Implementation of donor screening for infectious agents transmitted by blood by nucleic acid technology: update to 2003.
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Blood Donors↗
Biomedical subjects
C L van der Poel
Publications and source records attributed to C L van der Poel.
Cost-effectiveness of leucocyte depletion of red-cell transfusions for patients undergoing cardiac surgery.
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Cardiac Surgical Procedures↗
Paying for blood donations: still a risk?
It is presently disputed whether studies indicating a higher risk of infectious diseases among paid blood donors are lessons of the past, or still hold relevance. Comparative studies published between 1968 and 2001 were assessed for a possible trend of change in the relative risk for infectious disease markers between paid and unpaid blood or plasma donors. Studies reporting that paid donors had lower risk were found, but most studies, including recent ones, continued to report that paid donors have higher rates of infectious disease markers than unpaid donors. By log-linear regression analysis of the relative risk estimates for infectious disease markers among paid and unpaid donors from 28 published data sets, evidence was not found to indicate that the difference in risk for infectious disease markers between paid donors and unpaid donors had diminished over time (P = 0.128, not significant). Paid donors are still more likely than unpaid donors to donate blood in the period during which infectious donations escape detection by blood-screening tests (the "window-period"). Therefore, paid donations have a higher risk that labile blood components (such as red blood cells and platelets) are infected. Additional safety measures for handling plasma donations, and the preparation, purification and viral-inactivation steps employed for the production of plasma derivatives, may render the difference in infectious disease marker rates in donors irrelevant for plasma products. However, not all viruses are inactivated and paid donors were repeatedly found to have higher frequencies of markers for emerging agents. In a quality system, critical steps of the process should be addressed, and selection of the donor population is one of the first steps in this process. It is advised that blood establishments present yearly reports (with complete and raw data) to authorities on the incidence and prevalence of infectious disease markers among their donors as an ongoing surveillance on the "quality" of their donor populations. Paid blood or plasma donors still have higher rates for infectious disease markers than unpaid donors.
Blood Donors↗
Nucleic acid testing: the international status of NAT.
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Blood Proteins↗
Validation of the NucliSens Extractor in combination with the hepatitis C virus Cobas Amplicor 2.0 assay in four laboratories in the Netherlands utilizing nucleic acid amplification technology for blood screening.
BACKGROUND AND OBJECTIVES: Since July 1 1999, four laboratories in the Netherlands have been routinely screening plasma minipools for the release of labile blood components utilizing hepatitis C virus nucleic acid amplification technology (HCV NAT). This report describes the performance evaluation of the HCV NAT method and the quality control results obtained during 6 months of routine screening. MATERIALS AND METHODS: Plasma minipools of 48 donations were prepared on a Tecan Genesis robot. HCV RNA was isolated from 2 ml of plasma by using the NucliSens Extractor and amplified and detected with the Cobas HCV Amplicor 2.0 test system. For validation of the test system the laboratories used viral quality control (VQC) reagents of CLB. RESULTS: Initial robustness experiments demonstrated consistent detection of PeliSpy HCV RNA samples of 140 genome equivalents/ml (geq/ml) in each station of the installed Nuclisens Extractors. Further 'stress' tests with a highly viraemic sample of approximately 5 x 10(6) geq/ml did not contaminate negative samples processed on all Extractor stations in subsequent runs. In the validation period prior to July 1999, 1021 pools were tested with the following performance characteristics: 0.1%, initially false reactive; 0.89%, failure of internal control detection; 0.97%, no eluate generated by the Extractor; and 100% reactivity of the PeliSpy 140 geq/ml control in 176 Extractor runs and a 98% reactivity rate of the PeliSpy 38 geq/ml control in 102 test runs. By testing the PeliCheck HCV RNA genotype 1 dilution panels 49 times, an overall 95% detection limit of 30 geq/ml ( approximately 8 IU/ml) and a 50% detection limit of 5 geq/ml was found by the four laboratories. In the first 6 months of routine screening, the minimum requirement for invalid results (2%) was exceeded with some batches of silica and NucliSens Extractor cartridges. From November 1999 to February 2000, the manufacturer (Organon Teknika) improved the protocol for silica absorption of the Nuclisens Extractor -- the cartridge design as well as the software of the Extractor. During the next 6 months of observation in 2000, the percentages of false initial reactives and invalids were 0.05% and 1.4%, respectively, in 8962 pools tested. Of these invalid results, 0.74% and 0.66% were caused by Extractor failure and negative internal control signals, respectively. The PeliSpy HCV RNA 'stop or go' run control of 140 geq/ml was 100% reactive, but invalid in 16/1375 (1.2%) of cases. The PeliSpy run control of 38 geq/ml for monitoring sensitivity of reagent batches was reactive in 95% of 123 samples tested. CONCLUSIONS: Each of the four HCV NAT laboratories in the Netherlands have achieved similar detection limits that are well below the sensitivity requirements of the regulatory bodies. After improvement of the NucliSens Extractor procedure, the robustness of the test system has proved to be acceptable for routine screening and timely release of all labile blood components.
Equipment Failure↗
[Leukodepletion of blood products: a requirement for improvement of quality and safety].
The presence of leukocytes in blood products has no beneficial effect on the recipient, except in special situations such as for patients being prepared to receive an organ transplantation. On the other hand the leukocytes have a number of untoward side effects such as HLA immunisation, non haemolytic febrile transfusion reactions, virus transmission and postoperative infections. In response to a request of the Minister of Health, Welfare and Sports, the Health Council of the Netherlands prepared a recommendation on the need of routine leukodepletion by filtration of blood. Although the introduction of leukodepletion of blood products is favoured, it is emphasized that only data from selected patient groups are available while the costs of leukodepletion are considerable. Therefore, an evaluation of the benefits and cost effectiveness of blood filtration is recommended. It is argued that leukodepletion, already introduced in a number of countries, is now considered to be 'state of the art'. Furthermore product liability, public opinion about blood safety and the precaution duty of manufacturers should be taken into account.
Blood Banks↗
Evaluation of automated nucleic acid extraction devices for application in HCV NAT.
BACKGROUND: To further improve the safety of the blood supply, various national blood transfusion organizations presently use or are in the process of implementing routine HCV NAT in minipools. According to the Committee for Proprietary Medicinal Products (CPMP) of the European Union, the HCV NAT detection limit of the assay should be 100 IU per mL (270 geq/mL) for testing initial plasma pools. Paul Ehrlich Institute (PEI) regulations stipulate that 5000 IU per mL (13,500 geq/mL) must be detected to calculate the amount contributed by individual donations composing the minipool. The sensitivity for HCV RNA extraction achieved by three commercially available laboratory kits was compared. STUDY DESIGN AND METHODS: Nucleic acids from 1-in-3 serial dilutions of an HCV RNA run control (Pelispy, CLB) were extracted with three kits (Cobas Amplicor, Roche Diagnostic Systems; BioRobot 9604, Qiagen; and NucliSens Extractor, Organon Teknika). HCV PCR of all extracts was performed using a second-generation Cobas Amplicor HCV test and the Cobas Amplicor analyzer. RESULTS: The manual Cobas Amplicor, the BioRobot 9604, and the NucliSens Extractor setups allow a 95-percent HCV RNA detection limit of 129, 82, and 12 geq per mL, respectively. The maximal pool size for the manual Cobas Amplicor, the BioRobot 9604, and the NucliSens Extractor kits that would still meet the PEI criteria for HCV NAT in minipools was calculated at 104, 164, and 1125 donations, respectively. CONCLUSION: All three HCV NAT kits evaluated meet the criteria set by CPMP and PEI. The highest sensitivity for HCV NAT screening can be achieved with the high-volume NucliSens Extractor method in combination with the Cobas Amplicor HCV v2.0 test on the Cobas Amplicor analyzer.
Blood Donors↗
Hepatitis C virus and blood transfusion: past and present risks.
The risk of HCV transmission by blood and blood products has been greatly reduced since the early 1980's. Selection of non-remunerated donors, donor selection to prevent HIV transmission, initial surrogate testing in some regions, and introduction of anti-HCV testing have all contributed to this. ALT surrogate testing has become obsolete since the introduction of anti-HCV testing. The residual risk of HCV transmission due to donations in the anti-HCV window period at present is about 1 in 100 000 transfusions of cellular products, and transmission of HCV by plasma products treated with modern inactivation methods such as solvent-detergent treatment, has not been reported. Hemovigilance programmes, which are presently being installed, will provide more data on the safety of blood transfusion. Introduction of HCV nucleic amplification technology (NAT) as a quality control of manufacturing pools for plasma products or as a form of blood donor screening by minipools is anticipated in many European countries for the coming year. Given industrial developments, NAT testing of individual blood donations may become available within the next 2 years. HCV NAT testing will further annihilate the residual risk, and the cost-effectiveness will become relatively low in comparison with other public health measures.
Blood Donors↗
[Optimal versus maximal safety of the blood transfusion chain in The Netherlands; results of a conference. College for Blood Transfusion of the Dutch Red Cross].
An invitational conference was held on September 11, 1996 by the Medical Advisory Commission to the Blood Transfusion Council of the Netherlands Red Cross, addressing the issues of 'maximal' versus 'optimal' safety measures for the blood supply. Invited were blood transfusion specialists, clinicians, representatives of patient interest groups, the Ministry and Inspectorate of Health and members of parliament. Transfusion experts and clinicians were found to advocate an optimal course, following strategies of evidence-based medicine, cost-benefit analyses and medical technology assessment. Patient groups depending on blood products, such as haemophilia patients would rather opt for maximal safety. Insurance companies would choose likewise, to exclude any risk if possible. Health care juridical advisers would advise to choose for optimal safety, but to reserve funds covering the differences with 'maximal safety' in case of litigation. Politicians and the general public would sooner choose for maximal rather than optimal security. The overall impression persists that however small the statistical risk may be, in the eyes of many it is unacceptable. This view is very stubborn.
Blood Transfusion↗
New hepatitis B virus mutant form in a blood donor that is undetectable in several hepatitis B surface antigen screening assays.
BACKGROUND: Envelope mutant forms of hepatitis B virus (HBV), impairing HBV antibody recognition, have been reported with mutations in single or multiple sites of the hepatitis B surface antigen (HBsAg) group-specific "a" determinant. Blood donors infected with such an HBsAg mutant form of HBV may escape detection by HBsAg screening assays and therefore may affect the safety of the blood supply. CASE REPORT: A repeat blood donor became HBsAg-reactive in an enzyme immunoassay. Confirmatory testing yielded negative results for HBsAg in a radioimmunoassay and in four enzyme immunoassays used in blood donor screening. The specificity of the HBsAg reactivity in the first enzyme immunoassay was confirmed by HBsAg neutralization with antibody to HBsAg. Additional HBV confirmatory test results were positive for antibody to hepatitis B core antigen and antibody to hepatitis B e antigen; negative for antibody to HBsAg and for hepatitis B e antigen; and positive for HBV DNA. DNA sequence analysis of the "a" determinant region of HBsAg revealed amino acid substitutions from Q (Gln) to R (Arg) at codon 129 and from M (Met) to T (Thr) at codon 133. CONCLUSION: This case illustrates the presence of HBsAg mutant forms of HBV in a West European blood donor population that were undetected by several HBsAg screening assays. Adaptation of HBsAg screening is indicated to overcome deficiencies in sensitivity in detecting HBsAg mutant forms of HBV. Screening for antibody to hepatitis B core antigen or HBV DNA may also detect blood donors infected with HBsAg mutant forms of HBV
Adult↗
Hepatitis C virus: epidemiology, transmission and prevention.
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Blood Donors↗
A simple strategy to look back on posttransfusion hepatitis B in a multitransfused patient.
BACKGROUND AND OBJECTIVES: In January 1996, a case of hepatitis B virus (HBV) seroconversion in a multitransfused patient was reported to the blood bank From March through October 1995, the patient had received 23 units of red cells and 30 units of pooled platelet concentrates, encompassing an exposure to a total of 200 whole blood donations. MATERIALS AND METHODS: In order to trace hepatitis B surface antigen (HBsAg)-negative but HBV-infectious blood donation(s), we tested samples of the donors obtained > or = 3 months after the implicated donations for anti-HBc (Corezyme EIA, Abbott). From 172/200 donors, archived samples of subsequent donations were available for this purpose. The remaining 28 donors were reinvited to the blood bank to obtain an additional blood sample for anti-HBc testing. RESULTS: 1/200 follow-up donor samples was anti-HBc-positive. Retrospective testing of the implicated HBsAg-negative blood donation of this donor revealed anti-HBc-negative and HBV-DNA-positive results. The patient was transfused with the platelets of the HBV-infectious donation. On looking back, the other blood products prepared from this HBV-infectious donation caused posttransfusion HBV infection (PT-HBV) in 2 additional patients. CONCLUSION: Anti-HBc testing on mainly archived follow-up samples of 200 donors implicated in PT-HBV was a rapid, simple cost-effective and donor-friendly method to identify an infectious but HBsAg-negative, anti-HBc-negative and HBV-DNA PCR-positive blood donation. Routine anti-HBc screening would not have prevented this HBV transmission.
Adult↗
[Infection with T-lymphotropic virus in Dutch blood donors, 1993-1996].
Infection with human T-lymphotrophic virus (HTLV) type 1 causes a neurological disorder or leukaemia in a minority of infected persons. Since January 1993 the Dutch blood banks screen each donation for presence of HTLV-1 infection. Approximately 4,000,000 donations from 700,000 donors have been tested. The numbers of confirmed HTLV-1 positive donors were: 1993: 15; 1994: 6; 1995: 8; 1996: 3. In 1995 one case of HTLV-2 infection was detected as well. In 26/32 (81%) of the HTLV-1 positive cases either the donor or his/her partner originated from HTLV-1 endemic areas. The introduction of HTLV screening prevents the silent spread of HTLV via blood transfusion.
Blood Donors↗
Look-back of anti-HCV ELISA-positive, HCV-RNA PCR-negative donors and recipients of their blood products.
BACKGROUND AND OBJECTIVES: To establish the infectivity of anti-HCV ELISA-positive, but cDNA-PCR-negative blood components transfused before the introduction of routine anti-HCV blood donor screening, we enrolled recipients of such blood products in a look-back programme. MATERIALS AND METHODS: The blood components were donated by (A) RIBA-2-indeterminate and cDNA-PCR-negative donors, and (B) RIBA-2 and cDNA-PCR-negative donors. The look-back comprised 214 blood products from group A donors and 278 from group B. RESULTS: Of 211 recipients of group A components, 66 (31.3%) were available for testing. All other recipients could not be traced, had died, or refused collaboration. Of these 66, 3 patients had independent risk factors for HCV infection and were excluded. All remaining 63 recipients were anti-HCV ELISA-negative. Of 274 recipients of group B components, 84 (30.7%) were available for testing. All others could not be traced, had died, or refused collaboration. Of these 84, six patients had an independent risk factor for HCV infection and were excluded. All remaining 78 recipients were anti-HCV ELISA-negative. None of the recipients of blood products from previous donations of anti-HCV ELISA-positive, cDNA-PCR-negative, and RIBA-2-indeterminate or negative donors were HCV-infected. CONCLUSIONS: Donors and patients with such reactivities in anti-HCV ELISA, RIBA-2, and cDNA-PCR can be assured that they are not infected with HCV. The donors involved can re-enter the donor pool, provided that future donations are anti-HCV ELISA-negative.
Antigens, Viral↗
Evaluation of a new HTLV-I/II polymerase chain reaction.
AIM: Evaluation of a qualitative HTLV-I/II DNA polymerase chain reaction (PCR) test for the detection of HTLV-I/II DNA (Roche Diagnostic Systems, Branchburg, N.J., USA) in various panels. METHODS: The panels consisted of fresh EDTA blood samples from blood donors who were anti-HTLV-I/II ELISA repeatably reactive: 53 were Western blot (WB) positive, 228 were WB indeterminate and 15 were WB negative. Elevent ELISA-negative blood donors were used as negative controls. Furthermore, specimens from 1 HTLV-II-infected intravenous drug user and from 1 HTLV-II-infected blood donor were included in the panel. Peripheral blood lymphocytes were prepared by red blood cell lysis with the Roche washing solution and stored at < -23 degrees C until processing. Amplification products were analyzed with the HTLV-I/II detection kit. RESULTS: All 53 anti-HTLV-I/II ELISA- and WB-positive samples and both HTLV-II-positive samples tested positively by PCR. All 228 anti-HTLV-I/II ELISA-positive and WB-indeterminate, all 15 ELISA-positive and WB-negative and all II ELISA-negative control samples tested negative by PCR. CONCLUSION: The Roche Amplicor HTLV-I/II test is a simple test, suitable for the confirmation of HTLV-I and-II infection in individuals with indeterminate or positive WB patterns.
Blood Donors↗
Human immunodeficiency virus (HIV) antibodies detected by new assays that are enhanced for HIV-1 subtype O.
BACKGROUND: Human immunodeficiency virus type 1 (HIV-1) subtype O infections are not reliably detected by commonly used anti-HIV-1/2 screening assays. Therefore, anti-HIV-1/2 assays have been modified to increase their sensitivity in detecting antibodies to HIV-1 subtype O. STUDY DESIGN AND METHODS: Two new anti-HIV-1/2 enzyme-linked immunosorbent assays (ELISAs) (Abbott Plus and Ortho Enhanced) were compared with a currently used anti-HIV-1/2 ELISA (Abbott Recombinant) in various serum panels: 91 Western blot-confirmed anti-HIV-1-positive samples, 20 samples from Western blot-confirmed HIV-1-infected patients in log3 serial dilutions, and 1463 samples from consecutive, volunteer, nonremunerated blood donors. RESULTS: Among 91 anti-HIV-1 Western blot-positive samples, 2 (2.2%) were missed by the Abbott Recombinant ELISA, but all 91 were detected by the Abbott Plus and Ortho Enhanced ELISAs. In contrast, two discrepant samples were found to react in viral lysate-based assays. In serial dilutions, Ortho Enhanced ELISA was significantly less sensitive than the Abbott Recombinant and Abbott Plus ELISAs, with the latter two being of comparable sensitivity. The specificities of Abbott Recombinant, Abbott Plus, and Ortho Enhanced ELISAs in 1463 blood donors were 100, 99.93, and 99.86 percent, respectively. Routine testing of 29,102 donations with the enhanced Abbott Plus ELISA revealed a specificity of 99.93 percent. CONCLUSION: Two Western blot-confirmed anti-HIV-1-positive samples were missed by the Abbott Recombinant ELISA but detected by the Abbott Plus and Ortho Enhanced ELISAs. The analytic sensitivity of the Ortho Enhanced ELISA was inferior to that of both Abbott ELISAs. The specificities of the Abbott Recombinant, Abbott Plus, and Ortho Enhanced ELISAs were comparable.
Blood Donors↗
Performance of three generations of anti-hepatitis C virus enzyme-linked immunosorbent assays in donors and patients.
BACKGROUND: Prevention of posttransfusion non-A,non-B hepatitis in recipients of blood components improved considerably with the introduction of the second-generation of hepatitis C virus (HCV) antibody tests. In 1993, third-generation HCV antibody assays were introduced in Europe. STUDY DESIGN AND METHODS: The performance of three generations of anti-HCV enzyme-linked immunosorbent assay (ELISA) (ELISA-1, -2, -3) was compared in routine blood donor screening (99,394 donations were tested with ELISA-1, 167,999 donations with ELISA-2, and 262,090 donations with ELISA-3) and in serial samples from nine patients with documented acute posttransfusion HCV infection. RESULTS: Eight (0.01%) repeat donors, previously negative in ELISA-1, were found positive in ELISA-2 and were confirmed as positive in second-generation recombinant immunoblot assay and/or cDNA polymerase chain reaction. In the donor population, no difference in the sensitivity of ELISA-2 and -3 was observed. The specificity of the three generations of ELISAs was comparable (99.8, 99.7, and 99.7%). In seroconversion samples, ELISA-2 and -3 detected HCV antibodies at the same time in seven patients, but in two patients, ELISA-3 found HCV antibodies, respectively, 63 and 77 days earlier than ELISA-2 did. In the seroconversion samples, ELISA-2 and -3 were significantly more sensitive than second- and third-generation recombinant immunoblot assays. CONCLUSION: ELISA-3 did not detect more HCV-infected individuals in a donor population that previously tested negative in ELISA-2, but it did detect HCV antibodies earlier in some patients with acute HCV infection. ELISA-2 and -3 were significantly more sensitive than second- and third-generation recombinant immunoblot assays.
Blood Donors↗
Sensitivity and specificity of four assays to detect human T-lymphotropic virus type I or type I/II antibodies.
BACKGROUND: Assays that detect human T-lymphotropic virus type I and type II antibody (HTLV-I/II) are widely used in the routine screening of blood donors. STUDY DESIGN AND METHODS: Four commercially available anti-HTLV-I (Fujirebio and Organon Teknika) or -HTLV-I/II assays (Murex and Ortho) were evaluated in various serum panels: A) HTLV-I-positive specimens (n = 41), confirmed by Western blot and polymerase chain reaction; B) a commercially available anti-HTLV-I/II panel; C) serial dilutions of sera from HTLV-I-positive individuals (n = 30), confirmed by immunofluorescence assay and Western blot: D) serial dilutions of HTLV-II-positive blood donors (n = 20), confirmed by Western blot and polymerase chain reaction, and E) sera from first-time blood donors (n = 1055). RESULTS: All four assays elicited reactions in all 82 HTLV-I-positive samples in Panels A, B, and C. Of 32 HTLV-II-positive specimens in Panels B and D, 31 (96.9%) reacted in the Organon Teknika assay and all 32 reacted in the remaining tests. Probit analysis of test results in Panels C and D indicated that the Fujirebio test was the most sensitive assay, followed by Organon Teknika, Ortho, and Murex. The specificities of Fujirebio, Murex, Organon Teknika, and Ortho tests in 1055 first-time blood donors were 99.9, 100, 99.6, and 99.9 percent, respectively. CONCLUSION: All four studied assays for detecting HTLV-I or HTLV-I/II antibodies are appropriate as screening tests.
Blood Donors↗