Assessing the risk of transfusion-transmitted variant Creutzfeldt-Jakob disease: a European perspective.

Several countries have recently reassessed the international risk of variant Creutzfeldt-Jakob disease (vCJD) transmission through transfusion of blood and blood components (red blood cells, platelets and plasma) and relaxed donor deferrals based on geographic and transfusion exposure in countries formerly considered to be high risk, such as the UK. In this regard, the European Blood Alliance organised a consensus meeting of experts and involved professionals to discuss current knowledge, epidemiological data, prevention and various methods for assessing the risk of transfusion-transmitted vCJD, as well as to develop an appropriate position on possible approaches to address these challenges in Europe. Participants reached a consensus that the current risk of transfusion-transmitted vCJD associated with blood donors who either travelled to or received transfusions in the UK during the vCJD outbreak is minimal. In addressing such risks, it would be pragmatic that assessments and guidelines are developed by European expert bodies, rather than individual assessments by Member States. Regardless of the approach used, European or national, a qualitative risk assessment based on a review and analysis of available data, considering all the uncertainties and experiences of other countries, would provide crucial information to reassess blood donation strategies regarding the transfusion-associated vCJD risk.

Research partnerships between blood services and public health authorities: An international, cross-sectional survey.

BACKGROUND AND OBJECTIVES: The COVID-19 pandemic has brought to the fore how blood services can partner with public health (PH) authorities to inform decisions. Yet the scope of partnerships between blood services and PH authorities is inadequately documented. We explored how blood services partner with PH authorities outside the scope of COVID-19. MATERIALS AND METHODS: On 19 January 2022, survey was sent to employees of blood services located throughout the world. Survey questions mainly pertained to partnerships with PH authorities, including how blood specimens are used and collected. RESULTS: Twenty-seven recipients-4 (14.8%) in Africa, 3 (11.1%) in Asia, 9 (33.3%) in Europe, 6 (22.2%) in North America, 2 (7.4%) in Oceania and 3 (11.1%) in South America-completed the survey. Fifteen recipients (55.6%) indicated their blood service was directly or indirectly supervised by PH authorities. Twenty-four recipients (88.9%) indicated currently using or planning to use blood donor data or samples for PH research or pathogen surveillance. A substantial proportion of respondents reported using samples or results from non-routine tests for the surveillance of non-transfusion-transmitted infectious disease pathogens (n = 13 [48.1%]); samples or results of non-routine tests for PH research unrelated to pathogens (n = 10 [37.0%]); donor data for PH research unrelated to pathogens (n = 12 [44.4%]) and donor data for PH research unrelated to transfusion safety (n = 11 [40.7%]). Fourteen (51.9%) had established (or planned to establish) longitudinal cohorts and 19 (70.4%) biobanks. CONCLUSION: The majority of responding blood services were already involved in or planned to be involved in PH research or pathogen surveillance.

Current challenges of severe acute respiratory syndrome coronavirus 2 seroprevalence studies among blood donors: A scoping review.

BACKGROUND AND OBJECTIVES: Blood donors are increasingly being recognized as an informative resource for surveillance. We aimed to review severe acute respiratory syndrome coronavirus 2 seroprevalence studies conducted among blood donors to investigate methodological biases and provide guidance for future research. MATERIALS AND METHODS: We conducted a scoping review of peer-reviewed and preprint publications between January 2020 and January 2021. Two reviewers used standardized forms to extract seroprevalence estimates and data on methodology pertaining to population sampling, periodicity, assay characteristics, and antibody kinetics. National data on cumulative incidence and social distancing policies were extracted from publicly available sources and summarized. RESULTS: Thirty-three studies representing 1,323,307 blood donations from 20 countries worldwide were included (sample sizes ranged from 22 to 953,926 donations). The majority of the studies (79%) reported seroprevalence rates <10% (ranging from 0% to 76% [after adjusting for waning antibodies]). Overall, less than 1 in 5 studies reported standardized seroprevalence rates to reflect the demographics of the general population. Stratification by age and sex were most common (64% of studies), followed by region (48%). A total of 52% of studies reported seroprevalence at a single time point. Overall, 27 unique assay combinations were identified, 55% of studies used a single assay and only 39% adjusted seroprevalence rates for imperfect test characteristics. Among the nationally representative studies, case detection was most underrepresented in Kenya (1:1264). CONCLUSION: By the end of 2020, seroprevalence rates were far from reaching herd immunity. In addition to differences in community transmission and diverse public health policies, study designs and methodology were likely contributing factors to seroprevalence heterogeneity.

An international comparison of anti-SARS-COV-2 assays used for seroprevalence surveys from blood component providers.

BACKGROUND AND OBJECTIVES: Access to large pools of healthy adult donors advantageously positions blood component providers to undertake anti-SARS-CoV-2 seroprevalence studies. While numerous seroprevalence reports have been published by blood operators during the COVID-19 pandemic, details on the assay used has not been well documented. The objectives of this study were to evaluate the diversity of assays being used by blood operators and assess how this may affect seroprevalence estimates. MATERIALS AND METHODS: We surveyed 49 blood component providers from 39 countries. Questionnaire included information on the number and identity of assays used, the detected immunoglobulin(s) and target antigen, and performance characteristics (sensitivity, specificity). RESULTS: Thirty-eight of the 49 contacted blood suppliers provided at least partial responses. The results indicate that 19 commercial and five in-house serology assays have been used by surveyed blood operators. The Abbott SARS-CoV-2 IgG assay was the most commonly used kit and utilized by 15 blood suppliers. Two assays did not detect IgG, but detected either IgM/IgA or IgM. 68·2% of assays targeted the spike protein and 50% the nucleocapsid protein, while 18·2% targeted both viral proteins. The sensitivity and specificity of IgG-specific assays ranged from 71·9% to 100% and from 96·2% to 100%, respectively. As of 18 October 2020, the seroprevalence was below 5% in 10 of 14 countries reporting. CONCLUSION: Our results highlight the diversity of assays being used. Analyses comparing blood donor seroprevalence across countries should consider assay characteristics with optimization of signal/cut-off ratios and consistent methodology to adjust for waning antibody.

West Nile virus and blood transfusion safety: A European perspective.

BACKGROUND AND OBJECTIVES: There is a growing concern for the transmission of arboviral infections by blood transfusion in Europe. However, no assessment of the risk of transmission through all European blood supplies has been reported. Risk regulations at a European level should take differences in local transmission risk and the risk of transmission by travelling donors into consideration. MATERIALS AND METHODS: A risk model and publicly available tool were developed to calculate the risk of transmission by all European blood supplies for arboviral outbreaks within Europe. Data on individual European blood supplies from Council of Europe reports and inter-European travel data from EUROSTAT were used to populate this model. RESULTS: Each neuroinvasive case of WNV reported in Europe will on average result in 0·43 (95%CI: 0·32-0·55) infected blood product by locally infected donors and 0·010 (95%CI: 0·006-0·015) infected products by travelling donors. On basis of the 1373 neuroinvasive human WNV cases reported in the outbreak of 2018, it is estimated that without safety interventions this outbreak would have resulted in 708 (95%CI: 523-922) infected components derived from resident donors. Noncompliance to European regulations, which requires donor deferral or testing of donors who visited WNV-infected areas, would have resulted in 7.4 (95%CI: 4·7-11·1) infected blood components derived from infectious travelling donors exposed in outbreak areas throughout Europe. CONCLUSION: The risk of WNV transmission by a local outbreak is on average 113 times (95%CI: 95-139), so two orders of magnitude higher than the risk of transmission by travelling donors in Europe.

Research initiatives of blood services worldwide in response to the covid-19 pandemic.

BACKGROUND AND OBJECTIVES: While coronavirus (COVID-19) is not transfusion-transmitted, the impact of the global pandemic on blood services worldwide is complex. Convalescent plasma may offer treatment, but efficacy and safety are not established. Measuring seroprevalence in donors would inform public health policy. Here, we survey blood services around the world to assess the different research programmes related to COVID-19 planned or in progress. MATERIALS AND METHODS: Blood collection services were surveyed in June 2020 to determine whether they were participating in serosurveys or convalescent plasma collection and clinical trials. RESULTS: A total of 48 countries (77% of those contacted) responded. Seroprevalence studies are planned or in progress in 73% of countries surveyed and in all continents, including low- and middle-income countries. Most aimed to inform public health policy. Convalescent plasma programmes have been initiated around the globe (79% of surveyed), about three quarters as clinical trials in high-, middle- and low-income countries. CONCLUSION: Blood services around the world have drawn upon their operational capacity to provide much-needed seroprevalence data to inform public health. They have rapidly implemented preparation of potential treatment when few treatments are available and mostly as clinical trials. At the same time, they must continue to provide blood products for recipients despite challenges of working in a state of emergency. It is important to track and coordinate research efforts across jurisdictions to gain a composite evidence-based view that will influence future practice and preparative strategies.

[Blood safety in the Netherlands: prevention of blood-transmitted infections]. / De bloedveiligheid in Nederland.

Amongst the various blood-safety measures to prevent blood-transmitted infections in transfusion recipients, the most important are the selection of blood donors and the testing for infections of the donations. A look-back procedure aims to inform hospitals about potentially infected blood products and to trace the relevant recipients. The opposite, reverse look-back, can also occur: following a report that a patient has an infection of which blood transfusion may be the possible source, all possibly implicated donors will be screened for the particular agent. Over the period 2007-2017, 84 look-backs were carried out by the Dutch blood product organisation Sanquin. Transmission via blood products of the human immunodeficiency virus, hepatitis C virus, human T-cell Lymphotropic virus or Treponema pallidum were not found. Look-back identified four recipients with hepatitis-B virus infection. These recipients had received a blood product from donors with an occult chronic hepatitis-B virus infection. In the Netherlands, the risks associated with transmission of infection through blood products are minimal; however, transmission may still occur, despite extensive blood-safety measures.

West Nile and Usutu Virus Infections and Challenges to Blood Safety in the European Union.

West Nile virus (WNV) and Usutu virus (USUV) circulate in several European Union (EU) countries. The risk of transfusion-transmitted West Nile virus (TT-WNV) has been recognized, and preventive blood safety measures have been implemented. We summarized the applied interventions in the EU countries and assessed the safety of the blood supply by compiling data on WNV positivity among blood donors and on reported TT-WNV cases. The paucity of reported TT-WNV infections and the screening results suggest that blood safety interventions are effective. However, limited circulation of WNV in the EU and presumed underrecognition or underreporting of TT-WNV cases contribute to the present situation. Because of cross-reactivity between genetically related flaviviruses in the automated nucleic acid test systems, USUV-positive blood donations are found during routine WNV screening. The clinical relevance of USUV infection in humans and the risk of USUV to blood safety are unknown.

An assessment of the risk, cost-effectiveness, and perceived benefits of anti-parvovirus B19 tested blood products.

BACKGROUND: Parvovirus B19 (B19V) can cause severe anemia, hydrops foetalis, and even death in vulnerable patients. To prevent transfusion-transmitted B19V infection of at-risk patients, B19V antibody screening of blood donors was implemented. The cost-effectiveness of this intervention is unclear, as the likelihood of transmission through blood and subsequent complications for recipients are unknown. This study estimates the cost-effectiveness of anti-B19V donor screening in the Netherlands. STUDY DESIGN AND METHODS: The estimates needed for the cost-effectiveness model were: the occurrence of B19V in Dutch blood donors, the number of anti-B19V tested products required by hospitals, the likelihood of morbidity and mortality given B19V infection, treatment costs, and screening costs. These estimates were obtained from literature and observational data. When data were unavailable, structured expert judgment elicitation and statistical modeling were applied. RESULTS: The costs of preventing one transfusion transmitted B19V infection are estimated at €68,942 (€42,045 - €102,080). On average, 1.25 cases of morbidity and 0.12 cases of mortality are prevented annually. Although the perceived risk of transfusion transmitted B19V infection was low, half of the treating physicians favored anti-B19V screening. CONCLUSION: The estimated mortality and morbidity caused by B19V infection was low in the risk groups. The cost-effectiveness ratio is similar to other blood safety screening measures. No guidance exists to evaluate the acceptability of this ratio. The explicit overview of costs and effects may further guide the discussion of the desirability of B19V safe blood products.

Selection strategies for newly registered blood donors in European countries.

BACKGROUND: Two selection strategies for newly-registered blood donors are available: a single-visit selection called the standard selection procedure (SSP), and a two-stage selection named predonation and donation screening (PDS). This study reviews the selection strategies for newly-registered donors currently applied in European countries. MATERIAL AND METHODS: We collected data on donor selection procedures, blood donation, laboratory screening and HIV, HCV and HBV positive donors/donations from 2010 to 2013 in 30 European countries by using questionnaires. We grouped the countries according to the applied selection strategy, and for each country, we calculated the 4-year prevalence of confirmed positive results indicating the presence of overall and recent HIV, HCV and HBV infections among first-time and repeat donations and among newly-registered donors. RESULTS: Most of the 24 countries (80%) apply the SSP strategy for selection of newly-registered donors. Twenty-two countries (73.3%) employ a nucleic acid amplification testing in addition to the mandatory serological screening. The survey confirms a higher overall prevalence of HIV, HCV and HBV infections among first-time donations and newly-registered donors than among repeat donations. In contrast, the prevalence of recently acquired HIV and HCV infections was lower among first-time donations and newly-registered donors than among repeat donations, but higher for recent HBV infections (6.7/105 vs 2.6/105 in the SSP setting and 4.3/105 vs 0.5/105 in one country using PDS). The relatively low numbers of infected donors selected by PDS impeded accurate assessment of the prevalence of recent infections in first-time donations. DISCUSSION: The data from European countries provide inconclusive evidence that applying PDS reduces the risk of donations being made in the diagnostic window of first-time donors. The impact of PDS on the risk of window-period donations and blood donor management needs further investigation.

Rare transmission of hepatitis B virus by Dutch donors with occult infection.

BACKGROUND: To reduce the rate of transfusion-transmitted hepatitis B virus (HBV), HBV DNA testing was introduced for all Dutch blood donations in 2008, in addition to the existing screening for HBV surface antigen (HBsAg). This study describes the lookback results for repeat donors with an "HBV DNA-only" test result (HBV DNA-positive and HBsAg-negative). STUDY DESIGN AND METHODS: From November 2008 until June 2011, a total of 2.3 million blood donations were tested for HBV DNA and 22 donors showed the HBV DNA-only profile. Four donors had early preseroconversion HBV infection, two showed suppressed infection after vaccination, and 16 donors had occult chronic HBV infection (OBI). Potentially infectious donations were traced back as far as 1992. If possible the recipients were tested for current and past HBV infection. RESULTS: A total of 416 implicated donations could be traced in blood bank records, involving 448 issued blood products. For 170 (38%) of the recipients no information was obtained from the hospitals; 196 (44%) recipients had died, and 82 (18%) were tested for HBV. Six recipients tested positive for current (n = 4) or past (n = 2) HBV infection. For two recipients transfusion was ruled out as the source of infection. Three patients showed HBV DNA sequences matching with the HBV in one common OBI donor. Overall, in four of 82 tested recipients (5%) HBV transmission was likely. CONCLUSION: In our lookback study HBV testing was possible in only a minority (18%) of potentially exposed recipients. A low transmission rate (5%) was observed in recipients of blood components from donors with OBI.

Predonation screening of candidate donors and prevention of window period donations.

BACKGROUND: Infectious window period donations slip through routine donor screening procedures. To explore the potential value of predonation screening of candidate donors, we compared the proportion of incident transfusion-transmissible infections in candidate donors, in first-time donors, and in repeat donors. STUDY DESIGN AND METHODS: A retrospective analysis was performed of all incident hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) infections in candidate, first-time, and repeat donors in the Netherlands during the period 2009 to 2013. RESULTS: In total, 176,716 candidate donors, 144,226 first-time donations, and 4,143,455 repeat donations were screened for HBV, HCV, and HIV infection. Acute HBV infection was identified in the predonation sample of six candidate donors. One first-time donor, testing HIV-negative at predonation screening, tested positive for anti-HIV and HIV RNA in the first donation 29 days later. Among repeat donations we identified 15, one, and six incident HBV, HCV and HIV infections, respectively. The proportion of incident infections among candidate donors/first-time donations/repeat donations was for HBV, 3.40/0/0.36; for HCV, 0/0/0.02; and for HIV 0/0.69/0.14 per 100,000, respectively. CONCLUSION: Predonation screening of candidate donors very likely causes a loss of donations, but it might prevent undetected window period donations. Further studies are necessary to determine the value of predonation screening as an additional safety measure.

Travel behavior and deferral of Dutch blood donors: consequences for donor availability.

BACKGROUND: Donors returning from areas with outbreaks of infectious diseases may donate infectious blood back home. Geographic donor deferral is an effective measure to ensure the blood safety, but donor deferral may pose a threat for the blood supply especially after holiday seasons. Insight into the travel behavior of blood donors is a first step to define appropriate deferral strategies. This study describes the travel behavior of Dutch donors, the actual deferral, and the consequences of deferral strategies on donor availability. STUDY DESIGN AND METHODS: A questionnaire designed to assess travel behavior (destination, frequency, and duration of travels) was sent to 2000 Dutch donors. The impact of travel deferral policies on donor availability was calculated, expressed as proportionate decrease in donor availability. The deferral policies considered were 1) deferral based on entire countries instead of affected regions where an infection is prevalent and 2) deferral after any travel outside Europe ("universal deferral"). RESULTS: Of the 1340 respondents, 790 (58.9%) donors traveled within Europe only, 61 (4.6%) outside Europe only, and 250 (18.7%) within and outside Europe. The deferral for entire countries and universal deferral would lead to 11.1 and 11.4% decrease in donor availability, respectively. CONCLUSION: Most Dutch donors traveled outside the Netherlands, while 23.2% traveled outside Europe. Universal deferral resulted in an additional decrease in donor availability of 0.3% compared with deferral for entire countries instead of affected regions where an infection is prevalent. Thus, the universal deferral could be considered as a simpler and safer measure.

Effect on the quality of blood components after simulated blood transfusions using volumetric infusion pumps.

BACKGROUND: It is unknown whether the use of volumetric infusion pumps for the transfusion of red blood cells (RBCs) or platelet (PLT) concentrates (PCs) affects the quality of the blood components. We therefore investigated the in vitro quality of these components after use of infusion pumps. STUDY DESIGN AND METHODS: Ten different volumetric infusion pumps were used to simulate transfusion with RBCs and PCs. To prevent donor-dependent differences multiple units were pooled and divided into equal portions. The storage time of RBCs was 30 to 35 days (n=10 experiments), and for PCs, either 2 (n=5) or 7 days (n=5). For RBCs an infusion rate of 100 or 300mL/hr was used, and for PCs, 600mL/hr. Transfusions without an infusion pump served as a reference. RESULTS: None of the infusion pumps induced an increase of free hemoglobin, annexin A5 binding, or formation of echinocytes in RBCs compared to reference units. In 2- and 7-day-old PCs no effect was shown on PLT concentration, annexin A5 binding, mean PLT volume, and morphology score compared to the reference. The CD62P expression of 2-day-old PCs was significantly lower after transfusion compared to the reference, that is, 11.7±2.1% versus 8.1±1.3% (p<0.01). CONCLUSION: There was no adverse effect on the in vitro quality of RBCs or PCs after simulated transfusion using volumetric infusion pumps. A decrease in PLT activation was observed, which can probably be explained by capturing of activated or damaged PLTs in the 200-µm filter present in the infusion system.