Individual Donation Testing Research Articles

A prospective study to evaluate the clinical specificity of the cobas® MPX test kit for screening for HIV RNA, HCV RNA, and HBV DNA in blood donation samples using the cobas® 6800 system in HBV endemic areas

BackgroundNucleic acid testing (NAT) is widely used for screening blood donors for infectious diseases to enhance transfusion safety. Roche's advanced cobas® MPX assay detects human immunodeficiency virus (HIV), hepatitis C virus (HCV), and hepatitis B virus (HBV) using the cobas® 6800/5800 Systems, based on real-time PCR technology, providing improved sensitivity. This study aims to evaluate the clinical sensitivity and specificity of the cobas® MPX assay and its effectiveness in identifying infected donors in HBV endemic areas, particularly those with occult HBV infection (OBI). Materials and methodsA total of 12,067 donor samples from the Dalian Blood Center (DLBC, northern China) were tested for HIV, HCV, and HBV using both the cobas® MPX assay on the cobas® 6800 system and the previous generation cobas® TaqScreen MPX test v2.0 on the cobas s 201 system as the reference method. Testing was conducted using individual-donation testing (IDT) and primary pool of six donations (PP6), following the manufacturer's instructions and the operational procedures of the instruments. Samples with inconsistent results underwent repeated confirmation tests. ResultsCobas® MPX demonstrated 100.00 % overall percent agreement (95 % CI, 99.22 %-100.00 %) for IDT and 99.89 % (95 % CI, 99.82 %-99.95 %) for PP6. Kappa coefficients were 1.0 for IDT and 0.76 for PP6. Cobas® MPX specificity was 100.00 % (95 % CI, 99.22 %-100.00 %) for IDT and 99.99 % (95 % CI, 99.94 %-100.00 %) for PP6. Sensitivity was 100.00 % (95 % CI, 2.50 %-100.00 %) for IDT and 86.67 % (95 % CI, 68.36 %-95.64 %) for PP6. A total of 12 HBV NAT-yield cases were detected by cobas® MPX. ConclusionCobas® MPX demonstrated outstanding sensitivity and specificity in screening HIV, HCV, and HBV in routine blood donations, particularly enhancing occult HBV detection in endemic regions.

Detection of Babesia RNA and DNA in whole blood samples from US blood donations.

BackgroundHuman babesiosis is a zoonotic infection caused by an intraerythrocytic parasite. The highest incidence of babesiosis is in the United States, although cases have been reported in other parts of the world. Due to concerns of transfusion‐transmitted babesiosis, the US Food and Drug Administration (FDA) recommended year‐round regional testing for Babesia by nucleic acid testing or use of an FDA‐approved device for pathogen reduction. A new molecular test, cobas Babesia (Roche Molecular Systems, Inc.), was evaluated for the detection of the four species that cause human disease, Babesia microti, Babesia duncani, Babesia divergens, and Babesia venatorum.Study design and methodsAnalytical performance was evaluated followed by clinical studies on whole blood samples from US blood donations collected in a special tube containing a chaotropic reagent that lyses the red cells and preserves nucleic acid. Sensitivity and specificity of the test in individual samples (individual donation testing [IDT]) and in pools of six donations were determined.ResultsBased on analytical studies, the claimed limit of detection of cobas Babesia for B. microti is 6.1 infected red blood cells (iRBC)/mL (95% confidence interval [CI]: 5.0, 7.9); B. duncani was 50.2 iRBC/mL (95% CI: 44.2, 58.8); B. divergens was 26.1 (95% CI: 22.3, 31.8); and B. venatorum was 40.0 iRBC/mL (95% CI: 34.1, 48.7). The clinical specificity for IDT was 99.999% (95% CI: 99.996, 100) and 100% (95% CI: 99.987, 100) for pools of six donations.Conclusioncobas Babesia enables donor screening for Babesia species with high sensitivity and specificity.

High Yield of Minipool NAT in India using a Sensitive Multiplex Assay for Blood Donor Screening

Background and Objectives: Nucleic acid amplification testing (nucleic acid testing [NAT]) for blood donor screening is increasingly being adopted in India to reduce the risk of transfusion-transmitted diseases. The high sensitivity of NAT enables testing of a large volume of donations in minipool format; reducing the costs of testing compared to individual donation testing. This study was aimed at evaluating the yield of minipool NAT testing for hepatitis B, hepatitis C, and human immunodeficiency virus (HIV) in blood donors from Uttar Pradesh. Methods: Samples from routine blood donors collected between August 16, 2016, and December 31, 2020, that were seronegative for hepatitis B virus (HBV), hepatitis C virus (HCV) and HIV, syphilis, and malaria were further screened by NAT in pools of six donations (MP6) using the cobas TaqScreen MPX Test, version 2.0 (MPX2) on the cobas s 201 System. Members of reactive pools were tested to identify the reactive donation(s). Viral load testing was performed on randomly selected NAT-reactive samples. Results: Of 172,443 seronegative donors, 463 were NAT reactive: 369 HBV, 89 HCV, 2 HIV, and 3 co-infected with HBV and HCV. The overall NAT yield was 0.27%, with individual virus yield rates of 1/464 for HBV, 1/1874 for HCV, and 1/86,222 for HIV. Viral load testing of 19 HBV NAT-yield donations showed low concentrations in 16 samples and undetectable viral load in three; the two HCV NAT-yield donations tested had high viral loads. Conclusion: Screening of blood donations by minipool NAT using the highly sensitive MPX2 assay identified a high yield of serology negative, NAT-positive donations, including HBV reactive donations with low viral concentrations.

First Zika-positive donations in the continental United States.

Zika virus (ZIKV) has spread in the Americas, including parts of the southern United States, and infection can be associated with serious complications, including congenital brain abnormalities. Probable transfusion transmission of ZIKV has been documented in Brazil. Preemptive testing of blood donations for ZIKV RNA was implemented in southern US states at risk of local transmission using a test approved under a Food and Drug Administration (FDA) investigational new drug application, cobas Zika. Screening was expanded after issuance of an updated FDA guidance. Donations reactive on initial screening were further tested by nucleic acid and antibody tests to determine the donor status. Of 358,786 donations from US states screened by individual donation testing, 23 were initially reactive on cobas Zika. Fourteen of these represented probable ZIKV infection based on reactivity on additional nucleic acid testing or anti-Zika immunoglobulin M. Ten of the 14 donors reported travel to an identified ZIKV-active area within 90 days before donation (median time from end of travel to donation, 25 days; range, 6-71 days). Three donors with travel history also had a potential sexual exposure. Only seven of the 14 donations with probable ZIKV infection were detectable upon 1:6 dilution to simulate minipool testing. The estimated specificity of the cobas Zika test was 99.997%. Screening of donations for ZIKV RNA can interdict ZIKV-infected donors. Donor risk factors include travel more than 4 weeks before donation and sexual exposure. Minipool screening would have detected only 50% of the RNA-positive donations.

Hepatitis E virus: seroprevalence and frequency of viral RNA detection among US blood donors

Hepatitis E virus (HEV) is a nonenveloped emerging virus of increasing worldwide interest. Antibody prevalence, RNA frequencies, and transfusion transmissions have been reported. We investigated the HEV RNA and antibody frequencies in US blood donors. Individual-donation HEV RNA testing was performed on 18,829 donations from six US geographic regions using a CE-marked nucleic acid test (95% limit of detection, 7.9 IU/mL). Repeat-reactive donations were confirmed by in-house, real-time polymerase chain reaction (PCR; 10.3 IU/mL). Total HEV seroprevalence in a randomly selected subset of donations (n = 4499) was assessed by a direct, double-antigen sandwich assay; reactives were further tested for immunoglobulin (Ig)G and IgM. As part of the total antibody confirmatory algorithm, the cutoff was adjusted. Two donations tested confirmed-positive for RNA (PCR not quantifiable, IgM/IgG positive; and 14 IU/mL, antibody negative) for a frequency of 1 in 9500 (95% confidence interval [CI], 1:2850-1:56,180) and 99.96% specificity (95% CI, 99.92%-99.98%); both donors were from the Midwest United States. Antibody prevalence was 9.5% (95% CI, 8.7-10.5) before the cutoff adjustment and 7.7% (95% CI, 7.0%-8.5%) after adjustment; 0.58% (95% CI, 0.39%-0.85%) were IgM positive. We confirmed comparatively low rates and low viral loads of HEV RNA in US blood donors indicating the need for individual-donation testing if screening is implemented. Antibody prevalence rates were comparable to those reported by one US study using a different assay, but lower than those reported in another study using yet a third assay. We did not answer the question of whether US blood donation screening is warranted. Selective strategies involving providing HEV-negative blood to severely immunosuppressed patients at risk of developing hepatitis may be considered.

Keeping Blood Transfusion Safe From West Nile Virus: American Red Cross Experience, 2003 to 2012.

West Nile virus (WNV) appeared for the first time in the United States in 1999 and rapidly spread across the Western hemisphere within a few years causing hundreds of thousands of human infections and significant disease. In 2002, it was found to be transmissible by blood transfusion, and within less than a year, nucleic acid testing for WNV RNA was in place for all US donations. The American Red Cross (ARC) collects approximately 40% of blood donations in the United States and closely monitors the results of such testing and evaluates donors found to be reactive. This review describes the 10-year results of the ARC testing program during the period 2003 to 2012. Overall, more than 27 million donations were tested during the transmission periods with 1576 RNA-positive donations identified. The temporal and geographic distributions of the infected donors are described. Methods to initiate and discontinue periods of individual donation testing were developed and validated to maximize safety. The nature of WNV infection among donors was investigated, and the distribution of viral titers was defined and was found to be no greater than 720000 RNA copies per milliliter. The distribution of titers by time sequence of appearance of antibodies was determined. Donors who were identified as being in the earliest stages of infection were evaluated for the appearance of symptoms, and 26% developed at least 3 characteristic symptoms. The testing program has been successful in preventing transmission of WNV by transfusion, and only 1 of the 13 reported cases since the initiation of testing was attributable to the Red Cross; it was from a granulocyte product transfused before availability of the test result.

Factors in enhancing blood safety by nucleic acid technology testing for human immunodeficiency virus, hepatitis C virus and hepatitis B virus

In the last few decades through an awareness of transfusion transmitted infections (TTI), a majority of countries have mandated serology based blood screening assays for Human immunodeficiency virus (HIV), Hepatitis C virus (HCV), and Hepatitis B virus (HBV). However, despite improved serology assays, the transfusion transmission of HIV, HCV, and HBV continues, primarily due to release of serology negative units that are infectious because of the window period (WP) and occult HBV infections (OBI). Effective mode of nucleic acid technology (NAT) testing of the viruses can be used to minimize the risk of TTIs. This review compiles the examples of NAT testing failures for all three viruses; analyzes the causes for failure, and the suggestions from retrospective studies to minimize such failures. The results suggest the safest path to be individual donation testing (ID) format for highest sensitivity, and detection of multiple regions for rapidly mutating and recombining viruses. The role of blood screening in the context of the donation and transfusion practices in India, the donor population, and the epidemiology is also discussed. World wide, as the public awareness of TTIs increases, as the recipient rights for safe blood are legally upheld, as the possibility to manage diseases such as hepatitis through expensive and prolonged treatment becomes accessible, and the societal responsibility to shoulder the health costs as in the case for HIV becomes routine, there is much to gain by preventing infections than treating diseases.

Six-year pilot study on nucleic acid testing for blood donations in China

A six-year pilot study on nucleic acid testing for HBV, HCV and HIV-1 has been undertaken on sero-negative plasmas in mini-pool and individual donation testing at Shenzhen Blood Center. Of 307,740 sero-negative blood samples, 95 of 102 HBV DNA yields were confirmed positive, 80/95 (84.2%) were classified as occult HBV infection (OBI) and 15 (15.8%) as window period cases. Amongst OBIs, 45% carried anti-HBc only, 41.3% anti-HBc and anti-HBs and 13.7% anti-HBs only. HBV DNA yield was 1:3239. One HCV WP and one HIV-1 infected donations were detected. High residual risk was found in current blood donations screening in China.

Transfusion-Related West Nile Virus Infection

Many insect-borne pathogens that circulate in the bloodstream have been transmitted by transfusion. Since 2003, when the first transfusion-related West Nile virus (WNV) infections were confirmed, blood and blood products in the U.S. have been screened for this organism. Generally, nucleic-acid testing (NAT) is first done on minipooled samples from 6 or 16 donors (MP-NAT); if results are positive, individual donation testing (ID-NAT) is performed. Twelve transfusion-related transmissions of WNV have been …

Cost‐effectiveness of additional blood screening tests in the Netherlands

During the past decade, blood screening tests such as triplex nucleic acid amplification testing (NAT) and human T-cell lymphotropic virus type I or I (HTLV-I/II) antibody testing were added to existing serologic testing for hepatitis B virus (HBV), human immunodeficiency virus (HIV), and hepatitis C virus (HCV). In some low-prevalence regions these additional tests yielded disputable benefits that can be valuated by cost-effectiveness analyses (CEAs). CEAs are used to support decision making on implementation of medical technology. We present CEAs of selected additional screening tests that are not uniformly implemented in the EU. Cost-effectiveness was analyzed of: 1) HBV, HCV, and HIV triplex NAT in addition to serologic testing; 2) HTLV-I/II antibody test for all donors, for first-time donors only, and for pediatric recipients only; and 3) hepatitis A virus (HAV) for all donations. Disease progression of the studied viral infections was described in five Markov models. In the Netherlands, the incremental cost-effectiveness ratio (ICER) of triplex NAT is €5.20 million per quality-adjusted life-year (QALY) for testing minipools of six donation samples and €4.65 million/QALY for individual donation testing. The ICER for anti-HTLV-I/II is €45.2 million/QALY if testing all donations, €2.23 million/QALY if testing new donors only, and €27.0 million/QALY if testing blood products for pediatric patients only. The ICER of HAV NAT is €18.6 million/QALY. The resulting ICERs are very high, especially when compared to other health care interventions. Nevertheless, these screening tests are implemented in the Netherlands and elsewhere. Policy makers should reflect more explicit on the acceptability of costs and effects whenever additional blood screening tests are implemented.

A cost–benefit analysis of blood donor vaccination as an alternative to additional DNA testing for reducing transfusion transmission of hepatitis B virus

A survey-based, cost–benefit analysis was performed comparing blood screening strategies with vaccination strategies for the reduction of transfusion transmission of HBV. 231 whole blood donors and 126 apheresis donors were eligible and completed a questionnaire detailing their donation habits. The cost–benefit analysis included current mandatory HBV testing (HbsAg + anti-Hbc, A1), A1 with additional nucleic acid testing (NAT) for minipool (A2) or individual donation testing (A3), as well as HBV vaccination strategies using time-dependant (B1) or titre dependent booster vaccination solely (B2), or B2 in addition to current mandatory testing procedures (B3). Different cost models were applied using a 5% rate of discount. Absolute costs for current mandatory testing procedures (A1) over 20 years in Germany were €1009 million. Additional NAT would lead to incremental costs of 43% (A2) or 339% (A3), respectively. Vaccination strategies B1 and B2 showed cost-reductions relative to A1 of 30% and 14%, respectively. The number of remaining HBV infections could be reduced from 360 (for A1) to 13, using vaccination, compared with 144 or 105 remaining infections for A2 or A3, respectively. Absolute cost per prevented infection is similar (€2.0 million) for A2 and B3. HBV vaccination offers the near-elimination of transfusion infections while representing a potential cost-reduction.

The efficacy of individual‐donation and minipool testing to detect low‐level hepatitis B virus DNA in Taiwan

Financial constraints are the main concern in implementing nucleic acid testing (NAT) as routine blood screening in Taiwan. The PROCLEIX ULTRIO assay (Ultrio) on the TIGRIS System (Novartis Diagnostics) was evaluated for its operational performance both for individual-donation testing (IDT) and in minipools of 4 (MP4) to develop a feasible solution. Analytical sensitivity was determined by testing WHO international standards. We tested 10,290 blood donors, 4210 in IDT and 6080 in MP4. Potential hepatitis B virus (HBV) yield donors (hepatitis B surface antigen [HBsAg] negative/NAT reactive) were evaluated for up to 9 months' follow-up. Discordant results between the Ultrio assay and the HBsAg tests were further analyzed by HBV antibody serology, alternative NATs, HBV DNA quantification, and sequencing. The 95% limits of detection in IU/mL (95% confidence interval) were as follows: human immunodeficiency virus Type 1 (HIV-1), 18 (12-34); hepatitis C virus (HCV), 4.4 (2.8-8.9); and HBV, 6.3 (4.4-11). The retest rates were 0.55% for IDT and 0.33% for MP4. No HIV or HCV yield cases were found, while there were 12 potential HBV yield cases, nine from IDT and three from MP4 testing. Eleven of them were successfully genotyped as B2. Ten of them returned for follow-up and mostly were determined as occult HBV infection (OBI). The IDT yield rate of 9 in 4210 (0.21%) was fourfold greater than the MP4 yield rate of 3 in 6080 (0.05%; p < 0.05). The higher yield rate for IDT versus MP4 demonstrates the benefit to implement a more sensitive NAT strategy in regions having significant OBI carriers such as Taiwan.

A modeling framework for evaluation and comparison of trigger strategies for switching from minipool to individual‐donation testing for West Nile virus

To decrease the likelihood of transmission from donations containing West Nile virus (WNV) levels below minipool nucleic acid test (MP-NAT) detection limits, blood centers switch from MP-NAT to individual-donation testing (ID-NAT) after detection of MP-NAT-positive donations. The effectiveness of strategies to trigger or discontinue ID-NAT screening is largely unknown. Twenty-seven strategies to trigger and discontinue ID-NAT screening were evaluated with a statistical model based on known dynamics of WNV infection and historical data on WNV prevalence among blood donations. Breakthroughs were defined as WNV immunoglobulin M antibody-negative, viremic (RNA-positive) donations that could only be identified by ID-NAT, but were screened by MP-NAT. Effectiveness (proportional reduction of breakthroughs relative to MP-NAT screening alone) and efficiency (absolute reduction of breakthroughs relative to the number of tests performed) were estimated by simulating donation years of varying outbreak severities over a range of blood collection frequencies. Most strategies were effective (>75% reduction in breakthroughs) when daily donations exceeded 560. In larger centers (1008 donations daily), effectiveness of trigger-on strategies based on absolute number of MP-NAT-positive donations improved, but worsened for strategies using rate-based criteria. Effectiveness increased slightly by triggering on one MP-NAT-positive rather than two and increased substantially by increasing the duration from 7 to 14 days that no ID-NAT-positive donations are detected before resuming MP-NAT. Most trigger strategies become effective when test results from at least 560 donations daily are considered. A 14-day ID-NAT period may improve safety relative to the increase in the number of tests performed.

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

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). 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. The ICER of adding HBV MP-6-NAT or HBV ID-NAT in the Netherlands is Euro303,218 (95% confidence interval [CI], Euro233,001-Euro408,388) and Euro518,995 (95% CI, Euro399,359-Euro699,120) per quality-adjusted life-year, respectively. The ICER strongly correlates with the age of transfusion recipients. 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.

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

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). 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. 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. 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.

Feasibility of routine individual donation testing for West Nile virus RNA during epidemic season using the investigational Roche cobas TaqScreen West Nile virus test and cobas s 201 system prototype

Minipool (MP) screening for West Nile virus (WNV) RNA may fail to detect presumptive viremic donations (PVDs) detectable by individual donation screening (IDS). Most blood centers switch collection regions to IDS when PVD detection by MP screening reaches a certain frequency. Use of IDS for all donations during WNV season was assessed during a clinical trial of the Roche cobas TaqScreen WNV test. Also evaluated was whether PVD detection reliably identifies regions that should be targeted for IDS. Test results, deviation reports, and service records were reviewed for 13.5 weeks of IDS in 2006 and 11.5 weeks of IDS in 2007. Numbers of PVDs and clinical WNV cases were obtained from public health and AABB Web sites and regional donor centers. Approximately 1000 donations were tested per week divided in six test runs. Each run required 1.2 shifts of technologists plus volunteers. A total of 7.2 percent of samples were initially unreportable in 2006 and 4.8 percent in 2007. Of 26,952 donations screened by IDS, none were reactive for WNV. A comparison of PVD and clinical case reports indicates that PVD detection in areas with intermediate or high clinical case prevalence may not reach commonly used criteria for triggering testing to IDS. Seasonal IDS was feasible using the cobas TaqScreen WNV test on the s 201, although staffing was impacted and a relatively high number of samples required retesting because of error messages. Seasonal IDS utilizing this highly specific assay may be a reasonable alternative to IDS triggered by regional PVD detection.

PROCLEIX® West Nile virus assay based on transcription-mediated amplification

The PROCLEIX® West Nile virus (WNV) assay is based on transcription-mediated amplification and is the most sensitive nucleic acid test commercially available today for blood screening. Since 2003, in the USA, the assay has been used for year-round screening of blood donations in minipools of 16 and in an individual-donation testing format, when appropriate triggering guidelines for such switch become effective. The test can be run on the semiautomated PROCLEIX modular platform or the fully-automated PROCLEIX TIGRIS® System. This assay and the corresponding platforms have been developed and are manufactured by San Diego-based Gen-Probe, Inc., while they are marketed and distributed by Chiron, a Novartis business. This review covers some of the epidemiological and virological aspects of WNV, as well as clinical questions and technological assessment of the transcription-mediated amplification and alternative technologies used in WNV blood screening.

Transfusion‐associated transmission of West Nile virus, United States 2003 through 2005

National blood donation screening for West Nile virus (WNV) started in June 2003, after the documentation of WNV transfusion-associated transmission (TAT) in 2002. Blood donations were screened with investigational nucleic acid amplification assays in minipool formats. Blood collection agencies (BCAs) reported screening results to state and local public health authorities. Donor test results and demographic information were forwarded to CDC via ArboNET, the national electronic arbovirus surveillance system. State health departments and BCAs also reported suspect WNV TATs to CDC, which investigated these reports to confirm WNV infection in blood transfusion recipients in the absence of likely mosquito exposure. During 2003 to 2005, a total of 1,425 presumptive viremic donors were reported to CDC from 41 states. Of 36 investigations of suspected WNV TAT in 2003, 6 cases were documented. Estimated viremia levels were available for donations implicated in four TAT cases; the median estimated viremia was 0.1 plaque-forming units (PFUs) per mL (range, 0.06-0.50 PFU/mL; 1 PFU equals approximately 400 copies/mL). National blood screening for WNV identified and removed more than 1,400 potentially infectious blood donations in 2003 through 2005. Despite the success of screening in 2003, some residual WNV TAT risk remained due to donations containing very low levels of virus. Screening algorithms employing selected individual-donation testing were designed to address this residual risk and were fully implemented in 2004 and 2005. Continued vigilance for TAT will evaluate the effectiveness of these strategies.

Measures Taken for Effective Virus Reduction of Plasma-Derived Coagulation Factor Concentrates.

The application of the complementary approaches (i) selection and testing of starting material, (ii) testing the product intermediate at appropriate steps of the production and (iii) assessing the capacity of the production process to reduce a wide range of viruses as well as prions, the causative agent for vCJD, results in plasma-derived coagulation factor concentrates with a remote risk of pathogen transmission. Selecting donors only from low-risk geographic areas considerably reduces the risk of a donation entering the plasma pool for fractionation which harbors either viruses (currently) unknown in the donor population or prions. Use of a sensitive assay to detect virus genome sequences results in the interdiction of contaminants in donations during window periods. Single window period donations with a total virus load of up to 9.9 log10 HAV RNA IU, 6.0 log10 HBV DNA IU, 11.9 log10 HCV RNA IU, 10.9 log10 HIV RNA IU and 16.9 log10 B19V DNA IU are identified and destroyed, and will not enter the plasma pool for fractionation. Plasma pools for fractionation likewise are released for further processing only if non-reactive for serological virus markers and for sequences of virus genome. Thus, potential errors made by not discarding, but pooling window period donations can be precluded, as even one window period donation with a high virus titre would be detected in the plasma pool for fractionation, and the entire plasma pool would be destroyed. A wide range of enveloped and non-enveloped viruses are effectively inactivated by pasteurization (heat treatment at 60°C for 10 hours in stabilized aqueous solution). Additionally, the manufacturing process of plasma-derived coagulation factor concentrates, as the VWF/FVIII product Haemate® P / Humate-P®, contains process steps reliably contributing to the reduction of viruses. As demonstrated in virus validation studies, pasteurization inactivates not only the known blood-borne viruses but also potential “emerging viruses”.Virus Inactivation by Pasteurization of Haemate® P / Humate-P®VirusInactivation Factor [log10]Complete Virus Inactivation after × hoursEnveloped virusesHIV> 6.41BVDV // WNV> 6.4 // > 7.83 // 2PRV // HSV-14.6 // > 7.7(10) // 6SARS-CoV // TGEV> 4.0 // > 5.61 // 1Influenzaviruses (1)> 5.4 // > 4.9 // > 4.91 // 2 // 1Non-enveloped virusesHAV // poliovirus 14.2 // > 7.8(10) // 4B19V> 3.910FCV (2)> 5.01(1) A/PR/8/34 [H1N1] // A/FPV/Rostock/34 [H7/N1] // A/Chick/Pennsylvania /1/83 [H5N2]; (2) feline calicivirus, model virus for HEVFurthermore, scaled-down spiking studies demonstrate that the manufacturing process reliably removes deliberately added prions, derived from scrapie-infected hamster brains, by 6.4 log10 for a microsomal preparation and by 7.9 log10 for a purified, non membrane-associated PrPSc preparation. By these measures in the aggregate - selection of donors, testing of individual donations, retesting of plasma pools, implementation of effective pathogen reduction steps in manufacturing - a high margin of safety with regard to viruses and prions can be achieved for plasma-derived coagulation factor concentrates as Haemate® P / Humate-P®. As pasteurization very effectively inactivates a wide range of enveloped and non-enveloped viruses and further manufacturing steps contribute to virus reduction, indirect evidence is provided that the manufacturing procedure will inactivate/remove also other novel or unpredictable virus contamination.

The Cost-Effectiveness of Screening the U.S. Blood Supply for West Nile Virus

The spread of West Nile virus across North America and evidence of transmission by transfusion prompted the U.S. Food and Drug Administration to encourage the development of methods to screen the blood supply. To assess the cost-effectiveness of nucleic acid amplification testing for West Nile virus in the U.S. blood supply. Markov cohort simulation. Outcome probabilities estimated from nucleic acid testing done for West Nile virus in 2003, data from the Centers for Disease Control and Prevention, and published literature. Costs were taken from an economic study of West Nile virus infection and from estimated test costs. TARGET POPULATIONS: Transfusion recipients, 60 years of age or older, with and without underlying immunocompromise. Lifetime. Societal. The authors compared 6 strategies, taking into consideration minipool (pools of 6 to 16 donations) versus individual donation testing, and the geographic and seasonal nature of West Nile virus activity. Costs and effects of each strategy based on the prevention of transfusion-transmitted West Nile virus. The cost-effectiveness of annual, national minipool testing was 483,000 dollars per quality-adjusted life-year (QALY), whereas the cost-effectiveness of annual, national individual donation testing was 897,000 dollars/QALY. The cost-effectiveness of targeted individual donation testing in an area experiencing an outbreak coupled with minipool testing elsewhere was 520,000 dollars/QALY. In 1-way analyses, the most important influences were the prevalence of West Nile virus and the cost of minipool testing and individual donation testing. The 95% range of results from probabilistic sensitivity analysis for targeted individual donation testing was 256,000 dollars to 1,044,000 dollars/QALY. The outcomes of West Nile virus infection were based on data from the general population rather than from the population who received transfusions. The results are most useful in the context of geographically focused outbreaks of West Nile virus infection. Using targeted individual donation testing to interdict blood donations that are positive for the West Nile virus is relatively cost-effective but is highly dependent on West Nile virus prevalence.