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.

Short or damaged telomeres have been implicated in degenerative conditions. We hypothesized that analysis of telomere length (TL) in human T-cell lymphotropic virus (HTLV) infection and HTLV-associated neuropathy might provide clues to the etiology of HTLV-associated disease and viral dynamics. A subset of 45 human T-cell lymphotropic virus type 1 (HTLV-1), 45 human T-cell lymphotropic virus type 2 (HTLV-2), and 45 seronegative subjects was selected from the larger HTLV Outcomes Study (HOST) cohort, matched on age, sex and race/ethnicity. Telomere-to-single-copy gene (T/S) ratio (a measure of TL) and HTLV-1 and HTLV-2 proviral loads were measured in peripheral blood mononuclear cells (PBMCs) using quantitative PCR (qPCR). Vibration sensation measured by tuning fork during neurologic examinations performed as part of the HOST study allowed for an assessment of peripheral neuropathy. TL was compared between groups using t-tests, linear and logistic regression. Mean T/S ratio was 1.02 ± 0.16 in HTLV-1, 1.03 ± 0.17 in HTLV-2 and 0.99 ± 0.18 in HTLV seronegative subjects (p = 0.322). TL was not associated with HTLV-1 or -2 proviral load. Shorter TL was significantly associated with impaired vibration sense in the HTLV-2 positive group only. Overall, we found no evidence that telomere length was affected by chronic HTLV-1 and HTLV-2 infection. That TL was only associated with peripheral neuropathy in the HTLV-2-positive group is intriguing, but should be interpreted cautiously. Studies with larger sample size and telomere length measurement in lymphocyte subsets may clarify the relationship between TL and HTLV-infection.

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

No cases of transfusion-transmitted syphilis have been described for over four decades. While there is mandatory transfusion screening for syphilis, the absence of transmission is in part ascribed to a low prevalence of syphilis in the blood donor population, the concomitant use of antibiotics in a high proportion of transfusion recipients, allied with poor survival of T. pallidum during refrigerated storage of blood products.

Methods

A cross-sectional retrospective data analysis was conducted to ascertain the prevalence of Treponema pallidum antibodies in U.S. blood donors by demography and geography. Routine blood donation testing data and demographics were extracted from the data warehouse of a large network of U.S. blood centers. Crude and adjusted prevalence of T. pallidum antibodies and active syphilis infection were calculated, and GIS mapping was used to illustrate geographic distribution.

Results

The prevalence of T. pallidum seropositivity and active syphilis in first time donors was 162.6 (95% CI 145.5-181.2) per 100,000 donors and 15.8 (95% CI 10.8-22.3) per 100,000 donors, respectively. The odds of T. pallidum seropositivity were significantly elevated in African American (OR = 18.9, 95% CI 14.2-25.2), and Hispanic (OR = 2.8, 95% CI 2.0-3.8) as compared to Caucasian donors. Similarly, the odds of active T. pallidum infections were significantly higher in African American (OR 15.0, 95% CI 7.0-32.3) and Hispanic (OR = 5.8, 95% CI 2.9-11.6) as compared to Caucasian donors. Syphilis seropositivity was associated with first time blood donation, increasing age, lower education, birth outside the US, and positive tests for HIV and HCV. Geographically, T. pallidum seropositivity was increased in southern and western regions of the US.

Conclusions

Given the low seroprevalence of syphilis in blood donors, continued screening remains debatable; however it may provide a public health benefit through surveillance of at-risk populations.

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.

Human T-cell lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) develops in 1-5% of HTLV-1-infected individuals. Previous studies by us and others have shown that the expression of negative immune checkpoint receptors (NCRs) is significantly increased on CD8 T cells in various chronic viral infections and are associated with poor anti-viral immunity. We have previously identified the differential expression of NCRs on CD8 T cells in blood from patients with HAM/TSP and in central nervous system (CNS) tissues of HTLV-1 infected humanized mice and defined the association with neurological complications. In this study, we determined the co-expression patterns of several key NCRs (PD-1, TIGIT, TIM-3, and LAG-3) and their cognate ligands in HTLV-1 infection and assessed how combination strategies targeting these pathways would impact HTLV-1-specific CD8 T-cell effector functions as an approach to reduce CNS disease outcomes. We found that global CD8 T cells from HAM/TSP patients co-express multiple NCRs at significantly higher frequencies than asymptomatic carriers (AC). Moreover, NCR ligands (PVR and PD-LI) on both plasmacytoid and myeloid dendritic cells were also expressed at higher frequencies in HAM/TSP compared to AC. In both AC and HAM/TSP subjects, combination dual PD-L1/TIGIT or triple PD-L1/TIGIT/TIM-3 blockade with monoclonal antibodies resulted in increases in intracellular cytokine expression in CD8 T cells after virus stimulation, particularly CD107a, a marker of degranulation, and TNF-α, a key cytokine that can directly inhibit viral replication. Interestingly, almost all blockade combinations resulted in reduced IL-2+ HTLV-1-specific CD8 T cell frequencies in HAM/TSP subjects, but not in AC. These results define a novel combinatorial NCR immunotherapeutic blockade strategy to reduce HAM/TSP disease burden.

INTRODUCTION: Cardiometabolic diseases are associated with greater COVID-19 severity; however, the influences of cardiometabolic health on SARS-CoV-2 infections after vaccination remain unclear. Our objective was to investigate the associations between temporal blood pressure and total cholesterol patterns and incident SARS-CoV-2 infections among those with serologic evidence of vaccination. METHODS: In this prospective cohort of blood donors, blood samples were collected in 2020-2021 and assayed for binding antibodies of SARS-CoV-2 nucleocapsid protein antibody seropositivity. We categorized participants into intraindividual pattern subgroups of blood pressure and total cholesterol (persistently, intermittently, or not elevated [systolic blood pressure <130 mmHg, diastolic blood pressure <80 mmHg, total cholesterol <200 mg/dL]) across the study time points. RESULTS: Among 13,930 donors with 39,736 donations representing 1,127,071 person-days, there were 221 incident SARS-CoV-2 infections among those with serologic evidence of vaccination (1.6%). Intermittent hypertension was associated with greater SARS-CoV-2 infections among those with serologic evidence of vaccination risk (adjusted incidence rate ratio=2.07; 95% CI=1.44, 2.96; p<0.01) than among participants with consistent normotension on the basis of a multivariable Poisson regression. Among men, intermittently elevated total cholesterol (adjusted incidence rate ratio=1.90; 95% CI=1.32, 2.74; p<0.01) and higher BMI at baseline (adjusted hazard ratio=1.44; 95% CI=1.07, 1.93; p=0.01; per 10 units) were associated with greater SARS-CoV-2 infections among those with serologic evidence of vaccination probability; these associations were null among women (both p>0.05). CONCLUSIONS: Our findings underscore that the benefits of cardiometabolic health, particularly blood pressure, include a lower risk of SARS-CoV-2 infection after vaccination.

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.

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 4 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 4 weeks.

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.