Epidemiology of Hepatitis C over 28 years of monitoring Canadian blood donors: Insight into a low-risk undiagnosed population.

BACKGROUND: Hepatitis C is a blood-borne infection with the hepatitis C virus (HCV) that can progress to cirrhosis and liver cancer. About 70% (50-80%) of infections become chronic and exhibit anti-HCV and HCV nucleic acid (NAT) positivity. Direct acting oral pan genotypic antiviral treatment became available in 2014 and was free for most Canadians in 2018. Clinical screening for HCV infection is risk-based. About 1% of Canadians have been infected with HCV, with 0.5% chronically infected (about 25% unaware) disproportionately impacting marginalized groups. Blood donors are in good health, are deferred for risks such as injection drug use and can provide insight into the low-risk undiagnosed population. Here we describe HCV epidemiology in first-time blood donors over 28 years of monitoring. METHODS: All first-time blood donors in all Canadian provinces except Quebec (1993 to 2021) were analyzed. All blood donations were tested for HCV antibodies (anti-HCV) and since late 1999 also HCV NAT. A case-control study was also included. All HCV positive donors (cases) since 2005 and HCV negative donors (1:4 ratio controls) matched for age, sex and location were invited to complete a risk factor interview. Separate logistic regression models for anti-HCV positivity and chronic HCV assessed the association between age cohort, sex, region and neighbourhood material deprivation and ethnocultural concentration. CASE: control data were analysed by logistic regression. RESULTS: There were 2,334,238 donors from 1993 to 2021 included. Prevalence for anti-HCV was 0.33% (0.30,0.37) in 1993 and 0.07% (0.05,0.09) in 2021 (p < 0.0001). In 2021 0.03% (0.01,0.04) had chronic HCV. Predictors for both anti-HCV positivity and chronic HCV were similar, for chronic HCV were male sex (OR 1.8, 1.6,2.1), birth between 1945 and 1975 (OR 7.1, 5.9,8.5), living in the western provinces (OR 1.4, 1.2,1.7) and living in material deprived (OR 2.7, 2.1,3.5) and more ethnocultural concentrated neighbourhoods (OR 1.8, 1.3,2.5). There were 318 (35.4%) of chronic HCV positive and 1272 (39.6%) of controls who participated in case control interviews. The strongest risks for acquisition were injection drug use (OR 96.9, 22.3,420.3) and birth in a high prevalence country (OR 24.5, 11.2,53.6). CONCLUSIONS: Blood donors have 16 times lower HCV prevalence then the general population. Donors largely mirror population trends and highlight the ongoing prevalence of untreated infections in groups without obvious risks for acquisition missed by risk-based patient screening.

Prevalence of human T-cell lymphotropic virus-1/2 in Canada over 33 years: A unique contribution of blood donors to public health surveillance.

OBJECTIVES: Estimate HTLV-1/2 (human T-cell lymphotropic viruses) prevalence in Canadian blood donors and the association of demographic variables with infection and their corresponding risk factors. METHODS: First-time blood donors in all Canadian provinces (except Quebec) from 1990 to 2022 were included. Blood samples were tested for HTLV-1/2 by enzyme-linked immunoassay, confirmed by Western blot. Multivariable logistic regression with year, age group, sex, region, neighbourhood material deprivation, and ethnocultural composition indices predicted HTLV-1/2. Since 2005, all HTLV-1/2-positive donors (cases) were invited to participate in a risk factor interview, and 4 non-positive donors (controls per case) were matched for age, sex, and region. Case-control predictors of HTLV-1/2 were analyzed using logistic regression. RESULTS: There were 3,085,554 first-time donors from 1990 to 2022. HTLV-1/2 prevalence remained low (12 per 100,000 in 2022, 95% CI 6.4-23.5). The odds ratios predicting HTLV-1/2 were higher in females (2.0, 95% CI 1.5-2.6), older age groups (50 + ; 6.3, 95% CI 4.3-9.2), British Columbia and Ontario, those materially deprived (1.9, 95% CI 1.2-2.9), and those in ethnocultural neighbourhoods (7.5, 95% CI 3.2-17.3). Most HTLV-1/2 in Ontario was HTLV-1, whereas in British Columbia half were HTLV-2. Forty-three of 149 (28.8%) cases and 172 of 413 (41.6%) controls completed an interview. The strongest predictor of HTLV-1/2 in case-control analysis was birth in a high-prevalence country (OR 39.8, 95% CI 7.8-204.3) but about 50% of HTLV-1 and 90% of HTLV-2 were Canadian-born. CONCLUSION: HTLV-1/2 prevalence is low in blood donors. High-prevalence country of birth accounts for about half of HTLV-1; HTLV-2 positives are usually Canadian-born. HTLV-1/2 transmission likely occurs overseas and within Canada.

RéSUMé: OBJECTIFS: Estimer la prévalence des sous-types du virus T-lymphotrope humain (HTLV-1 et HTLV-2) dans le sang des donneurs de sang canadiens, et évaluer le lien avec des variables démographiques et des facteurs de risque donnés. MéTHODES: Cette étude a porté sur toutes les personnes ayant fait leur premier don entre 1990 et 2022 au Canada, sauf au Québec. Les échantillons de sang ont été soumis à un test immunoenzymatique, puis à un test Western Blot de confirmation. Les données ont été analysées au moyen de la régression logistique en utilisant comme indices l'année, la tranche d'âge, le sexe, la région, le quartier, la privation matérielle et la composition ethnoculturelle. Depuis 2005, tous les donneurs positifs au HTLV-1/2 (cas) ont été conviés à un entretien ayant pour but de déterminer leurs facteurs de risque, et quatre donneurs négatifs (cas-témoins) ont été appariés à chaque cas en fonction de l'âge, du sexe et de la région. Les facteurs de prédiction d'infection au HTLV-1/2 des cas-témoins ont été analysés au moyen de la régression logistique. RéSULTATS: Entre 1990 et 2022, le nombre de primodonneurs s'élevait à 3 085 554. La prévalence du HTLV-1/2 est demeurée faible (12,2 sur 100 000 en 2022, IC 95%: 6,4­23,5). Le rapport de cotes était plus élevé chez les femmes (2,0, IC 95% 1,5­2,6), chez les personnes de plus de 50 ans (6,3, IC 95% 4,3­9,2), en Colombie-Britannique et en Ontario, chez les personnes touchées par la privation matérielle (1,9, IC 95% 1,2­2,9) et chez les personnes vivant dans des quartiers ethnoculturels (7,5, IC 95% 3,2­17,3). La plupart des cas de HTLV-1/2 rencontrés en Ontario concernaient le HTLV-1, tandis qu'en Colombie-Britannique, la moitié des cas concernait le HTLV-2. Quarante-trois cas sur 149 (28,8 %) et 172 cas-témoins sur 413 (41,6 %) ont passé l'entretien. L'analyse des cas-témoins a révélé que le facteur de prédiction le plus important d'infection au HTLV-1/2 était le fait d'être né dans un pays à forte prévalence (RC 39,8, IC 95% 7,8­204,3); toutefois environ 50 % des cas-témoins de HTLV-1 et 90 % des cas témoins de HTLV-2 étaient nés au Canada. CONCLUSION: La prévalence du HTLV-1/2 est faible dans le sang des donneurs de sang. Pays de naissance à forte prévalence représente à peu près la moitié des cas de HTLV-1; les donneurs positifs au HTLV-2 la plupart du temps sont nés au Canada. La transmission du HTLV-1/2 survient probablement outre-mer et au Canada.

Porcine-derived pancreatic enzyme replacement therapy may be linked to chronic hepatitis E virus infection in cystic fibrosis lung transplant recipients.

OBJECTIVES: In high-income countries hepatitis E virus (HEV) is an uncommonly diagnosed porcine-derived zoonoses. After identifying disproportionate chronic HEV infections in persons with cystic fibrosis (pwCF) postlung transplant, we sought to understand its epidemiology and potential drivers. DESIGN: All pwCF post-transplant attending our regional CF centre were screened for HEV. HEV prevalence was compared against non-transplanted pwCF and with all persons screened for suspected HEV infection from 2016 to 2022 in Alberta, Canada. Those with chronic HEV infection underwent genomic sequencing and phylogenetic analysis. Owing to their swine derivation, independently sourced pancreatic enzyme replacement therapy (PERT) capsules were screened for HEV. RESULTS: HEV seropositivity was similar between transplanted and non-transplanted pwCF (6/29 (21%) vs 16/83 (19%); p=0.89). Relative to all other Albertans investigated for HEV as a cause of hepatitis (n=115/1079, 10.7%), pwCF had a twofold higher seropositivity relative risk and this was four times higher than the Canadian average. Only three chronic HEV infection cases were identified in all of Alberta, all in CF lung transplant recipients (n=3/29, 10.3%). Phylogenetics confirmed cases were unrelated porcine-derived HEV genotype 3a. Ninety-one per cent of pwCF were taking PERT (median 8760 capsules/person/year). HEV RNA was detected by RT-qPCR in 44% (47/107) of PERT capsules, and sequences clustered with chronic HEV cases. CONCLUSION: PwCF had disproportionate rates of HEV seropositivity, regardless of transplant status. Chronic HEV infection was evident only in CF transplant recipients. HEV may represent a significant risk for pwCF, particularly post-transplant. Studies to assess HEV incidence and prevalence in pwCF, and potential role of PERT are required.

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.

Translating bioactive peptides for COVID-19 therapy.

COVID-19 (Coronavirus disease 2019) is a global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a positive-sense RNA virus. This virus has emerged as a threat to global health, social stability, and the global economy. This pandemic continues to cause rampant mortality worldwide with the dire urgency to develop novel therapeutic agents. To meet this task, this article discusses advances in the research and potential application of bioactive peptides for possible mitigation of infection by SARS-CoV-2. Growing insight into the molecular biology of SARS-CoV-2 has revealed potential druggable targets for bioactive peptides. Bioactive peptides with unique amino acid sequences can mitigate such targets including, type II transmembrane serine proteases (TMPRSS2) inhibition, furin cleavage, and renin-angiotensin-aldosterone system (RAAS) members. Based on current evidence and structure-function analysis, multiple bioactive peptides present potency to neutralize the virus. To date, no SARS-CoV-2-explicit drug has been reported, but we here introduce bioactive peptides in the perspective of their potential activity against SARS-CoV-2 infection.

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.

Evaluation of the effect of T regulatory cell depletion and donor BCG vaccination on Mycobacterium tuberculosis H37Ra infection using an in vitro model of human PBMC infection.

This study evaluated the effect of T regulatory cells (Treg cells) and the impact of BCG vaccination history of donors using an in vitro model of Mycobacterium tuberculosis H37Ra infection of peripheral blood mononuclear cells (PBMCs). PBMCs from donors with or without prior BCG vaccination were depleted of Treg cells (PBMCs-Tregs) or not depleted with Treg cells (PBMCs + Tregs) were infected up to 8 days with Mtb H37Ra. Cell aggregates were smaller in PBMCs-Tregs compared to PBMCs + Tregs at day 8 post-infection. Mtb CFUs were higher in the PBMCs-Tregs compared to PBMCs + Tregs at days 3, 5 and 8. The levels of IL-17, IFN-γ (at days 3 and 5), and TNF-α and IL-6 (at day 3) were lower in PBMCs-Tregs compared to PBMCs + Tregs. In contrast, the levels of IL-10 and IL-4 cytokines were higher at day 3 in PBMCs-Tregs compared to PBMCs + Tregs. BCG vaccination status of donors had no impact on the mycobacterial culture, level of cytokines and immune cell populations. This study shows that depletion of Tregs in human PBMCs infected with Mtb H37Ra in vitro leads to a shift from a Th1 to a Th2 cytokine rich environment that supports the survival of Mtb in this model.

A simple protein-based surrogate neutralization assay for SARS-CoV-2.

Most of the patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mount a humoral immune response to the virus within a few weeks of infection, but the duration of this response and how it correlates with clinical outcomes has not been completely characterized. Of particular importance is the identification of immune correlates of infection that would support public health decision-making on treatment approaches, vaccination strategies, and convalescent plasma therapy. While ELISA-based assays to detect and quantitate antibodies to SARS-CoV-2 in patient samples have been developed, the detection of neutralizing antibodies typically requires more demanding cell-based viral assays. Here, we present a safe and efficient protein-based assay for the detection of serum and plasma antibodies that block the interaction of the SARS-CoV-2 spike protein receptor binding domain (RBD) with its receptor, angiotensin-converting enzyme 2 (ACE2). The assay serves as a surrogate neutralization assay and is performed on the same platform and in parallel with an ELISA for the detection of antibodies against the RBD, enabling a direct comparison. The results obtained with our assay correlate with those of 2 viral-based assays, a plaque reduction neutralization test (PRNT) that uses live SARS-CoV-2 virus and a spike pseudotyped viral vector-based assay.

A case series of inactivated Japanese encephalitis virus vaccination associated with positive West Nile virus blood donor screening nucleic acid tests.

BACKGROUND: West Nile Virus (WNV) is a member of the Japanese Encephalitis (JE) serocomplex within the Flaviviridae family. We report four whole blood donors and one plasma donor with WNV nucleic acid test (NAT)-reactive donations between September 2018 and November 2019, following recent Japanese Encephalitis virus (JEV) vaccination. CASE SERIES: Cases 1 and 4 had reactive WNV NAT donations 1 day after receiving the JEV vaccine. Case 2 had a reactive WNV donation 3 days after receiving the JEV vaccine. Case 3 had a reactive WNV NAT donation 3 days after returning from Arizona and 1 day after receiving the JEV vaccine. Case 5 had a reactive WNV donation the same day as receiving the JEV vaccine. STUDY DESIGN AND METHODS: WNV screening used the Roche cobas WNV nucleic acid test (NAT) (Roche Molecular Systems). Reference testing on WNV-reactive donations was carried out by the National Microbiology Laboratory (NML). JEV vaccine dilutions were also analyzed. RESULTS: Supplemental NAT was negative for WNV and JEV for Cases 1, 3, and 5. Case 2 had a weak amplification curve for one of two JEV NAT targets. Case 4 was JEV NAT-positive, WNV NAT-negative. Serologic testing on donation specimens for Cases 2, 4, and 5 did not support recent or remote WNV infection. JEV vaccine dilutions were detected by both cobas and supplemental NAT. CONCLUSIONS: We recommend implementing a temporary blood donor deferral following a JEV vaccination, if screening utilizes a WNV assay with the capability of detecting other members of the JE serocomplex.

A suspected septic transfusion reaction associated with posttransfusion contamination of a platelet pool by vancomycin-resistant Enterococcus faecium.

BACKGROUND: Vancomycin-resistant enterococci (VRE) are antibiotic-resistant organisms associated with both colonization and serious life-threatening infection in health care settings. Contamination of platelet concentrates (PCs) with Enterococcus can result in transfusion-transmitted infection. CASE PRESENTATION: This report describes the investigation of a septic transfusion case involving a 27-year-old male patient with relapsed acute leukemia who was transfused with a 5-day-old buffy coat PC pool and developed fever and rigors. DISCUSSION: Microbiology testing and pulse-field gel electrophoresis (PFGE) was done on patient blood cultures obtained from peripheral and central lines. Microbiology and molecular testing were also performed on the remaining posttransfusion PC pool, which was refrigerated for 24 hours before microbiology testing. Red blood cell (RBC) and plasma units associated with the implicated PCs were screened for microbial contamination. Patient blood cultures obtained from peripheral and central lines yielded vancomycin-resistant Enterococcus faecium. Gram stain of a sample from the platelet pool was negative but coagulase-negative Staphylococcus (CNST) and VRE were isolated on culture. Antibiotic sensitivity and PFGE profiles of several VRE isolates from the patient before and after transfusion, and the PC pool, revealed that all were closely related. Associated RBC and plasma components tested negative for microbial contamination. CONCLUSIONS: Microbiological and molecular investigations showed a relationship between VRE isolated from the patient before and after transfusion, and therefore it is postulated that a patient-to-PC retrograde contamination (from either blood or skin) occurred. As the CNST isolated from the PC pool was not isolated from patient samples, its implication in the transfusion event is unknown.