Risk of variant Creutzfeldt-Jakob disease in a simulated cohort of Canadian blood donors.

BACKGROUND AND OBJECTIVES: No transfusion-associated cases of variant Creutzfeldt-Jakob disease (vCJD) have occurred in more than 20 years. Yet, many countries have maintained blood donor deferral criteria for vCJD. We developed a risk simulation model to reassess the need for vCJD-related deferral criteria in Canada. MATERIALS AND METHODS: The model provides results separately for Héma-Québec (HQ) and Canadian Blood Services (CBS). The model used a Monte Carlo simulation approach to estimate the risk of having a vCJD-contaminated blood donation ('risk of vCJD') in a simulated cohort of 10 million donors followed for up to 85 years. The model assumed current deferral criteria for vCJD were lifted, which would allow new 'at-risk' donors to give blood. The model accounted for disease prevalence, donors' travel/immigration history, PRNP genotype at codon 129, demographics and the type of labile blood product. RESULTS: In the base case, the risk of vCJD was estimated at zero at both blood services. In the most pessimistic scenario, the risk of vCJD was 6.4 × 10-9 (i.e., 1 in 157 million donations) at HQ, or ≤1 in 77 million based on the upper bound of the 95% confidence interval (CI). At CBS, this risk was 4.8 × 10-8 (i.e., 1 in 21 million donations), or ≤1 in 16 million based on the upper bound of the 95% CI. CONCLUSION: vCJD poses minimal risks to the Canadian blood supply. Current vCJD deferral criteria may, therefore, be lifted with virtually no impact on safety, while significantly expanding the donor base.

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.

International survey of strategies to mitigate transfusion-transmitted Trypanosoma cruzi in non-endemic countries, 2016-2018.

BACKGROUND AND OBJECTIVES: Chagas disease, caused by Trypanosoma cruzi, is endemic to Mexico, Central and South America. While initially limited to the Americas, emigration of infected persons triggered geographically broader blood safety challenges. To mitigate transfusion-transmitted Chagas (TTC), transfusion services implemented approaches including risk factor questions and serologic testing. We sought to understand and compare strategies in non-endemic countries. MATERIALS AND METHODS: Transfusion services in International Society of Blood Transfusion (ISBT)-affiliated organizations and members of the ISBT Working Party on Transfusion-Transmitted Infectious Diseases were invited to complete an online survey on T. cruzi mitigation strategies. The survey queried about cases of TTC, risk factors, testing methodology, educational materials, pathogen reduction, donor/product management, donor deferral and perceived public health concerns surrounding TTC. RESULTS: Responses were received from 27 institutions in 22 countries. Most countries (77.3%) reported no historical TTC cases, while 18.2% reported 1-5 cases and 4.5% reported 6-10 cases. Concern about Chagas among the general public and public health authorities was low, but 12 of 25 blood centres reported moderate/high concern. Overall, 17 countries mitigated for TTC: 15 used risk factor questions and 10tested for T. cruzi antibodies. Ten countries used pathogen reduction but not specifically to prevent TTC. CONCLUSION: While Chagas is rarely cited as a public health concern, blood centres in many non-endemic countries, including those outside the Americas, implemented measures to mitigate risk. Mitigation focussed on risk factors associated with Latin American immigrants and serologic testing. Thus, despite the rarity of TTC, many non-endemic countries continue to address it as an ongoing blood safety risk.

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.

Evidence of SARS-CoV-2 Infection in Cells, Tissues, and Organs and the Risk of Transmission Through Transplantation.

The emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus responsible for the coronavirus disease 2019 (COVID-19) pandemic has raised concerns for programs overseeing donation and transplantation of cells, tissues, and organs (CTO) that this virus might be transmissible by transfusion or transplantation. Transplant recipients are considered particularly vulnerable to pathogens because of immunosuppression, and SARS-CoV-2 is likely to generate complications if contracted. Several signs and symptoms observed in COVID-19 positive patients reflect damage to multiple organs and tissues, raising the possibility of extrapulmonary SARS-CoV-2 infections and risk of transmission. At the beginning of the pandemic, a consensus has emerged not to consider COVID-19 positive patients as potential living or deceased donors, resulting in a global decrease in transplantation procedures. Medical decision-making at the time of organ allocation must consider safely alongside the survival advantages offered by transplantation. To address the risk of transmission by transplantation, this review summarizes the published cases of transplantation of cells or organs from donors infected with SARS-CoV-2 until January 2021 and assesses the current state of knowledge for the detection of this virus in different biologic specimens, cells, tissues, and organs. Evidence collected to date raises the possibility of SARS-CoV-2 infection and replication in some CTO, which makes it impossible to exclude transmission through transplantation. However, most studies focused on evaluating transmission under laboratory conditions with inconsistent findings, rendering the comparison of results difficult. Improved standardization of donors and CTO screening practices, along with a systematic follow-up of transplant recipients could facilitate the assessment of SARS-CoV-2 transmission risk by transplantation.

Transfusion-related Epstein-Barr virus (EBV) infection: A multicenter prospective cohort study among pediatric recipients of hematopoietic stem cell transplants (TREASuRE study).

BACKGROUND: Epstein-Barr virus (EBV) is carried in the blood of most adults, and transfusion-related infections have been reported. EBV is particularly deleterious in immunosuppressed transplant patients. The aim was to determine if EBV transmission occurred through leukodepleted blood product transfusion in pediatric recipients of hematopoietic stem cell transplants (HSCT). STUDY DESIGN AND METHODS: This prospective Canadian multi-center cohort study includes 156 allogeneic HSCT pediatric recipients. The association between EBV and transfusion was analyzed using Cox regressions. EBV infection, defined by a PCR+ test in the blood of seronegative recipients of an EBV-negative graft, was monitored in order to correlate the recipient EBV strain with that of the blood donors. EBV genotypes were determined by PCR amplification followed by DNA sequencing at two loci (EBNA3b and LMP1). RESULTS: No statistically significant associations were found between transfusions and EBV. One case of post-transplant EBV infection was identified among the 21 EBV-seronegative recipients receiving an EBV-negative graft. A total of 22 blood donors were retraced to determine whether the recipient's EBV strain matched that of a donor. One donor strain showed 100% sequence homology at the EBNA3b locus, but differed by one or two point mutations and by a 132-bp deletion at the LMP1 locus. The blood donor in question was alone among the 22 donors to show amplifiable virus in plasma. Blood from this donor readily produced an immortalized lymphoblastoid cell line in culture. CONCLUSION: While considered a rare event, EBV transmission through transfusion may occur in the context of severe immunosuppression.

Risk of transmission of severe acute respiratory syndrome coronavirus 2 by transfusion: A literature review.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel human coronavirus responsible for coronavirus disease 2019 (COVID-19). The emergence of this virus in Wuhan, China, at the end of 2019 and its worldwide spread to reach the pandemic stage has raised concerns about the possible risk that it might be transmissible by transfusion. This theoretical risk is further supported by reports of the detection of viral RNA in the blood of some infected individuals. To further address this risk, a thorough PubMed literature search was performed to systematically identify studies reporting data on the detection of SARS-CoV-2 RNA in blood or its components. Complementary searches were done to identify articles reporting data on the in vitro infectivity of blood components. At least 23 articles presenting data on the detection of SARS-CoV-2 RNA in blood, plasma, or serum were identified. Of these, three studies reported on blood donors with COVID-19 infection identified after donation, and no cases of transfusion transmission were identified. A few studies mentioned results of in vitro infectivity assays of blood components in permissive cell lines, none of which were able to detect infectious virus in blood or its components. Complementary searches have identified reports demonstrating that the correlation between the presence of viral RNA in a biologic sample and infectivity requires a minimal RNA load, which is rarely, if ever, observed in blood components. Overall, the available evidence suggests that the risk of transmission of SARS-CoV-2 by transfusion remains theoretical.

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.

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.

Bacillus cereus infection in neonates and the absence of evidence for the role of banked human milk: Case reports and literature review.

BACKGROUND: Banked human milk (BHM) has inherent infectious risks, even when pasteurized. Because of the ubiquity of Bacillus cereus in the environment and its ability to resist the Holder pasteurization process, there is a concern that BHM might lead to severe B. cereus infections. OBJECTIVE: We reviewed observed and published cases to determine the potential causal role of BHM as the source of these infections. METHODS: Two infants in the province of Québec (Canada) developed a B. cereus neonatal infection, and both had received BHM. We conducted bacteriological studies to compare clinical isolates and those found in these cases. RESULTS: After extended culture of BHM retention lots, B. cereus was found to have been involved in batches related to the first case. However, molecular typing showed that the strain was different from the clinical isolate, therefore excluding BHM as the source of contamination. In the second case, a Brevibacillus spp was isolated, a species distinct from the clinical isolate. CONCLUSION: Based on these cases and others reported in the literature, a causal link between B. cereus contaminated BHM and preterm neonatal infection has never been documented. Therefore, the risk that BHM can cause this infection remains theoretical. Given the widespread presence of B. cereus in the hospital environment and its capacity to resist standard cleaning procedures, it seems likely that airborne or direct or indirect contact are the main sources of most, if not all, cases of severe B. cereus neonatal infections, even in babies exposed to BHM.

Malaria blood safety policy in five non-endemic countries: a retrospective comparison through the lens of the ABO risk-based decision-making framework.

BACKGROUND: In non-endemic countries, malaria risk is addressed by selectively testing or deferring at-risk donors. These policy decisions were made using a variety of decision-making frameworks prior to the development of the Alliance of Blood Operators Risk Based Decision-Making Framework. It is unclear whether the range of items assessed in the decision-making process would be increased if the Framework were used. We compared assessments considered in France, England and Australia for decisions to implement selective testing, plus donor selection criteria (Canada and the USA included) with those recommended by the Framework. MATERIALS AND METHODS: Elements of the Framework were identified: the intervention, safety threat, availability threat, donor impact, financial implications, risk communication, stakeholder and regulatory aspects. Decisions about selective testing and donor selection criteria were analysed separately. Assessments were compared against elements of the Framework and the level of concern for considerations rated. RESULTS: Sufficiency of the blood supply (plus safety in France) were the drivers for selective testing; main trade-offs were high operational impact and cost. In three donor criteria examples, transfusion-transmitted malaria cases prompted the change. Social concerns were high in France and Australia, political/regulatory concerns influenced decisions in France, Australia and Canada, while sufficiency was a consideration in Canada and the USA. Decision trade-offs involved moderate operational impact. DISCUSSION: The assessments considered in each country were generally consistent with the assessments recommended by the Framework. When data supported quantified risk assessment, safety and operational feasibility had the greatest weight. When risk was not well defined, contextual factors such as social and political concern had greater weight.

Banked Human Milk and Quantitative Risk Assessment of Bacillus cereus Infection in Premature Infants: A Simulation Study.

BACKGROUND: Banked human milk (BHM) offers potential health benefits to premature babies. BHM is pasteurized to mitigate infectious risks, but pasteurization is ineffective against sporulating bacteria such as Bacillus cereus. Sepsis related to Bacillus cereus in premature infants is severe and can often be fatal. Even if a causal link has never been established, BHM has been suggested as a potential source of infection in premature infants. OBJECTIVE: Our aim was to estimate the potential risk of Bacillus cereus infection in preterm infants caused by the ingestion of contaminated pasteurized BHM using different post-pasteurization release criteria (i.e., 9 sampling of 100 microliters versus the HMBANA guideline of 1 sampling of 100 microliters per pool). METHODS: In the absence of scientific evidence regarding the risk of Bacillus cereus infection by the ingestion of BHM in premature infants, risk assessment using Monte Carlo simulation with the exponential dose-response model was performed. Three scenarios of infectious risk (annual incidence rate of 0.01%, 0.13%, and 0.2%) with 18 variations of the B. cereus virulent dose (from 0.5 CFU/ml to 200 CFU/ml) were simulated. RESULTS: The mean risk differential between the two methods of post-pasteurization bacteriological control for realistic infectious doses of 30 to 200 CFU/ml ranges from 0.036 to 0.0054, 0.47 to 0.070, and 0.72 to 0.11 per million servings, for each of the three scenarios. CONCLUSION: Simulation highlights the very small risk of Bacillus cereus infection following the ingestion of pasteurized BHM, even in the worst case scenarios, and suggests that a 100-microliter sample for post-pasteurization culture is sufficient.

International survey on the impact of parasitic infections: frequency of transmission and current mitigation strategies.

BACKGROUND AND OBJECTIVES: Globally, blood safety interventions have been successful in mitigating risk of the major transfusion-transmitted (TT) viruses. However, strategies that address risk from parasites are comparatively limited. TT parasites are often regional in nature, posing unique challenges; we sought to understand their impact on blood safety. MATERIALS AND METHODS: An electronic questionnaire was distributed to transfusion medicine leaders in 100 countries. The survey focused on specific questions pertaining to four parasitic diseases: babesiosis, Chagas, leishmaniasis and malaria. Respondents provided data on historical TT cases, local epidemiology, policies to mitigate risk and an assessment of public health perceptions for each aetiologic agent. RESULTS: Twenty-eight (28%) surveys were returned from countries in Europe (n = 13), the Americas (n = 6), Africa (n = 4), Asia (n = 3) and Oceana (n = 2). Historically, no cases of TT leishmaniasis were reported, TT babesiosis was exclusive to Canada and the USA, TT Chagas was limited to the Americas and Spain, while TT malaria was cosmopolitan. Mitigation efforts varied widely; malaria was the most frequently tested parasitic disease. The public's perception of risk for parasitic agents was low, while that of health authorities in endemic countries was higher. CONCLUSION: The global impact of parasitic infections on blood safety and related mitigation efforts varied widely by parasite epidemiology, test availability, public health priorities and socioeconomic constraints. While parasites continue to pose a risk to blood safety, the successful mitigation of viral risk has elevated the prominence of TT parasites in many locations, thereby requiring consideration of mitigation efforts.

Human T-cell lymphotropic virus: A simulation model to estimate residual risk with universal leucoreduction and testing strategies in Canada.

BACKGROUND AND OBJECTIVES: In Canada, transfusion transmission risk of Human T-cell lymphotropic virus -I/II (HTLV) is addressed by universal leucoreduction and universal antibody testing. We aimed to estimate the risk with the current policy, if testing only first-time donors and if testing were stopped. MATERIALS AND METHODS: Monte Carlo simulation was employed to estimate the proportion of red cell concentrate, random donor platelet and apheresis platelet units that would be released into inventory in each scenario (10 billion donors each). The model estimated the number of HTLV-positive donations not intercepted by testing, randomly assigned the number of HTLV particles/100 leucocytes using proportions from published data and randomly selected a postleucoreduction leucocyte count from quality control data. Units were considered infectious if ≥9 × 104 copies of HTLV provirus. RESULTS: With universal leucoreduction in place, the residual risk of releasing an HTLV potentially infectious unit with universal testing was 1 in 1·2 billion units (0, 1 in 55·9 million), with testing only first-time donors 1 in 7·1 million (0, 1 in 1·05 million) and with no testing 1 in 1·0 million (0, 1 in 178 600). The efficacy of leucoreduction was >99·5% (lower bound 95·7%) for all scenarios. CONCLUSION: With universal leucoreduction in place, switching from universal testing to testing first-time donors would incur very low risk.

Bordetella holmesii Contamination of Platelet Concentrates: Revisiting the Definition of a Positive Culture.

Bacterial contamination remains the most important infectious risk of platelet transfusion. After an initially positive result, a second test is performed on the blood products and the initial culture bottle to confirm the contamination. Based on the blood center's decision algorithm used, results can be either confirmed negative, positive, or indeterminate, or be unconfirmed or discordant. Here, we report the first cases of platelet concentrates contaminated with Bordetella holmesii The in vitro growth characteristics of this unusual contaminant in platelet concentrate were investigated. Two B. holmesii strains isolated from platelet concentrates, as well as a control strain (Serratia marcescens), were spiked into platelet concentrates (PCs) at 1 and 10 CFU/ml. PCs were stored at 20 to 24°C under agitation. Samples were collected on days 2, 3, 4, and 7 for colony count and for bacterial screening using the BacT/Alert 3D system. Two PCs were detected as being positive for B. holmesii However, recultures were negative. In vitro, B. holmesii did not grow but remained detectable in PCs. Its viability diminished rapidly in contact with human plasma. Upon screening using the BacT/Alert 3D system, the majority of products spiked with B. holmesii were negative. This is the first description of PCs contaminated with B. holmesii This bacterium survives in blood products and remains dormant at low concentrations in blood products stored at room temperature, thus making difficult its detection with the BacT/Alert 3D system. The present definition of a true-positive culture of PCs may be overly restrictive for certain bacterial strains.

Mitigation of the threat posed to transfusion by donors traveling to Zika-affected areas: a Canadian risk-based approach.

BACKGROUND: The recent spread of the Zika virus to the Americas and the recognition that it can cause severe disease in the developing fetus has prompted the adoption of measures to mitigate the risk that this virus might pose to transfusion safety. In nonendemic countries, the risk to transfusion results from donors traveling to an endemic region. Canada implemented a 21-day temporary deferral for prospective donors who traveled to such regions. We present the rationale for this policy, including a quantitative risk assessment supported by a Monte Carlo simulation. STUDY DESIGN AND METHODS: The model considered the following parameters, each with specified values and ranges: the probability that a donor recently returned from a Zika-endemic region, the duration of travel to this region, the daily risk of acquiring Zika while in an endemic region, and the incubation and viremic periods. We ran the simulation 20 times, each with 10 million iterations. RESULTS: In the absence of any travel deferral, 32 donors (range, 20-46 donors) would be able to donate while still being at risk of transmitting Zika, corresponding to a rate of 1:312,500 (range, 1:217,000 to 1:500,000). None of these donors would be viremic beyond 21 days after returning from their travel, with a risk estimated at less than 1:200,000,000. CONCLUSIONS: A 21-day temporary travel deferral offers an extremely wide margin of safety for the possible transmission of Zika by a donation obtained from someone who recently returned from a country where the virus is circulating.