Dendritic Cells Pulsed with HAM/TSP Exosomes Sensitize CD4 T Cells to Enhance HTLV-1 Infection, Induce Helper T-Cell Polarization, and Decrease Cytotoxic T-Cell Response.

HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a progressive demyelinating disease of the spinal cord due to chronic inflammation. Hallmarks of disease pathology include dysfunctional anti-viral responses and the infiltration of HTLV-1-infected CD4+ T cells and HTLV-1-specific CD8+ T cells in the central nervous system. HAM/TSP individuals exhibit CD4+ and CD8+ T cells with elevated co-expression of multiple inhibitory immune checkpoint proteins (ICPs), but ICP blockade strategies can only partially restore CD8+ T-cell effector function.

The prevalence of hepatitis B virus, human T-lymphotropic virus and human immunodeficiency virus in patients receiving blood transfusions in South Africa.

Background And Objectives: South Africa has a high prevalence of human immunodeficiency virus (HIV) and hepatitis B virus (HBV) and to a lesser extent human T-lymphotropic virus (HTLV). Each of these agents is transfusion-transmissible (TT) but deciding whether to implement preventive screening depends upon knowledge of background prevalence in transfused patients. We determined the prevalence of HIV, HBV and HTLV I/II among blood transfusion recipients in South African hospitals.

The impact of non-disclosure of HIV status and antiretroviral therapy on HIV recency testing and incidence algorithms.

Background And Objectives: Accurate HIV incidence estimates among blood donors are necessary to assess the effectiveness of programs aimed at limiting transfusion-transmitted HIV. We assessed the impact of undisclosed HIV status and antiretroviral (ARV) use on HIV recency and incidence estimates using increasingly comprehensive recent infection testing algorithms.

Materials And Methods: Using 2017 donation data from first-time and lapsed donors, we populated four HIV recency algorithms: (1) serology and limiting-antigen avidity testing, (2) with individual donation nucleic amplification testing (ID-NAT) added to Algorithm 1, (3) with viral load added to Algorithm 2 and (4) with ARV testing added to Algorithm 3.

A case-control study of risk factors for incident hepatitis B virus infection in South African blood donors.

Objectives: Hepatitis B virus (HBV) infection remains a global health problem. Risk factors for HBV infection are usually assessed in prevalent rather than incident infections. To identify demographic and behavioral risks associated with incident HBV among South African blood donors.

HTLV-1 and blood donation.

Human T-cell leukaemia virus type 1 (HTLV-1) is a human retrovirus that causes adult T-cell lymphoma and HTLV-associated myelopathy. In this issue, Rosadas et al. use data from a recent WHO report to describe how blood banks test for HTLV-1 and how this testing contributes to public health surveillance for the virus.

Association of ABO and RhD blood groups with the risk of HIV infection.

Naturally occurring antibodies against ABO antigens present in human sera have been shown to neutralize ABO-expressing HIV in vitro. We investigated associations between ABO and RhD blood groups and HIV infection among blood donors from all blood collection centers in eight of South Africa's nine provinces. Whole blood donations collected from first time donors between January 2012 and September 2016 were tested for HIV RNA by nucleic acid testing and HIV antibody using third generation serology assays.

Motivations for blood donation by HIV-positive individuals on antiretrovirals in South Africa: A qualitative study.

Objectives: We performed a mixed-methods study to explore the motivations associated with blood donation by donors with known, but undisclosed HIV-positive status and ARV use (HIV+/ARV+), seeking potential strategies to reduce such donations and mitigate risk for blood recipients. Here, we report predominantly the qualitative component.

Background: A safe and sustainable blood supply is dependent in part, on effective pre-donation donor assessment.

Systemic cytokines and GlycA discriminate disease status and predict corticosteroid response in HTLV-1-associated neuroinflammation.

Background: HTLV-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. Although HAM/TSP pathogenesis is not fully elucidated, older age, female sex and higher proviral load are established risk factors. We investigated systemic cytokines and a novel chronic inflammatory marker, GlycA, as possible biomarkers of immunopathogenesis and therapeutic response in HAM/TSP, and examined their interaction with established risk factors.

Blood Center Testing Allows the Detection and Rapid Treatment of Acute and Recent HIV Infection.

Blood donations in South Africa are tested for HIV RNA using individual donation NAT (ID-NAT), allowing detection and rapid antiretroviral therapy (ART) of acute HIV infections. We enrolled a cohort of acute and recent HIV-infected blood donation candidates in South Africa in 2015-2018, measured HIV antibody, ID-NAT, and recency of infection <195 days (Sedia LAg) at enrollment and initiated early ART. A small cohort of HIV elite controllers was followed without treatment.

Prevalence and Risk Factors for Human T-Cell Lymphotropic Virus (HTLV) in Blood Donors in Brazil-A 10-Year Study (2007-2016).

It is unknown whether HTLV-1/2 prevalence has been stable or changing with time in Brazil. We present a 10-year (2007-2016) analysis of HTLV-1/2 infection in first-time blood donors from four blood banks in Brazil. The Brazilian blood centers participating in this multicenter Recipient Epidemiology and Donor Evaluation Study (REDS) are located in Recife in the Northeast and in São Paulo, Rio de Janeiro and Belo Horizonte located in the Southeast of the country.

Trans-ancestral fine-mapping of MHC reveals key amino acids associated with spontaneous clearance of hepatitis C in HLA-DQβ1.

Spontaneous clearance of acute hepatitis C virus (HCV) infection is associated with single nucleotide polymorphisms (SNPs) on the MHC class II. We fine-mapped the MHC region in European (n = 1,600; 594 HCV clearance/1,006 HCV persistence) and African (n = 1,869; 340 HCV clearance/1,529 HCV persistence) ancestry individuals and evaluated HCV peptide binding affinity of classical alleles. In both populations, HLA-DQβ1Leu26 (p value = 1.

A novel high performing multiplex immunoassay Multi-HTLV for serological confirmation and typing of HTLV infections.

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.

Re-engineering the medical assessment of blood donors in South Africa: The balance between supply and safety.

Background: The balance between ensuring blood donor and recipient safety while maintaining a sufficient blood supply can be affected by excessive deferral of blood donors. In 2018, a biannual regulatory review of donor eligibility criteria provided the South African National Blood Service (SANBS) the opportunity to review the existing criteria. Changes to these criteria were implemented in April 2019 after an extensive review.

Undisclosed HIV status and antiretroviral therapy use among South African blood donors.

Background: Undisclosed antiretroviral drug (ARV) use among blood donors who tested HIV antibody positive, but RNA negative, was previously described by our group. Undisclosed ARV use represents a risk to blood transfusion safety. We assessed the prevalence of and associations with undisclosed ARV use among HIV-positive donors who donated during 2017.

An assessment of hepatitis B virus prevalence in South African young blood donors born after the implementation of the infant hepatitis B virus immunization program: Implications for transfusion safety.

Background: The prevalence of hepatitis B surface antigen is estimated to be 6.7% in the South African population and in April 1995 the nation introduced universal hepatitis B virus (HBV) vaccination for newborns and infants. We studied the temporal association of this program with HBV prevalence in young blood donors and the contemporary HBV incidence and residual risk of transfusion-transmitted HBV infection (TT-HBV).

Trends in serological markers of transfusion transmissible infections in blood donations at the Bamenda Hospital-based Blood Service, Cameroon.

Objectives: The rate and trend of transfusion transmissible infections (TTIs) in blood donations from 2012 to 2017 at the Bamenda Regional Hospital Blood Service (BRHBS), Cameroon was assessed.

Materials And Methods: A six-year retrospective study was conducted by reviewing the records of donors. Blood was screened for HIV, hepatitis B, hepatitis C and syphilis.

Phenotypic and Functional Analyses Guiding Combination Immune Checkpoint Immunotherapeutic Strategies in HTLV-1 Infection.

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.

A Multiancestry Sex-Stratified Genome-Wide Association Study of Spontaneous Clearance of Hepatitis C Virus.

Background: Spontaneous clearance of acute hepatitis C virus (HCV) infection is more common in women than in men, independent of known risk factors.

Methods: To identify sex-specific genetic loci, we studied 4423 HCV-infected individuals (2903 male, 1520 female) of European, African, and Hispanic ancestry. We performed autosomal, and X chromosome sex-stratified and combined association analyses in each ancestry group.

Multi-ancestry fine mapping of interferon lambda and the outcome of acute hepatitis C virus infection.

Clearance of acute infection with hepatitis C virus (HCV) is associated with the chr19q13.13 region containing the rs368234815 (TT/ΔG) polymorphism. We fine-mapped this region to detect possible causal variants that may contribute to HCV clearance.

NT-proBNP levels in the identification and classification of pulmonary transfusion reactions.

Background: Consensus definitions for transfusion-related acute lung injury (TRALI) and transfusion-associated circulatory overload (TACO) have recently been revised; however, pulmonary transfusion reactions remain difficult to diagnose. We hypothesized that N-terminal pro-brain natriuretic peptide (NT-proBNP) levels could have utility in the identification and classification of pulmonary transfusion reactions.

Study Design And Methods: We performed a secondary analysis of a case-control study of pulmonary transfusion reactions at four academic hospitals.

HIV incidence in South African blood donors from 2012 to 2016: a comparison of estimation methods.

Background: Measuring incidence is important for monitoring and maintaining the safety of the blood supply. Blood collected from repeat-donors has provided the opportunity to follow blood donors over time and has been used to estimate the incidence of viral infections. These incidence estimates have been extrapolated to first-time donors using the ratio of NAT yield cases in first-time versus repeat-donors.

Are different motivations and social capital score associated with return behaviour among Brazilian voluntary non-remunerated blood donors?

Background: We examined the association between social capital score, motivator factors and demographic and donation characteristics and donor return at three Brazilian blood centres in Recife, São Paulo and Belo Horizonte.

Material And Methods: A total of 5974 donors were interviewed about motivation factors to donate and cognitive and structural social capital just before an effective donation in three Brazilians blood centres in 2009. We assessed the return to a new donation within 2 years for each of these donors.