SARS-CoV-2 immunoassays in a predominantly vaccinated population: Performances and qualitative agreements obtained with two analytical approaches and four immunoassays.

BACKGROUND AND OBJECTIVES: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serosurveys are typically analysed by applying a fixed threshold for seropositivity ('conventional approach'). However, this approach underestimates the seroprevalence of anti-nucleocapsid (N) in vaccinated individuals-who often exhibit a difficult-to-detect anti-N response. This limitation is compounded by delays between the onset of infection and sample collection. To address this issue, we compared the performance of four immunoassays using a new analytical approach ('ratio-based approach'), which determines seropositivity based on an increase in anti-N levels. MATERIALS AND METHODS: Two groups of plasma donors and four immunoassays (Elecsys total anti-N, VITROS total anti-N, Architect anti-N Immunoglobulin G (IgG) and in-house total anti-N) were evaluated. First-group donors (N = 145) had one positive SARS-CoV-2 polymerase chain reaction (PCR) test result and had made two plasma donations, including one before and one after the PCR test (median = 27 days post-PCR). Second-group donors (N = 100) had made two plasma donations early in the Omicron wave. RESULTS: Among first-group donors (97.9% vaccinated), sensitivity estimates ranged from 60.0% to 89.0% with the conventional approach, compared with 94.5% to 98.6% with the ratio-based approach. Among second-group donors, Fleiss's κ ranged from 0.56 to 0.83 with the conventional approach, compared with 0.90 to 1.00 with the ratio-based approach. CONCLUSION: With the conventional approach, the sensitivity of four immunoassays-measured in a predominantly vaccinated population based on samples collected ~1 month after a positive test result-fell below regulatory agencies requirement of ≥95%. The ratio-based approach significantly improved the sensitivities and qualitative agreement among immunoassays, to the point where all would meet this requirement.

Evaluation of anti-nucleocapsid level variation to assess SARS-CoV-2 seroprevalence in a vaccinated population.

BACKGROUND: Serosurveys have been key to public health decision-making since the beginning of the SARS-CoV-2 pandemic. However, several studies have uncovered that vaccination blunts the anti-nucleocapsid (N) response to a subsequent infection, which hinders the ability of serologic assays (including commercial ones) to detect recent infections. We therefore developed a new analytical approach to increase the sensitivity of detection of infection in vaccinated individuals. METHODS: Two samples were obtained from 248 SARS-CoV-2-positive (PCR-confirmed), vaccinated donors: one before the infection (reference sample) and one after (test sample). All samples were tested using an in-house, anti-N enzyme-linked immunosorbent assay (ELISA) which had a sensitivity of 98.1% before the mass vaccination campaign. Instead of applying a seropositivity threshold based on a single absorbance value (i.e. conventional approach), seropositivity was determined based on the ratio between the anti-N absorbance of the test and reference samples. RESULTS: The sensitivity of the new approach to detect infection in vaccinated individuals was 95.2% using a cut-off of 1.5 for the anti-N ratio, whereas that of the conventional approach was 63.3%. CONCLUSION: The new analytical approach described herein captured a significantly greater proportion of vaccinated individuals with a known history of SARS-CoV-2 infection than the conventional approach used in most serosurveys.

Humoral Responses against BQ.1.1 Elicited after Breakthrough Infection and SARS-CoV-2 mRNA Vaccination.

The Omicron BQ.1.1 variant is now the major SARS-CoV-2 circulating strain in many countries. Because of the many mutations present in its Spike glycoprotein, this variant is resistant to humoral responses elicited by monovalent mRNA vaccines. With the goal to improve immune responses against Omicron subvariants, bivalent mRNA vaccines have recently been approved in several countries. In this study, we measure the capacity of plasma from vaccinated individuals, before and after a fourth dose of mono- or bivalent mRNA vaccine, to recognize and neutralize the ancestral (D614G) and the BQ.1.1 Spikes. Before and after the fourth dose, we observe a significantly better recognition and neutralization of the ancestral Spike. We also observe that fourth-dose vaccinated individuals who have been recently infected better recognize and neutralize the BQ.1.1 Spike, independently of the mRNA vaccine used, than donors who have never been infected or have an older infection. Our study supports that hybrid immunity, generated by vaccination and a recent infection, induces higher humoral responses than vaccination alone, independently of the mRNA vaccine used.

Cohort profile: A Québec-based plasma donor biobank to study COVID-19 immunity (PlasCoV).

PURPOSE: The long-term humoral immunity to COVID-19 is not well understood owing to the continuous emergence of new variants of concern, the evolving vaccine-induced and infection-induced immunity, and the limited duration of follow-up in previous studies. As the sole blood service in Québec (Canada), Héma-Québec established a COVID-19-focused biobank ('PlasCoV') in April 2021. PARTICIPANTS: As of January 2022, the biobank included 86 483 plasma samples from 15 502 regular donors (age range=18-84 years, females=49.7%), for an average of 5.6 donations per donor. Nearly two-thirds (65.6%) of biobank donors made at least two donations, with many donors having provided samples prevaccination and postvaccination (3061 (19.7%)) or preinfection and postinfection (131 (0.8%)), thus allowing for longitudinal studies on vaccine-induced and infection-induced immunity. FINDINGS TO DATE: A study that used PlasCoV samples revealed that previously infected individuals who received a single dose of the BNT162b2 COVID-19 vaccine exhibited the strongest immune response. By contrast, SARS-CoV-2-naïve individuals required two vaccine doses to produce a maximal immune response. Furthermore, the results of a four-phase seroprevalence study indicated that the antinucleocapsid (N) response wanes rapidly, so that up to one-third of previously infected donors were seronegative for anti-N. FUTURE PLANS: Donations from individuals who consented to participate before 1 October 2022 will be collected up until 31 March 2023. This plasma biobank will facilitate the conduct of longitudinal studies on COVID-19 immunity, thus helping to provide valuable insights into the anti-SARS-CoV-2 immune response and its persistence, and the effects of vaccination and variants on the specificity of the anti-SARS-CoV-2 immune response.

Whole blood donor return rates after deferral for tattooing or body piercing-Survey across blood donation services: The BEST collaborative study.

BACKGROUND AND OBJECTIVES: To protect transfusion recipients from transfusion-transmissible infections, blood donors are deferred from donating after recent tattooing or piercing. To explore to what extent and how this deferral impacts donor availability, we performed an international study to investigate how many donors were deferred for a recent tattoo or piercing and how many of these donors returned to donate. MATERIALS AND METHODS: We surveyed blood centre members of the Biomedical Excellence for Safer Transfusion (BEST) Collaborative and the European Blood Alliance Donor Studies Working Group on their numbers of donations, tattoo and piercing deferrals, and return rates in the year 2017. RESULTS: Eight blood centres participated. Overall, deferral rates were lower for repeat donors compared to new donors. Repeat donors were more likely to return than new donors. Women and young donors were more often deferred than male and older donors. Men were more demotivated by tattoo or piercing deferral, resulting in lower return rates compared to women. Return rates differed greatly between blood centres. CONCLUSION: Tattoo and piercing deferrals lead to missed donations and result in lower return rates. However, the numbers vary largely internationally, probably due to cultural and policy differences. Shortening deferral periods after tattooing or piercing may reduce the impact on donor availability, which should be investigated in single-centre studies.

Risk of transfusion-related acute lung injury and human immunodeficiency virus associated with donations from trans donors in Quebec, Canada.

BACKGROUND AND OBJECTIVES: Blood operator must establish selection criteria according to the populations at risk of blood-related infections and complications. Therefore, this study aimed to assess the risks of transfusion-related acute lung injury (TRALI) and human immunodeficiency virus (HIV) associated with donations from trans persons. MATERIALS AND METHODS: Donor screening data from Héma-Québec were used. The risks of TRALI and HIV were estimated based on internal data and assumptions derived from the literature. The risk was assessed under four scenarios: a most likely scenario, an optimistic scenario and two pessimistic scenarios. All scenarios assumed no prior screening for trans donors. RESULTS: The trans population comprised 134 donors, including 94 (70.1%) trans men. Of the 134 donors, 58 (43.3%) were deferred from donating a blood-derived product because of an ongoing gender-affirming genital surgery, and the remaining 76 (56.7%) were eligible donors. The risk of having a TRALI-causing donation, given that it comes from a trans man, was estimated at one every 115-999 years for all scenarios. The risk of having an HIV-contaminated donation, given that it comes from a trans woman, was estimated at one every 1881-37,600 years for all scenarios. CONCLUSION: This study suggests that donations from trans persons are associated with a negligible risk of TRALI and HIV.

Balancing non-discriminatory donor selection and blood safety in the Netherlands: Evaluation of an individual risk assessment of sexual behavior.

BACKGROUND: To better balance the safety of the blood supply and the inclusion of men who have sex with men (MSM), further improvements are needed to the risk management strategy employed in the Netherlands to reduce transfusion-transmissible infections (TTIs). A gender-neutral individual risk assessment could provide a solution by determining donor eligibility based on sexual behaviors known to increase the risk of TTIs. Our objective is to estimate the proportion of blood donors that would be deferred by such an assessment, as well as their discomfort answering such questions. STUDY DESIGN AND METHODS: Two surveys were distributed in May 2020 to assess sexual behavior in blood donors in the last 4, 6, and 12 months, as well as their discomfort reporting such information. A combination of both surveys measured the extent to which discomfort was associated with reporting sexual behavior. A high-risk sexual behavior pattern was defined as having had multiple sexual partners and having engaged in anal sex, without consistent condom use. RESULTS: Of all 2177 participating whole blood donors, 0.8% report engaging in high-risk sexual behaviors over the last 4 months and would therefore be ineligible to donate. When accounting for the additional proportion of donors that reported such questions would stop them from donating, 2.0% and 3.2% of female and male donors, respectively, would be lost. DISCUSSION: Gender-neutral eligibility criteria based on high-risk sexual behaviors may reduce the overall number of eligible donors in the Netherlands, but could make blood donation more accessible to a broader group of donors.

Cost-effectiveness of pathogen reduction technology for plasma and platelets in Québec: A focus on potential emerging pathogens.

BACKGROUND: The last economic evaluation of pathogen reduction technology (PRT) in Canada was conducted in 2007. We reassessed the cost-effectiveness of PRT in the province of Québec (which has its own blood supplier) and included an evaluation of the potential impact of emerging pathogens on cost-effectiveness. STUDY DESIGN AND METHODS: Decision analytic Markov models were developed to simulate the costs and quality-adjusted life-years (QALY) associated with PRT as an addition to existing safety measures for plasma and platelet products (except for bacterial culture). Models accounted for several infectious and noninfectious transfusion reactions, recipients' productivity losses ensuing from these reactions, and the impact of PRT on platelet function. Scenario analyses were conducted to evaluate the impact of a new highly contagious human immunodeficiency virus (HIV)-like or West Nile virus (WNV)-like pathogen, assuming various epidemiological scenarios. RESULTS: In the base case, the incremental cost-effectiveness ratio (ICER) of PRT was estimated at $8,088,974/QALY gained. Assuming the presence of an HIV-like pathogen, the ICER was $265,209/QALY gained in the "average transmission" scenario, $1,274,445/QALY gained in the "rapid testing scenario," and $123,063/QALY gained in the "highly contagious" scenario. Assuming the presence of a WNV-like pathogen, the ICER was $7,469,167/QALY gained in the "average transmission" scenario and $6,652,769/QALY gained in the "highly contagious" scenario. CONCLUSION: The cost-effectiveness of PRT may substantially improve in the event of a new, blood-borne pathogen. Given their significant impact on cost-effectiveness, the emergence of new pathogens should be considered when deciding whether to adopt PRT.

Seroprevalence of SARS-CoV-2 antibodies among blood donors in Québec: an update from a serial cross-sectional study.

OBJECTIVES: We previously estimated the seroprevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies following the first pandemic wave at 2.23% in Québec, Canada. Following the much bigger second wave in fall 2020 and early 2021, we estimated the seroprevalence of anti-SARS-CoV-2 in Québec during the first months of 2021. METHODS: Blood samples from regular, asymptomatic (for ≥ 14 days) donors were collected between January 25, 2021 and March 11, 2021. Anti-SARS-CoV-2 seropositivity was assessed using an enzyme-linked immunosorbent assay that captures antibodies directed against the receptor binding domain of the SARS-CoV-2 spike (and hence cannot discriminate between infection- and vaccine-induced seropositivity). Seroprevalence estimates were adjusted for regional distribution, age, and sex. RESULTS: Samples from 7924 eligible donors were analyzed, including 620 (7.8%) vaccinated donors and 7046 (88.9%) unvaccinated donors (vaccination status unknown for 258 (3.3%) donors). Overall, median age was 51 years; 46.4% of donors were female. The adjusted seroprevalence was 10.5% (95% CI = 9.7-11.3) in the unvaccinated population and 14.7% (95% CI = 13.8-15.6) in the overall population. Seroprevalence gradually decreased with age and was higher among donors who self-identified as having a racial/ethnic background other than white, both in the overall and in the unvaccinated populations. CONCLUSION: The seroprevalence of SARS-CoV-2 antibodies significantly increased in Québec since spring 2020, with younger persons and ethnic minorities being disproportionately affected. When compared with the cumulative incidence rate reported by public health authorities (i.e., 3.3% as of March 11, 2021), these results suggest that a substantial proportion of infections remain undetected despite improvements in access to COVID-19 testing.

RéSUMé: OBJECTIFS: Lors d'une première étude, nous avons estimé la séroprévalence des anticorps contre le syndrome respiratoire aigu sévère coronavirus 2 (SRAS-CoV-2) après la première vague pandémique à 2,23 % au Québec, Canada. Cette seconde étude estime la séroprévalence de l'anti-SRAS-CoV-2 au Québec lors de la deuxième vague pandémique. MéTHODES: Des échantillons de donneurs de sang asymptomatiques (≥ 14 jours) ont été prélevés entre le 25 janvier et le 11 mars 2021. La séropositivité a été évaluée à l'aide d'un dosage immuno-enzymatique qui capture les anticorps dirigés contre la protéine Spike du récepteur de domaine de liaison du SARS-CoV-2 (et ne peut donc distinguer l'immunité induite par l'infection et la vaccination). La séroprévalence a été ajustée en fonction de l'âge et du sexe par région. RéSULTATS: Des échantillons de 7 924 donneurs ont été analysés, dont 620 (7,8 %) étaient vaccinés et 7 046 (88,9 %) étaient non vaccinés (statut vaccinal inconnu pour 258 (3,3 %) donneurs). Dans l'ensemble, l'âge médian était de 51 ans et 46,4 % des donneurs étaient des femmes. La séroprévalence ajustée était de 10,5 % (IC 95 % = 9,7 à 11,3) dans la population non vaccinée et de 14,7 % (IC 95 % = 13,8 à 15,6) dans la population globale. La séroprévalence diminuait progressivement avec l'âge et était plus élevée chez les donneurs d'origine ethnique autre que blanche. CONCLUSION: La séroprévalence anti-SRAS-CoV-2 a considérablement augmenté au Québec depuis le printemps 2020, les personnes plus jeunes et les minorités ethniques étant plus touchées. Comparés au taux d'incidence cumulatif signalé par la santé publique (c.-à-d. 3,3 % au 11 mars 2021), ces résultats suggèrent qu'une proportion importante d'infections reste non détectée.

Reported non-compliance with pre-donation screening among blood donors in Québec, Canada: A focus on the 3-month deferral for men who have sex with men.

BACKGROUND AND OBJECTIVES: In Québec (Canada), the donation deferral for men who have sex with men (MSM) has recently been shortened to 3 months. Whether this change impacted compliance with pre-donation screening is unknown. We assessed compliance with the disclosure of male-to-male sex and other behavioural risk factors for HIV amid this change. MATERIALS AND METHODS: Québec residents who donated from 14 July 2020 to 30 November 2020 were invited to participate in an online survey. Donors were informed that the survey was optional and anonymous. Survey questions were those used for routine pre-donation screening. Rates of reported non-compliance were weighted based on several characteristics. RESULTS: Of 21,918 contacted donors, 7113 (32.45%) participated. Among male participants (N = 3347), six (0.27% [95% confidence interval (CI) = 0.09%-0.44%]) were not compliant with a 3-month MSM deferral. Among female participants (N = 3766), two (0.06% [95% CI = 0.00%-0.13%]) were not compliant with a 3-month deferral for sex with a man who had male-to-male sex ≤12 months. Other risk factors exhibited similar or lower rates of reported non-compliance. CONCLUSION: Reported non-compliance with a 3-month MSM deferral and the disclosure of other HIV behavioural risk factors was low. These results warrant the investigation of behavioural donor risk assessment approaches to further improve the inclusiveness of blood donation.

HIV residual risk in Canada for apheresis source plasma donation without deferral for men who have sex with men.

BACKGROUND AND OBJECTIVES: In Canada, men having sex with men (MSM) are deferred for 3 months from last sexual contact to reduce human immunodeficiency virus (HIV) risk to recipients. The aim of this paper was to model the Canadian residual risk of HIV-positive source plasma incorporating pathogen inactivation (PI) under no MSM deferral scenarios for apheresis plasma donations. MATERIALS AND METHODS: A combined Bayesian network (BN) and Monte Carlo approach were implemented to estimate the HIV residual risk under 3-month deferral compared with no deferral without quarantine scenarios for MSM donors. Models involve the stochastic generation of donation and its infection status based on its corresponding simulated donor profile. Viral load reduction conferred by PI used by source plasma fractionators was simulated. Model parameters were derived from Héma-Québec and Canadian Blood Services data, viral loads in a large sample of HIV-positive US blood donors, CSL Behring documentation and from published data. RESULTS: In the most likely scenario for the 3-month deferral model, there were 2.71 positive donations per 1,000,000 donations (95% confidence interval [CI] 2.63-2.78). For the no-deferral model, there were 3.01 positive donations per 1,000,000 donations (95% CI 2.94-3.09). For both scenarios, the risk of having an infectious pool was 0 in 300,000 pools (95% CI 0-0.0000123) after consideration of PI. CONCLUSION: Based on simulation results, there would be a negligible HIV residual risk associated with the removal of a time-based MSM deferral without quarantine for source plasma incorporating PI.

Risk of transfusion-transmitted Babesia microti in Canada.

BACKGROUND: Babesia microti has gained a foothold in Canada as tick vectors become established in broader geographic areas. B. microti infection is associated with mild or no symptoms in healthy individuals but is transfusion-transmissible and can be fatal in immunocompromised individuals. This is the first estimate of clinically significant transfusion-transmitted babesiosis (TTB) risk in Canada. STUDY DESIGN AND METHODS: The proportion of B. microti-antibody (AB)/nucleic acid amplification test (NAT)-positive whole blood donations was estimated at 5.5% of the proportion of the general population with reported Lyme Disease (also tick-borne) based on US data. Monte Carlo simulation estimated the number and proportion of infectious red cell units for three scenarios: base, localized incidence (risk in Manitoba only), and donor study informed (prevalence from donor data). The model simulated 1,029,800 donations repeated 100,000 times for each. RESULTS: In the base scenario 0.5 (0.01, 1.75), B. microti-NAT-positive donations would be expected per year, with 0.08 (0, 0.38) recipients suffering clinically significant TTB (1 every 12.5 years). In the localized incidence scenario, there were 0.21(0, 0.7) B. microti-NAT-positive donations, with 0.04 (0, 0.14) recipient infections (about 1 every 25 years). In the donor study informed scenario, there were 4.6 (0.3, 15.8) B. microti-NAT-positive donations expected, and 0.81 (0.05, 3.14) clinically significant TTB cases per year. DISCUSSION: The likelihood of clinically relevant TTB is low. Testing would have very little utility in Canada at this time. Ongoing pathogen surveillance in tick vectors is important as B. microti prevalence appears to be slowly increasing in Canada.

SARS-CoV-2 seroprevalence among blood donors in Québec, and analysis of symptoms associated with seropositivity: a nested case-control study.

OBJECTIVES: A substantial proportion of individuals infected with SARS-CoV-2 do not experience noticeable symptoms typical of COVID-19. Our objectives were to evaluate the impact of the first wave of the pandemic in Québec by measuring SARS-CoV-2 antibody seroprevalence in a convenience sample of healthy blood donors and to study the association between seropositivity and the occurrence of COVID-19 symptoms. METHODS: The study design was a cross-sectional serological survey with a nested case-control study. Residual blood samples from donations collected between May 25 and July 9, 2020 (well before vaccination rollout) in the province of Québec were tested for anti-Spike RBD antibodies by ELISA. Seropositive donors and a control group of seronegative donors were questioned about prior COVID-19 symptoms. All qualified blood donors were eligible for participation. RESULTS: A total of 7691 blood donors were included in the study. After adjustments, the seroprevalence rate was 2.2% (95% CI 1.9-2.6). Seropositive donors reported one or more symptoms in a proportion of 52.2% (95% CI 44.2-60.1); this proportion was 19.1% (95% CI 13.4-26.1) among seronegative donors, suggesting that approximately 50-66% of all infections were asymptomatic. Univariate analysis of associations between symptoms and seropositivity revealed that except for rhinorrhea, all symptoms were significantly associated with seropositivity. CONCLUSION: Assuming that blood donors are fairly representative of the general adult population, this study shows that less than 3% of 18-69-year-olds have been infected during the first wave of the pandemic in the province of Québec. Our data also confirm that many infections escaped detection, including a substantial proportion that were asymptomatic.

RéSUMé: OBJECTIFS: Une proportion substantielle de personnes infectées par le SRAS-CoV-2 ne présentent pas de symptômes visibles typiques de la COVID-19. Nos objectifs étaient d'évaluer l'impact de la première vague de la pandémie au Québec en mesurant la séroprévalence des anticorps anti-SRAS-CoV-2 chez les donneurs de sang en bonne santé, et d'étudier l'association entre la séropositivité et la survenue des symptômes de la COVID-19. MéTHODES: Le design de l'étude était une enquête de sérologie transversale avec une étude cas-témoins nichée dans la cohorte. Des échantillons de sang provenant de dons recueillis entre le 25 mai et le 9 juillet 2020 (bien avant le déploiement de la vaccination) dans la province de Québec ont été testés pour les anticorps anti-spicule RBD (Receptor Binding Domain) par ELISA. Les donneurs séropositifs et un groupe témoin de donneurs séronégatifs ont été interrogés sur les symptômes spécifiques à la COVID-19. Tous les donneurs qualifiés pour le don de sang étaient éligibles à participer à l'étude. RéSULTATS: Au total, 7 691 donneurs de sang ont été inclus dans l'étude. Après ajustements, le taux de séroprévalence était de 2,2 % (IC à 95% 1,9­2,6). Les donneurs séropositifs ont signalé un ou plusieurs symptômes dans une proportion de 52,2 % (IC à 95% 44,2­60,1); cette proportion était de 19,1 % (IC à 95% 13,4­26,1) parmi les donneurs séronégatifs, ce qui suggère qu'entre 50 % et 66 % de toutes les infections étaient asymptomatiques. Une analyse univariée des associations entre les symptômes et la séropositivité a révélé qu'à l'exception de la rhinorrhée, tous les symptômes étaient significativement associés à la séropositivité. CONCLUSION: En supposant que les donneurs de sang sont assez représentatifs de la population adulte générale, cette étude montre que moins de 3 % des 18­69 ans ont été infectés lors de la première vague de la pandémie dans la province du Québec. Nos données confirment également que de nombreuses infections n'ont pas fait l'objet d'un test moléculaire de dépistage, y compris une proportion importante qui était asymptomatique.

An international comparison of HIV prevalence and incidence in blood donors and general population: a BEST Collaborative study.

BACKGROUND AND OBJECTIVES: Efficiency in mitigating HIV transmission risk by transfusion may vary internationally. We compared HIV prevalence and incidence in blood donors across different jurisdictions in relation to those rates in the general population and differences in deferral practices. MATERIALS AND METHODS: Data from 2007 to 2016 were collected in Australia, Brazil (São Paulo), Canada, England, France, Italy, Ireland, Japan, the Netherlands, New Zealand, Norway, Spain (Basque Country), USA (Vitalant) and Wales. For each country/region, the number of HIV antibody-positive donations and nucleic acid testing (NAT)-only-positive donations was broken down according to first-time or repeat donor status, along with the relevant denominators. RESULTS: There is a modest correlation between HIV prevalence among first-time donors and HIV prevalence in the general population. However, rates of HIV-positive donations in repeat donors, a proxy for incidence, do not correlate with incidence rates in the general population. Rates in donors from Italy and Basque Country, where deferral criteria for men having sex with men are less stringent, are higher compared with most other jurisdictions. Rates of NAT-only-positive donations are extremely low and do not differ significantly after adjustment for multiple comparisons. CONCLUSION: Donor HIV rates are only weakly associated with those observed in the general population. Countries with less stringent deferral criteria have higher HIV rates in their donor population, but the rates remain very low.

Variations in hemoglobin measurement and eligibility criteria across blood donation services are associated with differing low-hemoglobin deferral rates: a BEST Collaborative study.

BACKGROUND: Determination of blood donor hemoglobin (Hb) levels is a pre-requisite to ensure donor safety and blood product quality. We aimed to identify Hb measurement practices across blood donation services and to what extent differences associate with low-Hb deferral rates. METHODS: An online survey was performed among Biomedical Excellence for Safer Transfusion (BEST) Collaborative members, extended with published data. Multivariable negative-binomial regression models were built to estimate adjusted associations of minimum donation intervals, Hb cut-offs (high, ≥13.5 g/dL in men or ≥ 12.5 g/dL in women, vs. lower values), iron monitoring (yes/no), providing or prescribing iron supplementation (yes/no), post-versus pre-donation Hb measurement and geographical location (Asian vs. rest), with low-Hb deferral rates. RESULTS: Data were included from 38 blood services. Low-Hb deferral rates varied from 0.11% to 8.81% among men and 0.84% to 31.85% among women. Services with longer minimum donation intervals had significantly lower deferral rates among both women (rate ratio, RR 0.53, 95%CI 0.33-0.84) and men (RR 0.53, 95%CI 0.31-0.90). In women, iron supplementation was associated with lower Hb deferral rates (RR 0.47, 95%CI 0.23-0.94). Finally, being located in Asia was associated with higher low-Hb deferral rates; RR 9.10 (95%CI 3.89-21.27) for women and 6.76 (95%CI 2.45-18.68) for men. CONCLUSION: Differences in Hb measurement and eligibility criteria, particularly longer donation intervals and iron supplementation in women, are associated with variations in low-Hb deferral rates. These insights could help improve both blood donation service efficiency and donor care.

HIV residual risk in Canada under a three-month deferral for men who have sex with men.

BACKGROUND AND OBJECTIVES: In Canada, the deferral for men who have sex with men (MSM) was decreased from a permanent deferral to a 5-year then a 12-month deferral. Current HIV testing can detect an HIV infection in donated blood within 2 weeks of exposure; thus, a 12-month deferral may be unnecessarily restrictive. We aimed to estimate the residual risk of HIV if the deferral were further decreased to 3 months. MATERIALS AND METHODS: Using a deterministic model with stochastic Monte Carlo simulation, residual risk of HIV was the sum of testing error, assay sensitivity and window-period risks. Data inputs were estimated from donor surveillance, donor surveys and published data. Residual risk was modelled at baseline and using three scenarios: (1) most likely - non-compliance, HIV prevalence and incidence rates of MSM are unchanged; (2) optimistic - non-compliance improves by 50%; and (3) pessimistic - non-compliance, HIV prevalence and incidence rates of MSM all double. RESULTS: HIV residual risk at baseline was 1 in 36·0 million donations (95% CI 1 in 1 504 907 million, 10·5 million); in the most likely scenario 1 in 34·2 million (1 in 225 534 million, 8·7 million); in the optimistic scenario 1 in 36·0 million (1 in 282 618 million, 9·5 million); in the pessimistic scenario 1 in 16·7 million (1 in 39 469 million, 6·0 million). All confidence intervals overlapped. CONCLUSION: With very low modelled risk under a 12-month deferral, the additional risk with a 3-month deferral is very low. This is true even with a pessimistic scenario.

The impact of age and sex on first-time donor return behavior.

BACKGROUND: This study examined the impact of age and sex of first-time donors who had not experienced an adverse event or deferral on their likelihood of and time to return. STUDY DESIGN AND METHODS: On behalf of the Biomedical Excellence for Safer Transfusion (BEST) Collaborative, international blood collection agencies (BCAs) were invited to provide data on first-time whole blood donors in 2014, including initial presentation date, collection site type, age, sex, blood type, return to donate within 24 months (yes/no), and subsequent presentation date. RESULTS: Eight BCAs contributed 706,789 records. The overall odds of returning to donate were slightly lower in female versus male donors, and the overall age trend was U-shaped with younger and older donors having higher odds for returning relative to middle-aged donors. However, variations by BCA were observed. Specifically, in three BCAs, women had higher odds of returning to donate than men. Further, while across seven BCAs the smallest cohort of older first-time donors returned at a higher rate and returned more quickly than middle-aged first-time donors, the behavior of younger donors varied substantially between BCAs. CONCLUSION: While older first-time donors are more likely to return and return more quickly than middle-aged donors they make up only a small proportion of first-time donors, whereas the larger group of younger donors exhibits less clear patterns of return compared to middle-aged donors. Further research is needed to determine whether targeting the recruitment of older donors or bolstering retention of middle-aged donors would be most effective in maintaining the blood supply.

Prevalence of Babesia in Canadian blood donors: June-October 2018.

BACKGROUND: The erythrocytic protozoan parasite Babesia microti, the cause of human babesiosis, is transmitted not only by tick bites but also via blood transfusion. B. microti is endemic in the northeastern/upper midwestern United States, where partial screening of blood donations has been implemented. In Canada, a 2013 study of approximately 14,000 donors found no B. microti antibody-positive samples, suggesting low risk at that time. METHODS: Between June and October 2018, 50,752 Canadian donations collected from sites near the US border were tested for Babesia nucleic acid by transcription-mediated amplification (TMA). Reactive donations were tested for B. microti by IgG immunofluorescence assay and polymerase chain reaction. A subset of 14,758 TMA nonreactive samples was also screened for B. microti antibody. Donors who tested reactive/positive were deferred, asked about risk factors, and were requested to provide a follow-up sample for supplemental testing. RESULTS: One sample from Winnipeg, Manitoba, was TMA and antibody reactive. Of the 14,758 TMA-nonreactive donations tested for antibody, four reactive donations were identified from southwestern Ontario near Lake Erie. None of the interviewed donors remembered any symptoms, likely tick exposure, or relevant travel within Canada or the United States. CONCLUSIONS: This is the largest B. microti prevalence study performed in Canada. The results indicate very low prevalence, with only one TMA-confirmed-positive donation of 50,752 tested. This donor was from the only region in Canada where autochthonous infection has been reported. Seropositive donations in southwestern Ontario suggest low prevalence; travel should not be ruled out given the proximity to the US border.

Changing the deferral for men who have sex with men - an improved model to estimate HIV residual risk.

BACKGROUND AND OBJECTIVES: Eight published studies modelled the impact of changing from a lifetime to time-limited deferral for men who have sex with men (MSM); each predicted greater risk impact than has been observed. This study uses these previous efforts to develop an 'optimized' model to inform future changes to MSM deferrals. MATERIALS AND METHODS: HIV residual risk was calculated using observed HIV incidence/prevalence prior to the change in MSM deferral, then with the additional MSM expected under a 12-month deferral for five compliance scenarios, and finally using data observed after implementation of the deferral. Monte Carlo simulation calculated 95% confidence intervals (CI). RESULTS: The architecture of reviewed models was sound, and two were selected for combination into the optimized model. HIV risk estimated by this in the UK under MSM lifetime deferral was 0·102 (95% CI: 0·050-0·172) per million. The model predicted from a 27·8% decrease to a 47·6% increase depending upon compliance pre-implementation of the 12-month deferral. A decrease of 0·9% was observed post-implementation. For Canada, HIV risk under a 5-year deferral was 0·050 (95% CI: 0·00003-0·122) per million. Pre-implementation of the 12-month deferral, the model predicted from 30·2% decrease to 10-fold increase. A decrease of 47·0% was observed after implementation. CONCLUSION: The optimized model predicted HIV risk under 12-month MSM deferral in UK and Canada would remain low, and this was confirmed post-implementation. While the model is adaptable to other deferral scenarios, improved data quality would improve precision, particularly estimates of incidence in individuals likely to donate.

Hepatitis E Virus Infection in Blood Donors and Risk to Patients in the United States and Canada.

Hepatitis E virus (HEV) is the most common cause of acute hepatitis worldwide including large water-borne outbreaks, zoonotic infections and transfusion transmissions. Several countries have initiated or are considering blood donor screening in response to high HEV-RNA donation prevalence leading to transfusion-transmission risk. Because HEV transmission is more common through food sources, the efficacy of blood donor screening alone may be limited. HEV-nucleic acids in 101 489 blood donations in the United States and Canada were studied. A risk-based decision-making framework was used to evaluate the quantitative risks and cost-benefit of HEV-blood donation screening in Canada comparing three scenarios: no screening, screening blood for all transfused patients or screening blood for only those at greatest risk. HEV-RNA prevalence in the United States was one per 16 908 (95% confidence interval [CI], 1:5786-1:81987), whereas Canadian HEV-RNA prevalence was one per 4615 (95% CI, 1:2579-1:9244). Although 4-fold greater, Canadian HEV-RNA prevalence was not significantly higher than in the United States. Viral loads ranged from 20 to 3080 international units per mL; all successfully typed infections were genotype 3. No HEV-RNA false-positive donations were identified for 100 percent specificity. Without donation screening, heart and lung transplant recipients had the greatest HEV-infection risk (1:366962) versus kidney transplant recipients with the lowest (1:2.8 million) at costs of $225 546 to $561 810 per quality-adjusted life-year (QALY) gained for partial or universal screening, respectively. Higher cost per QALY would be expected in the United States. Thus, HEV prevalence in North America is lower than in countries performing blood donation screening, and if implemented, is projected to be costly under any scenario.