Sensitivity of two hepatitis B virus, hepatitis C virus (HCV), and human immunodeficiency virus (HIV) nucleic acid test systems relative to hepatitis B surface antigen, anti-HCV, anti-HIV, and p24/anti-HIV combination assays in seroconversion panels

BACKGROUND: Accurate determination of the infectious window period (IWP) that remains with individual-donation (ID) or minipool (MP) NAT compared to those with serology assays is essential for residual risk estimations.
STUDY DESIGN AND METHODS: The relative sensitivity of the Procleix Tigris system (Gen-Probe/Chiron) used in ID-NAT format and cobas s 201 (Roche Molecular Systems) applied in 1:6 diluted samples to mimic six-minipool (MP6) nucleic acid test (NAT) was assessed by quadruplicate testing of five seroconversion panels per marker. A mathematical analysis based on the log-linear increase of viremia in the ramp-up phase, as established with bDNA 3.0 assays enabled estimation of the IWP for human immunodeficiency virus (HIV) and hepatitis B virus (HBV) assays.
RESULTS: The mean IWPs were Tigris HIV RNA 5.5 days, s 201 (1:6) HIV RNA 7.4 days, GenScreen Plus p24/anti-HIV 17.8 days, PRISM anti-HIV 19.0 days, Tigris HBV DNA 20.6 days, s 201 (1:6) HBV DNA 22.6 days, Bio-Rad hepatitis B surface antigen (HBsAg) 37.8 days, and PRISM HBsAg 35.5 days. At estimated 50 percent NAT seroconversion rates, s 201 (1:6) and Tigris showed mean window-period reduction times (WPRTs) of 30.5 to 35.5 days to hepatitis C virus antibody (anti-HCV) assays, 10.4 to 13.5 days to anti-HIV, or combination p24/anti-HIV assays and 12.8 to 17.2 days to HBsAg assays.
CONCLUSIONS: Tigris ID-NAT detected HIV RNA 2 days earlier than s 201 MP6-NAT, but the difference in sensitivity between the two NAT systems was not significant in HBV seroconversion panels. Insufficient seroconversion samples were available for reliable modeling of WPRT in early HCV infection, but 1.4 to 2.0 days could be predicted by translating analytical sensitivity data. Both multiplex NAT systems demonstrate significant WPRTs compared to (combined) antigen and antibody assays.     

One-year experience of nucleic acid technology testing for human immunodeficiency virus Type 1, hepatitis C virus, and hepatitis B virus in Thai blood donations

BACKGROUND: Blood donations collected at the National Blood Center, the Thai Red Cross Society, Bangkok, in 2007 were tested by nucleic acid amplification technology (NAT) using the Chiron TIGRIS/Procleix Ultrio test and the Roche cobas s 201/cobas TaqScreen multiplex (MPX) test.
STUDY DESIGN AND METHODS: The sensitivity, specificity, and robustness were determined by testing 486,676 seronegative blood donations. Samples from each day of collection were divided into two sets; the odd-numbered samples were tested individually on the TIGRIS and the even-numbered samples were tested in pools of 6 on the cobas s 201. The status of reactive samples was confirmed by duplicate testing of samples from the plasma bag to calculate the test specificity. Reactive samples were tested on the alternate system and followed up.
RESULTS: The analytical sensitivity of both systems met the 95% limits of detection claimed by the respective package inserts. No cross contamination was seen with either system. Test specificity was 99.93 and 99.90% for the Procleix Ultrio and cobas TaqScreen tests, respectively. The NAT yield rates for human immunodeficiency virus Type 1 (HIV-1), hepatitis C virus (HCV), and hepatitis B virus (HBV) were 1:97,000, 1:490,000, and 1:2800, respectively. Several occult HBV donors, the majority of whom were detected by both tests, were also identified. The HIV-1 and HCV window cases were detected with both tests.
CONCLUSION: The performances of the systems and tests indicated that both were acceptable for routine NAT by the National Blood Center, the Thai Red Cross Society. However, the Procleix Ultrio test appeared to be less sensitive than the cobas TaqScreen test for HBV.     

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.     

Impact of nucleic acid testing for hepatitis B virus, hepatitis C virus, and human immunodeficiency virus on the safety of blood supply in Italy: a 6-year survey

BACKGROUND: Nucleic acid testing (NAT) for hepatitis C virus (HCV) and human immunodeficiency virus (HIV) has been implemented in several European countries and in the United States, while hepatitis B virus (HBV) NAT is still being questioned by opinions both in favor and against such an option, depending on the HBV endemicity, health care resources, and expected benefits. STUDY DESIGN AND METHODS: This survey was aimed to assess the NAT impact in improving the safety of blood supply in Italy, 6 years after implementation. The study involved 93 Italian transfusion centers and was carried out in 2001 through 2006. A total of 10,776,288 units were tested for the presence of HCV RNA, 7,932,430 for HIV RNA, and 3,405,497 for HBV DNA, respectively. RESULTS: Twenty‐seven donations or 2.5 per million tested were HCV RNA–positive/anti‐HCV–negative; 14 or 1.8 per million units tested were HIV RNA–positive/anti‐HIV–negative; and 197 or 57.8 per million donations tested were HBV DNA–positive/hepatitis B surface antigen–negative. Of the latter, 8 (2.3/10⁶) were collected from donors in the window phase of infection and 189 (55.5/10⁶) from donors with occult HBV. Sixty‐eight percent of the latter donors had hepatitis B surface antibody, 74.5 percent of whom with concentrations considered protective (≥10 mIU/mL). CONCLUSION: NAT implementation has improved blood safety by reducing the risk of entering 2.5 HCV and 1.8 HIV infectious units per million donations into the blood supply. The yield of NAT in detecting infectious blood before transfusion was higher for HBV than for HCV or HIV. However, the benefit of HBV NAT in terms of avoided HBV‐related morbidity and mortality in blood recipients needs to be further evaluated.     

Evaluation of a multiplex human immunodeficiency virus-1, hepatitis C virus, and hepatitis B virus nucleic acid testing assay to detect viremic blood donors in northern Thailand

BACKGROUND: Screening of blood donors with nucleic acid testing (NAT) for human immunodeficiency virus (HIV) and hepatitis C virus (HCV) has been implemented recently in the United States. There are limited data, however, on the additional NAT yield of donors in developing countries in Asia where the prevalence of infection is higher. In addition, data on hepatitis B virus (HBV) NAT in high prevalence areas are minimal. STUDY DESIGN AND METHODS: A total of 5083 whole-blood donors at the Chiang Mai University Hospital, Thailand, blood bank were evaluated with a commercially available NAT assay (Procleix Ultrio, Gen-Probe, Inc.) to screen individual donations. RESULTS: No NAT yield cases were found for HIV-1 or HCV. There were 17 samples with discrepant HBV DNA NAT and hepatitis B surface antigen (HBsAg) tests, however. Seven of these were HBV DNA NAT-positive, HBsAg-negative; of these 7, 1 was NAT-positive at baseline, but negative on follow-up, and considered a false-positive, 1 had an acute infection, and 5 had chronic prevalent HBV infections, for a NAT yield of 6 in 4798 HBsAg negative donors (1:800). In addition there were 10 NAT-negative, HBsAg-positive serum samples. All were anti-hepatitis B core antigen immunoglobulin G-positive; on testing with a more sensitive NAT target capture assay, 5 were positive (1.8-20.6 IU/mL) and 5 were negative. CONCLUSION: Multiplex NAT screening of individual-donor serum samples in Northern Thailand detected approximately 1 per 800 HBV NAT-positive, HBsAg-negative donors. The especially high prevalence of HBV infection in Thailand and other Asian countries suggests that HBV NAT screening of donors will be more cost-effective than in other areas.     

Residual risk of transfusion-transmitted human immunodeficiency virus, hepatitis C virus, and hepatitis B virus infections in Italy

BACKGROUND: Estimating the risk of transfusion-transmitted infections (TTIs) is essential for monitoring blood safety. The residual risk of TTI was estimated for nearly 90 percent of the blood supply in Italy. STUDY DESIGN AND METHODS: Data were analyzed from 1,079,281 repeat donors, corresponding to 5,361,000 donations made in blood transfusion centers throughout Italy in the period 1999 through 2001. The residual risk of transfusion-transmitted human immunodeficiency virus (HIV), hepatitis C virus (HCV), and hepatitis B virus (HBV) infections was estimated with the incidence rate-window period model. The denominator for the incidence rate (i.e., the number of person-years at risk) was estimated on a sample of 5850 donors. RESULTS: The risk of an infectious donation entering the blood supply, per 1 million donations, was 1.91 (probable range, 0.52-3.32) for HIV, 16.74 (9.57-24.01) for HCV, and 69.16 (43.12-102.70) for total HBV (adjusted for vaccination and hepatitis B surface antigen transience). CONCLUSION: In Italy, the estimated residual risk of TTI is apparently low, particularly for HIV infection. Although the estimated risks are higher for HCV and HBV, the introduction of mandatory viral detection tests for HCV in 2002 should account for an 80 percent reduction in the HCV risk. Moreover, the ongoing HBV vaccination program will contribute to reducing the risk of transfusion-transmitted HBV.     

Comparison of the analytical and operational performance of two viral nucleic acid test blood screening systems: Procleix Tigris and cobas s 201

BACKGROUND: The operational and analytical performance of two automated triplex hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) nucleic acid test (NAT) systems were compared in four screening laboratories of the French Blood Service.
STUDY DESIGN AND METHODS: Two laboratories evaluated the Procleix Tigris system (Chiron/Gen-Probe) in individual donation (ID) format and two sites used the cobas s 201 system (Roche Molecular Systems) on minipools (MPs) of six donations. The analytical sensitivity, the specificity, and operational performance were compared.
RESULTS: The ID to MP-NAT relative sensitivity factors in standard dilution panels of different genotypes varied between 8.7 and 21.9 for HCV RNA, 6.7 and 14.8 for HIV RNA, and 0.71 and 11.6 for HBV DNA. Tigris was 800-fold more sensitive than cobas s 201 (1:6) for a HIV group O sample, but did not detect the HIV-2 sample picked up by cobas s 201 with equal sensitivity as the HIV-1 group M samples. The specificity of both NAT systems after initial screening of 10,520 donations with Tigris and 1444 test pools on s 201 was 99.9 percent for both systems, but reached 100 percent after the repeat and pool resolution test algorithms. A higher throughput of the pool test protocol on cobas s 201 became apparent when the daily workload was more than 400 donations.
CONCLUSIONS: Tigris ID-NAT format was significantly more sensitive than cobas s 201 MP-NAT in detecting HCV RNA and HIV RNA dilution panels, but despite the 1:6 dilution factor in s 201 the difference in sensitivity was not significant for some of the HBV genotype panels. Both NAT systems demonstrated acceptable operational performance, but for routine use further improvement in system reliability is desirable.     

Prevalence of serologic markers for hepatitis B and C viruses in Brazilian blood donors and incidence and residual risk of transfusion transmission of hepatitis C virus

BACKGROUND: We evaluate the current prevalence of serologic markers for hepatitis B virus (HBV) and hepatitis C virus (HCV) in blood donors and estimated HCV incidence and residual transfusion‐transmitted risk at three large Brazilian blood centers. STUDY DESIGN AND METHODS: Data on whole blood and platelet donations were collected from January through December 2007, analyzed by center; donor type; age; sex; donation status; and serologic results for hepatitis B surface antigen (HBsAg), antibody to hepatitis B core antigen (anti‐HBc), and anti‐HCV. HBV and HCV prevalence rates were calculated for all first‐time donations. HCV incidence was derived including interdonation intervals that preceded first repeat donations given during the study, and HCV residual risk was estimated for transfusions derived from repeat donors. RESULTS: There were 307,354 donations in 2007. Overall prevalence of concordant HBsAg and anti‐HBc reactivity was 289 per 100,000 donations and of anti‐HCV confirmed reactivity 191 per 100,000 donations. There were significant associations between older age and hepatitis markers, especially for HCV. HCV incidence was 3.11 (95% confidence interval, 0.77‐7.03) per 100,000 person‐years, and residual risk of HCV window‐phase infections was estimated at 5.0 per million units transfused. CONCLUSION: Improvement in donor selection, socioeconomic conditions, and preventive measures, implemented over time, may have helped to decrease prevalence of HBV and HCV, relative to previous reports. Incidence and residual risk of HCV are also diminishing. Ongoing monitoring of HBV and HCV markers among Brazilian blood donors should help guide improved recruitment procedures, donor selection, laboratory screening, and counseling strategies.     

Prevalence and trends of human immunodeficiency virus, hepatitis B virus, and hepatitis C virus among blood donors in Iran, 2004 through 2007

BACKGROUND: Evaluation and monitoring the prevalence of transfusion-transmissible viral infections in blood donors is a valuable index of donor selection and blood safety. This study analyzed the trends of blood-borne infections among Iranian blood donations during 4 years.
STUDY DESIGN AND METHODS: Viral screening results of 6,499,851 allogeneic donations from 2004 through 2007 were analyzed. All donations were screened for hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), and syphilis. The prevalence of HBV, HCV, and HIV infections per 100,000 donations and 95% confidence interval was calculated. The p value was estimated by chi-square test.
RESULTS: The prevalences of HBV, HCV, and HIV decreased during the 4-year study from 2004 through 2007. The overall prevalence was 0.56% for HBV, 0.004% for HIV, and 0.13% for HCV. There was a significant and impressive decrease in hepatitis B surface antigen prevalence from 0.73% in 2004 to 0.41% in 2007. The prevalence of HIV appeared to have decreased from 0.005% in 2004 to 0.004% in 2007 although the decrease was not significant. HCV prevalence showed a slight decline in blood donations from 0.14% in 2005 to 0.12% in 2007.
CONCLUSION: The trends of transfusion-transmitted infection prevalence in Iranian blood donations suggest that most of the safety measures employed in recent years in Iran have been effective.     

Infectivity of blood components with low hepatitis B virus DNA levels identified in a lookback program

BACKGROUND: Japanese Red Cross (JRC) blood centers implemented anti-hepatitis B core antigen (HBc) screening in 1989 and 50-minipool (MP)-nucleic acid testing (NAT) in 2000. A systematic lookback study has been conducted to determine the hepatitis B virus (HBV) transmission risk of donations drawn in the pre-hepatitis B surface antigen (HBsAg) and/or MP-NAT window phase and by donors with occult HBV infection. STUDY DESIGN AND METHODS: JRC blood centers have been storing aliquots of every blood donation since 1996. On the basis of the complete repository tube archives, all donations from repeat donors received from 1997 to 2004 were subjected to a lookback study. When repeat donors turned positive for HBV viral marker(s), repository tubes from their previous donations were tested for HBV with individual-donation (ID)-NAT. The frequency of ID-NAT-only-positive donations and the HBV transmission risk by the transfusion of those components were investigated. RESULTS: HBV ID-NAT was performed on 15,721 repository tubes, and 158 tubes (1.01%) were found positive for the presence of HBV DNA. Of these 158 ID-NAT-only-positive donations, 95 (60%) were derived from carriers with low anti-HBc titers. Of 63 patients transfused with ID-NAT-only-positive components, 12 (19%) proved to be infected with HBV. Only 1 of 33 components with low anti-HBc titers could be identified as infectious, whereas 11 of 22 anti-HBc-negative components proved to be infectious. None of the 16 identified hepatitis B surface antibody-positive components showed serologic evidence of infection. CONCLUSION: The clinically observed HBV infection risk caused by blood components from occult HBV carriers with low anti-HBc titers who slip through the JRC screening system is more than 10-fold lower than the transmission risk by donations in the pre-HBsAg and/or MP-NAT window phase.     

Cost-effectiveness of additional hepatitis B virus nucleic acid testing of individual donations or minipools of six donations in the Netherlands

BACKGROUND: To further reduce the risk of hepatitis B virus (HBV) transmission by blood transfusion, nucleic acid testing (NAT) can be employed. The aim of this study is to estimate the incremental cost-effectiveness ratio (ICER) in the Netherlands of employing a triplex NAT assay aimed at HBV nucleic acid detection in individual donations (ID-NAT) or in minipools of 6 donations (MP-6-NAT), compared to a triplex NAT assay in minipools of 24 donations (MP-24-NAT).
STUDY DESIGN AND METHODS: A mathematical model was made of the whole transfusion chain from donors to recipients of blood in the Netherlands. The annual number of avoided HBV transmissions was estimated with the window-period incidence model. The natural history of a HBV infection in recipients is described by a Markov model.
RESULTS: The ICER of adding HBV MP-6-NAT or HBV ID-NAT in the Netherlands is €303,218 (95% confidence interval [CI], €233,001-€408,388) and €518,995 (95% CI, €399,359-€699,120) per quality-adjusted life-year, respectively. The ICER strongly correlates with the age of transfusion recipients.
CONCLUSION: The cost-effectiveness of additional HBV NAT is limited by the limited loss of life caused by HBV transmission. Despite a higher effectiveness, HBV ID-NAT is less cost-effective than MP-6-NAT due to higher costs. A future equivalent participation of immigrants from HBV-endemic countries in the donor base renders HBV NAT only slightly more cost-effective.     

Prevalence,incidence, and residual risk of human immunodeficiency virus and hepatitis C virus infections among United States blood donors since the introduction of nucleic acid testing

BACKGROUND: Nucleic acid testing (NAT) for human immunodeficiency virus (HIV) and hepatitis C virus (HCV) was introduced for blood donation screening in the United States in 1999. This study analyzes temporal trends of these two infections since NAT introduction. STUDY DESIGN AND METHODS: Donation data from 1999 to 2008 were analyzed; each donation was tested for antibodies and viral RNA for HIV and HCV. Incidence for first‐time (FT) donors was derived by multiplying that among repeat (RP) donors by the ratio of NAT yield rates between FT and RP donors. Incidence for all donors was the weighted mean based on percentage of FT and RP donors. Residual risk (RR) was determined using the window‐period model. RESULTS: During the 10‐year period approximately 66 million donations were screened with 32 HIV (1:2 million) and 244 HCV (1:270,000) NAT yield donations identified. HCV prevalence among FT donors decreased by 53% for 2008 compared to 1999. HIV and HCV incidence among RP donors increased in 2007 through 2008 compared to 2005 through 2006. During 2007 through 2008, HIV incidence was 3.1 per 10⁵ person‐years (py), with an RR estimate of 0.68 per 10⁶ (1:1,467,000) donations; HCV incidence was 5.1 per 10⁵ py, with an RR estimate of 0.87 per 10⁶ (1:1,149,000). The increase in HIV incidence was primarily among 16‐ to 19‐year‐old, male African American donors and that in HCV was primarily among Caucasian donors of 50 or more years. Donors from the Southern United States had higher incidence rates. CONCLUSION: HCV prevalence decreased significantly since NAT introduction. The increase in HIV and HCV incidence in 2007 through 2008 warrants continued monitoring and investigation.     

单检及16份混样检测模式对献血者核酸检测效果的比较研究

目的 探讨单份及16份混合标本2种检测模式对献血者血液病毒核酸检测(nucleic acid test,NAT)效果的影响.方法 2009年2至6月顺序留取北京无偿献血者标本,用诺华Procleix ULTRIO Assay进行单份(ID)或16份混合标本(P16)乙型肝炎病毒(HBV)、丙型肝炎病毒(HCV)和人类免疫缺陷病毒-1( HIV-1)三项联合核酸检测.单份NAT反应性同时HBsAg、抗-HCV或抗-HIV血清学不合格的标本,血清学合格的单份NAT反应性经双孔NAT复检阳性的标本,以及混合NAT反应性/拆分NAT为阳性的标本,进一步用诺华Procleix HBV、HCV和HIV-1鉴别试剂进行鉴别试验.血清学合格、HBV NAT单独阳性标本进一步用Roche HBV定量实验加以验证和进行病毒含量测定、血清学分析、并进行稀释以模拟是否能被P16-NAT检出.阳性检出率进行四格表连续校正的x2检验.结果 (1)在7613份单份NAT (ID-NAT)标本中,检出NAT阳性26份,ID-NAT阳性率0.34％(26/7613);(2)在16 064份共1004份P16混合标本NAT(P16-NAT)中,检出NAT阳性27份,P16-NAT阳性率为0.17％ (27/16 064);(3)在血清学合格标本中,单份检测的NAT单独阳性检出率为0.12％ (9/7438),高于16份混样检测的NAT单独阳性检出率0.01％ (2/15 750)(x2=11.880,P＜0.05).9份ID-NAT及2份P16-NAT单独阳性标本经鉴别均为HBV NAT阳性,未检出 HCV NAT单独阳性或HIV NAT单独阳性;(4)9份ID-NAT HBV单独阳性血样模拟P16-NAT,仅有2份可被检出;(5)对8份ID-NAT及2份P16-NAT单独阳性标本进行Roche HBV定量测定,均可确证其核酸检测结果,但病毒含量很低.其中2份HBV病毒含量为472 IU/ml及15 IU/ml,6份含量＜12 IU/ml,另2份原倍不能定量经10倍浓缩处理后测得含量为＜ 12 IU/ml和14.3 IU/ml;(6)11份HBV NAT单独阳性标本中,3份(27.3％)为潜在的窗口期感染,其余8份(72.7％)抗-HBc阳性或抗-HBe阳性,但抗-HBc-IgM均为阴性,为隐匿性感染;(7) P16-NAT初检呈反应性需要进行拆分试验的混合样本比率为2.49％ (25/1004),其中由血清学合格标本所致初检反应性的混合样本比率为0.20％ (2/1004).结论 ID-NAT单独阳性检出率高于P16-NAT单独阳性检出率.为避免低病毒含量HBV的漏检,应选用灵敏度高的核酸检测试剂,并尽量采用小标本量混合检测,甚至采用单份检测方式.     

A pilot study for screening blood donors in Taiwan by nucleic acid amplification technology: detecting occult hepatitis B virus infections and closing the serologic window period for hepatitis C virus

BACKGROUND: Blood donors in Taiwan currently are screened for hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) infection by immunoassay. The risk of enzyme immunoassay (EIA)-negative, nucleic acid amplification technology (NAT)-reactive donations is not well understood. This study aimed to screen for such donors in Taiwan by a multiplex test (cobas TaqScreen, Roche) on a commercially available NAT system (cobas s 201 system, Roche). STUDY DESIGN AND METHODS: NAT was performed on donors without prescreening in pools of six and NAT-reactive pools were then resolved to the single donation. Individual-donor NAT-reactive samples were discriminated by a commercially available polymerase chain reaction (PCR)-based diagnostic assay (COBAS AmpliScreen, Roche). Samples with EIA- and NAT-discordant results were investigated with supplemental serologic and confirmatory tests. Each sample taken from follow-up of HBV NAT yield cases was tested for HBV serologic profile, NAT, and viral load. The sensitivity and performance efficacy were also evaluated. RESULTS: The 95 percent limit of detection (LOD) for HBV, HCV, and HIV were 5.09, 11.83, and 62.53 IU per mL, respectively. Among 10,727 seronegative donations, 12 HBV NAT yield cases (0.11%) and 1 HCV NAT yield case (0.01%) were detected. Follow-up results for 1 to 8 months showed that the HCV yield case was a window case and all HBV NAT yield cases were occult carriers. CONCLUSION: The use of NAT detected occult HBV and reduced HCV window period. The yield rate, especially occult HBV, was 10- to 100-fold higher than that in developed, HBV nonendemic countries. Therefore, NAT implementation for routine donor screening in a more cost-effective manner should contribute to safer blood transfusion in Taiwan.     

献血者HBV、HCV、HIV的单人份核酸检测

目的应用Procleix ULTRIO Assay和Procleix TIGRIS System进行献血者单人份病毒核酸检测（ID-NAT）,以了解ELISA法筛查的HBV、HCV、HIV漏检率,同时对ID-NAT和汇集NAT（MP-NAT）模式进行比较。方法在进行2次ELISA法筛查的同时,应用ULTRIO试剂在TIGRIS系统上行ID-NAT检测,对有活性的标本再分别进行HBV、HCV、HIV的鉴别测定,对ID-NAT阳性标本再进行8个（MP-8-NAT）和16个（MP-16-NAT）样品的模拟混样检测。结果在10064名无偿献血者中,共检出10例ELISA法阴性、ID-NAT阳性标本,ELISA法筛查漏检率为0.99‰,该10例标本经鉴别实验确定为HBV DNA阳性;共检出28例ELISA法阳性、ID-NAT阳性标本,其中HCV6例、HBV22例。将28例ELISA法阳性、ID-NAT阳性及10例ELISA法阴性、ID-NAT阳性标本进行8个、16个样品模拟汇集,结果 MP-8-NAT、MP-16-NAT的阳性检出率分别下降为78.6%、75.0%和30.0%、20.0%。结论 2次ELISA法血清学筛查模式存在较高的HBV漏检;ID-NAT的灵敏度高于MP-NAT,对于ELISA法阴性、ID-NAT阳性标本,MP-NAT存在很高的漏检率。     

Sensitivity of hepatitis B virus DNA transcription-mediated amplification testing in hepatitis B surface antigen-positive blood donations

BACKGROUND: The objective was to evaluate the performance of nucleic acid testing (NAT) in the detection of hepatitis B virus (HBV) infection in hepatitis B surface antigen (HBsAg)-positive blood donations. STUDY DESIGN AND METHODS: A total of 253 HBsAg- and anti-hepatitis B core antigen (HBc)-positive samples (50 hepatitis B e antigen [HBeAg]-positive and 203 anti-HBe-positive) from blood donations collected in France were studied. The samples were investigated with a blood screening assay (Procleix Ultrio, Chiron/Gen-Probe) in minipool (MP; x8) and in individual-donation (ID) testing. All nonreactive samples were retested once, and nonreactive MP samples were assayed for viral load (VL). RESULTS: All 50 HBeAg-positive samples were reactive in MP-NAT and ID-NAT. Of the 203 anti-HBe-positive donations, 80.3 percent were MP- and ID-reactive, 17.2 percent were MP-nonreactive and ID-reactive, and 2.5 percent were nonreactive in ID-NAT. Overall the sensitivity of ID-NAT was 98 percent versus 84 percent for MP-NAT. After retesting, 16 of the 35 MP-nonreactive and/or ID-reactive donations became MP-reactive and 2 of the ID-nonreactive donations became NAT-reactive. The capacity of Procleix Ultrio to detect HBV DNA was not related to HBsAg subtype, but correlated with the VL: the mean VL in the group of MP-nonreactive samples was 1,420 copies per mL vs. 17,000 copies per mL in the group of 40 MP-reactive samples. CONCLUSION: These results demonstrate that HBV-NAT in ID format is far more effective in detecting viremia in chronic HBsAg carriers than in MP-NAT. The sensitivity of the NAT assay needs to be improved to be considered for replacing the current HBsAg assays, especially when anti-HBc testing is not performed.     

Experience of German Red Cross blood donor services with nucleic acid testing: results of screening more than 30 million blood donations for human immunodeficiency virus-1, hepatitis C virus, and hepatitis B virus

BACKGROUND: The risk of transfusion-transmitted human immunodeficiency virus-1 (HIV-1), hepatitis C virus (HCV), and hepatitis B virus (HBV) infections is predominantly attributable to donations given during the early stage of infection when diagnostic tests may fail. In 1997, nucleic acid amplification technique (NAT)-testing was introduced at the German Red Cross (GRC) blood donor services to reduce this diagnostic window period (WP). STUDY DESIGN AND METHODS: A total of 31,524,571 blood donations collected from 1997 through 2005 were screened by minipool NAT, predominantly with pool sizes of 96 donations. These donations cover approximately 80 percent of all the blood collected in Germany during that period. Based on these data, the WP risk in the GRC blood donor population was estimated by using a state-of-the-art mathematic model. RESULTS: During the observation period, 23 HCV, 7 HIV-1, and 43 HBV NAT-only-positive donations were detected. On the basis of these data and estimated pre-NAT infectious WPs, the residual risk per unit transfused was estimated at 1 in 10.88 million for HCV (95% confidence interval [CI], 7.51-19.72 million), 1 in 4.30 million for HIV-1 (95% CI, 2.39-21.37 million), and 1 in 360,000 for HBV (95% CI, 0.19-3.36 million). Based on observed cases of breakthrough infections, the risk of transfusion-related infections may be even lower. CONCLUSION: The risk of a blood recipient becoming infected with HCV, HIV-1, or HBV has reached an extremely low level. Introduction of individual donation testing for HCV and HIV-1 would have a marginal effect on interception of WP donations.     

Efficacy of individual nucleic acid amplification testing in reducing the risk of transfusion‐transmitted hepatitis B virus infection in Switzerland,a low‐endemic region

BACKGROUND: The risk of transfusion‐transmitted hepatitis B virus (HBV) in Switzerland by testing blood donors for hepatitis B surface antigen (HBsAg) alone has been historically estimated at 1:160,000 transfusions. The Swiss health authorities decided not to introduce mandatory antibody to hepatitis B core antigen (anti‐HBc) testing but to evaluate the investigation of HBV nucleic acid testing (NAT). STUDY DESIGN AND METHODS: Between June 2007 and February 2009, a total of 306,000 donations were screened routinely for HBsAg and HBV DNA by triplex individual‐donation (ID)‐NAT (Ultrio assay on Tigris system, Gen‐Probe/Novartis Diagnostics). ID‐NAT repeatedly reactive donors were further characterized for HBV serologic markers and viral load by quantitative polymerase chain reaction. The relative sensitivity of screening for HBsAg, anti‐HBc, and HBV DNA was assessed. The residual HBV transmission risk of NAT with or without anti‐HBc and HBsAg was retrospectively estimated in a mathematical model. RESULTS: From the 306,000 blood donations, 31 were repeatedly Ultrio test reactive and confirmed HBV infected, of which 24 (77%) and 27 (87%) were HBsAg and anti‐HBc positive, respectively. Seven HBV‐NAT yields were identified (1:44,000), two pre‐HBsAg window period (WP) donations (1:153,000) and five occult HBV infections (1:61,000). Introduction of ID‐NAT reduced the risk of HBV WP transmission in repeat donors from 1:95,000 to 1:296,000. CONCLUSIONS: Triplex NAT screening reduced the HBV WP transmission risk approximately threefold. NAT alone was more efficacious than the combined use of HBsAg and anti‐HBc. The data from this study led to the decision to introduce sensitive HBV‐NAT screening in Switzerland. Our findings may be useful in designing more efficient and cost‐effective HBV screening strategies in low‐prevalence countries.     

Detection of an early HIV-1 infection by HIV RNA testing in an Italian blood donor during the preseroconversion window period

BACKGROUND: The implementation of NAT technologies for HIV screening has further reduced the diagnostic window in recent HIV infection. There is still a debate regarding the cost effectiveness of genomic screening of blood donations for transfusion-transmitted viruses (HBV, HCV, HIV). STUDY DESIGN AND METHODS: Since October 2001, at the Transfusion Service of Verona, single-donation NAT testing for HCV and HIV-1 (Procleix TMA HIV-1/HCV Assay) of all blood donations has been performed. CASE REPORT: A case of acute HIV-1 infection detected by HIV NAT in a repeat blood donor who donated during the preseroconversion window period is reported. All blood components donated were discarded, and the donor started antiretroviral therapy 2 weeks after blood donation. HIV-1 p24 antigen was still negative 10 days after the HIV-1 RNA-positive blood donation. Seroconversion was documented by Day 41 after donation. CONCLUSION: This case report testifies that HIV NAT screening of blood donation is effective in preventing the transmission of HIV infection through blood components.     

Residual risk of transfusion-transmitted viral infections in Shenzhen, China, 2001 through 2004

BACKGROUND: There are no current estimates of the residual risks of transmission by blood of hepatitis B virus (HBV) or hepatitis C virus (HCV) and human immunodeficiency virus (HIV) in China. Such estimates are an essential prerequisite to monitoring and improving transfusion safety as well as supporting evidence based assessment of the value of implementing new screening interventions. STUDY DESIGN AND METHODS: Viral screening data for donors from Shenzhen, China, for the period 2001 to 2004, were retrospectively analyzed. The data were applied to a published model to estimate the residual risk of transmitting HIV, HBV, and HCV by blood transfusion in Shenzhen, as well as to assess the residual risk reduction value of various new tests. RESULTS: The point estimates for the combined 2003 and 2004 period calculate as 1 in 17,501 for HBV, 1 in 59,588 for HCV, and 1 in 903,498 for HIV. The predicted yield for improved hepatitis B surface antigen (HBsAg) assays, minipool (MP) nucleic acid testing (NAT), and individual-donation (ID) NAT was 6.9, 9.5, and 28.3 per million donations, respectively. The predicted yield for implementing a fourth-generation HCV (antigen-antibody) or MP NAT assay was 13.4 or 14.7 per million donations, respectively. For HIV, the predicted yield for implementing a fourth-generation HIV (antigen-antibody) or MP NAT assay was markedly smaller, 0.25 or 0.65 per million donations, respectively. CONCLUSIONS: Relative to that reported for Western blood systems, the prevalence and the residual risk of HBV and HCV are high, whereas HIV is comparable. Pending a formal cost-effectiveness study for NAT, implementing improved HBsAg and combination HCV antibody-antigen assays in Shenzhen would markedly reduce the residual risk.