Current value of serologic test for syphilis as a surrogate marker for blood-borne viral infections among blood donors in the United States

BACKGROUND: Serologic screening for syphilis has been justified in part as a surrogate marker for infections caused by other pathogens such as human immunodeficiency virus (HIV). This study assessed the current surrogate value of the test.
STUDY DESIGN AND METHODS: Testing results for blood donors with the American Red Cross Blood Services between January 1, 2006, and December 31, 2007, were analyzed. All donations were tested according to standard procedures for markers of HIV, hepatitis B virus (HBV), hepatitis C virus (HCV), human T-lymphotropic virus (HTLV), syphilis, and other infections. The frequency of window-period (w-p) infections interdicted by syphilis testing was estimated.
RESULTS: There were significantly higher frequencies of HIV, HCV, hepatitis B surface antigen (HBsAg), and HTLV confirmed-positive donations among those with positive syphilis test results, although the sensitivity of syphilis test positivity in these groups was low. Among more than 3 million repeat donors with complete testing through reactive donation confirmation for both syphilis and HIV (anti-HIV and HIV RNA), 225 seroconverted for syphilis but not for anti-HIV or HIV RNA and 83 converted for HIV (anti-HIV or HIV RNA) but not for syphilis, with only 1 who converted for both syphilis and HIV, resulting in an incidence ratio of 150 (95% confidence interval, 21-1080) and a sensitivity of 1.2 percent. No syphilis seroconverters converted for HCV, HBsAg, or anti-HTLV.
CONCLUSION: Syphilis testing presents no surrogate value for incident HCV, HBV, and HTLV infections and could only remove approximately 1 HIV w-p unit of every 148 million donations.     

Antigen testing for human immunodeficiency virus (HIV) and the magnet effect: will the benefit of a new HIV test be offset by the numbers of higher risk,test-seeking donors attracted to blood centers? Retrovirus Epidemiology Donor Study

Background: There currently is debate on whether to include new assays for viral antigens and nucleic acids in the battery of screening tests applied to all blood donations. Proposals call for implementation of p24 antigen screening tests to help identify donors who are infected with human immunodeficiency virus type 1 (HIV-1) but have not yet seroconverted (window-period donors). There is concern, however, that people at higher risk for HIV infection will be attracted to blood centers in order to obtain the results of an HIV assay that is not routinely available elsewhere. Therefore, the benefit of antigen testing may be offset by an increase in the HIV incidence rate among blood donors. Study Design and Methods: Estimates were obtained from previous reports for the HIV incidence rate among blood donors, the percentage of donations from test-seeking donors, the duration of the HIV-infectious window period, and the performance of p24 antigen screening assays. Sensitivity analyses were performed by using various percentages of test-seeking donors following implementation of antigen testing and various HIV incidence rate ratios of test-seekers to nonseekers. Hypothetical residual HIV risks were calculated for multiple scenarios and compared to the current estimate of HIV risk without antigen screening of blood donations. Results: If antigen testing reduces the window period by 27 percent (e.g., from 22 days to 16 days), and the HIV incidence rate among test-seekers is 30 times that among nonseekers, then the benefit of antigen testing will be eliminated if the percentage of test-seekers (currently estimated at 3.2%) increases to 5.7 percent. If antigen testing reduces the window period by approximately 45 percent (e.g., from 22 days to 10 days or from 13 days to 6 days) and the HIV incidence rate ratio (test-seekers vs. nonseekers) is assumed to be equal to the HIV prevalence ratio (5.3), then the percentage of donations from test-seeking donors would have to increase to 25 percent of all donations to offset the benefit of antigen screening. Conclusion: This model helps identify the key measures for assessing the potential adverse effect of increased test seeking as a consequence of the addition of p24 antigen (or other direct virus) assays to blood donor screening programs. In most scenarios, the beneficial effect of antigen screening exceeded the potential detrimental effect of attracting higher-risk, test-seeking donors. The possibility cannot be ruled out, however, that a subgroup of high-risk, test-seeking donors attracted to the blood centers by a new HIV test will offset the reduction in the residual risk of HIV infection associated with antigen screening.     

Transfusion-transmitted human immunodeficiency virus (HIV) from seroconverting donors is rare in England and Wales: results from HIV lookback, October 1995 through December 2008

BACKGROUND: Lookback is considered when human immunodeficiency virus (HIV) is detected in a repeat blood donor in case the immediately previous negative donation was donated in the infectious window period (IWP) or the assay(s) produced a false‐negative result. HIV lookback investigations undertaken by NHS Blood and Transplant and the Welsh Blood Service between October 1995 and December 2008 are described. STUDY DESIGN AND METHODS: Investigations were undertaken into the previous negative donations of 113 HIV‐infected donors, including retrospective testing of archive samples, tracing of components, and identification of recipients who were offered HIV testing when appropriate. Data were collated on HIV seroconverters and outcome of the lookback was summarized. RESULTS: Two previous negative donations given before the introduction of minipool nucleic acid testing (MP‐NAT) screening were confirmed positive by individual retrospective polymerase chain reaction (PCR) testing of the archive specimen. Red blood cell components had been transfused from both donations. One recipient died after transfusion, and the other was alive and tested HIV positive. All 23 (20%) donations previously testing negative by MP‐NAT were confirmed to be PCR negative on individual testing of an archive specimen and none of the tested recipients of these donations had evidence of transfusion‐transmitted HIV. CONCLUSION: The yield of lookback was low with one positive recipient identified over 13 years of surveillance: HIV transmission occurred from a window period donation given before the introduction of MP‐NAT screening and would have been detected using current testing methods. Current residual risk estimates for the United Kingdom predict that HIV lookback will be of limited benefit, as demonstrated by our data.     

Predictive value of past and current screening tests for syphilis in blood donors: changing from a rapid plasma reagin test to an automated specific treponemal test for screening

BACKGROUND: This study evaluated the change from a rapid plasma reagin (RPR) test to an automated specific treponemal test (PK-TP) in screening for syphilis in blood donors. STUDY DESIGN AND METHODS: A cross-sectional seroprevalence analysis was performed on 4,878,215 allogeneic blood donations from 19 American Red Cross Blood Services regions from May 1993 through September 1995. Positive predictive values relative to the confirmatory fluorescent treponemal antibody absorption test (FTA-ABS) were calculated. Differences in seroprevalence were compared in RPR and PK-TP tests for 1) unconfirmed and confirmed tests, 2) first-time and repeat donors, and 3) "recent" versus "past" infections. Donation data from three additional Red Cross regions were evaluated for repeat donation patterns of blood donors who had a donation that was positive in a serologic screening test for syphilis. The value of RPR and PK-TP tests as surrogate markers for HIV infection was compared. RESULTS: Reactive rates were lower but the positive predictive values was higher for the PK-TP test than for the RPR test. Initially, donors screened by PK-TP were more likely to be confirmed as positive than were donors screened by RPR, but these rates became comparable. It is estimated that a single HIV window-period donation was removed by serologic testing for syphilis each year of this study period. CONCLUSIONS: The change to the PK-TP test resulted in a lower repeatedly reactive rate, better prediction that a confirmed-positive test for syphilis would occur in testing in the FTA-ABS, fewer donations lost, and comparable deferral rates. Because of the high rate of reactivity to serologic testing for syphilis among donors previously confirmed positive for syphilis, indefinite deferral after a confirmed-positive index donation may be warranted. Serologic testing for syphilis is ineffective as a marker of HIV-infectious window-period donations.     

Detection of HIV-1 infection in blood donors during the immunological window period using the nucleic acid-amplification technology

summary .  Individual nucleic acid-amplification testing (NAT) was recently recommended by Brazilian legislation and has been implemented at some blood banks in the city of São Paulo, Brazil, in an attempt to reduce the transfusion transmission of human immunodeficiency virus (HIV) and hepatitis C viruses. This screening test can identify donations made during the immunological window period before seroconversion. The impact of this technology in our blood donors and transfusion routine was studied. In all, 47 866 donations were tested from March 2004 until November 2005, according to Brazilian legislation, using two approved enzyme immunoassays for HIV antibodies and individual NAT. Supplemental tests included Western blot, p24 antigen detection and quantitative PCR-HIV-1. Among the donors screened, two (one first-time and one repeat donor) were non-reactive in enzyme immunoassays, with negative confirmatory p24 antigen and Western blot, but positive for HIV-1 NAT. Although serological analysis for HIV is a primary tool for diagnostic testing, the addition of NAT allowed for identification and prevention of component transfusion from two HIV-positive blood donations during an 18-month period. The screening of donors reduced the immunological window period, permitting the identification of very early stage HIV infections. In addition, this report also emphasized the fact that the risk of HIV transmission is not limited to the first-time donors.     

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.     

Hepatitis B virus DNA-positive, hepatitis B surface antigen-negative blood donations intercepted by anti-hepatitis B core antigen testing: the Canadian Blood Services experience

BACKGROUND: The benefit of introducing anti-hepatitis B core antigen (HBc) screening for intercepting potentially infectious donations missed by hepatitis B surface antigen (HBsAg) screening in Canada was studied. STUDY DESIGN AND METHODS: Anti-HBc testing of all donations was implemented in April 2005, along with antibody to hepatitis B surface antigen (anti-HBs) and hepatitis B virus (HBV) DNA supplemental testing of anti-HBc repeat-reactive, HBsAg-negative donations. The proportion of potentially infectious donations intercepted by anti-HBc over the initial 18 months of testing was calculated based on three assumptions relating infectivity of HBV DNA-positive units to anti-HBs levels. Lookback was conducted for all DNA-positive donations. RESULTS: Of 493,344 donors, 5,585 (1.13%) were repeat-reactive for the presence of anti-HBc, with 29 (0.52%) being HBV DNA-positive and HBsAg-negative. The proportion of potentially infectious donations intercepted by anti-HBc screening was 1 in 17,800 if all HBV DNA-positive donations were infectious, 1 in 26,900 if infectivity was limited to donations with an anti-HBs level of not more than 100 mIU per mL, and 1 in 69,300 if only donations with undetectable anti-HBs were infectious. For 279 components in the lookback study, no traced recipients were HBsAg-positive and 7 recipients were anti-HBc-reactive in association with 4 donors, 3 of whom had an anti-HBs level of more than 100 mIU per mL and 1 of whom had a level of 61 mIU per mL. CONCLUSION: Implementation of anti-HBc screening reduced the risk of transfusing potentially infectious units by at least as much as had been expected based on the literature. The lookback did not provide proof of transfusion transmission of HBV from HBV DNA-positive, anti-HBc-reactive, HBsAg-negative donors but it did not establish lack of transmission either.     

The increasing prevalence of serologic markers for syphilis among Chinese blood donors in 2008 through 2010 during a syphilis epidemic

BACKGROUND: In China, the growing syphilis epidemic parallels the spread of human immunodeficiency virus (HIV) in the general population. This study evaluated the prevalence and incidence of serologic markers for syphilis among donors at five Chinese blood centers. STUDY DESIGN AND METHODS: We examined whole blood and apheresis donations collected from January 2008 through December 2010. Postdonation testing of syphilis was conducted using two different Treponema pallidum antibody enzyme‐linked immunosorbent assay kits. The prevalence of serologic markers for syphilis (%), and the rate of coinfection with HIV‐1/2, hepatitis B virus (HBV), and hepatitis C virus (HCV) were calculated. A multivariable logistic regression analysis was conducted examining donor characteristics associated with positive syphilis serology. Seroconversion rate and syphilis incidence were estimated. RESULTS: Of 801,511 donations, 60% were from first‐time donors and 40% were from repeat donors. There was a significant increase in syphilis serologic markers among first‐time donors with 0.41, 0.45, and 0.57% positivity over 3 years (p < 0.001). Approximately 2.8, 0.8, and 0.5% of HIV‐1/2–, HBV‐, and HCV‐positive donations also tested reactive for syphilis. Logistic regression results suggest that first‐time donors were nine times more likely to be syphilis positive than repeat donors. Higher syphilis positivity was associated with donors older than 25 years and with less education. Estimated incidence among repeat donations was 33 (95% confidence interval, 29‐39) per 100,000 person‐years. CONCLUSION: The increase in syphilis serologic prevalence reflected the syphilis epidemic in the general population. Without screening, most of these syphilis‐positive donations would get into the blood supply. Thus, during a syphilis epidemic, continued syphilis screening of blood donations may be important to maintain blood safety and public health.     

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.     

Evaluation of the Roche cobas s 201 system and cobas TaqScreen multiplex test for blood screening: a European multicenter study

BACKGROUND: The Roche cobas TaqScreen test, an automated, multiplex nucleic acid test for blood screening for hepatitis B virus (HBV) DNA, hepatitis C virus (HCV) RNA, human immunodeficiency virus type 1 (HIV‐1) groups M and O, and HIV‐2 RNA, on the cobas s 201 platform, was evaluated by six European blood screening laboratories. STUDY DESIGN AND METHODS: The 95 percent limit of detection (LOD) of the cobas TaqScreen test for HBV, HCV, and HIV‐1, using dilutions of the WHO International Standards, were evaluated. The clinical performance was determined by testing between 2000 to 6000 routine donor samples. Some laboratories evaluated the robustness, cross‐contamination, and workflow. RESULTS: The mean 95 percent LOD (95% lower and upper confidence intervals) for HBV, HCV, and HIV‐1 across all the laboratories were 3.8 (range, 3.0‐5.2), 10.8 (range, 8.4‐14.4), and 56.7 (range, 43.0‐79.2) IU/mL, respectively. A total of 23,716 donors were tested in pools of 6. Fourteen initially reactive pools were detected, of which 6 contained a reactive donation, giving a positive predictive value of the pool results of 43 percent. One of the reactive donations was a HBV yield case (hepatitis B surface antigen–negative/anti‐HBc–positive). Evaluation of the workflow for the system showed that an optimized batch loading in which a pipettor (Hamilton Microlab Star IVD) was utilized to half capacity was better than a full batch loading. CONCLUSION: The 95 percent LOD for the three viruses were comparable to those obtained by Roche. The test and platform were shown to be sensitive, specific, flexible, and robust.     

Face-to-face interviewing in predonation screening: lack of effect on detected human immunodeficiency virus and hepatitis C virus infections

BACKGROUND: Predonation screening has become more elaborate over the years, while human immunodeficiency virus (HIV)- and hepatitis C virus (HCV)-positive donations have declined. The impact of face-to-face interviewing and of the format of the Donor Health Assessment Questionnaire (DHAQ) have not been evaluated. STUDY DESIGN AND METHODS: Canadian Blood Services DHAQ records between 1990 and 2004 were examined, and changes in them were tracked. The proportion of first-time donors permanently deferred for HIV or HCV risk, and the HIV and HCV rates per 100,000 donations, were calculated annually. Time-series analysis was used to determine whether major predonation screening changes had any effect on the HIV or HCV rates or permanent deferrals. RESULTS: In 1992, receiving money or drugs for sex was added to the DHAQ; otherwise, the content of high-risk questions changed little between 1990 and 2004. In 1997, the method of administration of the DHAQ changed from donor-completed to face-to-face interviewing for high-risk questions. Permanent deferrals for HIV or HCV risk factors and HIV and HCV rates in first-time donors decreased over this period. The HIV rates were close to 0 before 1997, whereas HCV rates decreased steadily through 2004. There was no interruption in rates in 1997 when the method of administration changed. CONCLUSION: Face-to-face interviewing for high-risk questions had no effect on HIV or HCV rates in first-time donations over 15 years of observation (during the latter 8 of which face-to-face interviewing was in place), and it did not increase permanent deferrals for HIV or HCV risk factors.     

Trends in prevalence,incidence, and residual risk of major transfusion‐transmissible viral infections in United Arab Emirates blood donors: impact of individual‐donation nucleic acid testing, 2004 through 2009

BACKGROUND: United Arab Emirates (UAE) has a heterogeneous population consisting of more than 160 nationalities and 85% of the population being non‐UAE. In 2007, Dubai Blood Donation Centre (DBDC), the major local supplier of blood in the UAE, introduced six‐minipool nucleic acid test (NAT) for hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV), which in 2008 upgraded to individual‐donation (ID)‐NAT. The aim of this study was to analyze the efficacy of the donor screening program in the UAE and evaluate the impact of NAT on the yield and residual risk of transfusion‐transmissible viral infections (TTVIs). STUDY DESIGN AND METHODS: A total of 169,781 blood donations collected at DBDC between 2004 and 2009 were screened for TTVIs. During the period 2008 through 2009, a total of 59,283 donations were tested with both ID‐NAT and serologic assays. The incidence, prevalence, and residual risk for each viral agent were estimated and analyzed. RESULTS: The individual prevalences of HBV, HCV, and HIV per 100,000 donation were 234.4, 110, and 4, respectively. Calculated residual risk per million donations for HBV was decreased from 1.41 in pre‐NAT period to 0.92 in post‐NAT period. These figures were decreased for HCV and HIV from 1.73 and 0.39 to 0 and 0.32, respectively. CONCLUSION: Incidence rates and estimated residual risk indicate that the current risk of TTVIs attributable to blood donation is relatively low in the UAE. The study recommends the parallel use of both serology and ID‐NAT TTVIs screening in blood donations and suggests the exclusion of antibody to hepatitis B core antigen–positive donations as this can eliminate the potential infectivity of these units with marginal effects on the blood stock in UAE.     

A new strategy to improve the cost-effectiveness of human immunodeficiency virus, hepatitis B virus, hepatitis C virus, and syphilis testing of blood donations in sub-Saharan Africa: a pilot study in Burkina Faso

BACKGROUND: In Africa where blood-borne agents are highly prevalent, cheaper and feasible alternative strategies for blood donations testing are specifically required.
STUDY DESIGN AND METHODS: From May to August 2002, 500 blood donations from Burkina Faso were tested for hepatitis B surface antigen (HBsAg), human immunodeficiency virus (HIV), syphilis, and hepatitis C virus (HCV) according to two distinct strategies. The first strategy was a conventional simultaneous screening of these four blood-borne infectious agents on each blood donation by using single-marker assays. The second strategy was a sequential screening starting by HBsAg. HBsAg-nonreactive blood donations were then further tested for HIV. If nonreactive, they were further tested for syphilis. If nonreactive, they were finally assessed for HCV antibodies. The accuracy and cost-effectiveness of the two strategies were compared.
RESULTS: By using the simultaneous strategy, the seroprevalences of HBsAg, HIV, syphilis, and HCV among blood donors in Ouagadougou were estimated to be 19.2, 9.8, 1.6, and 5.2%. No significant difference of HIV, syphilis, and HCV prevalence rates was observed by using the sequential strategy (9.2, 1.9, and 4.7%, respectively). Whatever the strategy used, 157 blood donations (31.4%) were found to be reactive for at least one transfusion-transmissible agent and were thus discarded. The sequential strategy allowed a cost decrease of €908.6, compared to the simultaneous strategy. Given that approximately there are 50,000 blood donations annually in Burkina Faso, the money savings reached potentially €90,860.
CONCLUSIONS: In resource-limited settings, the implementation of a sequential strategy appears as a pragmatic solution to promote safe blood supply and ensure sustainability of the system.     

Quantitative estimate of the risks and benefits of possible alternative blood donor deferral strategies for men who have had sex with men

BACKGROUND: Implementation of sensitive screening methods for human immunodeficiency virus (HIV) and hepatitis viruses prompts the question of what quantitative risks may result from altered deferral strategies for donation of blood by men who have had sex with men (MSM).
STUDY DESIGN AND METHODS: Quantitative probabilistic models were developed to assess changes in the residual risk of transfusion-transmitted HIV and hepatitis B virus (HBV) associated with blood testing and quarantine release errors (QREs) in the initial year of two hypothetical policy scenarios that would allow donations from donors who have abstained from MSM behavior for at least 5 years (MSM5) or at least 1 year (MSM1).
RESULTS: The MSM5 and MSM1 models, respectively, predicted annual increases in units of HIV-infected blood of 0.5% (0.03 mean additional units; 95% confidence interval [CI], 0-1) and 3.0% (0.18 mean additional units; 95% CI, 0-1) over current estimated HIV residual risk using recent, nationwide biologic product deviation reports to estimate QRE rates. These estimates are approximately 10-fold lower than estimates based on New York State QRE data from the previous decade. The models predicted smaller increases in infectious HBV donations.
CONCLUSIONS: QREs remain the most significant preventable source of risk. More accurate inputs, including the percentage of MSM in the population, the percentage of MSM who have abstained from MSM activity for 1 or 5 years, the prevalence of HIV and HBV in MSM who have abstained from MSM activity for 1 or 5 years, the rate of self-deferral, and QRE rates, are required before making more precise predictions.     

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.     

Viral safety of solvent/detergent-treated plasma

BACKGROUND: Pooling of plasma donations increases the risk for blood-borne infections. In solvent/detergent (SD)-treated plasma, lipid-enveloped viruses are efficiently inactivated. This method, however, does not affect non-lipid-enveloped viruses. The current study investigated the viral safety of SD-treated plasma (Octaplas) and paid particular attention to the transmission of non-lipid-enveloped viruses. STUDY DESIGN AND METHODS: The study comprised 343 adults undergoing cardiac surgery. Follow-up was performed 6 to 12 months and 2 years after operation. The sera were tested for hepatitis B surface antigen and specific antibodies against hepatitis A, B, and C; cyto-megalovirus; HIV, human T-lymphotropic virus types I and II; and human parvovirus B19 (B19). A total of 25 batches of SD-treated plasma prepared from Norwegian plasma were used. All batches were tested for hepatitis A virus and B19 by nucleic acid amplification testing and investigated for neutralizing antibodies directed against these viruses. RESULTS: In patients who received SD-treated plasma, B19 seroconversion occurred at a rate similar to that in nontransfused patients. No other seroconversions could be ascribed to the transfusion of SD-treated plasma. All 25 SD-treated plasma batches contained neutralizing antibodies against hepatitis A virus and B19. In nucleic amplification testing, all SD-treated plasma batches tested positive for B19, while five demonstrated borderline reactions for hepatitis A virus. CONCLUSION: Transfusion of SD-treated plasma was found to be safe with regard to lipid-enveloped viruses. Immune antibodies neutralize viral particles in plasma and are of importance in avoiding clinical disease with the non-lipid-enveloped hepatitis A virus and B19.     

Donor testing and risk: current prevalence, incidence, and residual risk of transfusion-transmissible agents in US allogeneic donations

Over the past 20 years, there has been a major increase in the safety of the blood supply, as demonstrated by declining rates of posttransfusion infection and reductions in estimated residual risk for such infections. Reliable estimates of residual risk have been possible within the American Red Cross system because of the availability of a large amount of reliable and consistent data on donations and infectious disease testing results. Among allogeneic blood donations, the prevalence rates of infection markers for hepatitis C virus (HCV) and hepatitis B virus have decreased over time, although rates for markers of human immunodeficiency virus (HIV) and human T-cell lymphotropic virus did not. The incidence (/100?000 person-years) of HIV and HCV among repeat donors showed apparent increases from 1.55 and 1.89 in 2000 through 2001 to 2.16 and 2.98 in 2007 through 2008. These observed fluctuations confirm the need for continuous monitoring and evaluation. The residual risk of HIV, HCV, and human T-cell lymphotropic virus among all allogeneic donations is currently below 1 per 1 million donations, and that of hepatitis B surface antigen is close to 1 per 300?000 donations.     

Potential increased risk of virus transmission due to exclusion of older donors because of concern over Creutzfeldt-Jakob disease. The National Heart, Lung, and Blood Institute Retrovirus Epidemiology Donor Study

BACKGROUND: Concern over the theoretical possibility of disease transmission via blood from donors who develop Creutzfeldt-Jakob disease has led to proposals to exclude older individuals from donating plasma for further manufacture into pooled plasma donations. The impact of extending this age-deferral policy to blood donors was examined with respect to the risk for known transmissible viruses. STUDY DESIGN AND METHODS: Demographic characteristics and confirmed prevalence rates (/10(5) first-time donations) and incidence rates (/10(5) person-years for repeat donors) for viral markers were compared for donors < 50 years old (n = 1,259,805 [85%]) and > or = 50 years old (n = 219,856 [15%]) and for donors < 60 years old (n = 1,409,176 [95%]) and > or = 60 years old (n = 70,485 [5%]). Incidence rates were combined with infectious window-period estimates for each virus, to calculate the risk of virus transmission per 10(6) donations. RESULTS: Unadjusted prevalence rates were significantly greater for younger than for older donor groups for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), and hepatitis C virus (HCV) (p < or = 0.05). Incidence rates (and transmission risk estimates) for HBsAg were significantly higher in the < 50 donor group than in the > or = 50 group (p < or = 0.05), and those for HIV, human T-lymphotropic virus, and HCV were not significantly higher (p > 0.05). Blanket removal of donors over the age of 50 would potentially lead to the following significant increases in the risk of infected units: HIV, 12 percent; HCV, 21 percent; and hepatitis B virus (HBsAg), 22 percent. CONCLUSION: Removal of donors over the age of 60 would not significantly affect the risk of infected units. Deferral of donors > or = 50 years of age from whole-blood donations for unfounded concerns about Creutzfeldt-Jakob disease could have adverse effects on both blood availability and safety.     

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.