Residual risk of transfusion‐transmitted hepatitis B virus (HBV) infection caused by blood components derived from donors with occult HBV infection in Japan

BACKGROUND: Nucleic acid amplification testing (NAT) for hepatitis B virus (HBV) during blood screening has helped to prevent transfusion‐transmitted HBV infection (TT‐HBV) in Japan. Nevertheless, 4 to 13 TT‐HBV infections arise annually. STUDY DESIGN AND METHODS: The Japanese Red Cross (JRC) analyzed repository samples of donated blood for TT‐HBV that was suspected through hemovigilance. Blood donations implicated in TT‐HBV infections were categorized as either window period (WP) or occult HBV infection (OBI) related. In addition, we analyzed blood from 4742 donors with low antibody to hepatitis B core antigen (anti‐HBc) and antibody to hepatitis B surface antigen (anti‐HBs) titers using individual‐donation NAT (ID‐NAT) to investigate the relationship between anti‐HBc titer and proportion of viremic donors. RESULTS: Introduction of a more sensitive NAT method for screening minipools of 20 donations increased the OBI detection rate from 3.9 to 15.2 per million, while also the confirmed OBI transmission rate increased from 0.67 to 1.49 per million. By contrast the WP transmission rate decreased from 0.92 to 0.46 per million. Testing repository samples of donations missed by minipools of 20 donations NAT showed that 75 and 85% of TT‐HBV that arose from WP and OBI donations, respectively, would have been interdicted by ID‐NAT. The ID‐NAT trial revealed that 1.94% of donations with low anti‐HBc and anti‐HBs titers were viremic and that anti‐HBc titers and the frequency of viremia did not correlate. CONCLUSIONS: The JRC has elected to achieve maximal safety by discarding all units with low anti‐HBc and anti‐HBs titers that account for 1.3% of the total donations.     

Blood donation screening for hepatitis B virus markers in the era of nucleic acid testing: are all tests of value?

BACKGROUND: The American Red Cross implemented hepatitis B virus (HBV) minipool (MP)‐nucleic acid testing (NAT) in June 2009, in addition to existing tests for hepatitis B surface antigen (HBsAg) and antibodies to hepatitis B core antigen (anti‐HBc). The value of all three tests was evaluated. STUDY DESIGN AND METHODS: HBsAg, anti‐HBc, and HBV DNA (Ultrio MP‐NAT, Gen‐Probe/Novartis) donation results were analyzed during a 12‐month period (July 1, 2009‐June 30, 2010). Additional testing by individual‐donation (ID) polymerase chain reaction (PCR) to confirm donor infection was performed when any HBV screening test was reactive or positive, except in the case of HBsAg neutralization‐positive, anti‐HBc–reactive samples. Numbers of blood donations identified as reactive or positive versus nonreactive or negative were compared. RESULTS: Of about 6.5 million donations, 699 were defined as from HBV‐infected donors, of which 64% (444) were reactive for all three markers. More than 99% (697) had reactivity to one or both serologic tests with 68% (477) showing reactivity by MP‐NAT. Only two donations were DNA‐positive, seronegative NAT‐yield donations (1 per 3.23 million), fewer than expected (p = 0.0075). Among MP‐NAT–reactive donors, only small numbers represented early infection (2 or 0.4% with negative serology and 10 or 2.1% who were HBsAg confirmed positive, anti‐HBc nonreactive). Of the 142 occult HBV‐infected donors, 85% were MP‐NAT nonreactive requiring ID‐PCR for detection (121 or 54.5% of all MP‐NAT nonreactives vs. 21 or 4.4% of all MP‐NAT reactives). CONCLUSIONS: The HBV DNA–positive yield rate from MP‐NAT was lower than expected, likely representing the rarity of such findings even in very large studies. With the implementation of HBV MP‐NAT, the value of maintaining anti‐HBc for the detection of low‐level HBV DNA–positive donors was confirmed; however, HBsAg screening showed no blood safety value.     

Sensitivity comparison of two Food and Drug Administration-licensed, triplex nucleic acid test automated assays for hepatitis B virus DNA detection and associated projections of United States yield

BACKGROUND: There have been no comparisons of the relative sensitivity of the two Food and Drug Administration–licensed multiplex (MPX) nucleic acid test (NAT) systems (Procleix Ultrio [Gen‐Probe], TIGRIS platform [Novartis]; and cobas TaqScreen MPX [Roche Molecular Systems], cobas s 201 platform [Roche Instrument Center]) for detecting hepatitis B virus (HBV)‐infected donors in minipool sizes (MP) used in the United States. STUDY DESIGN AND METHODS: Routine blood samples from Thailand were obtained from plasma units from 129 hepatitis B surface antigen (HBsAg)‐negative, HBV NAT–yield donations. Blinded US testing included antibody to hepatitis B core antigen (anti‐HBc), NAT using both manufacturers' systems (undiluted‐individual donation [ID], in singlet and diluted 1:6 and 1:16 in triplicate), quantitative antibody to hepatitis B surface antigen, HBV DNA viral loads, and HBV genotyping. HBV yields in the United States were estimated using the incidence/window period (WP) model and compared to the calculated assay sensitivities. RESULTS: Eighty samples were classified as occult HBV (anti‐HBc reactive) and 49 as WP (anti‐HBc nonreactive). For US pool sizes, MPX detected significantly more samples than Ultrio (MPX MP6 vs. Ultrio MP16; p < 0.0001 for occult and WP). Ultrio MP16 results were not statistically different from Ultrio MP6 (p = 0.68 for occult; p = 0.42 for WP). There was no difference between platforms for MP sizes used in most of the world (MPX MP6 vs. Ultrio ID; p = 0.70 for occult and p = 0.34 for WP). Viral loads were higher in WP samples. Modeled yield estimates were consistent with measured assay sensitivity on the Thai donor samples. CONCLUSIONS: As used in the United States, MPX MP6 is more sensitive than Ultrio MP16, but the impact of this difference is mitigated by low numbers of HBV WP infections.     

Hepatitis B virus transmission by blood transfusion during 4 years of individual-donation nucleic acid testing in South Africa: estimated and observed window period risk

BACKGROUND: Since October 2005, a total of 2,921,561 blood donations have been screened by the South African National Blood Service for hepatitis B virus (HBV) by individual‐donation nucleic acid testing (ID‐NAT). Over 4 years, 149 hepatitis B surface antigen–negative acute‐phase HBV NAT–positive donations were identified (1:19,608). The lookback program identified one probable HBV transmission. STUDY DESIGN AND METHODS: The complete genomes of HBV isolated from the donor and recipient were sequenced, cloned, and analyzed phylogenetically. The HBV window period (WP) transmission risk was estimated assuming a minimum infectious dose of 3.7 HBV virions and an incidence rate correction factor of 1.34 for transient detectability of HBV DNA. RESULTS: Of 149 acute‐phase HBV NAT yields, 114 (1:25,627) were classified as pre–antibody to hepatitis B core antigen (anti‐HBc) WP and 35 (1:83,473) as post–anti‐HBc WP. The acute‐phase transmission risk in the HBV DNA–negative pre‐ and post–anti‐HBc WPs (of 15.3 and 1.3 days, respectively) was estimated at 1:40,000 and 1:480,000, respectively. One HBV transmission (1:2,900,000) was identified in a patient who received a transfusion from an ID‐NAT–nonreactive donor in the pre–anti‐HBc WP. Sequence analysis confirmed transmission of HBV Subgenotype A1 with 99.7% nucleotide homology between donor and recipient strains. The viral burden in the infectious red blood cell unit was estimated at 32 (22‐43) HBV DNA copies/20 mL of plasma. CONCLUSION: We report the first known case of transfusion‐transmitted HBV infection by blood screened using ID‐NAT giving an observed HBV transmission rate of 0.34 per million. The estimated pre–acute‐phase transmission risk in the ID‐NAT screened donor population was 73‐fold higher than the observed WP transmission rate.     

Significance of detecting anti‐HBc among Egyptian male blood donors negative for HBsAg*

Background: Screening for hepatitis B virus surface antigen (HBsAg) reduces the risk of transfusion‐transmitted hepatitis B viral (HBV) infection. However, the absence of HBsAg in the blood of apparently healthy individuals may not be sufficient to ensure the lack of circulating HBV. Blood containing anti‐hepatitis B core antibody (anti‐HBc) without detectable presence of HBsAg might be infectious; therefore, screening for anti‐HBc has been implemented in some countries resulting in a decrease in the risk of post‐transfusion HBV infection. Aim: To study the seroprevalence of anti‐HBc. The relationship between anti‐HBc positivity and the presence of circulating HBV among healthy blood donors negative for HBsAg will be helpful to decide whether supplemental testing may bring additional safety to blood products. Material and methods: A total of 1026 serum samples collected from HBsAg‐negative Egyptian healthy male donors were tested for the presence of anti‐HBc (both IgM and IgG types) using the competitive enzyme‐linked immunosorbent assay technique. Anti‐HBc‐positive samples were subjected to real‐time polymerase chain reaction to confirm the presence of HBV DNA. Results: Of the 1026 samples tested, 80 (7·8%) blood samples were found to be reactive to anti‐HBc. Of those, HBV DNA was detected in five of the samples (6·25%). The levels of detected viraemia were variable among the five donors. Conclusion: This study shows the insufficient effectiveness of HBsAg screening in protecting blood recipients from HBV infection. Inclusion of anti‐HBc testing should be considered in the screening of blood donors.     

Hepatitis B virus (HBV) DNA screening of blood donations in minipools with the COBAS AmpliScreen HBV test

BACKGROUND: The risk of hepatitis B virus (HBV) transmission by blood transfusion (estimated at 1 in 63,000-1 in 205,000 units in the United States) exceeds that of hepatitis C virus (HCV) or human immunodeficiency virus (HIV). Reduction of window-period HBV transmissions through detection of HBV DNA-positive units by minipool nucleic acid testing (MP NAT) would be expected to decrease this risk. STUDY DESIGN AND METHODS: A large multicenter study of the COBAS AmpliScreen HBV test (Roche Molecular Systems) was conducted on minipools of 24 blood donation specimens. The yield of HBV DNA-positive, hepatitis B surface antigen (HBsAg)-negative window-period donations was determined relative to current and newly licensed HBsAg assays. Donors with selected HBV DNA, HBsAg, and anti-hepatitis B core antigen (HBc) results were further evaluated. RESULTS: The detection rate of window-period units was 1 in 352,451 (95% confidence interval, 1 in 2,941,176-1 in 97,561). Assay specificity was high (99.9964%). HBV DNA was detected in 84 percent of HBsAg-positive, anti-HBc-positive donations by MP NAT and in 94 percent when individual-donation (ID) NAT was added. HBV DNA was detected in 0.03 percent of HBsAg-negative, anti-HBc-positive donations by MP NAT and in 0.41 percent when ID NAT was added. CONCLUSIONS: Implementation of HBV MP NAT will provide an increment in safety relative to HBV serologic screening, similar to that for HCV and in excess of that for HIV. Our data indicate that the implementation of HBV MP NAT would likely interdict 39 HBV window-period units and prevent 56 cases of transfusion-transmitted HBV infection annually. The current data indicate that HBV MP NAT should not lead to discontinuation of anti-HBc testing but that discontinuation of HBsAg testing with retention of anti-HBc testing may be possible.     

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.     

Refinement of a viral transmission risk model for blood donations in seroconversion window phase screened by nucleic acid testing in different pool sizes and repeat test algorithms

BACKGROUND: In minipool nucleic acid test (MP‐NAT) screening protocols, the donations implicated in reactive test pools are released for transfusion when they are nonreactive in a repeat test on the individual samples, but in individual‐donation (ID)‐NAT screening algorithms the release of nonrepeatable reactive (NRR) donations is under discussion. STUDY DESIGN AND METHODS: A previously developed window phase (WP) transmission risk model for NAT‐screened blood transfusions has been refined to take the effect of repeat tests of initially reactive (IR) MP‐ or ID‐NAT results into account. The model has then been applied to simulate the effect of different screening algorithms with ULTRIO and the new‐generation ULTRIO Plus assay (Novartis Diagnostics) on transmission risk for hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV). RESULTS: We calculated WP risk‐day equivalents for MP16‐, MP8‐, and ID‐NAT with and without duplicate retesting of IR results of 3.1, 2.7, 1.5, and 1.3 days for HCV; 6.3, 5.5, 3.3, and 2.9 days for HIV; and 24.4, 22.2, 15.6, and 14.1 days for HBV, respectively. These latter infectious HBV WPs reduced to 20.4, 18.2, 11.6, and 10.3 days, respectively, with the more sensitive ULTRIO Plus assay. CONCLUSION: ULTRIO Plus ID‐NAT screening reduces the virus transmission risk in the WP by 54% to 58% compared to ULTRIO MP16‐NAT, while the incremental risk caused by releasing donations with duplicate ID‐NAT NRR results is 5% to 6%. To achieve maximum safety and specificity a similar repeat test algorithm can be applied to ID‐NAT as used for serologic assays.     

Evaluation of algorithms for the diagnostic assessment and the reentry of blood donors who tested reactive for antibodies against hepatitis B core antigen

BACKGROUND: Screening of blood donations for antibodies against hepatitis B core antigen (anti‐HBc) is an accepted method to prevent some transfusion‐transmitted hepatitis B virus (HBV) infections. However, anti‐HBc testing may result in donor loss due to unspecific results in the currently available anti‐HBc tests. Algorithms to distinguish true‐positive from false‐positive results and for reentry of those donors who tested false anti‐HBc positive were evaluated retrospectively. STUDY DESIGN AND METHODS: Samples that tested reactive for anti‐HBc by chemiluminescent microparticle immunoassay (CMIA) were investigated for anti‐HBc by microparticle immunoassay, for anti‐HBs and hepatitis B surface antigen (HBsAg) by CMIA, and for HBV DNA by individual‐donor nucleic acid testing. Results were classified true positive, indeterminate, and false positive for anti‐HBc. Donors who tested indeterminate and false positive were admitted for reentry if follow‐up testing for anti‐HBc became negative and no further evidence for an HBV infection was apparent. RESULTS: A total of 554 of 148,000 samples, taken from 30,000 individuals within 3 years tested reactive for anti‐HBc by CMIA. Of those, 553 could be further classified: 142 (26%) true positive, 76 (14%) indeterminate, and 335 (60%) false positive. A total of 214 of 411 (52%) samples termed indeterminate or false positive were admitted for reentry and able to provide further donations. In one donor, anti‐HBc–positive/HBsAg‐ and HBV DNA–negative HBV DNA was detectable during follow‐up. CONCLUSION: According to our proposed algorithm, 26% of anti‐HBc–reactive results tested by CMIA were true positive. Many donors tested indeterminate or false positive can provide future donations if our proposed algorithm for reentry is applied. One donor at risk for transmitting HBV was identified solely by anti‐HBc testing.     

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.     

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.     

Impact of individual-donation nucleic acid testing on risk of human immunodeficiency virus, hepatitis B virus, and hepatitis C virus transmission by blood transfusion in South Africa

BACKGROUND: In 2005, the South African National Blood Service introduced individual-donation (ID) nucleic acid test (NAT) screening for human immunodeficiency virus (HIV) RNA, hepatitis C virus (HCV) RNA, and hepatitis B virus (HBV) DNA. At the same time the use of ethnic origin to prioritize the transfusion of blood according to a hierarchy of residual risk was discontinued.
STUDY DESIGN AND METHODS: ID-NAT (Ultrio on Procleix Tigris, Chiron) and serology (PRISM, Abbott) repeat test and confirmation testing algorithms were designed to enable differentiation between false-positive and true-NAT and -serology yields. After 1 year, the NAT and serology yield rates in first-time, lapsed, and repeat donors were analyzed and used to estimate the residual risk of HIV, HBV, and HCV infections by blood transfusion.
RESULTS: The HIV, HBV, and HCV ID-NAT window phase yield rates in 732,250 blood donations were 1:45,765, 1:11,810, and 1:732,200, respectively. Seven of 16 HIV window phase donations with viral loads above 16,000 copies/mL were HIV p24 antigen enzyme-linked immunosorbent assay positive. PRISM detected anti-HIV and hepatitis B surface antigen (HBsAg) in 89.4 and 73.9% of early infections in repeat donors. The Procleix assay detected viremia in 99.7 and 95.5% of anti-HIV– and HBsAg-positive first-time donors. In these donors, the occult HBV DNA carrier rate was 1:5200. The residual transmission risk of ID-NAT HIV, HBV, and HCV window phase donations was estimated at 1:479,000, 1:61,500, and 1:21,000,000 respectively.
CONCLUSION: One-year ID-NAT screening of 732,250 donations interdicted 16 HIV, 20 HBV, and 1 HCV window phase donations and 42 anti-hepatitis B core antigen–reactive infections during an early recovery or a later stage of occult HBV infection.     

Two cases of transfusion‐transmitted hepatitis B virus (HBV) infection in a low‐endemic country before implementation of HBV nucleic acid testing

BACKGROUND: The risk of hepatitis B virus (HBV) transmission by transfusion is higher than that of other blood‐borne viruses. In France, before the introduction of HBV nucleic acid testing (NAT) in 2010, blood donations were tested for hepatitis B surface antigen (HBsAg) and antibodies against hepatitis B core antigen, and the residual risk of HBV transfusion related to preseroconversion acute phase was estimated at 0.54 per million donations. The additional value of the implementation of a highly sensitive HBV NAT to prevent such transmissions is discussed. STUDY DESIGN AND METHODS: Two lookback investigations based on HBV seroconversion of repeat donors were performed. Donors and recipients were followed up in multiple samples that were tested for HBV serologic and molecular markers. RESULTS: The recipients have shown posttransfusion HBsAg seroconversion. The archived samples from the implicated donations were positive for HBV DNA at extremely low viral load in both cases. HBV isolates from donors and recipients of each case were organized in the same cluster with 100% identities into Genotypes A2 and B4, respectively. One recipient spontaneously recovered from infection while the second was successfully treated. CONCLUSION: The present cases highlight the importance of introducing highly sensitive HBV NAT to prevent transmission. Moreover, the lookback studies based on appropriate molecular and serologic investigations of patients transfused with previous donations from newly identified HBV‐infected repeat donors offer the opportunity to treat a recently infected recipient.     

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.     

Occult hepatitis B virus infection in Thai blood donors

BACKGROUND: An evaluation by the National Blood Center, the Thai Red Cross Society, of two commercial multiplex nucleic acid tests (NATs; the Chiron PROCLEIX ULTRIO test and the Roche Cobas TaqScreen MPX test) for screening Thai blood donors for hepatitis B virus (HBV), hepatitis C virus, and human immunodeficiency virus Type 1 identified 175 HBV NAT–reactive/hepatitis B surface antigen (HBsAg)‐negative donors. The classification of the HBV infection of these donors was confirmed by follow‐up testing. STUDY DESIGN AND METHODS: Index samples were tested for HBV serologic markers and HBV viral loads were determined. Donors were followed for up to 13 months and samples were tested with both NAT assays and for all HBV serological markers. RESULTS: Of 175 HBV NAT–yield donors, 72 (41%) were followed. Based on the follow‐up results, the majority of donors who were followed had an occult HBV infection (66.7%), followed by donors with a primary, acute infection (26.4%). The majority of donors in this latter group (20.8%) were in the window period. Three donors (4.2%), who were anti‐HBs positive, had a reinfection or breakthrough infection. CONCLUSION: The majority of donors detected during routine screening, who were HBsAg negative and NAT reactive, had an occult HBV infection, thus validating the decision to introduce NAT for blood donations in Thailand.     

Performance of an algorithm for the reentry of volunteer blood donors deferred due to false-positive test results for antibody to hepatitis B core antigen

BACKGROUND: Blood donor testing for antibody to hepatitis B core antigen (anti‐HBc) has been used in the United States for more than 20 years as a surrogate to prevent transmission by transfusion of non‐A,non‐B hepatitis, as a human immunodeficiency virus surrogate, and to reduce transmission of hepatitis B virus (HBV). Nonspecific anti‐HBc assays have caused deferral of hundreds of thousands of otherwise qualified donors. A more specific anti‐HBc test and a sensitive HBV DNA test should permit donor reentry after false‐positive anti‐HBc. STUDY DESIGN AND METHODS: A total of 1324 otherwise eligible volunteer donors, deferred for anti‐HBc reactivity on more than one occasion, were recruited from four collection facilities. They were tested using a licensed, more specific anti‐HBc test, a licensed hepatitis B surface antigen (HBsAg) test, and a licensed HBV DNA assay with a 95 percent limit of detection of not more than 10 copies per mL. RESULTS: From 11 to 32 percent of donors contacted by participating sites entered the study. Overall, 488 (37%) of the donors were negative on the more specific anti‐HBc test. The proportion of putative false‐positive samples varied according to the test responsible for the original deferral. A single donor, negative for the presence of anti‐HBc and HBsAg, was positive for the presence of HBV DNA in one of three replicates. Repeat testing of this donor 10 months later was negative for the presence of all markers of HBV infection, and the donor had a history of HBV vaccination with documented postimmunization anti‐HBs seroconversion 10 years before her anti‐HBc deferral, and was considered HBV DNA false positive. CONCLUSION: These data support reentry of donors with false‐positive anti‐HBc results on the relatively nonspecific assays that have been in use in the United States for more than 20 years.     

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.     

West Nile virus infection in blood donors in the New York City area during the 2010 seasonal epidemic

BACKGROUND: A uniform threshold strategy for converting from minipool (MP)‐nucleic acid testing (NAT) to individual donation (ID)‐NAT screening for acute West Nile virus (WNV) infection among blood donors is lacking. We report on WNV screening at the New York Blood Center during the 2010 seasonal WNV epidemic, the most severe epidemic in that state since the original outbreak in 1999. STUDY DESIGN AND METHODS: Between July 1 and October 31, 2010, blood donations were screened by MP‐NAT or ID‐NAT and the presence of anti‐WNV immunoglobulin (Ig)M and IgG was evaluated among NAT‐positive donations. RESULTS: Twenty presumed viremic donations were identified for a frequency of 0.0129% (1 in 7752 donations). Nine donations that could have been missed by MP‐NAT were identified. Two of these donations were both IgM and IgG negative, one of which would have been missed if more than one positive donation was required for initiating ID‐NAT. Retrospective ID‐NAT revealed two positive donations. The majority of the NAT‐positive donations in New York (16/19) were from donors who lived in counties that had the highest incidence of human WNV cases in the state. CONCLUSION: Our data details the identification of WNV NAT‐positive blood donations during a severe seasonal epidemic in the New York area. By initiating ID‐NAT after one positive donation, using retrospective testing, and triggering ID‐NAT regionally, we were able to prevent the release of presumably infectious donations. The detection of NAT‐positive donations with retrospective testing, however, may indicate the need for changes in our trigger criteria.     

Hepatitis B virus nucleic acid testing in Chinese blood donors with normal and elevated alanine aminotransferase

BACKGROUND: Nucleic acid testing (NAT) is currently not a routine donor test in China. The aim of this study was to evaluate the current residual risk of hepatitis B virus (HBV) transmission and the value of ALT testing in preventing HBV infection. STUDY DESIGN AND METHODS: From January 2008 to September 2009, a total of 5521 qualified donations by routine screening and 5034 deferred donations due to elevated ALT alone were collected from five blood centers. Samples were tested for HBV DNA by triplex individual‐donation (ID)‐NAT (ULTRIO assay, on the TIGRIS system, Novartis Diagnostics). HBV NAT–reactive samples were further analyzed by HBV serology, alternative NAT, and viral load and were diluted to simulate if they could be detected in a minipool‐NAT. RESULTS: There was no significant difference in the HBV NAT–yield rate between the qualified donations group (5/5521) and the deferred donations group (4/5034). Of these nine potential HBV‐yield cases, one donor (11%) was a possible HBV window‐period donor, one (11%) was a chronic HBV carrier, and seven (78%) had probable or confirmed occult HBV infections. Of seven potential HBV‐yield cases quantified, the viral loads were less than or equal to 70.0 IU/mL. Minipool testing (minipools of 4, 8, and 16 donations) would miss 43% to 79% of the nine HBV‐yield donations. CONCLUSIONS: Based on our findings in qualified donations, we estimate that the nationwide implementation of ID‐NAT testing for HBV DNA in China would detect an additional 9964 viremic donations per year. ALT testing seems to have no significant value in preventing transfusion‐transmitted HBV infection. ID‐NAT versus simulated minipool‐NAT using the ULTRIO test demonstrates the benefit to implement a more sensitive NAT strategy in regions of high HBV endemicity.     

Prevalence of antibodies to hepatitis B core antigen and occult hepatitis B virus infections in Korean blood donors

BACKGROUND: This study was performed to determine the prevalence of antibodies to hepatitis B core antigen (anti‐HBc) among Korean blood donors and frequencies of hepatitis B virus (HBV) DNA and antibodies to hepatitis B surface antigen (anti‐HBs) in anti‐HBc–positive donors. STUDY DESIGN AND METHODS: A total of 12,461 consenting blood donors were consecutively enrolled from Korean Red Cross Blood Services from April to October 2008. All of the donors were screened for anti‐HBc with an electrochemiluminescence immunoassay. Repeat‐reactive anti‐HBc–positive donors were assayed for anti‐HBs and for HBV DNA using a multiplex test (Cobas TaqScreen, Roche Molecular Systems) on individual donation. RESULTS: Of the 12,461 donors, 1682 (13.5%) were reactive for anti‐HBc. Among different age groups, there was a steady increase in the anti‐HBc–positive rate, ranging from 2.0% in the age group of less than 20 years to 80.0% in the age group of 60 years and older (p < 0.0001). Of the anti‐HBc–positive donors, 1523 (90.5%) were anti‐HBs positive. HBV DNA was detected in two donors who were anti‐HBc positive and hepatitis B surface antigen negative. The prevalence of occult HBV infection was 0.016%, and the HBV nucleic acid test (NAT) yield was 1 in 838 (0.12%). CONCLUSION: This study helps to determine the current status of hepatitis B infection and the prevalence of occult HBV infection in the blood donor population in Korea. We estimate that in Korea, up to 161 units per million donated units from blood donors may contain HBV DNA. Although the potential infectivity of these units has been debated upon, the HBV NAT assay could prevent certain transfusion‐transmitted HBV infections.