An international review of the characteristics of viral nucleic acid-amplification testing (NAT) reveals a trend towards the use of smaller pool sizes and individual donation NAT.

BACKGROUND AND OBJECTIVES: Nucleic acid-amplification testing (NAT) is used for screening blood donations/donors for blood-borne viruses. We reviewed global viral NAT characteristics and NAT-yield confirmatory testing used by blood operators. MATERIALS AND METHODS: NAT characteristics and NAT-yield confirmatory testing used during 2019 was surveyed internationally by the International Society of Blood Transfusion Working Party Transfusion-Transmitted Infectious Diseases. Reported characteristics are presented herein. RESULTS: NAT was mainly performed under government mandate. Human immunodeficiency virus (HIV), hepatitis C virus (HCV) and hepatitis B virus (HBV) NAT was performed on all donors and donation types, while selective testing was reported for West Nile virus, hepatitis E virus (HEV), and Zika virus. Individual donation NAT was used for HIV, HCV and HBV by ~50% of responders, while HEV was screened in mini-pools by 83% of responders performing HEV NAT. Confirmatory testing for NAT-yield samples was generally performed by NAT on a sample from the same donation or by NAT and serology on samples from the same donation and a follow-up sample. CONCLUSION: In the last decade, there has been a trend towards use of smaller pool sizes or individual donation NAT. We captured characteristics of NAT internationally in 2019 and provide insights into confirmatory testing approaches used for NAT-yields, potentially benefitting blood operators seeking to implement NAT.

International review of blood donation nucleic acid amplification testing.

BACKGROUND AND OBJECTIVES: Nucleic acid amplification testing (NAT), in blood services context, is used for the detection of viral and parasite nucleic acids to reduce transfusion-transmitted infections. This project reviewed NAT for screening blood donations globally. MATERIALS AND METHODS: A survey on NAT usage, developed by the International Society of Blood Transfusion Working Party on Transfusion-transmitted Infectious Diseases (ISBT WP-TTID), was distributed through ISBT WP-TTID members. Data were analysed using descriptive statistics. RESULTS: Forty-three responses were received from 32 countries. Increased adoption of blood donation viral screening by NAT was observed over the past decade. NAT-positive donations were detected for all viruses tested in 2019 (proportion of donations positive by NAT were 0.0099% for human immunodeficiency virus [HIV], 0.0063% for hepatitis C virus [HCV], 0.0247% for hepatitis B virus [HBV], 0.0323% for hepatitis E virus [HEV], 0.0014% for West Nile virus [WNV] and 0.00005% for Zika virus [ZIKV]). Globally, over 3100 NAT-positive donations were identified as NAT yield or solely by NAT in 2019 and over 22,000 since the introduction of NAT, with HBV accounting for over half. NAT-positivity rate was higher in first-time donors for all viruses tested except WNV. During 2019, a small number of participants performed NAT for parasites (Trypanosoma cruzi, Babesia spp., Plasmodium spp.). CONCLUSION: This survey captures current use of blood donation NAT globally. There has been increased NAT usage over the last decade. It is clear that NAT contributes to improving blood transfusion safety globally; however, there is a need to overcome economic barriers for regions/countries not performing NAT.

Safety Analysis of Extended Platelet Shelf-Life with Large-Volume Delayed Sampling on BACT/ALERT® VIRTUO® in Australia.

Transfusion-transmitted bacterial infection (TTBI) is the leading cause of transfusion-transmitted infections. Platelet components are more likely to be associated with bacterial contamination due to their storage requirements. Australian Red Cross Lifeblood introduced the bacterial contamination screening (BCS) of all platelet components in 2008. The process was recently updated with the use of BACT/ALERT® VIRTUO®, a large-volume delayed sampling (LVDS) protocol and extending platelet shelf-life to seven days. This article describes the results from the routine BCS of platelet components in Australia. Use of VIRTUO has resulted in lower false-positive rates, reducing wastage and improving platelet inventory. Our findings show that the combination of LVDS and VIRTUO improves the safety of platelet transfusions through earlier time to detection, especially for pathogenic bacterial species. Pathogenic bacteria grew within 24 h of incubation with a clear delineation between pathogenic and non-pathogenic species. The data show this protocol is very safe, with no TTBI cases during this time. There were no TTBI reports in recipients of platelet components that subsequently had a positive culture with Cutibacterium species, probably due to the low pathogenic potential of these organisms and slow replication in aerobic platelet bags. We conclude there is no advantage in incubating culture bottles beyond five days.

Removal of UK-donor deferral for variant Creutzfeldt-Jakob disease: A large donation gain in Australia.

BACKGROUND AND OBJECTIVES: Until 25 July 2022, people who spent more than 6 months in the United Kingdom during the variant Creutzfeldt-Jakob disease (vCJD) risk period 1980-1996 (UK donors) were deferred from blood donation in Australia. Regulatory approval to remove the deferral was underpinned by published mathematical modelling predicting negligible vCJD transmission risk increase with a gain of 58,000 donations. MATERIALS AND METHODS: The donor questionnaire retained the UK deferral screening question until a version update effective 12 February 2023, which enabled identification of the newly eligible cohort of UK donors. Their donations were tracked for a 6-month period (25 July 2022-24 January 2023) and compared with baseline Lifeblood donation metrics and predicted gains. RESULTS: A total of 38,462 UK donors attended to donate 78,762 times in the 6 months. Of these, 32,358 donors (females = 19,456, males = 12,902) successfully donated 67,914 times representing 8.4% of total collections. CONCLUSION: Cessation of the UK deferral resulted in donation gains exceeding modelled predictions because of a higher than predicted number of donors who donated at a higher rate. Had these newly eligible donors not donated, overall donation numbers would have been 88% of target rather than the 96% achieved.

Risk of variant Creutzfeldt-Jakob disease transmission by blood transfusion in Australia.

BACKGROUND AND OBJECTIVES: Most of the 233 worldwide cases of variant Creutzfeldt-Jakob disease (vCJD) have been reported in the United Kingdom and 3 have been associated with transfusion-transmission. To mitigate the potential vCJD risk to blood safety, Australian Red Cross Lifeblood imposes restrictions on blood donation from people with prior residency in, or extended travel to, the United Kingdom during the risk period 1980-1996. We have modified a previously published methodology to estimate the transfusion-transmission risk of vCJD associated with fresh component transfusion in Australia if the UK residence deferral was removed. MATERIALS AND METHODS: The prevalence of current pre-symptomatic vCJD infection in the United Kingdom by age at infection and genotype was estimated based on risk of exposure to the bovine spongiform encephalopathy agent for the period 1980-1996. These results were used to estimate the age-specific prevalence of undiagnosed, pre-symptomatic vCJD in the Australian population in the current year due to prior UK residency or travel. The primary model outputs were the 2020 vCJD risks/unit of vCJD contamination, transfusion-transmission (infections) and clinical cases. RESULTS: The overall (prior UK residency in and travel to United Kingdom, 1980-1996) mean risk of contamination per unit was 1 in 29,900,000. The risks of resulting vCJD transmission (infection) and clinical case were 1 in 389,000,000 and 1 in 1,450,000,000, respectively. CONCLUSION: Our modelling suggests that removing the Lifeblood donation deferral for travel to, or UK residence, would result in virtually no increased risk of vCJD transfusion-transmission and would be a safe and effective strategy for increasing the donor base.

Effect of HIV pre-exposure prophylaxis (PrEP) on detection of early infection and its impact on the appropriate post-PrEP deferral period.

INTRODUCTION: HIV antivirals for pre-exposure prophylaxis (PrEP) are known to affect detection of early HIV infection through suppression of viral load and delayed seroconversion. To cover potential delay in HIV detection associated with PrEP use by blood donors in the context of international reductions in sexual activity-based deferral periods, we analysed the available data to determine the appropriate minimum post-PrEP deferral period for blood donation. MATERIALS AND METHODS: Published cases of incident HIV infection when PrEP use was objectively demonstrable were identified, consisting principally of seroconverters from the Partners PrEP study (a clinical trial of PrEP efficacy). Data were reviewed to determine the impact of PrEP on the detection of HIV RNA, p24 Ag and seroconversion delay. RESULTS: Nucleic acid testing (NAT) detected early HIV infection in the presence of PrEP prior to or in concordance with serological testing in approximately 90% of cases. Undetectable HIV RNA would rebound to detectable levels within two months of PrEP cessation. PrEP delayed p24 antigen detection and antibody seroconversion by about 7 days. CONCLUSION: Even when daily PrEP is continued, it is likely that the majority of early HIV infections are detectable by individual donation (ID)-NAT, with p24 Ag or antibody seroconversion occurring conservatively within four weeks of exposure. HIV RNA levels also rebound rapidly in the absence of PrEP. In Australia, a three-month deferral period for blood donation after the last dose of PrEP provides an appropriate safety margin to mitigate the residual risk of transfusion-transmitted HIV.

Blood safety assessment of hepatitis A outbreak linked to frozen pomegranate arils: are foodborne outbreaks an emerging blood safety risk?

BACKGROUND: Foodborne hepatitis A virus (HAV) outbreaks are becoming more common in high-income countries with low HAV incidence, and the associated blood safety risk may not be adequately mitigated by routine HAV risk mitigation strategies. This study describes the rapid risk modeling undertaken in response to a 2018 HAV outbreak in Australia associated with imported frozen pomegranate arils. STUDY DESIGN AND METHODS: The input parameters used in the modeling were the outbreak-associated HAV incidence, duration of viremia, population seroprevalence, and rate of symptomatic infection in adults. The number and risk of viremic components issued, cases of transfusion transmission, and symptomatic infections among recipients were estimated. RESULTS: The incidence of pomegranate-associated HAV infection among donors was very low, with fewer than 0.1 viremic fresh components estimated to have been released during the risk period. The risk of this event was less than one in 500,000, and the risks of transfusion transmission and symptomatic illness in recipients were less than one in one million. When considering only donors who had consumed the pomegranate product, the risk was much higher, with approximately one in 1000 components estimated to be viremic. CONCLUSION: Rapid risk assessment indicated that the overall risk to blood safety associated with a small foodborne outbreak of HAV was negligible. Because fresh components collected from donors known to have consumed the affected product were at high risk, these donors were identified via signage in donor centers and deferred. The contribution of factors other than outbreak size to risk management decisions is discussed.

Modeling the parvovirus B19 blood safety risk in Australia.

BACKGROUND: Three probable cases of transfusion-transmitted (TT) parvovirus B19 (B19V) occurred in Australia between 2014 and 2017. This study aimed to determine the B19V DNA prevalence among blood donors, to model the risk to recipients of fresh components, and to assess risk management options. STUDY DESIGN AND METHODS: Plasma samples from 4232 donors were tested for B19V DNA by polymerase chain reaction. Reactive samples were confirmed and viral load determined. A transmission-risk model was used to estimate recipient risk, and the risk from community exposure was estimated using seroprevalence data. RESULTS: Two samples (0.0473%, 95% confidence interval [CI] 0.0130-0.172) confirmed positive for B19V DNA had a potentially infectious viral load of 105 IU/mL or higher. The estimated risk of a TT-B19V-associated significant complication was low overall at approximately 1 in 300,000 (95% CI, 1 in 82,000 to 1 in 1 million) fresh components transfused, with 3.1 (95% CI, 0.85-11.3) complications modeled per year. Among vulnerable recipient groups, the risk was higher than 1 in 15,000 patients, but the risk from community exposure far exceeded the transfusion risk for all patient and age groups. CONCLUSION: In the context of the small contribution of transfusion to the burden of B19V disease, the significant costs that would be incurred by any strategy to reduce the risk, and given the significant uncertainties and likely overestimation of the risk, we conclude TT-B19V is a tolerable risk to blood safety, despite being high for some vulnerable recipient groups.

Modelling the risk of transfusion-transmitted syphilis: a reconsideration of blood donation testing strategies.

BACKGROUND AND OBJECTIVES: Donor syphilis testing began in the 1940s amidst widespread transfusion-transmitted syphilis (TTS). Since then, the introduction of penicillin, pre-donation screening questionnaires and improved storage conditions have contributed to reducing transmission risk. Consequently, universal testing may no longer be cost-effective. This study analysed alternative options for donor syphilis testing to determine the optimal strategy. MATERIALS AND METHODS: A model was developed using conservative parameter estimates for factors affecting TTS and 2009-2015 Australian donations to calculate risk outcomes (TTS infections, tertiary syphilis in recipients and transfusion-associated congenital syphilis) and cost-effectiveness of alternative testing strategies. The strategies modelled were as follows: universal testing, targeted-testing of high-risk groups (males ≤50 years old and first-time donors) and no testing. RESULTS: The estimated risk of TTS is one in 49·5 million transfusions for universal testing, one in 6 million for targeted-testing of males ≤50 years old, one in 4 million for targeted-testing of first-time donors and one in 2·8 million for no testing. For all strategies, the risk of tertiary and congenital syphilis is <1 in 100 million. Universal testing is the least cost-effective strategy with an incremental cost-effectiveness ratio (ICER) estimated at $538·5 million per disability-adjusted life year averted. CONCLUSION: Universal testing is not required to maintain the risk of TTS within tolerable limits and is estimated to greatly exceed acceptable ICERs for blood safety interventions. However, despite a strong economic and risk-based rationale, given the epidemiology of syphilis in Australia is changing, feedback from critical stakeholders is not currently supportive of reducing testing.

Estimation of human T-lymphotropic virus incidence in blood donors from observed prevalence.

Repeat donors in Australia will shortly cease to be tested for human T-lymphotropic virus (HTLV), removing the ability to measure repeat donor incidence. A risk threshold for repeat donors was investigated based on previous modelling and a conservative ratio between prevalent and incident infections. It was estimated that 26 infections per 100 000 new-donor donations would be associated with an incidence in repeat donors approaching the tolerable risk threshold if sustained over several years. We propose to trigger formal risk assessment at this point, and believe this solution may be useful for other blood services that reduce their HTLV testing requirements.

Daily iron supplementation for improving anaemia, iron status and health in menstruating women.

BACKGROUND: Iron-deficiency anaemia is highly prevalent among non-pregnant women of reproductive age (menstruating women) worldwide, although the prevalence is highest in lower-income settings. Iron-deficiency anaemia has been associated with a range of adverse health outcomes, which restitution of iron stores using iron supplementation has been considered likely to resolve. Although there have been many trials reporting effects of iron in non-pregnant women, these trials have never been synthesised in a systematic review. OBJECTIVES: To establish the evidence for effects of daily supplementation with iron on anaemia and iron status, as well as on physical, psychological and neurocognitive health, in menstruating women. SEARCH METHODS: In November 2015 we searched CENTRAL, Ovid MEDLINE, EMBASE, and nine other databases, as well as four digital thesis repositories. In addition, we searched the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) and reference lists of relevant reviews. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs comparing daily oral iron supplementation with or without a cointervention (folic acid or vitamin C), for at least five days per week at any dose, to control or placebo using either individual- or cluster-randomisation. Inclusion criteria were menstruating women (or women aged 12 to 50 years) reporting on predefined primary (anaemia, haemoglobin concentration, iron deficiency, iron-deficiency anaemia, all-cause mortality, adverse effects, and cognitive function) or secondary (iron status measured by iron indices, physical exercise performance, psychological health, adherence, anthropometric measures, serum/plasma zinc levels, vitamin A status, and red cell folate) outcomes. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures of Cochrane. MAIN RESULTS: The search strategy identified 31,767 records; after screening, 90 full-text reports were assessed for eligibility. We included 67 trials (from 76 reports), recruiting 8506 women; the number of women included in analyses varied greatly between outcomes, with endpoint haemoglobin concentration being the outcome with the largest number of participants analysed (6861 women). Only 10 studies were considered at low overall risk of bias, with most studies presenting insufficient details about trial quality.Women receiving iron were significantly less likely to be anaemic at the end of intervention compared to women receiving control (risk ratio (RR) 0.39 (95% confidence interval (CI) 0.25 to 0.60, 10 studies, 3273 women, moderate quality evidence). Women receiving iron had a higher haemoglobin concentration at the end of intervention compared to women receiving control (mean difference (MD) 5.30, 95% CI 4.14 to 6.45, 51 studies, 6861 women, high quality evidence). Women receiving iron had a reduced risk of iron deficiency compared to women receiving control (RR 0.62, 95% CI 0.50 to 0.76, 7 studies, 1088 women, moderate quality evidence). Only one study (55 women) specifically reported iron-deficiency anaemia and no studies reported mortality. Seven trials recruiting 901 women reported on 'any side effect' and did not identify an overall increased prevalence of side effects from iron supplements (RR 2.14, 95% CI 0.94 to 4.86, low quality evidence). Five studies recruiting 521 women identified an increased prevalence of gastrointestinal side effects in women taking iron (RR 1.99, 95% CI 1.26 to 3.12, low quality evidence). Six studies recruiting 604 women identified an increased prevalence of loose stools/diarrhoea (RR 2.13, 95% CI 1.10, 4.11, high quality evidence); eight studies recruiting 1036 women identified an increased prevalence of hard stools/constipation (RR 2.07, 95% CI 1.35 to 3.17, high quality evidence). Seven studies recruiting 1190 women identified evidence of an increased prevalence of abdominal pain among women randomised to iron (RR 1.55, 95% CI 0.99 to 2.41, low quality evidence). Eight studies recruiting 1214 women did not find any evidence of an increased prevalence of nausea among women randomised to iron (RR 1.19, 95% CI 0.78 to 1.82). Evidence that iron supplementation improves cognitive performance in women is uncertain, as studies could not be meta-analysed and individual studies reported conflicting results. Iron supplementation improved maximal and submaximal exercise performance, and appears to reduce symptomatic fatigue. Although adherence could not be formally meta-analysed due to differences in reporting, there was no evident difference in adherence between women randomised to iron and control. AUTHORS' CONCLUSIONS: Daily iron supplementation effectively reduces the prevalence of anaemia and iron deficiency, raises haemoglobin and iron stores, improves exercise performance and reduces symptomatic fatigue. These benefits come at the expense of increased gastrointestinal symptomatic side effects.

A refined method for estimating the size of the potential blood donor pool in Australia.

BACKGROUND: To be eligible to donate blood, potential donors must meet certain eligibility criteria to ensure safety to the donor and to the blood supply. In Australia, there is no reliable estimate of the size of the donor-eligible population. This study uses a refinement to a published method to determine the population prevalence of donor-exclusion factors and subsequently estimates the size of the potential donor pool in Australia. STUDY DESIGN AND METHODS: A total of 70 donor-exclusion factors (in addition to age) were identified. The donor-eligible population was estimated by subtracting the prevalence of the exclusion factors from the total population. Prevalence of the donor-exclusion factors was adjusted for age, deferral period, and overlap of multiple conditions. Overlap was adjusted by extending a published random-probability model according to known association of epidemiologic data on overlapping conditions. RESULTS: The most prevalent (deferral period-adjusted) donor-exclusion factor among the 16- to 80-year-old Australian population was variant Creutzfeldt-Jakob disease-related travel risk (6.8%) followed by upper respiratory tract infections (6.4%). After exclusion of all factors, and accounting for overlapping factors, 62% of 16- to 80-year-olds or 47.3% of the total population were donor eligible in Australia. CONCLUSION: We developed a refined method for estimating the size of the donor-eligible population. Applying this method to Australia, we estimate that approximately 10.7 million people (62% of the 16- to 80-year-olds) were eligible to donate blood in Australia in 2012.