Virological safety of the UK blood supply in the era of individual risk assessments and HIV PrEP.

A more individualised donor selection policy was implemented in the UK in 2021, which replaced the previous 3-month deferral for men who have sex with men (MSM). Other blood services have a variety of policies in place to ensure the virological safety of blood components, ranging from an indefinite ban on MSM, to a defined period of exclusion, or to an individualised risk assessment that is not based on gender or sexual orientation. Justification of these policies should be based on scientific evidence including assessment of lengths of virological window periods, infectious disease epidemiology within donor populations and donation screening assay sensitivities. Developments in molecular technology and assays which can detect both antibodies and antigens in the very early stages of infection have significantly reduced the risk in most developed countries. However, the increasing usage of pre-exposure prophylaxis (PrEP) to prevent acquisition of HIV infection after possible high-risk sexual contact within the UK blood donor population has been recently noted. It has brought with it new diagnostic challenges within blood screening, notably possible non-detection of HIV RNA and serological markers following PrEP use despite potential infectivity. The use of other testing strategies such as detection of HIV DNA and screening for non-declared PrEP usage should be investigated further.

Undeclared pre-exposure or post-exposure prophylaxis (PrEP/PEP) use among syphilis-positive blood donors, England, 2020 to 2021.

An individualised blood donor selection policy was implemented in the United Kingdom from summer 2021. We have investigated the impact of this policy by comparing the extent of undeclared use of HIV pre-exposure or post-exposure prophylaxis (PrEP/PEP) before and after this change. The rate of PrEP usage in syphilis-positive male blood donors has not changed since individualised donor assessment was implemented but provides continuing evidence of undisclosed PrEP use which may be associated with current or past higher-risk sexual behaviours.

Challenges for the maintaining the microbiological safety of the UK blood supply.

The supply of blood, blood products and components in the UK, as elsewhere, is safe, although there is no cause for complacency. Use of blood, blood products and components is not without risk of morbidity and mortality. Transfusion-transmitted infections (TTIs) continue to occur and may severely affect the health and welfare of recipients. As indicated by recent and current inquiries, public interest in these TTIs is huge. The risk of TTI can be mitigated but not abolished. Measures to reduce risk include screening of donors, testing of donations and, where appropriate, treatment of donations. The introduction of newer screening tests might identify some infectious donations but come at a cost, which could exceed a justifiable limit. Thus, the recognition, detection, reporting and investigation of cases of possible TTIs need to be improved. Recipients of blood should understand that, although transfusion in the UK is safe, it is not free of risk and so should be provided with full information so that properly informed consent can be given.

Absence of detectable monkeypox virus DNA in 11,000 English blood donations during the 2022 outbreak.

BACKGROUND: A large, worldwide outbreak of mpox (formerly referred to as monkeypox) involving mainly men who have sex with men commenced in May 2022. We evaluated the frequency of positivity for the causative agent, monkeypox virus (MPXV), in blood donations collected in August 2022, during the outbreak period in Southern England. METHODS/MATERIALS: The sensitivity and specificity of an MPXV-specific PCR and a generic non-variola orthopoxvirus (NVO) PCR were evaluated using samples from mpox cases and synthetic DNA standards. Residual minipools from nucleic acid testing were obtained from 10,896 blood donors in Southern England, with 21% from London. RESULTS: MPXV and NVO PCRs were both capable of detection of single copies of target sequence with calculated limits of detection (LOD)90 s of 2.3 and 2.1 DNA copies and analytical sample sensitivities of 46 and 42 MPXV DNA copies/ml, respectively. 454 minipools produced from 10,896 unique donors were assayed for MPXV DNA by both methods. No positive minipools were detected by either PCR. CONCLUSIONS: Although blood donors are unrepresentative of the UK population in terms of MPXV infection risk, the uniformly negative MPXV DNA testing results provide reassurance that MPXV viraemia and potential transmission risk were rare or absent in donors during the outbreak period. Minipools from blood donors allow rapid implementation of large-scale population-based screening for emerging pathogens and represent an important resource for pandemic preparedness.

Communicating the move to individualized donor selection policy: Framing messages focused on recipients and safety.

BACKGROUND: Men-who-have-sex-with-men (MSM) have been deferred from donating blood. However, recent evidence supports the adoption of donor screening based on individuals' sexual behavior over population-based criteria. We explore how best to frame communications about adopting this change to minimize any potential negative consequences (e.g., reduced donor numbers). We examine the effectiveness of risk (emphasizing safety vs. emphasizing low risk), and focus (donor vs. recipient) frames on intentions to donate blood (approach) or feeling deterred from donating (avoid), and mechanisms linked to under-reporting sexual behavior. STUDY DESIGN AND METHODS: We conducted a 2 (risk frame: risk vs. safety) by 3 (focus: donor vs. recipient vs. both) between-subjects online experiment (n = 2677). The main outcomes were intentions to donate and feelings of being put-off/deterred from donating (both for self and others). We also assessed the extent that forgetting, embarrassment/shame, and question irrelevance were perceived to be associated with under-reporting sexual behavior. RESULTS: Frames that focused on safety or a recipient resulted in people reporting being less deterred from donating. Regardless of frame, people from ethnic minorities were more likely to feel deterred. Embarrassment/shame followed by forgetting and perceived irrelevance were the main reasons for under-reporting sexual behaviors, especially in ethnic minorities, and smartphones were perceived as an acceptable memory aid for sexual behavior. DISCUSSION: Blood services moving to an individualized policy should frame donor selection in terms of safety and/or a recipient focus, explore sensitivities in ethnic minority communities, consider ways to normalize reporting sexual behavior, and use smartphones as a memory aid.

Trust and distrust: Identifying recruitment targets for ethnic minority blood donors.

BACKGROUND: We explore the role of trust, distrust, and the prevailing socio-political context to better understand why people from ethnic minority communities are less likely to be blood donors compared to people from White communities. Recruiting more ethnic minority donors will enhance representativeness, reduce inequality, and help meet the clinical need to increase the proportion of blood with Ro Kell antigen to treat Sickle Cell Disease (SCD). STUDY DESIGN AND METHODS: A 2 (donor-status: current donor; non-donors) by 4 (ethnicity: People from Asian, Black, Mixed and White ethnic backgrounds) quasi-experiment (N = 981) was conducted to examine perceptions of trust/distrust and their influence on willingness to donate blood, within the socio-political context of the Windrush scandal and Brexit. RESULTS: We identified five domains of trust ('National Health Service [NHS] and staff,' 'NHS Blood and Transplant,' 'outgroups,' 'individuals' and 'politics'), and a single domain of conditional distrust domain. Trust across all the domains was lower, and 'conditional distrust' higher for ethnic minorities. Trust in 'individuals' and 'NHSBT' predicted willingness to donate in non-donors from ethnic minorities and White non-donors, respectively. Concerns about the Windrush scandal were related to lower political trust. Viewing Brexit as 'positive for the UK' was related to lower trust across domains and reduced willingness to donate in White non-donors through its influence on reduced trust in NHSBT. CONCLUSION: Distinct domains of trust and distrust are identified, and targeting 'trust in others' through conditional cooperation is recommended as a strategy to increase donor numbers from ethnic minority communities.

Re-assessing the risk of undetected HBV, HCV and HIV in deceased tissue and living surgical bone donors in England.

Testing of living surgical bone and deceased tissue donors by NHS Blood and Transplant (NHSBT) has included individual donation (ID) nucleic acid testing (NAT) for HBV, HCV and HIV since 2008. Here, the well-established window period methodology was used to estimate residual risk (RR). Prevalence of viral markers was calculated among both tissue donor populations. Incidence was derived by adjusting incidence among new blood donors by the prevalence ratio for tissue and new blood donors. Residual risk (RR) was calculated as the product of incidence and duration of WP for single donor HBV NAT at 0.058 years (21 days), HCV NAT at 0.008 years (3 days) and HIV NAT at 0.014 (5 days). Between 2013 and 2017, 7886 living surgical bone donors were tested, 16 were positive for markers of HBV, HCV and HIV. HCV had the highest prevalence at 114/100,000 donors. Incidence and RR was highest for HBV at 3.55/100,000-person years and 0.32/100,000 donors (95% CI 0.11/100,000-1.42/100,000). Among 9751 deceased tissue donors tested, 22 were positive for viral markers. HBV had highest prevalence at 174/100,000 donors, and the highest incidence and RR at 8.12/100,000 person years and 0.74/100,000 donors (95% CI 0.08/100,000-2.99/100,000). Using ID NAT, RR of not detecting a HBV, HCV and HIV WP donation among tissue donors is less than 1/100,000 donors. These estimates provide a good starting point for discussing potential risks of viral transmission through tissue transplant with patients.

Blood donation by men who have sex with men: using evidence to change policy.

BACKGROUND: In 2011 in the United Kingdom (UK), excluding Northern Ireland, the deferral of men who have sex with men (MSM) changed from lifetime to 12 months. We describe MSM who donated before and after this to inform further policy reviews. MATERIALS AND METHODS: Characteristics and sexual behaviours of donors identifying as male from routine surveillance are described. Rates of infections are compared pre- and post-implementation of a 12-month deferral. Donors are compared with screen negative male donors responding to a large-scale survey during 2013/2014. RESULTS: Comparing the five years pre- and post-change, the rate of confirmed positives for markers of HBV, HCV, HIV and syphilis decreased by 6·9% from 14·1 to 13·1/100 000 donations. The rate of recent infections was unchanged (1·72/100 000). Of 22 776 survey responses identifying as male, MSM disclosed sex between men over 12 months ago giving 99·35% compliance among male donors. Two-thirds of the 72 non-compliant MSM reported one to two partners and one-third had no new partners within 12 months. The most commonly reported reason for non-compliance from MSM both positive and negative for infection was 'not important to declare' (37·2% and 40·7%). Test seeking was rare (9·3% and 2·1%). CONCLUSION: Compliance with the 12-month MSM deferral policy was very high. The very low rates of infections post-change demonstrated the effectiveness of the policy. These data were an important part of the 2017 review of all sexual behaviour deferrals.

A typology of blood donor motivations.

BACKGROUND: Although the need for whole blood is declining, so too are the number of first-time and repeat blood donors. To develop new recruitment and retention strategies, therefore, we need to draw on as wide a variation in blood donor motivations as possible. The primary aim of this study is to draw on a large survey of donors to develop a broad, theoretically instantiated typology of donor motivations to identify new and less common, yet practically important, motivations that have not been previously reported. STUDY DESIGN AND METHODS: Using data from the UK Blood Donor Survey run by NHS Blood and Transplant/Public Health England Epidemiology Unit (N = 61 123 donors), we analyze fixed (N = 52 225) and free (N = 8867) responses to develop a more comprehensive typology of blood donor motivations based on theories from the biology, psychology, philosophy, economics, and sociology of altruism. RESULTS: We identified 54 motivations, including a number of newly identified motivations, for blood donations which we organized into 12 superordinate categories (eg, "inspiration via moral elevation," "perceived social closeness," and "fungibility of donations"). These are linked to intervention suggestions such as donating blood in memoriam or donating blood as an alternative to other charitable acts. CONCLUSION: We present the most comprehensive account of blood donor motivations to-date. This work also offers a structure for coding free-text responses, developing motivational measures, and identifying tangible interventions. Thus, we feel that this is a valuable resource for blood donor researchers, marketers, and policy makers.

What are blood donors telling us about injecting drug use?

BACKGROUND AND OBJECTIVES: Injecting drug use (IDU), a permanent deferral for blood donors, was included in a review of donor selection criteria completed in 2017. Here, we describe what is known about IDU in blood donors in the United Kingdom (UK). MATERIALS AND METHODS: Data were obtained from routine surveillance of donation testing and confirmed positive donors and a 2013/2014 UK survey of behaviour and compliance in screen-negative donors. RESULTS: Between 2009 and 2018, of 22 UK million donations screened, IDU was self-reported at the post-test discussion in 5% (86/1777) of donors with confirmed positive donations. Recent injecting within 12 months was reported in 8 HCV-positive donors, but only in 1/14 donors where it was clear HCV infection had been acquired in the previous 12 months. Of 65 439 survey responders, 25 reported IDU, which when weighted to the donor population gave 99·95% compliance. Most of the 111 donors reporting IDU felt it was not important to their donation, mainly because their injecting was in the past, while three HCV-positive recent injectors reported not sharing needles so presumably felt safe to donate. CONCLUSION: Compliance with the permanent deferral appeared extremely high with low levels of injecting reported by donors, mainly in the past. This agreed with the low-incident HCV infection observed in UK donors. These data contributed to a recommendation to reduce the deferral to 1 year. Ways of improving compliance in those few donors at current increased risk of infection need to be investigated.

In the NAT era, is routine lookback to recipients still required when donors seroconvert for HIV infection?

Human immuno virus screening assays have improved in sensitivity over the last 20 years and our data demonstrates that there is no evidence of missed HIV positive window period donations since the introduction of pooled HIV NAT screening. Here we recommend that extensive lookback investigations are not routinely required if the most recent negative donation is negative on individual sample HIV PCR testing.

Hepatitis E virus in blood donors in England, 2016 to 2017: from selective to universal screening.

IntroductionHepatitis E virus (HEV), the most common cause of acute hepatitis in many European countries, is transmitted through consumption of processed pork but also via blood transfusion and transplantation. HEV infection can become persistent in immunocompromised individuals.AimWe aimed to determine the incidence and epidemiology of HEV infection in English blood donors since the introduction of donation screening in 2016.MethodsBetween March 2016 and December 2017, 1,838,747 blood donations were screened for HEV RNA. Donations containing HEV RNA were further tested for serological markers, RNA quantification and viral phylogeny. Demographics, travel and diet history were analysed for all infected donors.ResultsWe identified 480 HEV RNA-positive blood donations during the 22-month period, most (319/480; 66%) donors were seronegative. Viral loads ranged from 1 to 3,230,000 IU/ml. All sequences belonged to genotype 3, except one which likely represents a new genotype. Most viraemic donors were over 45 years of age (279/480; 58%), donors aged between 17 and 24 years had a seven-times higher incidence of HEV infection than other donors between March and June 2016 (1:544 donations vs 1:3,830). HEV-infected blood donors were evenly distributed throughout England. Screening prevented 480 HEV RNA-positive blood donations from reaching clinical supply.ConclusionHEV screening of blood donations is a vital step in order to provide safer blood for all recipients, but especially for the immunosuppressed. The unusually high rates of HEV infection in young blood donors may provide some insight into specific risks associated with HEV infection in England.

Infections and associated behaviors among deceased organ donors: Informing the assessment of risk.

BACKGROUND: For infectious disease risk assessment among deceased organ donors, pre-donation clinical, microbiological, and behavioral information are reviewed; however, uncertainty may arise due to false negative screening results of recently acquired infections. METHOD: The burden of hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV), and residual risks (RR) of undetected virus was estimated, with the impact of more sensitive screening. RESULTS: For United Kingdom potential deceased organ donors between 2010 and 2014, prevalence of HBsAg was 0.1%, HIV 0.06% and HCV 0.9%, increasing to 25.7% in people who injected drugs (PWID). Incidence, derived from new blood donors, was multiplied by duration of screening assay window periods to give RR per 100 000 donors as 0.43 (95% confidence interval [CI] 0.03-3.99) for HBV, 0.08 (95% CI 0.02-0.21) for HIV, and 5.96 (95% CI 0.82-37.89) for HCV. For PWID, HCV RR was 163.3 (95% CI 22.8-1107.8) compared to 2.76 (95% CI 0.35-17.36) for non-PWID. RR decreased significantly with nucleic acid testing (NAT), and, for HCV, antigen testing had a similar impact. CONCLUSION: While the burden of HCV risk lies within PWID, these are in small numbers therefore few HCV antigen or NAT tests would be needed to more accurately assess risk.

Blood donors in England and North Wales: demography and patterns of donation.

BACKGROUND: As populations in the developed world shift toward an older and more ethnically diverse population, the challenges of recruiting and retaining sufficient donors to secure an adequate, safe supply of blood in the future will increase. STUDY DESIGN AND METHODS: The study population included all first-time (n = 348,740) and repeat (n = 1,805,255) blood donors and their donations (n = 3,854,460) received by NHS Blood and Transplant during 2010 and 2011. Rates of new and repeat donors per 1000 population were estimated using Office for National Statistics 2011 population estimates. Factors associated with new blood donors returning within 6 months were analyzed using multivariate logistic regression. RESULTS: The majority (87.9%) of donors were white British; 5.5% were unknown; 3.4% white Irish or white other; and 3.2% composed of all other ethnic groups. The median ages of new and repeat donors in 2010 were 28.0 and 45.0 years, respectively, compared to 29.0 and 47.0 years in 2011. Rates of donation varied by ethnicity, ranging from 1.59 per 1000 among Asian Bangladeshi origin, compared to 22.1 per 1000 among white British origin. Approximately two in five (38.4%) new blood donors returned within 6 months and were more likely to be male and of white ethnicity. CONCLUSIONS: Blood supply is impacted by numerous factors, including an aging population and an increasing population of migrant communities with lower donation rates. It is therefore critical that changes within the blood donor and wider population are monitored to inform donor recruitment and retention strategies.

Acute hepatitis B in blood donors over a 5-year period in England and North Wales: who is getting infected?

BACKGROUND: Hepatitis B virus (HBV) remains the infection most frequently recognized by donation testing in blood donors. It is usually a persistent infection and mostly reflects the country of origin of the donor or the donor's family. There are, however, a minority of acute infections and this study undertook their phylogenetic analysis to determine the likely source of infection. STUDY DESIGN AND METHODS: Plasma samples from 11 donors donating between July 2005 and June 2010, whose test results revealed recent infection with hepatitis B, were available for further analysis. Plasma DNA was extracted, amplified, sequenced, and analyzed phylogenetically. Donor and virus characteristics were compared with the overall demography of all hepatitis B-infected donors attending over the same period. RESULTS: Three of the 11 individuals were first-time donors. Nine were male, of whom eight were white British. All had serum markers of very recent infection. Only two indicated known HBV exclusion risk factors at postdonation discussion not declared previously. Genotype A was present in seven, Genotype B in two, and Genotype C in two, contrasting with the pattern in persistently infected persons in the United Kingdom. A single A2 strain was identified in six of the white British male donors, suggesting epidemiologic linkage. CONCLUSION: Phylogenetic analysis of HBV-infected donors performed in real time can potentially lead to identification of undeclared risk factors that donor health questionnaires may fail to identify.

Evaluation of an ethidium monoazide-enhanced 16S rDNA real-time polymerase chain reaction assay for bacterial screening of platelet concentrates and comparison with automated culture.

BACKGROUND: Culture-based systems are currently the preferred means for bacterial screening of platelet (PLT) concentrates. Alternative bacterial detection techniques based on nucleic acid amplification have also been developed but these have yet to be fully evaluated. In this study we evaluate a novel 16S rDNA polymerase chain reaction (PCR) assay and compare its performance with automated culture. STUDY DESIGN AND METHODS: A total of 2050 time-expired, 176 fresh, and 400 initial-reactive PLT packs were tested by real-time PCR using broadly reactive 16S primers and a "universal" probe (TaqMan, Invitrogen). PLTs were also tested using a microbial detection system (BacT/ALERT, bioMérieux) under aerobic and anaerobic conditions. RESULTS: Seven of 2050 (0.34%) time-expired PLTs were found repeat reactive by PCR on the initial nucleic acid extract but none of these was confirmed positive on testing frozen second aliquots. BacT/ALERT testing also failed to confirm any time-expired PLTs positive on repeat testing, although 0.24% were reactive on the first test. Three of the 400 "initial-reactive" PLT packs were found by both PCR and BacT/ALERT to be contaminated (Escherichia coli, Listeria monocytogenes, and Streptococcus vestibularis identified) and 14 additional packs were confirmed positive by BacT/ALERT only. In 13 of these cases the contaminating organisms were identified as anaerobic skin or oral commensals and the remaining pack was contaminated with Streptococcus pneumoniae. CONCLUSION: These results demonstrate that the 16S PCR assay is less sensitive than BacT/ALERT and inappropriate for early testing of concentrates. However, rapid PCR assays such as this may be suitable for a strategy of late or prerelease testing.

The diversity of chronic hepatitis B virus infections within blood donors in England and North Wales 2005 through 2010.

BACKGROUND: In 2010 hepatitis B virus (HBV) was the most frequently detected infection in UK blood donation screening, typically found in first-time, male, chronically infected donors born abroad. To date there has been no comprehensive characterization of the virologic profile of these infections. STUDY DESIGN AND METHODS: Epidemiologic and serologic data were collected retrospectively for 344 chronically HBV-infected blood donors identified from July 2005 to June 2010. Additional laboratory testing was carried out to determine the HBV genotype, viral load, and prevalence of clinically significant mutations and to detect hepatitis delta virus (HDV) coinfection. RESULTS: Five HBV genotypes (A-E) were found, Genotypes D (45%), A (20%), and E (20%) were the most prevalent. A strong association was seen between genotype and donor ethnicity (p < 0.001) and between genotype and place of residence (p = 0.006). Clinically significant mutations were observed across hepatitis B surface antigen (17%), basal core promoter (25%) and precore (78%) regions. An antiviral resistance profile was identified in one donor. Evidence of HDV coinfection was found in 2% of donors. CONCLUSION: The data show the diversity of HBV in asymptomatic chronic infections detected in blood donors in England and North Wales and demonstrates the presence of mutations which may impact on disease. The global nature of these infections and the inability to identify chronically infected donors before donation highlights the importance of using screening assays capable of detecting a broad range of genotypes and mutations. Furthermore, the integration of the virologic and demographic data allows us to more accurately construct a profile of our chronically HBV-infected blood donors.

The effect of body mass index on the outcome of pregnancy in women with recurrent miscarriage.

BACKGROUND: Maternal obesity is associated with menstrual disorders, infertility and sporadic miscarriages. Recurrent miscarriage (RM) affects at least 1% of couples trying to conceive. In over 50% of cases, the cause of the loss of pregnancy remains unexplained. The aim of this study was to determine the relationship between maternal Body Mass Index (BMI) and future outcomes of pregnancy in couples with "unexplained" RM. METHODS AND RESULTS: All couples referred to the specialist recurrent miscarriage clinic at St. Mary's Hospital, London, were investigated for an underlying cause. Those with unexplained RM were eligible. Demographic and clinical data were retrieved from a computerised database and medical records. The World Health Organisation (WHO) classification of BMI was used. Univariate analysis demonstrated that BMI, maternal age, number of previous miscarriages and ethnicity were significantly associated with pregnancy outcome. Logistic regression demonstrated that maternal obesity (BMI ≥ 30 kg/m(2)) significantly increased the risk of miscarriage in couples with unexplained RM (OR 1.73; 95% CI 1.06 - 2.83). Asian women with a BMI similar to Caucasian women had a higher risk of a further miscarriage (OR 2.87, 95% CI, 1.52 - 5.39). CONCLUSIONS: Maternal obesity is an independent factor associated with an increased risk of miscarriage in couples with RM. All women with RM should have their BMI recorded at their first clinic visit. The potential effect of weight loss on the outcome of subsequent pregnancies should be assessed in future studies. The increased risk of miscarriage in Asian women needs to be explored further.