International review of blood donation screening for anti-HBc and occult hepatitis B virus infection.

BACKGROUND: Hepatitis B core antibody (anti-HBc) screening has been implemented in many blood establishments to help prevent transmission of hepatitis B virus (HBV), including from donors with occult HBV infection (OBI). We review HBV screening algorithms across blood establishments globally and their potential effectiveness in reducing transmission risk. MATERIALS AND METHODS: A questionnaire on HBV screening and follow-up strategies was distributed to members of the International Society of Blood Transfusion working party on transfusion-transmitted infectious diseases. Screening data from 2022 were assimilated and analyzed. RESULTS: A total of 30 unique responses were received from 25 countries. Sixteen respondents screened all donations for anti-HBc, with 14 also screening all donations for HBV DNA. Anti-HBc prevalence was 0.42% in all blood donors and 1.19% in new donors in low-endemic countries; however, only 44% of respondents performed additional anti-HBc testing to exclude false reactivity. 0.68% of anti-HBc positive, HBsAg-negative donors had detectable HBV DNA. Ten respondents did universal HBV DNA screening without anti-HBc, whereas four respondents did not screen for either. Deferral strategies for anti-HBc positive donors were highly variable. One transfusion-transmission from an anti-HBc negative donor was reported. DISCUSSION: Anti-HBc screening identifies donors with OBI but also results in the unnecessary deferral of a significant number of donors with resolved HBV infection and donors with false-reactive anti-HBc results. Whilst confirmation of anti-HBc results could be improved to reduce donor deferral, transmission risks associated with anti-HBc negative OBI donors must be considered. In high-endemic areas, highly sensitive HBV DNA testing is required to identify infectious donors.

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.

Characterization of transfusion-relevant bacteria reference strains in a lyophilized format.

BACKGROUND AND OBJECTIVES: Blood safety measures used by blood establishments to increase blood component safety can be validated using Transfusion-Relevant Bacterial Reference Strains (TRBRS). Ultra-cold storage conditions and manual preparation of the current TRBRS may restrict their practical use. To address this issue, the ISBT Transfusion-Transmitted Infectious Diseases Working Party's Bacterial Subgroup organized an international study to validate TRBRS in a user-friendly, lyophilised format. MATERIALS AND METHODS: Two bacterial strains Klebsiella pneumoniae PEI-B-P-08 and Staphylococcus aureus PEI-B-P-63 were manufactured as lyophilised material. The lyophilised bacteria were distributed to 11 different labs worldwide to assess the robustness for enumeration, identification and determination of growth kinetics in platelet concentrates (PCs). RESULTS: Production of lyophilised TRBRS had no impact on the growth properties compared with the traditional format. The new format allows a direct low-quantity spiking of approximately 30 bacteria in PCs for transfusion-relevant experiments. In addition, the lyophilised bacteria exhibit long-term stability across a broad temperature range and can even be directly rehydrated in PCs without losing viability. Interlaboratory comparative study demonstrated the robustness of the new format as 100% of spiked PC exhibited growth. CONCLUSION: Lyophilised TRBRS provide a user-friendly material for transfusion-related studies. TRBRS in the new format have improved features that may lead to a more frequent use in the quality control of transfusion-related safety measures in the future.

An international review of the characteristics of viral nucleic acid-amplification testing (NAT) reveals a trend towards the use of smaller pool sizes and individual donation NAT.

BACKGROUND AND OBJECTIVES: Nucleic acid-amplification testing (NAT) is used for screening blood donations/donors for blood-borne viruses. We reviewed global viral NAT characteristics and NAT-yield confirmatory testing used by blood operators. MATERIALS AND METHODS: NAT characteristics and NAT-yield confirmatory testing used during 2019 was surveyed internationally by the International Society of Blood Transfusion Working Party Transfusion-Transmitted Infectious Diseases. Reported characteristics are presented herein. RESULTS: NAT was mainly performed under government mandate. Human immunodeficiency virus (HIV), hepatitis C virus (HCV) and hepatitis B virus (HBV) NAT was performed on all donors and donation types, while selective testing was reported for West Nile virus, hepatitis E virus (HEV), and Zika virus. Individual donation NAT was used for HIV, HCV and HBV by ~50% of responders, while HEV was screened in mini-pools by 83% of responders performing HEV NAT. Confirmatory testing for NAT-yield samples was generally performed by NAT on a sample from the same donation or by NAT and serology on samples from the same donation and a follow-up sample. CONCLUSION: In the last decade, there has been a trend towards use of smaller pool sizes or individual donation NAT. We captured characteristics of NAT internationally in 2019 and provide insights into confirmatory testing approaches used for NAT-yields, potentially benefitting blood operators seeking to implement NAT.

International review of blood donation nucleic acid amplification testing.

BACKGROUND AND OBJECTIVES: Nucleic acid amplification testing (NAT), in blood services context, is used for the detection of viral and parasite nucleic acids to reduce transfusion-transmitted infections. This project reviewed NAT for screening blood donations globally. MATERIALS AND METHODS: A survey on NAT usage, developed by the International Society of Blood Transfusion Working Party on Transfusion-transmitted Infectious Diseases (ISBT WP-TTID), was distributed through ISBT WP-TTID members. Data were analysed using descriptive statistics. RESULTS: Forty-three responses were received from 32 countries. Increased adoption of blood donation viral screening by NAT was observed over the past decade. NAT-positive donations were detected for all viruses tested in 2019 (proportion of donations positive by NAT were 0.0099% for human immunodeficiency virus [HIV], 0.0063% for hepatitis C virus [HCV], 0.0247% for hepatitis B virus [HBV], 0.0323% for hepatitis E virus [HEV], 0.0014% for West Nile virus [WNV] and 0.00005% for Zika virus [ZIKV]). Globally, over 3100 NAT-positive donations were identified as NAT yield or solely by NAT in 2019 and over 22,000 since the introduction of NAT, with HBV accounting for over half. NAT-positivity rate was higher in first-time donors for all viruses tested except WNV. During 2019, a small number of participants performed NAT for parasites (Trypanosoma cruzi, Babesia spp., Plasmodium spp.). CONCLUSION: This survey captures current use of blood donation NAT globally. There has been increased NAT usage over the last decade. It is clear that NAT contributes to improving blood transfusion safety globally; however, there is a need to overcome economic barriers for regions/countries not performing NAT.

Changing Strategies for the Detection of Bacteria in Platelet Components in Ireland: From Primary and Secondary Culture (2010-2020) to Large Volume Delayed Sampling (2020-2023).

Bacterial contamination of platelet components (PC) poses the greatest microbial risk to recipients, as bacteria can multiply over the course of PC storage at room temperature. Between 2010 and 2020, the Irish Blood Transfusion Service (IBTS) screened over 170,000 buffy coat-derived pooled (BCDP) and single-donor apheresis platelets (SDAPs) with the BACT/ALERT 3D microbial detection system (Biomerieux, L'Etoile, France), using a two-step screening protocol which incorporated primary and secondary cultures. Although the protocol was successful in averting septic transfusion reactions (STRs), testing large sample volumes at later time points was reported to improve detection of bacterial contamination. A modified large-volume delayed sampling (LVDS)-type protocol was adopted in 2020, which in the case of SDAP was applied to collections rather than individual splits (2020-2023, 44,642 PC screened). Rates of bacterial contamination for BCDP were 0.125% on Day-2, 0.043% on Day-4 vs. 0.191% in the post-LVDS period. SDAP contamination rates in the pre-LVDS period were 0.065% on Day-1, 0.017% on Day-4 vs. 0.072% in the post-LVDS period. Confirmed STRs were absent, and the interdiction rate for possibly contaminated SDAP was over 70%. In the post-LVDS period, BCDPs had a higher total positivity rate than SDAPs, 0.191% (1:525) versus 0.072% (1:1385), respectively, (chi-squared 12.124, 1 df, p = 0.0005). The majority of organisms detected were skin-flora-type, low pathogenicity organisms, including coagulase-negative staphylococci and Cutibacterium acnes, with little change in the frequency of clinically significant organisms identified over time. Both protocols prevented the issue of potentially harmful components contaminated (rarely) with a range of pathogenic bacteria, including Escherichia coli, Serratia marcesens, Staphylococcus aureus, and streptococci. Culture positivity of outdates post-LVDS whereby 100% of expired platelets are retested provides a residual risk estimate of 0.06% (95% CI 0.016-0.150). However, bacterial contamination rates in expired platelets did not demonstrate a statistically significant difference between the pre-LVDS 0.100% (CI 0.033-0.234) and post-LVDS 0.059% (0.016-0.150) periods (chi-squared = 0.651, 1 df, p = 0.42).

The changing profile of SARS-CoV-2 serology in Irish blood donors.

Background: The present study aimed to investigate the progression of the SARS-CoV-2 pandemic in Ireland over the first three waves of infection. Method: A selection of blood donor serum samples collected between February 2020 and December 2021 were analysed by various commercially available serological assays for antibodies to SARS-CoV-2 (n = 15,066). Results: An increase in seropositivity was observed between wave 1 (February to September 2020) and wave 2 (November and December 2020) of 2.20% to 3.55%. A large increase in estimated seroprevalence to 11.89% was observed in samples collected in February and March 2021 (wave 3 of infection).The rate of seropositivity varied by age group, with the highest rate observed in the youngest donors (18-29 years) peaking at 18.79% in wave 3. The results of spike antibody (anti-S) testing indicated that 44/1009 (4.36%) of seroreactive donors in wave 3 had a serological profile consistent with vaccination. By November 2021, we detected an overall seropositivity of 97.04%. Conclusions: The present study provides a comprehensive estimation of the level of circulating SARS-CoV-2 antibodies in Irish blood donors, enabling differentiation between vaccination and natural infection, as well as real-time monitoring of the progression of the COVID-19 pandemic in Ireland. Seroepidemiology has a role in determining reliable estimates of transmission, infection fatality rates and vaccine uptake. The continued screening of blood donors for this purpose has the potential to generate important data to assist with the management of future waves of SARS-CoV-2.

Human T-lymphotropic virus in Irish blood donors: Impact on future testing strategy.

AIM: A risk-based approach to the testing of blood donations for Human T-Lymphotropic Virus (HTLV) should include an assessment of blood donation seroepidemiology. The objectives of the present study were to determine the proportion of HTLV positive units in Irish blood donations, and subsequently, to estimate the current risk of transfusion transmitted HTLV (TT-HTLV). METHODS: Over 3 million donations screened between 1996 and 2020, were included in the study (n = 3,666,253). Factors considered in the assessment of TT-HTLV risk included: (I) HTLV seropositivity, (ii) probability of a leucodepletion failure, and (iii) the HTLV testing strategy. RESULTS: Six HTLV positive donations were detected throughout the study period, all of them in previously unscreened blood donors (0.000164%; n = 6/3,666,253), 3 of whom had donated prior to the introduction of HLTV antibody testing. On average 0.11% of manufactured blood components assessed, failed to satisfy the leucodepletion quality assurance criteria of less than 1 × 106 cells/unit. In using these values to model the risk of TT-HTLV, it was shown that the combination of leucodepletion with either universal screening of all = donors, or selective testing of first-time donors, a possible HTLV transfusion transmitted infection would be prevented every 468-3776 years. CONCLUSIONS: This is the first report on the proportion of HTLV positive in Irish blood donations (1996-2020) and will be used to inform blood donation screening policy in Ireland. Evidence is provided for recommending a selective HTLV donor screening algorithm in Ireland that is accompanied by a robust framework for continued surveillance of leucodepletion failure rate.

Confirmed circulation of SARS-CoV-2 in Irish blood donors prior to first national notification of infection.

INTRODUCTION: Blood donor studies offer a unique opportunity to screen healthy populations for the presence of antibodies to emerging infections. We describe the use of blood donor specimens to track the 'first-wave' of the COVID-19 pandemic in Ireland. METHODOLOGY: A random selection of donor samples received by the Irish Blood Transfusion Service (IBTS) between February and September 2020 (n = 8,509) were screened by multiple commercial SARs-CoV-2 antibody assays. The antibody detection rate was adjusted to the population to determine the SARS-CoV-2 seroprevalence in Ireland. RESULTS: SARS-CoV-2 antibody detection rose significantly during the first peak of COVID-19 infection, increasing from 0.3% in March, to 2.9% in April (p < 0.0001, The first SARS-CoV-2 antibody positive donor samples were collected on the 17th February 2020, 2 weeks prior to the first official notification. This is the earliest serological evidence of SARS-CoV-2 circulating in the Irish population. Our results also show a significantly higher antibody prevalence in the Capital city and in donors less than 40 years of age. CONCLUSIONS: The present study demonstrates evidence of SARS-CoV-2 antibody reactivity across all age groups and counties. The critical value of blood donor seroprevalence studies is apparent in this report which identified the earliest serological evidence of SARS-CoV-2 infection in Ireland, as well as documenting the evolution of COVID-19 pandemic in Ireland over time.

Seroprevalence of human herpesvirus 8 in Ireland among blood donors, men who have sex with men, and heterosexual genitourinary medicine and infectious diseases clinic attendees.

Human herpesvirus 8 (HHV-8) seroprevalence varies geographically and between subpopulations. High seroprevalence rates have been ascribed to men who have sex with men (MSM), African migrants, and HIV-infected individuals. The objective of this study was to determine the seroprevalence of HHV-8 in an Irish population, including specific risk groups. A cross-sectional study of 200 blood donors and 200 genitourinary medicine (GUM) and infectious diseases (ID) clinic patients was performed, with testing for Immunoglobulin G (IgG) antibodies to HHV-8 lytic antigens using a commercial indirect fluorescence assay (Scimedx Corp.). Verification was performed at the Centers for Disease Control and Prevention (CDC). All 200 blood donor samples were negative for HHV-8 IgG antibodies. 21% of GUM and ID patients were positive for HHV-8 IgG antibodies. One hundred of these patients were MSM, 35% of whom were HHV-8 seropositive (46% of HIV-positive MSM and 24% of HIV-negative MSM). Of 100 heterosexual patients, only 7% were HHV-8 seropositive. The absence of seropositivity in 200 Irish blood donors may suggest that Ireland has a low overall population HHV-8 seroprevalence. The proportion of HHV-8 seropositivity in the MSM population was significantly higher than in the heterosexual population and most marked in HIV-positive MSM.

Establishment of transfusion-relevant bacteria reference strains for red blood cells.

BACKGROUND AND OBJECTIVES: Red blood cell concentrates (RBCC) are susceptible to bacterial contamination despite cold storage. A reliable evaluation of strategies to minimize the risk of RBCC-associated bacterial transmission requires the use of suitable reference bacteria. Already existing Transfusion-Relevant Bacteria Reference Strains (TRBRS) for platelet concentrates fail to grow in RBCC. Consequently, the ISBT TTID, Working Party, Bacterial Subgroup, conducted an international study on TRBRS for RBCC. MATERIALS AND METHODS: Six bacterial strains (Listeria monocytogenes PEI-A-199, Serratia liquefaciens PEI-A-184, Serratia marcescens PEI-B-P-56, Pseudomonas fluorescens PEI-B-P-77, Yersinia enterocolitica PEI-A-105, Yersinia enterocolitica PEI-A-176) were distributed to 15 laboratories worldwide for enumeration, identification, and determination of growth kinetics in RBCC at days 7, 14, 21, 28, 35 and 42 of storage after low-count spiking (10-25 CFU/RBCC). RESULTS: Bacterial proliferation in RBCC was obtained for most strains, except for S. marcescens, which grew only at 4 of 15 laboratories. S. liquefaciens, S. marcescens, P. fluorescens and the two Y. enterocolitica strains reached the stationary phase between days 14 and 21 of RBCC storage with a bacterial concentration of approximately 109  CFU/ml. L. monocytogenes displayed slower growth kinetics reaching 106 -107  CFU/ml after 42 days. CONCLUSION: The results illustrate the importance of conducting comprehensive studies to establish well-characterized reference strains, which can be a tool to assess strategies and methods used to ameliorate blood safety. The WHO Expert Committee on Biological Standardization adopted the five successful strains as official RBCC reference strains. Our study also highlights the relevance of visual inspection to interdict contaminated RBC units.

Blood Donor Screening for Hepatitis E Virus in the European Union.

This review article summarises hepatitis E virus (HEV) blood donation screening strategies in effect in the European Union (EU). Since 2012, eight EU countries have implemented HEV screening. Local rates of seroprevalence, RNA incidence, and molecular epidemiology are variable and not usually directly comparable. We report a range of HEV-RNA reactivity rates from 1 in 744 donations (France) to 1 in 8,636 donations (Wales) with an overall EU rate of 1 in 3,109 donations (3.2 million donations screened). HEV genotypes 3c, 3e, and 3f are the most frequently reported subtypes. In these 8 countries, both universal (n = 5) and selective (n = 3) screening policies have been introduced utilising either individual donation (ID; n = 1) or mini-pool (MP; n = 7; MP-6, -16, -24, and -96) testing. We also describe the Irish experience of HEV screening utilising an ID-NAT-based donor screening algorithm which intercepts donations even from those with low-level viraemia; 21 of 56 donors (37.5%) had a viral load (VL) < 100 IU/mL. We performed a MP-24 experiment which may prove useful to colleagues in relation to donor screening and associated blood component transmissibility. Irish results indicate that 59% of donors with a HEV-VL < 450 IU/mL may have screened negative in a MP-24.

Hepatitis E virus - key points for the clinical haematologist.

In recent years there has been a paradigm shift in our understanding of the epidemiology and clinical features of hepatitis E virus (HEV) infection. Once classically described as an acute hepatitis associated with waterborne outbreaks in areas of poor sanitation, HEV is now recognised to be endemic in Europe and is probably zoonotic in origin. Evidence for transfusion-transmitted HEV has prompted the introduction of blood donor screening in a number of countries, but the risk to the haematology patient from food sources remains. The aim of this review therefore, is to equip the clinical haematologist with the knowledge required to diagnose HEV infection and to aid decision-making in patient management. The article also provides information on addressing patient concerns about their risk of acquiring hepatitis E and how this risk can be mitigated.

How to use central venous catheter tip cultures.

Central venous catheter (CVC) tip cultures are useful in the assessment of a patient with a potential catheter-related bloodstream infection (CRBSI). However, these results can be misleading particularly in the absence of concomitant peripheral and central line blood cultures. Catheter tip cultures should not be submitted to the laboratory unless CRBSI is suspected as the predictive value of culture results depends on the pretest probability of CRBSI. A positive CVC tip culture does not usually warrant further investigation or therapy (except in the case of Staphylococcus aureus and possibly Candida sp) while a negative catheter tip culture in isolation does not definitively exclude CRBSI. Clinicians can use alternative criteria for the diagnosis of CRBSI that do not require catheter tip cultures if necessary. Further research into the significance of CVC tip cultures in the absence of concomitant bacteraemia is required.

Abiotrophia defectiva endocarditis and associated hemophagocytic syndrome--a first case report and review of the literature.

In this manuscript we describe the first association in the literature between Abiotrophia defectiva endocarditis and the hemophagocytic syndrome. There are multiple important clinical points of information that must be highlighted from this case. A. defectiva is an aggressive organism with a high level of resistance to antibiotic pharmacotherapy with a high predilection for embolic complications and valvular destruction despite treatment with sensitive antibiotics. A. defectiva endocarditis has not been previously associated with the hemophagocytic syndrome. However, this case highlights the serious hematological complications that can occur with this dangerous bacterial pathogen.