Vulnerability to APOBEC3G linked to the pathogenicity of deltaretroviruses.

Human retroviruses are derived from simian ones through cross-species transmission. These retroviruses are associated with little pathogenicity in their natural hosts, but in humans, HIV causes AIDS, and human T-cell leukemia virus type 1 (HTLV-1) induces adult T-cell leukemia-lymphoma (ATL). We analyzed the proviral sequences of HTLV-1, HTLV-2, and simian T-cell leukemia virus type 1 (STLV-1) from Japanese macaques (Macaca fuscata) and found that APOBEC3G (A3G) frequently generates G-to-A mutations in the HTLV-1 provirus, whereas such mutations are rare in the HTLV-2 and STLV-1 proviruses. Therefore, we investigated the mechanism of how HTLV-2 is resistant to human A3G (hA3G). HTLV-1, HTLV-2, and STLV-1 encode the so-called antisense proteins, HTLV-1 bZIP factor (HBZ), Antisense protein of HTLV-2 (APH-2), and STLV-1 bZIP factor (SBZ), respectively. APH-2 efficiently inhibits the deaminase activity of both hA3G and simian A3G (sA3G). HBZ and SBZ strongly suppress sA3G activity but only weakly inhibit hA3G, suggesting that HTLV-1 is incompletely adapted to humans. Unexpectedly, hA3G augments the activation of the transforming growth factor (TGF)-ß/Smad pathway by HBZ, and this activation is associated with ATL cell proliferation by up-regulating BATF3/IRF4 and MYC. In contrast, the combination of APH-2 and hA3G, or the combination of SBZ and sA3G, does not enhance the TGF-ß/Smad pathway. Thus, HTLV-1 is vulnerable to hA3G but utilizes it to promote the proliferation of infected cells via the activation of the TGF-ß/Smad pathway. Antisense factors in each virus, differently adapted to control host cellular functions through A3G, seem to dictate the pathogenesis.

Trans-ancestral fine-mapping of MHC reveals key amino acids associated with spontaneous clearance of hepatitis C in HLA-DQß1.

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-DQß1Leu26 (p valueMeta = 1.24 × 10-14) located in pocket 4 was negatively associated with HCV spontaneous clearance and HLA-DQß1Pro55 (p valueMeta = 8.23 × 10-11) located in the peptide binding region was positively associated, independently of HLA-DQß1Leu26. These two amino acids are not in linkage disequilibrium (r2 < 0.1) and explain the SNPs and classical allele associations represented by rs2647011, rs9274711, HLA-DQB1∗03:01, and HLA-DRB1∗01:01. Additionally, HCV persistence classical alleles tagged by HLA-DQß1Leu26 had fewer HCV binding epitopes and lower predicted binding affinities compared to clearance alleles (geometric mean of combined IC50 nM of persistence versus clearance; 2,321 nM versus 761.7 nM, p value = 1.35 × 10-38). In summary, MHC class II fine-mapping revealed key amino acids in HLA-DQß1 explaining allelic and SNP associations with HCV outcomes. This mechanistic advance in understanding of natural recovery and immunogenetics of HCV might set the stage for much needed enhancement and design of vaccine to promote spontaneous clearance of HCV infection.

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. Commentary on: Rosadas et al. HTLV-1 screening of blood donations: we are systematically missing opportunities. Br J Haematol 2023;202:1220-1223.

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. Algorithm-specific mean durations of recent infection (MDRI) and false recency rates (FRR) were calculated and used to derive and compare incidence estimates. RESULTS: Compared with Algorithm 4, progressive algorithms misclassified fewer donors as recent: Algorithm 1: 61 (12.1%); Algorithm 2: 14 (2.8%) and Algorithm 3: 3 (0.6%). Algorithm-specific MDRI and FRR values resulted in marginally lower incidence estimates: Algorithm 1: 0.19% per annum (p.a.) (95% confidence interval [CI]: 0.13%-0.26%); Algorithm 2: 0.18% p.a. (95% CI: 0.13%-0.22%); Algorithm 3: 0.17% p.a. (95% CI: 0.13%-0.22%) and Algorithm 4: 0.17% p.a. (95% CI: 0.13%-0.21%). CONCLUSION: We confirmed significant misclassification of recent HIV cases when not including viral load and ARV testing. Context-specific MDRI and FRR resulted in progressively lower incidence estimates but did not fully account for the context-specific variability in incidence modelling. The inclusion of ARV testing, in addition to viral load and ID-NAT testing, did not have a significant impact on incidence estimates.

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. We previously described failure by HIV+/ARV+ blood donors to disclose their status. Such donations may lead to transfusion-transmitted HIV. METHODS: The social ecological model provided the conceptual framework for this study. Previously identified HIV+/ARV+ donors were invited to complete a survey (including a validated stigma scale) and qualitative interview, which underwent inductive and deductive thematic analysis. RESULTS: We uncovered two primary motivational paths to HIV+/ARV+ blood donations: privacy and altruism. The latter included a motivation not previously reported in the literature: donating specifically for other people living with HIV (PLWH). The other primary factor was a lack of privacy. These accounts often included donors encountering donation opportunities when accompanied by people to whom they had not and did not plan to disclose their HIV status. Most were highly confident their donations would be identified as HIV-positive and discarded. CONCLUSION: We demonstrated a complex interaction between individual, social, cultural, and structural/policy factors in blood donations by PLWH who take ARV. Recommendations to limit HIV + ARV+ donations include: (1) Targeted communication strategies to increase knowledge among PLWH of their deferral from blood donation-without increasing stigma, and (2) development of procedures to assist those who feel unable to opt-out of donation due to privacy concerns.

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. PATIENTS AND METHODS: We recruited 110 People living with HTLV-1 (PLHTLV-1, 67 asymptomatic individuals and 43 HAM/TSP patients) with a total of 946 person-years of clinical follow-up. Plasma cytokine levels (IL-2, IL-4, IL-6, IL-10, IL-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 used multivariable regression, machine learning algorithms and Bayesian network learning for biomarker identification. RESULTS: We found that systemic IL-6 was positively correlated with both age (r = 0.50, p < 0.001) and GlycA (r = 0.45, p = 0.00049) in asymptomatics, revealing an 'inflammaging" signature which was absent in HAM/TSP. GlycA levels were higher in women (p = 0.0069), but cytokine levels did not differ between the sexes. IFN-γ (p = 0.007) and IL-17A (p = 0.0001) levels were increased in untreated HAM/TSP Multivariable logistic regression identified IL-17A and proviral load as independent determinants of clinical status, resulting in modest accuracy of predicting HAM/TSP status (64.1%), while a machine learning-derived decision tree classified HAM/TSP patients with 90.7% accuracy. Pre-treatment GlycA and TNF levels significantly predicted clinical worsening (measured by Osame Motor Disability Scale), independent of proviral load. In addition, a poor prednisolone response was significantly correlated with higher post-treatment IFN-γ levels. Likewise, a transcriptomic IFN signaling score, significantly correlated with previously proposed HAM/TSP biomarkers (CASP5/CXCL10/FCGR1A/STAT1), was efficiently blunted by in vitro prednisolone treatment of PBMC from PLHTLV-1 and incident HAM/TSP. CONCLUSIONS: An age-related increase in systemic IL-6/GlycA levels reveals inflammaging in PLHTLV-1, in the absence of neurological disease. IFN-γ and IL-17A are biomarkers of untreated HAM/TSP, while pre-treatment GlycA and TNF predict therapeutic response to prednisolone pulse therapy, paving the way for a precision medicine approach in HAM/TSP.

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. RESULTS: A male-specific region near the adenosine diphosphate-ribosylation factor-like 5B (ARL5B) gene was identified. Individuals with the C allele of rs76398191 were about 30% more likely to have chronic HCV infection than individuals with the T allele (OR, 0.69; P = 1.98 × 10-07), and this was not seen in females. The ARL5B gene encodes an interferon-stimulated gene that inhibits immune response to double-stranded RNA viruses. We also identified suggestive associations near septin 6 and ribosomal protein L39 genes on the X chromosome. In box sexes, allele G of rs12852885 was associated with a 40% increase in HCV clearance compared with the A allele (OR, 1.4; P = 2.46 × 10-06). Septin 6 facilitates HCV replication via interaction with the HCV NS5b protein, and ribosomal protein L39 acts as an HCV core interactor. CONCLUSIONS: These novel gene associations support differential mechanisms of HCV clearance between the sexes and provide biological targets for treatment or vaccine development.

Effect of donor, component, and recipient characteristics on hemoglobin increments following red blood cell transfusion.

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.

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). METHODS: We used blood donation data from January 2011 to December 2019. Estimation of HBV prevalence donations made by first-time blood donors were analyzed by birth cohort and covariates. To estimate the incidence and residual risk of TT-HBV, mathematical models used data from both first time and repeat donors. RESULTS: HBV prevalence in first-time donors decreased from 0.84% (95% confidence interval [CI] 0.78-0.90) in 2011 to 0.66% (95% CI 0.61-0.70) in 2019. The post-1995 birth cohort had a significantly lower HBV prevalence of 0.14% (95% CI 0.13-0.15) than the pre-1985 birth cohort of 1.29% (95% CI 1.25-1.33) and the odds of HBV infection were reduced in a multivariable model (odds ratio [OR] = 0.28, 95% CI 0.24-0.34). The residual risk of TT-HBV occurring from window-period, occult, and possible vaccine breakthrough infections were estimated at 36.9, 5.8, and 2.2 per million red blood cell transfusions, respectively. CONCLUSION: Donors born after the start of routine HBV immunization had significantly lower prevalence of HBV infection, supporting the effectiveness of the vaccination program. The contemporary residual risk of TT-HBV has decreased and should decline further as more vaccinated young people join the donor pool.

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. STUDY DESIGN AND METHODS: South African National Blood Service (SANBS) blood donors are screened by self-administered questionnaire, semi-structured interview, and individual donation nucleic acid amplification testing for HIV. Stored samples from HIV-positive donations were tested for ARV and characterized as recent/longstanding using lag avidity testing. RESULTS: Of the 1462 HIV-positive donations in 2017, 1250 had plasma availability for testing of which 122 (9.8%) tested positive for ARV. Undisclosed ARV use did not differ by gender (p = .205) or ethnicity (p = .505) but did differ by age category (p < .0001), donor (p < .0001), clinic type (p = .012), home province (p = .01), and recency (p < .0001). Multivariable logistic regression found older age (adjusted odds ratio [aOR] 3.73, 95% confidence interval [CI] 1.98-7.04 for donors >40 compared with those <21), first-time donation (aOR 5.24; 95% CI 2.48-11.11), and donation in a high HIV-prevalence province (aOR 9.10; 95% CI 2.70-30.72) compared with Northern Rural provinces to be independently associated with undisclosed ARV use. DISCUSSION: Almost 1 in 10 HIV-positive blood donors neglected to disclose their HIV status and ARV use. Demographic characteristics of donors with undisclosed ARV use differed from those noted in other study. Underlying motivations for nondisclosure among blood donors remain unclear and may differ from those in other populations with significant undisclosed ARV use.

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. STUDY DESIGN AND METHODS: We conducted a cross-sectional study of SANBS whole-blood donor presentations to determine the impact of the changed donor eligibility criteria on deferrals and blood safety. We compared donor presentations, deferrals, and HIV-positive cases for the 12-month period (April 2019-March 2020) after the implementation of the updated donor eligibility criteria to those of the previous year. RESULTS: Of the 2,112,917 donor presentations, 51.1% (1079506) occurred in the post-implementation study period. Overall, deferrals decreased from 18.6% to 14.5%, whereas HIV-positive donations increased by 0.03%. A multivariable logistic regression analysis adjusted for sex, age, geographical location, donor, and clinic type showed significantly lower odds of deferral (OR 0.70; 95% CI: 0.69-0.70) and greater odds of HIV-positive cases in the study period than those in the control period (OR 1.17; 95% CI: 1.10-1.25). CONCLUSION: We confirmed that the change in donor eligibility criteria was associated with a decrease in deferrals and an increase in the country's blood supply. The impact of the increased number of HIV-positive donations on blood safety in a country performing individual donation nucleic acid amplification testing requires further investigation.

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. We describe a model to estimate incidence in first-time donors using the limiting antigen (LAg) avidity assay and compare its results with those from established models. METHODS: HIV-positive first-time donations were tested for recency using the LAg assay. Three models were compared; incidence estimated for (1) first-time donors using LAg avidity, (2) first-time and repeat-donors separately using the NAT yield window period (WP) model and (3) repeat-donors using the incidence/WP model. RESULTS: HIV incidence in first-time donors was estimated at 3·32 (CI 3·11, 3·55) and 3·81 (CI 3·07, 4·73) per 1000 PY using the LAg assay and NAT yield WP models, respectively. Incidence in repeat-donors was between 2·0- and 2·5-fold lower than in first-time donors estimated at 1·56 (CI 1·37, 1·77) and 1·94 (CI 1·86-2·01) per 1000 PY using the NAT yield/WP and incidence/WP models, respectively. CONCLUSION: Testing HIV-positive donations using the LAg assay provides a reliable method to estimate incidence in first-time donors for countries that collect the majority of blood from first-time donors and do not screen with NAT.

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. First, we performed sequencing of IFNL1-IFNL4 region in 64 individuals sampled according to rs368234815 genotype: TT/clearance (N = 16) and ΔG/persistent (N = 15) (genotype-outcome concordant) or TT/persistent (N = 19) and ΔG/clearance (N = 14) (discordant). 25 SNPs had a difference in counts of alternative allele >5 between clearance and persistence individuals. Then, we evaluated those markers in an association analysis of HCV clearance conditioning on rs368234815 in two groups of European (692 clearance/1 025 persistence) and African ancestry (320 clearance/1 515 persistence) individuals. 10/25 variants were associated (P < 0.05) in the conditioned analysis leaded by rs4803221 (P value = 4.9 × 10-04) and rs8099917 (P value = 5.5 × 10-04). In the European ancestry group, individuals with the haplotype rs368234815ΔG/rs4803221C were 1.7× more likely to clear than those with the rs368234815ΔG/rs4803221G haplotype (P value = 3.6 × 10-05). For another nearby SNP, the haplotype of rs368234815ΔG/rs8099917T was associated with HCV clearance compared to rs368234815ΔG/rs8099917G (OR: 1.6, P value = 1.8 × 10-04). We identified four possible causal variants: rs368234815, rs12982533, rs10612351 and rs4803221. Our results suggest a main signal of association represented by rs368234815, with contributions from rs4803221, and/or nearby SNPs including rs8099917.

Multi-Ancestry Genome-Wide Association Study of Spontaneous Clearance of Hepatitis C Virus.

BACKGROUND & AIMS: Spontaneous clearance of hepatitis C virus (HCV) occurs in approximately 30% of infected persons and less often in populations of African ancestry. Variants in major histocompatibility complex (MHC) and in interferon lambda genes are associated with spontaneous HCV clearance, but there have been few studies of these variants in persons of African ancestry. We performed a dense multi-ancestry genome-wide association study of spontaneous clearance of HCV, focusing on individuals of African ancestry. METHODS: We performed genotype analyses of 4423 people from 3 ancestry groups: 2201 persons of African ancestry (445 with HCV clearance and 1756 with HCV persistence), 1739 persons of European ancestry (701 with HCV clearance and 1036 with HCV persistence), and 486 multi-ancestry Hispanic persons (173 with HCV clearance and 313 with HCV persistence). Samples were genotyped using Illumina (San Diego, CA) arrays and statistically imputed to the 1000 Genomes Project. For each ancestry group, the association of single-nucleotide polymorphisms with HCV clearance was tested by log-additive analysis, and then a meta-analysis was performed. RESULTS: In the meta-analysis, significant associations with HCV clearance were confirmed at the interferon lambda gene locus IFNL4-IFNL3 (19q13.2) (P = 5.99 × 10-50) and the MHC locus 6p21.32 (P = 1.15 × 10-21). We also associated HCV clearance with polymorphisms in the G-protein-coupled receptor 158 gene (GPR158) at 10p12.1 (P = 1.80 × 10-07). These 3 loci had independent, additive effects of HCV clearance, and account for 6.8% and 5.9% of the variance of HCV clearance in persons of European and African ancestry, respectively. Persons of African or European ancestry carrying all 6 variants were 24-fold and 11-fold, respectively, more likely to clear HCV infection compared with individuals carrying none or 1 of the clearance-associated variants. CONCLUSIONS: In a meta-analysis of data from 3 studies, we found variants in MHC genes, IFNL4-IFNL3, and GPR158 to increase odds of HCV clearance in patients of European and African ancestry. These findings could increase our understanding of immune response to and clearance of HCV infection.

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. We evaluated clinical data and measured NT-proBNP levels prior to and following transfusion in patients with TACO (n = 160), transfused acute respiratory distress syndrome (ARDS) [n = 51], TRALI [n = 12], TACO/TRALI [n = 7], and controls [n = 335]. We used Wilcoxon Rank-Sum tests to compare NT-proBNP levels, and classification and regression tree (CART) algorithms to produce a ranking of covariates in order of relative importance for differentiating TACO from transfused controls. RESULTS: Pre-transfusion NT-proBNP levels were elevated in cases of transfused ARDS and TACO (both P < .001) but not TRALI (P = .31) or TACO/TRALI (P = .23) compared to transfused controls. Pre-transfusion NT-proBNP levels were higher in cases of transfused ARDS or TRALI with a diagnosis of sepsis compared to those without (P < .05 for both). CART analyses resulted in similar differentiation of patients with TACO from transfused controls for models utilizing either NT-proBNP levels (AUC 0.83) or echocardiogram results (AUC 0.80). CONCLUSIONS: NT-proBNP levels may have utility in the classification of pulmonary transfusion reactions. Prospective studies are needed to test the predictive utility of pre-transfusion NT-proBNP in conjunction with other clinical factors in identifying patients at risk of pulmonary transfusion reactions.

Antenatal blood transfusion in South Africa: indications and practice in a high-HIV-prevalence setting.

BACKGROUND: Globally, data on antenatal blood transfusion practices are scarce. We sought to characterize the epidemiology of antenatal transfusion in South Africa. STUDY DESIGN AND METHODS: A cross-sectional study was conducted of women who were transfused during pregnancy (>48 hr before anticipated delivery) at two hospitals in Durban and Soweto in 2014 to 2015. Medical record data on demographics, obstetric history, anemia, HIV status, and indications for blood transfusion were abstracted. RESULTS: The records on a total of 560 transfused pregnant women were evaluated; mean age was 28 years, 98% were of black African ethnicity, and 28% were HIV positive. At time of transfusion, one-half were in the first trimester. Hemorrhage was noted in 76% of women, most of which was associated with abortion (67%) or ectopic pregnancy (27%). Most women were transfused with red blood cells (RBCs; median, 2 units); 14% of women were transfused with plasma and 2% with platelets. Median pre- and posttransfusion hemoglobin levels were 6.9 g/dL and 9.2 g/dL, respectively; the latter differed by hospital (8.7 g/dL vs. 9.5 g/dL; p < 0.01). Hemorrhage was associated with missing HIV status, lower gestational age, and transfusion of 3 or more RBC units (all p < 0.01). In contrast, diagnoses of anemia (Soweto only) were associated with HIV infection, later gestational age, and lower (<3 units) RBC dose (all p < 0.01). CONCLUSION: Abortion and ectopic pregnancy with associated hemorrhage were the leading indications for antenatal transfusion and were concentrated in early gestation. By contrast, anemia was associated with HIV infection and transfusion in the third trimester.

High rate of hepatitis C virus and human immunodeficiency virus false-positive results in serologic screening in sub-Saharan Africa: adverse impact on the blood supply.

BACKGROUND: False positivity in blood screening may cause unnecessary deferral of healthy donors and exacerbate blood shortages. An international multicenter study was conducted to estimate the frequency of HCV and HIV false seropositivity in seven African countries (Burundi, Cameroon, Democratic Republic of Congo, Madagascar, Mali, Mauritania, and Niger). STUDY DESIGN AND METHODS: Blood donations were tested for hepatitis C virus (HCV) and human immunodeficiency virus (HIV) with rapid detection tests (RDTs), third-generation enzyme immunoassays (EIAs), or fourth-generation EIAs. HCV (456/16,613 [2.74%]) and HIV (249/16,675 [1.49%]) reactive samples were then confirmed with antigen/antibody assays, immunoblots, and nucleic acid testing. Partial viral sequences were analyzed when possible. RESULTS: The HCV reactivity rate with RDTs was significantly lower than with EIAs (0.55% vs. 3.52%; p < 0.0001). The HIV reactivity rate with RDTs was lower than with third-generation EIAs (1.02% vs. 2.38%; p < 0.0001) but similar to a fourth-generation assay (1.09%). Only 16.0% (57/357) and 21.5% (38/177) of HCV and HIV initial reactive samples, respectively, were repeatedly reactive. HCV and HIV infections were confirmed in 13.2% and 13.7%, respectively, of repeated reactive donations. The predominant HCV genotype 2 and 4 strains in West and Central Africa showed high genetic variability. HIV-1 subtype CRF02_AG was most prevalent. CONCLUSION: High rates (>80%) of unconfirmed anti-HCV and anti-HIV reactivity observed in several sub-Saharan countries highlights the need for better testing and confirmatory strategies for donors screening in Africa. Without confirmatory testing, HCV and HIV prevalence in African blood donors has probably been overestimated.

The use of the GeeniusTM HIV-1/2 Rapid confirmatory test for the enrolment of patients and blood donors in the WHO Universal Test and Treat Strategy in Cameroon, Africa.

BACKGROUND AND OBJECTIVE: In the WHO Universal test and treat strategy, false-positive HIV blood donors and patients may be unnecessarily put under antiretroviral treatment and false-negative subjects may be lost to follow-up. This study assessed the false positivity rate of the Cameroonian national HIV screening testing algorithm and the benefit of a confirmation test in the enrolment of patients and donors in the HIV care programme. METHODS: We included initial HIV reactive blood donors and patients in a cross-sectional study conducted in two Cameroonian hospitals. Samples were retested according to the Cameroon national algorithm for HIV diagnosis. A positive or discordant sample was retested with the Geenius Bio-Rad HIV 1&2 (Bio-Rad, Marnes-la-Coquette, France) for confirmation. The Geenius HIV-1-positive results with 'poor' profiles were retested for RNA as well as the Geenius indeterminate results. RESULTS: Of the 356 participants, 190/225 (84·4%) patients and 76/131 (58%) blood donors were declared positive with the national algorithm; 257 participants (96·6%) were confirmed HIV-1-positive. The study revealed that about 34/1000 blood donors and patients are false-positive and unnecessarily put on treatment; 89/1000 blood donors and patients declared discordant could have been included immediately in the HIV care programme if confirmatory testing was performed. The second test of the algorithm had a false-negative rate of 3%. Eleven samples (3·1%) were Geenius poor positive and NAT negative. CONCLUSION: The universal test and treat strategy may identify and refer more individuals to HIV care if a third rapid confirmatory test is performed for discordant cases.

Early and sustained improvement in fatigue-related quality of life following red blood cell transfusion in outpatients.

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.

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. Demographic and donation characteristics, motivators and scores of social capital and their association with donors' return were assessed. RESULTS: Overall, 3123 (52.3%) of the study subjects returned for a blood donation at least once. Predictors of donors' return were male gender (adjusted odds ratio [AOR] = 1.6, 1.3-1.9, for replacement and AOR = 1.3, 1.2-1.6, for community donors), previous donation (AOR = 2.7, 2.3-3.3, for replacement and AOR = 2.9, 2.5-3.5, for community donors) and high altruism (AOR = 1.3, 1.1-1.7, for replacement and AOR = 1.2, 1.0-1.5, for community donors). Altruism was the only motivator associated with return behaviour. Donors from Recife and São Paulo were more likely to return for replacement and/or for community donations than donors from Belo Horizonte. There was no association between social capital score and donor return behaviour. CONCLUSION: The likelihood to return for a subsequent blood donation is dependent upon characteristics of individual donors and also varies in different regions of Brazil. However, social capital was not associated with the likelihood of return behaviour. A better understanding of altruistic categories and appeals may help to improve donor recruitment and retention.