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ImportanceBlood donor selection policies should be evidence-based. Individual risk assessment allows potential donors to be evaluated based on their own behaviors.ObjectiveThe Assessing Donor Variability and New Concepts in Eligibility (ADVANCE) study examined behavioral and biomarkers of HIV risk in sexually active men who have sex with men (MSM) to estimate the proportion of the study population who would not be deferred for higher risk HIV sexual behaviors and might be eligible to donate.DesignA cross-sectional assessment of sexually active MSM interested in blood donation. Setting: An 8-city study of MSM aged 18 – 39 years assigned male sex at birth.Interventions or ExposuresParticipants completed surveys during 2 study visits to define eligibility, self-reported sexual and HIV prevention behaviors. Blood was drawn at study visit 1 and tested for HIV and the presence of tenofovir, 1 of the drugs in oral HIV pre-exposure prophylaxis (PrEP).Main Outcomes and MeasuresAssociations between HIV infection status or HIV PrEP use and self-reported HIV risk behaviors, including number of male sex partners, new partners, and anal sex.ResultsAmong 1788 screened MSM, 1593 were eligible and 1566 completed the visit 1 HIV risk questionnaire and blood draw. A median of 22 days later, 1197 completed the visit 2 follow-up questionnaire. Four individuals tested HIV positive (0.25%). Among HIV-negative participants, 789 (50.4%) reported no PrEP use in the past 3 months. The number of sex partners in the past 3 months was significantly higher among PrEP users versus non-users, as was the number reporting a new male sex partner in the same period. Among HIV-negative, non-PrEP using participants, 66.2% reported only 1 sexual partner or no anal sex and 69% reported no new sexual partners or no anal sex with a new partner in the past 3 months.Conclusion and RelevanceAmong sexually active MSM, there are subgroups who self-report no new sexual partners and only 1 sexual partner within the past 3 months. These individuals are likely at lower risk of HIV infection than other MSM and would meet proposed individual risk assessment criteria for blood donation in the U.S.Key PointsQuestionCan a set of blood donor screening questions based on individual behaviors identify a population of lower HIV risk men who have sex with men (MSM) who wish to donate blood?FindingsIn this cross-sectional study of 1566 enrolled MSM, among 1562 persons without HIV, 789 (50.4%) were not taking pre-exposure prophylaxis (PrEP). Of those not taking PrEP, 66.2% reported only 1 sexual partner or no anal sex and 69% reported no new sexual partners or no anal sex with a new partner in the past 3 months.MeaningPotential blood donor history questions were able to identify sexually active MSM with lower-risk sexual behaviors who may be eligible to donate blood.

Summary Background Characterisation of the dynamics of Zika virus persistence following acute infection is needed to inform blood donor and diagnostic testing policies and understand the natural history of Zika virus infection. We aimed to characterise the natural history, persistence, and clinical outcomes of Zika virus infection through a prospective study in initially asymptomatic Zika virus RNA-positive blood donors. Methods Zika virus-infected blood donors identified through Zika virus nucleic acid amplification test (NAAT) screening at three blood collection organisations in the USA were enrolled into a 1-year follow-up study, with blood and body fluid samples and detailed symptom data collected at up to seven visits. All samples were tested for Zika virus RNA by real-time PCR (rtPCR); follow-up plasma, whole blood, and urine were also tested by replicate NAAT. Plasma was tested for flavivirus-specific IgM and IgG by ELISA. Zika virus RNA persistence for each assay or sample type and plasma antibody persistence from estimated date of plasma NAAT-detectable infection were calculated from follow-up data using survival statistical methods. Findings Between July 6, 2016 and March 7, 2017, we enrolled 53 participants. From the estimated date of plasma NAAT-detectable infection, Zika virus RNA was detectable in plasma for 9·9 days (95% CI 8·1–12·0), in red blood cells for 95·4 days (62·8–129·1), and in whole blood for 73·5 days (39·8–107·5). Replicate NAATs (one or more of eight replicates positive) extended detection of Zika virus RNA in plasma to 34·8 days (19·9–56·2) and in whole blood (at least one of two tests positive) to 104·8 days (76·7–129·9). Urine was rtPCR reactive up to 14·5 days (10·5–20·3) and saliva up to 26·4 days (19·7–38·7). Zika virus IgM persisted for 237·7 days (128·7–459·5) from estimated time since plasma NAAT-detectable infection. Zika virus RNA fell below detectable limits more rapidly in the saliva of participants with pre-existing dengue virus IgG than in those without. Of 25 donors identified pre-seroconversion with symptom data at the first or second study visit, 16 (64%) developed multiple Zika virus-related symptoms after asymptomatic index donations, compared with nine (36%) of 25 donors detected after seroconversion. Interpretation Determination of viral marker persistence is enhanced by follow-up of blood donors who are pre-symptomatic or asymptomatic, Zika virus RNA-positive, and antibody negative. Zika virus RNA persists in red blood cells for several months following clearance from plasma and body fluids, and replicate, highly sensitive NAATs extend RNA detection in all compartments. Whole blood testing can extend detection of acute infection for diagnostics and monitoring of pregnant women, sexual partners, and travellers. Funding National Heart, Lung, and Blood Institute, Biomedical Advanced Research and Development Authority.

Background and objectives Comparison of two models for estimating residual transfusion transmission risk by NAT screened window period (WP) donations in South African repeat donors gave identical results for HIV but not for HBV. In order to understand discrepant HBV modelling outcomes, the values of input parameters in three HBV WP risk models were reviewed and subsequently applied to the same South African screening data generated by HBsAg PRISM and two NAT assays (Ultrio and Ultrio Plus). Two of the models were also compared using individual donation (ID)-NAT screening data from different geographical regions. Methods Values of input parameters were derived from two published data sources and used in three risk models [(1) the incidence rate-WP risk day equivalent model, (2) the NAT yield WP ratio model and (3) the anti-HBc-negative HBsAg yield period ratio model] and subsequently applied to the same ID-NAT screening data. Results The HBV WP transmission risk in South African repeat donations during a one-year Ultrio Plus NAT screening period was estimated as 22, 43 and 17 per million, respectively, for the three models, as compared to 56, 117 and 48 per million for HBsAg PRISM screening. The approximate two-fold higher estimate calculated with the NAT yield WP ratio model was corroborated in repeat donations from three of four regions in a multi-regional study. When another set of model input values (with shorter viraemia periods and a higher proportion of acute occult infections) was applied to the South African screening data, the relative difference in risk estimates between the three models became smaller. Conclusions Window period risk modelling for HBV is more complex than for HIV. Multiple factors affect the modelling outcomes. These include the values used for the length of transient HBsAg and HBV-DNA-positive phases, the proportion of acute occult and vaccine breakthrough infections and the assumption of random appearance of donors throughout the entire acute resolving infection phase. A substantial proportion of HBV WP NAT yields have very low viral load and lack donor follow-up data calling into question their definitive classification into the early acute (infectious) replication stage. Since these possible WP NAT yields most highly impact the NAT yield WP ratio model, we recommend relying on the more conservative estimates of the incidence rate-WP risk day equivalent model.

BackgroundA national serosurvey of U.S. blood donors conducted in partnership with the Centers for Disease Control and Prevention (CDC) was initiated to estimate the prevalence of SARS-CoV-2 infections and vaccinations.MethodsBeginning in July 2020, the Nationwide Blood Donor Seroprevalence Study collaborated with multiple blood collection organizations, testing labs, and leadership from government partners to capture, test, and analyze approximately 150,000 blood donation specimens per month in a repeated, cross-sectional seroprevalence survey.ResultsA CDC website (https://covid.cdc.gov/covid-data-tracker/#nationwide-blood-donor-seroprevalence) provided stratified, population-level results to public health professionals and the general public.DiscussionThe study adapted operations as the pandemic evolved, changing specimen flow and testing algorithms, and collecting additional data elements in response to changing policies on universal blood donation screening and administration of SARS-CoV-2 spike-based vaccines. The national serosurvey demonstrated the utility of serosurveillance testing of residual blood donations and highlighted the role of the blood collection industry in public-private partnerships during a public health emergency.

BACKGROUNDWith the introduction of direct-acting antivirals to treat and cure hepatitis C virus (HCV) infection, HCV elimination is achievable. In 2017, San Francisco’s HCV elimination initiative, End Hep C SF, generated an estimate of city-wide HCV prevalence in 2015, but only incorporated limited information about population HCV treatment. Using additional data and updated methods, we aimed to update the 2015 estimate to 2019 and provide a more accurate estimate of the number of people with untreated, active HCV infection overall and in key subgroups – people who inject drugs (PWID), men who have sex with men (MSM), and low socioeconomic status transgender women (low SES TW).METHODSOur estimates are based on triangulation of data from blood bank testing records, cross-sectional and longitudinal observational studies, and published literature. We calculated subpopulation estimates based on biological sex, age and/or HCV risk group. When multiple sources of data were available for subpopulation estimates, we calculated an average using inverse variance weighting. Plausible ranges (PRs) were conservatively estimated to convey uncertainty.RESULTSThe total number of people estimated to have anti-HCV antibodies in San Francisco in 2019 was 22,585 (PR:12,014–44,152), with a citywide seroprevalence of 2.6% (PR:1.4%–5.0%) – similar to the 2015 estimate of 21,758 (PR:10,274–42,067). Of all people with evidence of past or present infection, an estimated 11,582 (PR:4,864–35,094) still had untreated, active HCV infection, representing 51.3% (PR:40.5%–79.5%) of all people with anti-HCV antibodies, and 1.3% (PR:0.6%–4.0%) of all San Franciscans. PWID comprised an estimated 2.8% of the total population of San Francisco, yet 73.1% of people with anti-HCV antibodies and 90.4% (n=10,468, PR:4,690–17,628) of untreated, active HCV infections were among PWID. MSM comprised 7.8% of the total population, yet 11.7% of people with anti-HCV antibodies and 1.0% (n=119, PR:0–423) of those with untreated active infections. Low SES TW comprised an estimated 0.1% of the total population, yet 1.4% of people with HCV antibodies and 1.6% (n=183, PR:130–252) of people with untreated active infections.CONCLUSIONSDespite the above-average number (2.6%) of people with anti-HCV antibodies, we estimate that only 1.3% (PR:0.6%–4.0%) of all San Francisco residents have untreated, active HCV infection – likely a reflection of San Francisco’s robust efforts to diagnose infection among high-risk groups and initiate curative treatment with as many people as possible. While plausible ranges of infections are wide, these findings indicate that while the overall number of people with anti-HCV antibodies may have increased slightly, the number of people with active HCV infection may have decreased slightly since 2015. This estimate improves upon the 2015 calculations by directly estimating the impact of curative treatment citywide and in subgroups. However, more research is needed to better understand the burden of HCV disease among other subgroups at high risk, such as Blacks/African Americans, people with a history of injection drug use (but not injecting drugs in the last 12 months), people who are currently or formerly incarcerated, and people who are currently or formerly unhoused.

BACKGROUND: Recent publications have reported conflicting findings regarding associations of blood donor demographics and mortality of transfused patients. We hypothesized that the analysis of additional donor characteristics and consideration of alternative outcomes might provide insight into these disparate results. STUDY DESIGN AND METHODS: We analyzed data from a retrospective cohort of transfused patients from the Recipient Epidemiology and Donor Evaluation Study (REDS-III). We used stratified Cox regression models to estimate associations between blood donor characteristics and hospital mortality and post-transfusion length of stay among patients transfused red blood cell (RBC) units. Donor characteristics evaluated included age, body mass index, hemoglobin levels, and smoking status. The statistical analyses were adjusted for recipient factors, including total number of transfusions. RESULTS: We studied 93,726 patients in 130,381 hospitalizations during which 428,461 RBC units were transfused. There were no associations between blood donor characteristics and hospital mortality. Receipt of RBC units from donors less than 20 years of age was associated with a shorter hospital length of stay (hazard ratio for discharge per transfused unit 1.03; 95% confidence interval, 1.02 to 1.04; p

Significant research has focused individually on blood donors, product preparation and storage, and optimal transfusion practice. To better understand the interplay between these factors on measures of red blood cell (RBC) transfusion efficacy, we conducted a linked analysis of blood donor and component data with patients who received single-unit RBC transfusions between 2008 and 2016. Hemoglobin levels before and after RBC transfusions and at 24- and 48-hour intervals after transfusion were analyzed. Generalized estimating equation linear regression models were fit to examine hemoglobin increments after RBC transfusion adjusting for donor and recipient demographic characteristics, collection method, additive solution, gamma irradiation, and storage duration. We linked data on 23 194 transfusion recipients who received one or more single-unit RBC transfusions (n = 38 019 units) to donor demographic and component characteristics. Donor and recipient sex, Rh-D status, collection method, gamma irradiation, recipient age and body mass index, and pretransfusion hemoglobin levels were significant predictors of hemoglobin increments in univariate and multivariable analyses (P < .01). For hemoglobin increments 24 hours after transfusion, the coefficient of determination for the generalized estimating equation models was 0.25, with an estimated correlation between actual and predicted values of 0.5. Collectively, blood donor demographic characteristics, collection and processing methods, and recipient characteristics accounted for significant variation in hemoglobin increments related to RBC transfusion. Multivariable modeling allows the prediction of changes in hemoglobin using donor-, component-, and patient-level characteristics. Accounting for these factors will be critical for future analyses of donor and component factors, including genetic polymorphisms, on posttransfusion increments and other patient outcomes.

BackgroundHTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) is an incapacitating neuroinflammatory disorder for which no disease-modifying therapy is available, but corticosteroids provide some clinical benefit.ObjectiveTo investigate systemic cytokines and GlycA as possible biomarkers of immunopathogenesis and therapeutic response to corticosteroid pulse therapy in HAM/TSP.MethodsWe prospectively followed 110 People living with HTLV-1 (PLwHTLV-1, 67 asymptomatic individuals and 43 HAM/TSP patients), for a total of 906 person-years. Plasma cytokine levels (IL-2/4/6/10/17A, IFN-γ, TNF) and GlycA were quantified by Cytometric Bead Array and 1NMR, respectively. Cytokine signaling and prednisolone response were validated in an independent cohort by nCounter digital transcriptomics. We applied logistic regression and machine learning algorithms to predict disease progression and glucocorticoid response.ResultsIL-6 was positively correlated with age and GlycA in asymptomatics but not HAM/TSP patients. Systemic IFN-γ and IL-17A levels were increased in HAM/TSP patients, as compared to asymptomatics. All patients significantly decreased IL-17A levels post-treatment but only prednisolone-responders decreased IFN-γ levels post-treatment. Higher pre-treatment GlycA and TNF levels significantly predicted a negative therapeutic outcome, which was associated with higher post-treatment IFN-γ levels. Low IL-4 and IL-10 levels in incident HAM/TSP can be reverted to increased IL-10 and IL-4/IL-13 signaling by prednisolone in vitro.Conclusions1) An age-related increase in systemic IL-6/GlycA levels reveals inflammaging in PLwHTLV-1. 2) IFN-γ and IL-17A are biomarkers of untreated, active HAM/TSP disease, while pre-treatment GlycA and TNF predict therapeutic response to prednisolone pulse therapy. 3) Low IL-4/IL-10 and high IFN-γ signaling in incident HAM/TSP can be normalized by prednisolone.

Background Human T-Cell Lymphotropic Viruses (HTLV) type 1 and type 2 account for an estimated 5 to 10 million infections worldwide and are transmitted through breast feeding, sexual contacts and contaminated cellular blood components. HTLV-associated syndromes are considered as neglected diseases for which there are no vaccines or therapies available, making it particularly important to ensure the best possible diagnosis to enable proper counselling of infected persons and avoid secondary transmission. Although high quality antibody screening assays are available, currently available confirmatory tests are costly and have variable performance, with high rates of indeterminate and non-typable results reported in many regions of the world. The objective of this project was to develop and validate a new high-performance multiplex immunoassay for confirmation and discrimination of HTLV-1 and HTLV-2 strains. Methodology/Principal findings The multiplex platform was used first as a tool to identify suitable antigens and in a second step for assay development. With data generated on over 400 HTLV-positive blood donors sourced from USA and French blood banks, we developed and validated a high-precision interpretation algorithm. The Multi-HTLV assay demonstrated very high performance for confirmation and strain discrimination with 100% sensitivity, 98.1% specificity and 100% of typing accuracy in validation samples. The assay can be interpreted either visually or automatically with a colorimetric image reader and custom algorithm, providing highly reliable results. Conclusions/Significance The newly developed Multi-HTLV is very competitive with currently used confirmatory assays and reduces considerably the number of indeterminate results. The multiparametric nature of the assay opens new avenues to study specific serological signatures of each patient, follow the evolution of infection, and explore utility for HTLV disease prognosis. Improving HTLV diagnostic testing will be critical to reduce transmission and to improve monitoring of seropositive patients., Author summary HTLV viruses are responsible for more than 10 million cases of infection worldwide. The infection is considered as a neglected disease due to lack of vaccines and treatments. Accurate diagnosis is crucial for counselling infected persons and prevention of secondary transmissions. In spite of the development of excellent serological screening assays, many cases of indeterminate and untyped results are still regularly reported and their infection status remain uncertain. To address the need of more precise diagnosis, we have developed a new cutting-edge in-vitro diagnostic confirmation test, named Multi-HTLV, which has been validated on a large panel of HTLV samples. The test is a multiplex immunoassay allowing powerful detection of antibodies against HTLV through combination of a set of selective and validated virus-specific antigens in a blood sample. The Multi-HTLV assay increases the reliability of HTLV diagnostics and strain typing thanks to a high precision mathematical algorithm.

In 2015, the US Food and Drug Administration published revised guidance that recommended a change in blood donor deferral of men who have sex with men (MSM) from an indefinite to a 12-month deferral since the donor last had sex with a man. We assessed whether HIV incidence in first-time blood donors or associated transfusion risk increased. Donations in 4 major blood collection organizations were monitored for 15 months before and 2 years after implementation of the 12-month MSM deferral policy. HIV-positive donations were classified as recently acquired or long-term using a recent infection testing algorithm and incidence in both periods estimated. Residual transfusion transmission risk was estimated by multiplying incidence by the length of the infectious window period. The latter was estimated using a model based on infectious dose and the sensitivity of nucleic acid testing. Factors associated with incident infection in each period were assessed using Poisson regression. Overall HIV incidence in first-time donors before implementation of the 12-month MSM deferral was estimated at 2.62 cases per 100 000 person-years (105 PY) (95% credible interval [CI], 1.53-3.93 cases/105 PY), and after implementation at 2.85 cases/105 PY (95% CI, 1.96-3.93 cases/105 PY), with no statistically significant change. In male first-time donors, the incidence difference was 0.93 cases/105 PY (95% CI, −1.74-3.58 cases/105 PY). The residual risk of HIV transfusion transmission through components sourced from first-time donors was estimated at 0.32 transmissions per million (106) packed red blood cell transfusions (95% CI, 0.29-0.65 transmissions/106 transfusions) before and 0.35 transmissions/106 transfusions (95% CI, 0.31-0.65 transmissions/106 transfusions) after implementation. The difference was not statistically significant. Factors associated with incident infection were the same in each period. We observed no increase in HIV incidence or HIV transfusion transmission risk after implementation of a 12-month MSM deferral policy.

BACKGROUND Monitoring of transfusion-transmissible infections in the blood supply is essential for blood safety, as the donor population is not static, and changes in policy, donor behavior, or other factors could increase the risk of recipient infection. We assessed patterns of recently acquired HIV infection in US blood donors, including before and after the implementation of the 12-month deferral for men who have sex with men (MSM). STUDY DESIGN AND METHODS A large convenience sample of donations from donors testing HIV-1 nucleic acid testing (NAT) and serology-reactive were further tested with the Sedia HIV-1 Limiting Antigen enzyme immunoassay. Samples were analyzed across available demographic and donation data to provide an assessment of recently acquired HIV infection in US blood donors from 2010 to 2018. RESULTS Overall, 317 of 1154 (27.5%; 95% confidence interval, 24.9%-30.1%) donations from HIV NAT and serology-reactive donors had recently acquired HIV infection. There was no evidence of change in the percentages of recent HIV infection by year over the study period, either in all donors or in male donors, including after the MSM policy change. In multivariable logistic regression analysis, donors aged 24 years or younger were over 2.7 times more likely and repeat donors 2.2 times more likely to have recently acquired HIV infection compared to donors aged 55 years or older and first-time donors, respectively. CONCLUSION Patterns of recently acquired HIV infection varied by demographics but not over time. These findings suggest no impact of the MSM policy change on recently acquired HIV infection in US blood donors.

PURPOSE: Outpatients with hematologic disease often receive red cell transfusion to treat anemia and fatigue. The effect of transfusion on fatigue-related quality of life and how well this effect is sustained has not been quantified. The study aim was to describe the early and sustained impact over four weeks of red cells on patient-reported fatigue in outpatients age ≥ 50 receiving transfusion as routine clinical care. METHODS: FACIT-Fatigue scale scores were measured pre-transfusion and at visits targeting 3, 7, and 28 days post-transfusion. Group-based trajectory modeling of patient fatigue scores by study day was used to identify the number of distinct trajectories (Groups), then longitudinal mixed-effects modeling of fatigue scores was used to estimate group-specific mean improvements early after transfusion and between days 3 and 28 post-transfusion. RESULTS: Four distinct fatigue score trajectory groups were identified and were found to be correlated with baseline fatigue scores (means 12, 26, 34, and 47 points). In the three groups with the lowest fatigue trajectories (indicating greater fatigue), improvements in fatigue early after transfusion achieved the established minimum clinically important difference (≥ 3 points, Group p=0.0039). In all trajectory groups, mean fatigue levels did not change significantly between 3 and 28 days (± 1 point, Group p=0.60). CONCLUSION: Patient-reported fatigue varies widely among older adult outpatients with hematologic disorders. Nonetheless, trajectory modeling suggests that most anemic patients can expect a noticeable improvement in fatigue in the first few days after transfusion that generally is sustained up to four weeks.

Introduction: T-cell large granular lymphocyte (T-LGL) leukemia is a rare lymphoproliferative disorder with recurrent somatic STAT3 mutations. It has been suggested that viral antigens act as the initial stimuli resulting in clonal expansion of CD8+ cells in the disease. However, less is known whether chronic exposure to viral antigens is associated with acquisition of somatic mutations in CD8+ T cells among individuals without clinically detectable lymphoproliferations. Human T-cell leukemia virus type 2 (HTLV-2) antibody positivity has been detected in patients with T-LGL leukemia. Here, we examined whether CD8+ T cells from HTLV-2 positive healthy blood donors harbor somatic mutations in STAT3 or other immune-associated genes, potentially identifying individuals at risk of subsequent lymphoproliferative diseases. Methods: We analyzed HTLV-2 infected (n=30) and uninfected (n=35) healthy blood donor samples obtained from University of California San Francisco and Vitalant Research Institute, which were enrolled in the United States-based HTLV Outcomes Study (HOST) cohort. All cases had serologic evaluation for HTLV-2 infection at the time of sampling. We examined somatic mutations of STAT3 in CD4+ and CD8+ T-cell populations using ultra-deep targeted amplicon sequencing. In addition, we applied a custom sequencing panel covering the coding regions of 2,533 immune-related genes to characterize a larger spectrum of somatic mutations in CD8+ T cells. Results: Somatic STAT3 mutations were detected in CD8+ but not in CD4+ T cells of four (13.3%, 4/30) HTLV-2 positive healthy blood donors (p.Y640F, p.N647I, p.D661Y, and p.Y657_K658insY with variant allele frequencies of 11.9%, 0.5%, 4.9%, and 1.2%, respectively) using amplicon sequencing. The detected STAT3 mutations have been previously described and reported in T-LGL leukemia. Total white blood cell and lymphocyte counts were similar between STAT3 mutated and non-mutated cases. No STAT3 mutations were discovered in HTLV-2 negative donors with amplicon sequencing. Of the 28 HTLV-2 positive cases, 19 had at least one somatic variant in CD8+ T cells based on the immunogene panel sequencing (n=28). 8 cases had variants in genes previously identified in T-LGLL (STAT3, KMT2D, TYRO3, DIDO1, BCL11B, CACNB2, KRAS, LRBA and FANCA), and 5 cases had variants in genes involved in JAK-STAT signaling (NFKBIA, PIK3R5, MAPK14, EP300, MPL, IFNAR1, IL6ST and IL20RA). Three recurrently mutated genes were detected: VWF, SMAD7 and MXRA5. The four HTLV-2 positive blood donors harboring STAT3 mutations had more somatic mutations (median=6) than HTLV-2 positive donors without STAT3 mutations (median=1, p=0.06). Conclusion: We report the presence of somatic gain-of-function STAT3 mutations in CD8+ T cells of 13% of HTLV-2 positive healthy blood donors. We identified additional somatic mutations in genes associated with JAK-STAT signaling, immune regulation and lymphoproliferation in CD8+ T cells of HTLV-2 positive cases. While STAT3 activation, with or without mutations, is considered as a hallmark of T-LGLL, our results reveal the presence of STAT3 mutations in CD8+ T cells of healthy blood donors harboring HTLV-2 without clinical history of lymphoproliferative disease. Additional research is warranted to elucidate whether HTLV-2 carriers harboring STAT3 and other mutations are at increased risk of subsequent T-LGL leukemia or other lymphoproliferative diseases. Disclosures Mustjoki: Pfizer: Research Funding; BMS: Research Funding; Novartis: Research Funding; Janpix: Research Funding.

BACKGROUND Blood transfusion is one of the most common medical procedures during hospitalization in the United States. To understand the benefits of transfusion while mitigating potential risks, a multicenter database containing detailed information on transfusion incidence and recipient outcomes would facilitate research. STUDY DESIGN AND METHODS The Recipient Epidemiology and Donor Evaluation Study-III (REDS-III) program has developed a comprehensive transfusion recipient database utilizing data from hospital electronic health records at 12 participating hospitals in four geographic regions. Inpatient and outpatient data on transfusion recipients from January 1, 2013 to December 31, 2014 included patient age, sex, ethnicity, primary diagnosis, type of blood product provided, issue location, pretransfusion and post-transfusion hemoglobin (Hgb), and hospital outcomes. Transfusion incidence per encounter was calculated by blood product and various patient characteristics. RESULTS During the 2-year study period, 80,362 (12.5%) inpatient encounters involved transfusion. Among inpatients, the most commonly transfused blood products were red blood cells (RBCs; 10.9% of encounters), followed by platelets (3.2%) and plasma (2.9%). Among patients who received transfusions, the median number of RBC units was one, the pretransfusion Hgb level was 7.6 g/dL, and the Hgb increment per unit was 1.4 g/dL. Encounter mortality increased with patient age, the number of units transfused, and the use of platelet or plasma products. The most commonly reported transfusion reaction was febrile nonhemolytic. CONCLUSION The database contains comprehensive data regarding transfusion use and patient outcomes. The current report describes an evaluation of the first 2 years of a planned, 4-year, linked blood donor-component-recipient database, which represents a critical new resource for transfusion medicine researchers.

Importance Evidence regarding associations of blood donor sex with mortality among red blood cell transfusion recipients is conflicting. Objective To study associations of donor sex and prior pregnancy with mortality of transfusion recipients. Design, Setting, and Participants Data from 3 retrospective cohorts of transfusion recipients (the Kaiser Permanente Northern California [KPNC] and Recipient Epidemiology and Donor Evaluation Study-III [REDS-III] databases of data from January 2013 to December 2016 and the Scandinavian Donations and Transfusions [SCANDAT] database with data from January 2003 to December 2012) were analyzed. Final dates of follow-up were December 31, 2016, for the KPNC and REDS-III cohorts and December 31, 2012, for the SCANDAT cohort. Stratified Cox regression models were used to estimate associations between donor exposure groups with risk of mortality, adjusting for the number of red blood cell unit transfusions. Exposures The number of transfused red blood cell units from female donors, previously pregnant donors, and sex-discordant donors (male donor and female recipient or female donor and male recipient). Main Outcomes and Measures In-hospital mortality. Results The study population included 34 662 patients (mean age, 69 years; 18 652 [54%] women) from the KPNC cohort, 93 724 patients (mean age, 61 years; 48 348 [52%] women) from the REDS-III cohort, and 918 996 patients (mean age, 72 years; 522 239 [57%] women) from the SCANDAT cohort. The median number of red blood cell transfusions per patient was 3 in the KPNC cohort, 2 in the REDS-III cohort, and 3 in the SCANDAT cohort. The percentage of transfusions from previously pregnant or parous donors was 9% in the KPNC cohort, 18% in the REDS-III cohort, and 25% in the SCANDAT cohort. The percentage of transfusions in the 3 cohorts from female donors ranged from 39% to 43%, from previously pregnant or parous donors ranged from 9% to 25%, and from sex-discordant donors ranged from 44% to 50%. There were 3217 in-hospital deaths in the KPNC cohort, 8519 in the REDS-III cohort, and 198 537 in the SCANDAT cohort. There were no statistically significant associations between any of the 3 donor exposures and in-hospital mortality in the 3 cohorts. Hazard ratios for in-hospital mortality per transfused unit from female donors were 0.99 (95% CI, 0.96-1.03) for the KPNC cohort, 1.00 (95% CI, 0.99-1.01) for the REDS-III cohort, and 1.00 (95% CI, 0.99-1.00) for the SCANDAT cohort. For units from previously pregnant or parous female donors, hazard ratios were 1.00 (95% CI, 1.00-1.01) for the KPNC cohort, 1.01 (95% CI, 0.98-1.03) for the REDS-III cohort, and 1.00 (95% CI, 1.00-1.01) for the SCANDAT cohort. For units from sex-discordant transfusions, hazard ratios were 1.02 (95% CI, 0.99-1.05) for the KPNC cohort, 0.99 (95% CI, 0.98-1.00) for the REDS-III cohort, and 1.00 (95% CI, 0.99-1.00) for the SCANDAT cohort. Conclusions and Relevance Among red blood cell transfusion recipients, transfusions from female, previously pregnant, or sex-discordant donors were not significantly associated with increased mortality.

The influence of living in small remote villages on the diversity of viruses in the nasal mucosa was investigated in three Colombian villages with very different levels of geographic isolation. Metagenomic analysis was used to characterize viral nucleic acids in nasal swabs from 63 apparently healthy young children. Sequences from human virus members of the families Anelloviridae, Papillomaviridae, Picornaviridae, Herpesviridae, Polyomaviridae, Adenoviridae, and Paramyxoviridae were detected in decreasing proportions of children. The number of papillomavirus infections detected was greater among Hispanic children most exposed to outside contacts, while anellovirus infections were more common in the isolated indigenous villages. The diversity of the other human viruses detected did not differ among the villages. Closely related variants of rhinovirus A or B were identified in 2 to 4 children from each village, reflecting ongoing transmission clusters. Genomes of viruses not currently known to infect humans, including members of the families Parvoviridae, Partitiviridae, Dicistroviridae, and Iflaviridae and circular Rep-encoding single-stranded DNA (CRESS-DNA) virus, were also detected in nasal swabs, possibly reflecting environmental contamination from insect, fungal, or unknown sources. Despite the high levels of geographic and cultural isolation, the overall diversity of human viruses in the nasal passages of children was not reduced in highly isolated indigenous villages, indicating ongoing exposure to globally circulating viruses. IMPORTANCE Extreme geographic and cultural isolation can still be found in some indigenous South American villages. Such isolation may be expected to limit the introduction of otherwise common and widely distributed viruses. Very small population sizes may also result in rapid local viral extinction due to a lack of seronegative subjects to maintain transmission chains for rapidly cleared viruses. We compared the viruses in the nasal passages of young children in three villages with increasing levels of geographic isolation. We found that isolation did not reduce the overall diversity of viral infections. Multiple infections with nearly identical rhinoviruses could be detected within each village, likely reflecting recent viral introductions and transmission clusters among epidemiologically linked members of these very small communities. We conclude that, despite their geographic isolation, remote indigenous villages show evidence of ongoing exposure to globally circulating viruses.

Background Patients with cancer or other diagnoses associated with chronic anemia often receive red blood cell (RBC) transfusion as outpatients, but the effect of transfusion on functional status is not well demonstrated. Study design and methods To estimate the effect of transfusion on functional status and quality of life, we measured 6-minute walk test distance and fatigue- and dyspnea-related quality-of-life scores before and 1 week after RBC transfusion in 208 outpatients age ≥50 with at least one benign or malignant hematology/oncology diagnosis. To account for potential confounding effects of cancer treatment, patients were classified into two groups based on cancer treatment within 4 weeks of the study transfusion. Minimum clinically important improvements over baseline were 20 meters in walk test distance, 3 points in fatigue score, and 2 points in dyspnea score. Results The median improvement in unadjusted walk test distance was 20 meters overall and 30 meters in patients not receiving recent cancer treatment. Fatigue scores improved overall by a median of 3 points and by 4 points in patients without cancer treatment. There was no clinically important change in dyspnea scores. In multiple linear regression analysis, patients who maintained hemoglobin (Hb) levels of 8 g/dL or greater at 1 week posttransfusion, who had not received recent cancer treatment, and who did not require hospitalization during the study showed clinically important increases in mean walk test distance. Conclusions Red blood cell transfusion is associated with a modest, but clinically important improvement in walk test distance and fatigue score outcomes in adult hematology/oncology outpatients.

BACKGROUND There has been increased worldwide emphasis on the many benefits of human immunodeficiency virus (HIV) serostatus awareness for both infection prevention and improved treatment outcomes. Previous studies indicate that donors may use blood donation to be tested; the objectives of this analysis were to assess, among donors with previously undisclosed risk behavior in the 12 months before donation, the frequency of those who have previously been tested for HIV and the demographic and behavioral factors associated with such testing. STUDY DESIGN AND METHODS In this secondary analysis from an HIV case-control study of blood donors in Brazil, we analyzed the response to the question, “Other than blood donation, have you ever been tested for HIV?” Demographic and disclosed risk behaviors associated with previous testing were determined. RESULTS The study included 341 HIV-positive cases and 791 HIV-negative controls (1:2 case/control ratio). Overall, 31% of blood donors (40% of cases and 26% of controls) reported having been tested for HIV outside of blood donation. History of HIV testing varied according to sex, HIV status, and reported sexual risk behavior. CONCLUSION Although it is encouraging that previous testing was more frequent in donors with acknowledged sexual risk behavior in Brazil, 60% still had not been tested for HIV outside of the blood donation setting. Educating donors on the importance of not using blood centers as a means to get tested for HIV in Brazil, especially if they engage in higher risk behaviors, and seeking alternate testing venues instead could improve the safety of donated blood.

BACKGROUND Babesia microti is the foremost infectious risk to the US blood supply for which a Food and Drug Administration (FDA)-licensed test is unavailable for donation screening. Characterization of the antibody response to B. microti and correlation with parasitemia is necessary to guide screening and donor management policies. STUDY DESIGN AND METHODS During an FDA licensure trial, blood donors were prospectively screened (July-November 2013) using a B. microti-specific antibody enzyme immunoassay (EIA, Immunetics) in highly endemic (New York [NY]; n = 13,688), moderately endemic (Minnesota [MN]; n = 4583), and nonendemic (New Mexico [NM]; n = 8451) regions. Blood donors with repeat-reactive (RR) results participated in a 12-month prospective cohort study using B. microti EIA, immunofluorescent assay, polymerase chain reaction (PCR), blood smear, and clinical questionnaire. RESULTS Thirty-seven (61.67%; 24 NY, seven MN, six NM) of 60 eligible RR donors enrolled in the study; 20 of 37 (54%) completed the 12-month follow-up visit of which 15 (75%) were still seroreactive. Nine PCR-positive donors were identified during index screening; five participated in the follow-up study, three were PCR positive at 6 months, and two remained positive at final follow-up (378 and 404 days). Most RR donors displayed low-level seroreactivity that was either stable or waning during follow-up. The level and pattern of reactivity correlated poorly with PCR positivity. CONCLUSION The findings indicate prolonged seropositivity in blood donors. Although rare, asymptomatic, persistent PCR positivity supports the current policy of indefinite deferral for donors with a history of babesiosis or positive test results. Repeat testing by PCR and serology will be necessary if reinstatement is to be considered.

BACKGROUND In current blood banking practices, platelets (PLTs) are stored in plasma at 22°C, with gentle agitation for up to 5 days. To date, the effects of storage and donor variability on PLT regulation of vascular integrity are not known. STUDY DESIGN AND METHODS In this study, we examined the donor variability of leukoreduced fresh (Day 1) or stored (Day 5) PLTs on vascular endothelial barrier function in vitro and in vivo. In vitro, PLT effects on endothelial cell (EC) monolayer permeability were assessed by analyzing transendothelial electrical resistances (TEER). PLT aggregation, a measure of hemostatic potential, was analyzed by impedance aggregometry. In vivo, PLTs were investigated in a vascular endothelial growth factor A (VEGF-A)-induced vascular permeability model in NSG mice, and PLT circulation was measured by flow cytometry. RESULTS Treatment of endothelial monolayers with fresh Day 1 PLTs resulted in an increase in EC barrier resistance and decreased permeability in a dose-dependent manner. Subsequent treatment of EC monolayers with Day 5 PLTs demonstrated diminished vasculoprotective effects. Donor variability was noted in all measures of PLT function. Day 1 PLT donors were more variable in their effects on TEER than Day 5 PLTs. In mice, while all PLTs regardless of storage time demonstrated significant protection against VEGF-A–induced vascular leakage, Day 5 PLTs exhibited reduced protection when compared to Day 1 PLTs. Day 1 PLTs demonstrated significant donor variability against VEGF-A–challenged vascular leakage in vivo. Systemic circulating levels of Day 1 PLTs were higher than those of Day 5 PLTs CONCLUSIONS In vitro and in vivo, Day 1 PLTs are protective in measures of vascular endothelial permeability. Donor variability is most prominent in Day 1 PLTs. A decrease in the protective effects is found with storage of the PLT units between Day 1 and Day 5 at 22°C, thereby suggesting that Day 5 PLTs are diminished in their ability to attenuate vascular endothelial permeability.

Background Although a majority of the studies conducted to date on platelet (PLT) storage have been focused on PLT hemostatic function, the effects of 4°C PLTs on regulation of endothelial barrier permeability are still not known. In this study, we compared the effects of room temperature (22°C) stored and (4°C) stored PLTs on the regulation of vascular endothelial cell (EC) permeability in vitro and in vivo. Study design and methods Day 1, Day 5, and Day 7 leukoreduced apheresis PLTs stored at 4 or 22°C were studied in vitro and in vivo. In vitro, PLT effects on EC permeability and barrier function, adhesion, and impedance aggregometry were investigated. In vivo, using a mouse model of vascular leak, attenuation of vascular leak and circulating PLT numbers were measured. Results Treatment of EC monolayers with Day 5 or Day 7 PLTs, stored at both 22°C and 4°C, resulted in similar decreases in EC permeability on average. However, analysis of individual samples revealed significant variation that was donor dependent. Additional in vitro measurements revealed a decrease in inflammatory mediators, nonspecific PLT-endothelial aggregation and attenuated loss of aggregation over time to TRAP, ASPI, ADP, and collagen with 4°C storage. In mice, while 22°C and 4°C PLTs both demonstrated significant protection against vascular endothelial growth factor A (VEGF-A)-induced vascular leak 22°C PLTs exhibited increased protection compared to 4°C PLTs. Systemic circulating levels of 4°C PLTs were decreased compared to 22°C PLTs. Conclusions In vitro, 4°C-stored PLTs exhibit a greater capacity to inhibit EC permeability than 22°C-stored PLTs. In vivo, 22°C PLTs provide superior control of vascular leak induced by VEGF-A. This discrepancy may be due to increased clearance of 4°C PLTs from the systemic circulation.

Background Patients with cancer or chronic hematologic disorders frequently receive red blood cell (RBC) transfusions. Based on long-standing assumptions, each RBC unit is thought to increase recipient hemoglobin by 1 g/dL, but smaller increments can occur. A better understanding of recipient factors affecting hemoglobin increments could help providers manage these patients. Methods Data were collected as a part of the observational Red Cells in Outpatients Transfusion Outcomes (RETRO) study of outpatients with hematologic or cancer-related diagnoses. Hemoglobin was measured before transfusion and 30 minutes after transfusion. A classification and regression tree (CART) analysis was performed to identify statistically significant associations with clinical variables. A corresponding prediction equation was developed and validated using linear regression. Results A total of 195 participants had both pre- and posttransfusion hemoglobin values for analysis. The median age was 66 years, and patients received one (73%) or two (27%) RBC units during the transfusion episode. The overall median change in hemoglobin was 0.6 g/dL per RBC unit. Both CART analysis and linear regression identified the following significant predictors of hemoglobin increment: number of units received (positive correlation), patient estimated circulating blood volume (negative correlation), pretransfusion hemoglobin (negative correlation), and patient age (negative correlation). Conclusion In this study of outpatients with hematologic disease, most patients had a hemoglobin increment of less than 1 g/dL/unit. Recipient-specific factors influenced the hemoglobin increment at 30 minutes, and providers should consider circulating blood volume, pretransfusion hemoglobin, and recipient age, when developing patient-specific RBC transfusion plans for this unique cohort.

An estimated 2.4 million volunteer apheresis blood donation procedures were performed in the United States in 2010, and increases in the proportion of transfused blood products derived from apheresis blood collections have been consistently reported. Anticoagulation is required during apheresis and is achieved with citrate. Donor exposure to citrate causes an acute physiological response to maintain serum mineral homeostasis. Some data are available on the sequelae of this acute response in the days and weeks following exposure, raising questions about bone mineral density in regular apheresis donors. New research is emerging that addresses the potential long-term health outcomes of repeated citrate exposure. This article reviews the acute physiological response to citrate anticoagulation in volunteer blood donors, presents contrasting perspectives on the potential effects of citrate exposure on bone density, and identifies key knowledge gaps in our understanding of long-term health outcomes in apheresis donors. J. Clin. Apheresis 31:459-463, 2016. © 2015 Wiley Periodicals, Inc.

Background Abnormally high levels of T-cell activation can persist in HIV-infected subjects despite effective anti-retroviral therapy (ART) and has been associated with negative health outcomes. The nature of the antigenic drivers or other causes of this residual T-cell activation remain uncertain. Anelloviruses are universally acquired soon after birth, resulting in persistent viremia, and considered part of the commensal human virome. Reduced immunocompetence results in increased anellovirus levels. Objectives To test whether increased levels of anelloviruses or other viruses in plasma are associated with higher levels of persistent T-cell activation during ART. Study design Two amplification methods combined with next generation sequencing were used to detect all viruses and estimate relative anellovirus levels in plasma from 19 adults on effective ART who exhibited a wide range of T-cell activation levels. Results Nucleic acids from HBV and HCV were detected in one patient each while pegivirus A (GBV-C) was found in three patients. Anellovirus DNA was detected in all patients with some individuals carrying up to eight different genotypes. Specific anellovirus genotypes or higher level of co-infections were not detected in subjects with higher levels of T-cell activation. No association was detected between relative plasma anellovirus DNA levels and the percentage of activated CD4 or CD8 T cells. Conclusions Human anelloviruses were detected in all HIV suppressed subjects, exhibited a wide range of viremia levels, and were genetically highly diverse. The level of persistent T-cell activation was not correlated with the level of viremia or genotypes present indicating that anellovirus antigens are unlikely to be a dominant source of antigens driving chronic T-cell activation.

BACKGROUND False-positive infectious transfusion screening results remain a challenge with continued loss of both donors and blood products. We sought to identify associations between donor demographic characteristics (age, race, sex, education, first-time donor status) and testing false positive for viruses during routine blood donation screening. In addition the study assessed the prevalence of high-risk behaviors in false-positive donors. STUDY DESIGN AND METHODS Blood Systems, Inc. donors with allogeneic donations between January 1, 2011, and December 31, 2012, were compared in a case-control study. Those with a false-positive donation for one of four viruses (human immunodeficiency virus [HIV], human T-lymphotropic virus [HTLV], hepatitis B virus [HBV], and hepatitis C virus [HCV]) were included as cases. Those with negative test results were controls. For a subset of cases, infectious risk factors were evaluated. RESULTS Black race and Hispanic ethnicity were associated with HCV and HTLV false-positive results. Male sex and lower education were associated with HCV false positivity, and age 25 to 44 was associated with HTLV false positivity. First-time donors were more likely to be HCV false positive although less likely to be HBV and HTLV false positive. No significant associations between donor demographics and HIV false positivity were observed. A questionnaire for false-positive donors showed low levels of high-risk behaviors. CONCLUSION Demographic associations with HCV and HTLV false-positive results overlap with those of true infection. While true infection is unlikely given current testing algorithms and risk factor evaluation, the findings suggest nonrandom association. Further investigation into biologic mechanisms is warranted.

BACKGROUND The relative contribution of serologic screening and nucleic acid testing (NAT) to prevent hepatitis C virus (HCV) transmission has not been rigorously addressed. STUDY DESIGN AND METHODS Twenty-one blood organizations in seven geographical regions performing individual-donation (ID)-NAT in parallel with anti-HCV screening provided data from 10,897,105 donations to establish HCV infection rates in first-time, lapsed, and repeat donations. Screening efficacy was modeled for: anti-HCV alone, HCV antigen/antibody (combo), minipool (MP)-NAT in pools of 8 and 16 with anti-HCV, ID-NAT and anti-HCV, and ID-NAT alone. Probabilities of infectivity for red blood cell transfusions were estimated as 100% from window period (WP) and concordant HCV RNA/antibody-positive (concordantly positive [CP]) donations and 0.028% from anti-HCV-positive and RNA-negative probable resolved (PR) donations. RESULTS There were 5146 confirmed infections (30 WP, 3827 CP, and 1289 PR). Infection rates and transmission risks varied substantially across regions and by donation status. Residual risk with ID-NAT and serology screening was estimated at one in 250,000 in Egypt and at one in 10,000,000 in other regions combined; risk would increase to one in 7300 and one in 312,000, respectively, if NAT had not been performed. ID-NAT with or without anti-HCV testing showed higher efficacy than either MP-NAT or combo assays, particularly in lapsed or repeat donors in whom 99.2, 98.5, and 93.2% of infectious donations were estimated to be interdicted by these respective testing strategies. CONCLUSIONS The incremental efficacy of anti-HCV testing when ID- NAT screening is performed was minimal, particularly for screening lapsed and repeat donations.

Blood transfusion is one of the most common medical procedures during hospitalization in the United States. To understand the benefits of transfusion while mitigating potential risks, a multicenter database containing detailed information on transfusion incidence and recipient outcomes would facilitate research.The Recipient Epidemiology and Donor Evaluation Study-III (REDS-III) program has developed a comprehensive transfusion recipient database utilizing data from hospital electronic health records at 12 participating hospitals in four geographic regions. Inpatient and outpatient data on transfusion recipients from January 1, 2013 to December 31, 2014 included patient age, sex, ethnicity, primary diagnosis, type of blood product provided, issue location, pretransfusion and post-transfusion hemoglobin (Hgb), and hospital outcomes. Transfusion incidence per encounter was calculated by blood product and various patient characteristics.During the 2-year study period, 80,362 (12.5%) inpatient encounters involved transfusion. Among inpatients, the most commonly transfused blood products were red blood cells (RBCs; 10.9% of encounters), followed by platelets (3.2%) and plasma (2.9%). Among patients who received transfusions, the median number of RBC units was one, the pretransfusion Hgb level was 7.6 g/dL, and the Hgb increment per unit was 1.4 g/dL. Encounter mortality increased with patient age, the number of units transfused, and the use of platelet or plasma products. The most commonly reported transfusion reaction was febrile nonhemolytic.The database contains comprehensive data regarding transfusion use and patient outcomes. The current report describes an evaluation of the first 2 years of a planned, 4-year, linked blood donor-component-recipient database, which represents a critical new resource for transfusion medicine researchers.

Objectives: To gather benchmarking data on blood utilization so as to inform blood management strategies at regional hospitals. Methods: We conducted a cross-sectional pilot study of 40 regional hospitals in Northern California using a paper-based survey designed to capture blood component utilization and transfusion management practices. The data were analyzed based on size and complexity of the respondent hospitals. Results: Twenty-seven (68%) of 40 hospitals responded, ranging in size from 23- to 600-bed facilities. Results showed a wide range of transfusions for each component. All hospitals reported some level of blood utilization oversight in place. Overall, 88.5% had a computerized laboratory information system, of which 17% performed an electronic cross-match. Transfusion triggers for RBCs, platelets, plasma, and cryoprecipitate were in use in 61.5%, 65.4%, 57.7%, and 46.2% of hospitals, respectively. Conclusions: There is awareness of the need for transfusion oversight. However, the findings show a wide spectrum of transfusion practice, and high-yield measures, such as electronic cross-match and transfusion triggers, have not been uniformly implemented. The results indicate that there is a role for blood centers to assist client hospitals to maximize their efficiency and reduce blood utilization.

Background Donation eligibility is based on hemoglobin (Hb) level among other factors. This study assesses factors that influence Hb levels among first-time (FT) donors returning for a second donation. Study Design and Methods Allogeneic FT donors who successfully donated a red blood cell (RBC)-containing donation on their index presentation and returned to donate at least once more between August 1, 2009, and July 31, 2012, were included. Interdonation intervals and delta Hb (subsequent donation – index donation value) were calculated. Multivariable logistic regression and survival analysis methods were used to determine factors associated with 1) Hb recovery to preindex donation value or 2) deferral at the second presentation. Results During the study, 135,040 FT donors returned to donate. Overall, 44% of donors returned with a Hb level at or above their index value (defined as recovery for this study), 48.1% for males and 39.9% for females. Logistic regression revealed that the factor most strongly associated with Hb recovery was index Hb, with lower Hb having much higher odds of recovery. Shorter interdonation intervals were associated with decreased likelihood of recovery. Certain demographic characteristics were also associated with higher odds of recovery. Factors associated with deferral were similar to the factors associated with recovery, except for donor sex. Conclusions As early as the second blood donation, allogeneic donors can be differentiated into two subpopulations: those who recover to index Hb levels and those who do not. Current data routinely collected by US blood centers cannot reliably distinguish between the two groups.

BACKGROUND: Reducing risk of HIV window period transmission requires understanding of donor knowledge and attitudes related to HIV and risk factors. STUDY DESIGN AND METHODS: We conducted a survey of 7635 presenting blood donors at three Brazilian blood centres from 15 October through 20 November 2009. Participants completed a questionnaire on HIV knowledge and attitudes about blood donation. Six questions about blood testing and HIV were evaluated using maximum likelihood chi-square and logistic regression. Test seeking was classified in non-overlapping categories according to answers to one direct and two indirect questions. RESULTS: Overall respondents were male (64%) repeat donors (67%) between 18 and 49 years old (91%). Nearly 60% believed blood centres use better HIV tests than other places; however 42% were unaware of the HIV window period. Approximately 50% believed it was appropriate to donate to be tested for HIV but 67% said it was not acceptable to donate with risk factors even if blood is tested. Logistic regression found that less education Hemope-Recife blood centre replacement potential and self-disclosed test-seeking were associated with less HIV knowledge. CONCLUSION: HIV knowledge related to blood safety remains low among Brazilian blood donors. A subset finds it appropriate to be tested at blood centres and may be unaware of the HIV window period. These donations may impose a significant risk to the safety of the blood supply. Decreasing test-seeking and changing beliefs about the appropriateness of individuals with behavioural risk factors donating blood could reduce the risk of transfusing an infectious unit. (c) 2013 International Society of Blood Transfusion.

Background Twenty-one blood organizations from five geographical regions provided HIV individual donation (ID)-NAT and serology data on 11,787,610 donations. Infections were classified as anti-HIV-/RNA+ window period (WP), anti-HIV+/RNA+ concordant positive (CP) or anti-HIV+/RNA- elite controller (EC). Residual risk and efficacy of several screening scenarios were estimated for first time, lapsed and repeat donations. Methods WP residual risk estimates assumed a 50% infectious dose of 3.16 virions and a 50% detection limit of 2.7 HIV RNA copies/mL for ID-NAT and 10,000 copies/mL for p24Ag. Infectivity for CP (100%) and EC (2.2%) donations was estimated based on viral load distributions and 100-fold reduced infectivity by antibody neutralization as reported elsewhere. Efficacy was calculated as proportion of transmission risk removed from baseline (i.e. in absence of any screening). Results There was no significant difference in transmission risk between lapsed and repeat donations in any region. Risk was 3.8-fold higher in first time than combined lapsed/repeat donations in South Africa but not in other regions. Screening strategies were most efficacious at interdicting infectious transfusions in first time (98.7-99.8%) followed by lapsed (97.6-99.7%) and repeat (86.8-97.7%) donations in all regions combined. In each donor category the efficacy of ID-NAT alone (97.7-99.8%) was superior to that of minipool (MP)-NAT/anti-HIV (95.0-99.6%) and p24 Ag/anti-HIV (89.8-99.1%). Conclusions Efficacy patterns were similar by donor/donation status in each region despite large differences in HIV prevalence and transmission risk. As similar data become available for HBV and HCV, this modeling may be useful in cost effectiveness analyses of alternative testing scenarios.

Despite improvements in blood safety making transfusion a much safer clinical procedure, the general public still perceives it as risky. We systematically reviewed available literature to examine evidence regarding the reasons and causes behind this perception. Electronic databases including PubMed, Cochrane Library, and EMBASE for literature dating back to the 1980s were searched. Eligible studies collected information on blood recipients' demographics, measures of risk domains (sets of values that risks encompass), and general knowledge of blood transfusion in terms of risks and benefits. Each study was assessed for quality of data, research method, and relevant findings. A scoring system was used to subjectively rate the overall quality of each study. Each study was reviewed for its method of data collection and information abstracted on hazards and conceptual dimensions used to measure risk. Risk perception between blood transfusion and other hazards including alternatives to transfusion were compared. Fifteen studies met the inclusion criteria, all of which were conducted outside the United States, with most of the studies published more than 10 years ago and conducted by only 3 research groups. Five studies were rated as being very good, four good, five fair, and one of poor quality. The finding of the studies consistently show that objective or raw knowledge is not correlated with risk perception, but subjective or calibrated knowledge is. Thus, it is what people think they know rather than what they actually do know that influences risk perception of transfusion. Of the 3 common conceptual domains-dread, unknown risk, and benefits-blood transfusion was found to be of intermediate dread, intermediate unknown risk, and most beneficial compared with other hazards. Donated blood was found to have lower perceived risk than all other alternatives to transfusion, except for use of autologous blood. There is a lack of recent studies on allogeneic transfusion. However, the more recent studies show that perceived high risk is still prevalent in the general public. The available risk perception studies suggest that although blood transfusion is safe, elevated risk perception of infections persists. Studies of the US population are needed to better understand the influence of both psychological and scientific factors.

Although a majority of the studies conducted to date on platelet (PLT) storage have been focused on PLT hemostatic function, the effects of 4°C PLTs on regulation of endothelial barrier permeability are still not known. In this study, we compared the effects of room temperature (22°C) stored and (4°C) stored PLTs on the regulation of vascular endothelial cell (EC) permeability in vitro and in vivo.Day 1, Day 5, and Day 7 leukoreduced apheresis PLTs stored at 4 or 22°C were studied in vitro and in vivo. In vitro, PLT effects on EC permeability and barrier function, adhesion, and impedance aggregometry were investigated. In vivo, using a mouse model of vascular leak, attenuation of vascular leak and circulating PLT numbers were measured.Treatment of EC monolayers with Day 5 or Day 7 PLTs, stored at both 22°C and 4°C, resulted in similar decreases in EC permeability on average. However, analysis of individual samples revealed significant variation that was donor dependent. Additional in vitro measurements revealed a decrease in inflammatory mediators, nonspecific PLT-endothelial aggregation and attenuated loss of aggregation over time to TRAP, ASPI, ADP, and collagen with 4°C storage. In mice, while 22°C and 4°C PLTs both demonstrated significant protection against vascular endothelial growth factor A (VEGF-A)-induced vascular leak 22°C PLTs exhibited increased protection compared to 4°C PLTs. Systemic circulating levels of 4°C PLTs were decreased compared to 22°C PLTs.In vitro, 4°C-stored PLTs exhibit a greater capacity to inhibit EC permeability than 22°C-stored PLTs. In vivo, 22°C PLTs provide superior control of vascular leak induced by VEGF-A. This discrepancy may be due to increased clearance of 4°C PLTs from the systemic circulation.

Human T-cell lymphotropic virus types 1 and 2 (HTLV-1 and HTLV-2) and the more recently recognized HTLV-3 and HTLV-4 are human retroviruses of the genus Deltaretrovirus originally derived from closely related simian viruses. Proviral DNA is integrated in the host genome and propagated by lymphocytic division with only a minimal production of infectious virus. A small viral genome encodes several structural and regulatory proteins that in concert with the host cellular immune response control the burden of infection, as measured by the proportion of lymphocytes harboring HTLV proviral DNA. Most chronically infected humans are asymptomatic, but 2% to 4% of HTLV-1 carriers develop a mature T-cell malignancy called adult T-cell lymphoma (ATL). HTLV-2 infection does not cause malignant disease. Another 1% to 2% of HTLV-1 and HTLV-2 carriers develop a spinal cord disease known as HTLV- associated myelopathy (HAM) characterized by a progressive weakness and spasticity of the lower extremities as well as a hyperactive bladder. Various inflammatory conditions have been associated with infection, and long-term mortality may be increased. HTLV-1 and HTLV-2 are transmitted from mother to child via breast-feeding, by sexual intercourse, and parenterally by the infusion of infected blood or injection drug use. From its presumed origins in Central Africa and Melanesia, HTLV-1 has spread globally along with human migrations and the historical slave trade. HTLV-2, endemic in Amerindian and African pygmy populations, has had a more limited geographic distribution except for hyperendemic spread among injection drug users (IDUs) in the United States and Europe.

BACKGROUND: Blood centers rely heavily on adolescent donors to meet blood demand, but presyncope and syncope are more frequent in younger donors. Studies have suggested administration of water before donation may reduce syncope and/or presyncope in this group. STUDY DESIGN AND METHODS: We conducted a randomized, controlled trial to establish the effect of preloading with 500 mL of water on the rate of syncope and presyncope in adolescent donors. School collection sites in Eastern Cape Province of South Africa were randomized to receive water or not. Incidence of syncope and presyncope was compared between randomization groups using multivariable logistic regression. RESULTS: Of 2464 study participants, 1337 received water and 1127 did not; groups differed slightly by sex and race. Syncope or presyncope was seen in 23 (1.7%) of the treatment and 18 (1.6%) of the control arm subjects. After adjusting for race, sex, age, and donation history, there was no difference in outcome between the water versus no water arms (adjusted odds ratio [OR], 0.80; 95% confidence interval [CI], 0.42-1.53). Black donors had sevenfold lower odds of syncope or presyncope than their white counterparts (adjusted OR, 0.14; 95% CI, 0.04-0.47). CONCLUSION: Preloading adolescent donors with 500 mL of water did not have a major effect in reducing syncope and presyncope in South African adolescent donors. Our adolescent donors had lower overall syncope and presyncope rates than similar populations in the United States, limiting the statistical power of the study. We confirmed much lower rates of syncope and presyncope among young black donors. © 2012 American Association of Blood Banks.

BACKGROUND: At most blood centers in the United States routine testing of donations for Trypanosoma cruzi using an enzyme-linked immunosorbent assay (ELISA) is followed by supplemental testing by radioimmunoprecipitation assay (RIPA). The objective of this study was to report the results of routine testing and risk factor data from allogeneic blood donors. STUDY DESIGN AND METHODS: T. cruzi testing data from January 2007 through December 2009 were analyzed, and risk factor interviews and follow-up studies were conducted on seroreactive donors. Prevalences of confirmed infection and risk factors associated with infection were assessed using logistic and multivariable logistic regression. RESULTS: Of 2,940,491 allogeneic donations from 1,183,076 donors, 305 (0.01% per donation tested and 0.026% per blood donor) were repeat reactive (RR) and 89 of those were confirmed positive by RIPA, yielding an overall seroprevalence of 1 per 33,039 donations and 1 per 13,292 donors. Country of birth and US blood center location differences in the seroprevalence of T. cruzi were evident. The odds of confirmed infection were highest if the donor reported having been bitten by the reduviid (kissing) bug (odds ratio [OR], 76.1; 95% confidence interval [CI], 11.1-3173) followed by having lived in a rural area of Latin America (OR, 38.6; 95% CI, 15.1-102.5). In multivariable analyses, having spent 3 months or more in Mexico or Central and/or South America was associated with the highest odds of RIPA-confirmed infection (OR, 8.5; 95% CI, 2.7-26.5). Polymerase chain reaction (PCR) testing of ELISA RR donors exhibited low sensitivity (1/22 [4%] RIPA-confirmed donors was PCR positive). CONCLUSION: Risk factors for confirmed infection in US blood donors are consistent with the known epidemiology of Chagas disease. Blood donors or transfusions do not substantially contribute to the burden of T. cruzi infection in the United States.

Aim: The aim of the study was to compare selenium levels in plasma and aqueous humour in subjects with and without primary open-angle glaucoma (POAG). Methods: Forty-seven POAG cases and 54 controls in this case–control study were recruited from surgery patients at the University Physician’s Ophthalmology Clinic in Tucson, Arizona, USA. Aqueous humour and plasma selenium were determined by high-performance liquid chromatography ion channel plasma mass spectrometry (HPLC ICP-MS). Potential confounders were assessed via a questionnaire. Biological samples were collected and processed at surgery and analysed for selenium content after collection was complete. Outcome measures included the odds of glaucoma in relationship to plasma selenium, aqueous humour selenium, and the ratio of levels of aqueous humour selenium to plasma selenium. Results: Tertile of selenium and its relationship to POAG was examined. After adjustment for common glaucoma risk factors, the odds of glaucoma in the highest tertile of plasma selenium (OR = 11.3; p = 0.03) and the middle tertile of aqueous humour selenium (OR = 0.06; p = 0.02) was significantly associated with glaucoma. Conclusion: Although a causal pathway cannot be inferred from our analysis, our data, added to that of others, suggest that the pathology is selenium-related.

Objective: The extent to which modifiable dietary factors may account for some of the variability demonstrated in mammographic density across ethnic groups is unknown. The purpose of this study was to provide pilot data describing the relationship between dietary variables and mammographic density in pre- and postmenopausal Hispanic and non-Hispanic white (NHW) women (N = 238) ranging in age from 41 to 50 years (premenopausal only) or 56 to 70 years (postmenopausal only). Design: Using a cross-sectional design, computer-assisted density assessments were performed on mammograms of both breasts and averaged for analysis. The Arizona Food Frequency Questionnaire was used to estimate dietary intake. Results: Study participants were well educated and overweight, with mean mammographic densities ranging from 20.25% for postmenopausal Hispanic women to 46.94% for premenopausal NHW women. Hispanic women reported higher energy intake than NHW women, but energy-adjusted intake of other nutrients was generally comparable. There was preliminary evidence of ethnic variability in dietYmammographic density associations. Among premenopausal Hispanic women, density was inversely associated with dairy, calcium, and vitamin D intakes (P e 0.05 for all). Among premenopausal NHW women, lower mammographic density was associated with greater intake of vegetables (P e 0.05), and higher density was associated with greater fruit intake (P e 0.05). Among postmenopausal Hispanic women, for every 4.54 increase in the polyunsaturated-to-saturated fat ratio, there was a 9.0% reduction in mammograph density. Conclusions: These preliminary results suggest that a differential pattern of dietary nutrient associations with mammographic density could potentially exist among Hispanic and NHW women. These ethnic differences in diet and mammographic density associations need to be further explored in larger studies.