100%. CONCLUSIONS: The positive predictive value of HIV RNA assays in individuals presenting for PEP is unacceptably low for bDNA-based testing and possibly acceptable for PCR- and TMA-based testing. Routine use of HIV RNA assays in such individuals is not recommended.

Anti-HIV Agents↗

PubMed2004

Higher CD4+ T cell counts associated with low viral pol replication capacity among treatment-naive adults in early HIV-1 infection.

BACKGROUND: Infection with primary drug-resistant human immunodeficiency virus type 1 (HIV-1) has been associated with higher CD4(+) T cell counts in drug-naive patients, suggesting that altered viral pol replication capacity (RC) associated with drug resistance diminishes immune injury in vivo, independent of exposure to drugs. METHODS: Virus replication over a single cycle was measured by use of a viral test vector containing patient-derived HIV-1 protease and reverse transcriptase gene segments. RESULTS: Among 191 recently infected patients, pol RC ranged widely, with only 6% of the variance explained by drug-resistance mutations. Patients infected with a virus with a low pol RC (</=43% of the reference virus) had significantly higher CD4(+) T cell counts at study entry, independent of drug resistance and plasma HIV-1 RNA level, and over time, both before and during combination antiretroviral therapy. CONCLUSIONS: Viral pol RC may influence HIV-1 disease progression by affecting the amount and tissue distribution of viral replication. The pol RC value of 43% may represent a threshold below which HIV-1 has lowered virulence and is less able to deplete CD4(+) T cell counts.

Adult↗

PubMed2004

Hepatitis B and C viral load changes following initiation of highly active antiretroviral therapy (HAART) in patients with advanced HIV infection.

Chronic infection with either hepatitis B (HBV) or hepatitis C virus (HCV) is frequently present in patients seropositive for human immunodeficiency virus (HIV) because of shared routes of transmission. With the advent of highly active antiretroviral therapy (HAART) regimens capable of controlling HIV replication and dramatically prolonging the survival of HIV-infected patients, the impact of co-morbid infections such as HBV and HCV has come into focus. Several studies have monitored HBV or HCV viral loads following initiation of HAART, with disparate results. The effects of HAART on hepatitis B and C plasma viral loads (n = 9 and 32, respectively) and on liver enzyme levels were studied in a large cohort of prospectively studied subjects with advanced stage HIV disease. Comparing the mean pre- and post-HAART levels, there was an estimated increase of (a) 1.40 log(10) from 4.83 to 6.24 log(10) for HBV plasma viral load (P = 0.07), (b) 0.74 log(10) from 6.38 to 7.12 log(10) for HCV plasma viral load (P = 0.001), and (c) 19.4 U/L from 37.4 to 56.8 U/L for serum alanine aminotransferase (P < 0.001). While the number of subjects co-infected with HIV and HBV was limited, these data collected in a population of advanced stage HIV-infected patients raises questions regarding the interactions of these viruses with each other and the host immune system and has implications regarding the order in which antiviral therapies are initiated.

Adult↗

PubMed2004

Emerging infections in transfusion medicine.

The risk of transfusion-transmitted infectious diseases (TTIDs) has declined dramatically in high-income nations over the past 2 decades, primarily because of extraordinary success in preventing HIV and other established transfusion-transmitted viruses from entering the blood supply. Despite this achievement, TTIDs remain a public health concern, and attention is refocusing on new and emerging pathogens, such as West Nile virus, infectious proteins (the presumed cause of variant Creutzfeldt-Jakob disease), and other transmissible organisms such as bacteria and parasites. In this article the authors concentrate on this heterogeneous group of infectious agents, describe individual pathogens and the risks they pose to transfusion recipients, and comment on existing and evolving procedures that are designed to protect the blood supply from this threat.

Blood-Borne Pathogens↗

PubMed2004

Quantitation of HTLV-I and II proviral load using real-time quantitative PCR with SYBR Green chemistry.

BACKGROUND: Human T-lymphotropic virus type I (HTLV-I) is linked etiologically with adult T cell leukemia/lymphoma and HTLV-I-associated myelopathy/tropical spastic paraparsis (HAM/TSP). Human T-lymphotropic virus type II (HTLV-II) is associated with HAM/TSP and, in HIV coinfected patients only, rare cases of cutaneous T cell lymphoma. Proviral load may be important in the pathogenesis of HTLV-associated disease. MATERIALS AND METHODS: A real time quantitative PCR assay using SYBR Green intercalation was established. Primers targeting the tax region were standardized against MT2 and MOT cell line DNA for HTLV-I and HTLV-II, respectively. HTLV-I/II copy number was normalized to the amount of cellular DNA by quantitation of the HLA-DQ alpha gene. We measured proviral load in peripheral blood mononuclear cells (PBMCs) in a large cohort of 120 HTLV-I and 335 HTLV-II seropositive former blood donors. We also assessed the intra- and inter-assay reproducibility of the assay. RESULTS: Proviral load for HTLV-I infected patients ranged from 3.1 x 10(0) to 1.8 x 10(5)copies/10(6) PBMCs with a mean of 1.6 x 10(4) and a median of 3.0 x 10(3). HTLV-I was undetectable in 7 of 120 cases (5.8%). Proviral load for HTLV-II infected patients ranged from 1.1 x 10(0) to 1.0 x 10(6)copies/10(6) PBMCs with a mean of 2.8 x 10(4) and a median of 5.0 x 10(2). HTLV-II was undetectable in 31 out of 335 cases (9.3%). CONCLUSION: The assay has excellent dynamic range from 10(6) to 10(0)copies/reaction, good intra- and inter-assay reproducibility, and a lower limit of detection of a single copy per reaction. The sensitivity and high dynamic range allow determination of a broad range of HTLV-I/II proviral load in clinical subjects. This assay will facilitate the study of the relationship between proviral load and pathogenesis.

Benzothiazoles↗

PubMed2004

Should HBV DNA NAT replace HBsAg and/or anti-HBc screening of blood donors?

Prevention of transfusion-transmitted hepatitis B virus (HBV) has historically relied on serological screening of blood donors using progressively more sensitive HBsAg assays; in some countries anti-HBc assays have also been employed to detect chronic carriers with low-level viremia who lack detectable HBsAg. Nucleic acid amplification testing (NAT) for HCV and HIV has been successfully introduced to screen donors in many developed countries over the past several years; for logistical and cost reasons HCV/HIV NAT screening has been applied to mini-pools (MP) of eight to 96 donor specimens, with only minimal impact of MP dilutions on clinical sensitivity for interdiction of window period (WP) donations. In several countries (e.g., Japan and Germany), HBV NAT has been added to HIV/HCV MP-NAT blood donor screening with small incremental yields of HBsAg/anti-HBc-negative donations, and the major vendors of NAT systems (Roche and Chiron/Gen-Probe) have been developing triplex assays that include HBV DNA detection capacity without compromising HIV or HCV detection. Pooled specimen HBV NAT has also become the standard of practice for screening source plasma donors, with pressure to include HBV DNA detection as a required procedure for use of recovered plasma in manufacture of fractionated derivatives. However, there is controversy over the magnitude of the incremental yield and clinical benefit of HBV MP-NAT over serological screening strategies, as well as the impact of implementation of HBV NAT on need for retention of HBsAg and anti-HBc screening. This presentation will review recent modeled and empirical data on the value of HBV MP- and individual donation (ID)-NAT for detection of (1) pre-HBsAg WP units and (2) chronic anti-HBc-reactive carriers with undetectable HBsAg. The presentation will also review policy considerations and data that address the potential for discontinuation of either HBsAg or anti-HBc following implementation of HBV NAT. Finally it will address the cost effectiveness of incorporation of HBV DNA detection into HBV screening and NAT testing algorithms.

Blood Donors↗

PubMed2004

Evidence for Selection of more Adapted Human Immunodeficiency Virus Type 1 Recombinant Strains in a Dually Infected Transfusion Recipient.

Human immunodeficiency virus type-1 (HIV-1) genetic diversity is one of the remarkable characteristics of these viruses, and the mechanisms involved in the selective forces driving HIV-1 evolution are of great interest. Samples from hosts infected with multiple distinct strains represent a valuable in vivo resource to investigate the role of recombination in the natural evolution of HIV-1. This work describes a detailed study regarding the evolution of the envelope gene (env) (C2-V5 region) in a dually infected child who received blood transfusions simultaneously from two distinct HIV-1 infected donors. In this study, we were able to directly compare the data obtained from the dually infected recipient with data obtained from two other singly HIV-1 infected children who had received blood transfusion from each of the two donors. Sequences from the singly infected children clustered into two distinct groups, each related to the respective donor-derived sequence by phylogenetic analysis, and hence were consistent with the epidemiological data. In the case of the dually infected child, a high degree of recombination between the two donor-derived sequences was observed at the C2-V3 region, whereas in the V4-V5 region selection of only one derived donor sequence was seen. Measurement of nonsynonymous versus synonymous substitution rates at each region revealed that negative selection was the main evolutionary force acting on the viral population of the dually infected child, regardless of the genetic mechanism by which each region evolved. Based on direct comparison with data obtained for the two singly infected children we propose that the higher amount of viral diversity observed in HIV-1 multi-infection events, as in the case of the dually infected patient, might contribute to maximizing selective advantage and possibly minimizing immune response. We conclude that recombination shaped by selective forces may increase the adaptive potential of HIV-1.

Adaptation, Physiological↗

PubMed2004

Blood transfusion is associated with donor leukocyte microchimerism in trauma patients.

INTRODUCTION: Blood transfusion can result in survival of donor leukocyte subpopulations in the recipient. Persistence of donor leukocytes in the transfusion recipient is termed microchimerism. Microchimerism likely reflects engraftment of the recipient with donor hematopoietic stem cells and is very uncommon with transfusion for elective surgery, sickle cell anemia, thalassemia, and HIV. We have found, however, that microchimerism may be more common in trauma patients. OBJECTIVE: To determine how frequently transfusion after trauma is associated with microchimerism. METHODS: We prospectively enrolled 45 trauma patients who were transfused > or =2 units of PRBCs. We sampled blood before hospital discharge and determined microchimerism by polymerase chain reaction (PCR) analysis of specimens using quantitative allele-specific HLA DR assays to detect non-recipient alleles. Data are expressed as median with interquartile range. RESULTS: Patients had a median age of 38 (interquartile range 25, 58) years, ISS of 19 (13, 29), and mortality of 7%. Seventy-eight percent were men, and 84% had blunt trauma. Patients received a median of 6 (4, 16) (range 2, 87) units of PRBCs. Of the 45 patients, 24 (53%) had evidence of microchimerism. Compared with patients without evidence of microchimerism, these patients had no difference in mean age, gender, ISS, units of PRBCs transfused, time from transfusion to blood sampling, or proportion that underwent splenectomy. Twenty-one of the 24 patients with microchimerism had only 1 or 2 non-recipient DR alleles identified by PCR. CONCLUSIONS: Transfusion after trauma is associated with over half of recipients having evidence of microchimerism. Age, sex, ISS, and splenectomy of the recipient and the number of transfused units did not correlate with microchimerism. Because the median time from transfusion to sampling for PCR analysis was not longer in the group without microchimerism, it is unlikely microchimerism is due merely to failure of the recipient to clear transfused donor leukocytes.

Adult↗

PubMed2004

Clinical significance of nondiscriminated reactive results with the Chiron Procleix HIV-1 and HCV assay.

BACKGROUND: A NAT was developed (Procleix multiplex, Chiron Corporation) to simultaneously detect HIV-1 and HCV RNA with multiplex transcription-mediated amplification (mTMA) on pooled or single donations. HIV-1 and/or HCV RNA discriminatory probes confirm infection and discriminate the virus type. When a multiplex reactive sample does not react in discriminatory assays, the result is considered nondiscriminated reactive (NDR) and the donor status is uncertain. This study was designed to determine the clinical significance of NDR results. STUDY DESIGN AND METHODS: Three years of donor NAT and serology results were reviewed to determine HCV and HIV-1 infection rates as well as NDR events. Index NDR and seronegative donations were retested by mTMA and serology. Follow-up samples were tested by serology, mTMA, and PCR (selected samples). RESULTS: From April 1999 through April 2002, 5.1 million donations were screened with Procleix HIV-1 and HCV mTMA. The observed NDR rate declined from 0.014 percent (1 in 7242) to 0.0053 percent (1 in 18,795). None of the 462 donors with index NDR donations and additional NAT and serology data (from 724 donation and follow-up samples) were found infected. CONCLUSION: In most NDRs, the original mTMA reactivity is not reproducible and likely related to technical errors (mTMA cross-contamination). The retest and clinical follow-up data, combined with published evidence that the two discriminatory assays have the same sensitivity as multiplex HIV-1 and HCV, support the recommendation that donors with an NDR result for whom the multiplex reactivity cannot be reproduced should either not be notified or be deferred or should be counseled that they are not infected and expeditiously reinstated.

Blood Donors↗

PubMed2004

Triggers for switching from minipool testing by nucleic acid technology to individual-donation nucleic acid testing for West Nile virus: analysis of 2003 data to inform 2004 decision making.

BACKGROUND: Concern about West Nile virus (WNV) transfusion-transmitted infections missed by minipool (MP) nucleic acid testing (NAT) has prompted consideration of the use of individual-donation (ID) NAT. Strategies were investigated for the application of limited ID-NAT capacity in 2004. STUDY DESIGN AND METHODS: Patterns of WNV MP-NAT-reactive donations tested by the Blood Systems Laboratory each week for 79 blood centers from June 29 to November 23, 2003 (196 MP-NAT repeat-reactive [RR] donations among 801,697 units), were analyzed. ID-NAT initiation strategies were developed consisting of counts of RR donations and/or weekly RR rates, together with three ID-NAT discontinuation strategies, and ID testing burden was assessed based on these combined start and stop strategies. RESULTS: The effectiveness, reported as the percentage of MP-RR donations that would trigger ID-NAT based on each initiation strategy, ranged from 57 to 100 percent. The addition of a 1- or 2-week no-yield requirement for ID discontinuation substantially increased testing burden. Combined strategies resulted in projected ID-NAT of between 10 and 50 percent of donations for a 10- to 20-week period. For this organization, the most feasible ID-NAT initiation strategy was 2 MP-reactive donations and a weekly rate of 1 in 1000, which had an effectiveness of 81 percent and led to peak weekly ID-NAT of 20 to 25 percent of donations depending on the discontinuation rule. CONCLUSION: This new approach of targeted ID-NAT based on ongoing monitoring of MP-NAT yield may prove to be a rational policy for agents like WNV that cause seasonal and regional epidemics.

Blood Banks↗