Postdonation iron replacement for maintaining iron stores in female whole blood donors in routine donor practice: results of two feasibility studies in Australia.

BACKGROUND: Iron deficiency represents a risk to donor health and the blood supply. Efficacy trials indicate that postdonation iron replacement improves iron stores but they do not account for complexities of implementation in the routine collection context. We therefore conducted two prospective feasibility studies in Australian donor centers. STUDY DESIGN AND METHODS: In both studies we recruited female donors between 18 and 45 years who had made at least one donation in the previous 12 months. In READ (replacement advice), female donors were given a recommendation to self-procure postdonation iron. In DIRECT (donor iron replacement), donors were provided with a course of iron supplements. Donors could return to donate at their discretion and were surveyed after the recruitment visit and again toward the end of the 13-month follow-up. Donor uptake, adverse effects, effectiveness in maintaining iron stores, and workflow impact were assessed. RESULTS: We recruited 1404 (70.9% of invited) donors to READ and 768 (53.2% of invited) to DIRECT. READ and DIRECT extended predonation interviews by 1 and 5 minutes, respectively. Among participants, 44 and 88% took iron in READ and DIRECT, respectively. Adverse effects were common but usually mild. READ failed to maintain iron stores in the population, but was effective in donors who consumed more than 75% of the recommended dose. DIRECT was effective in preventing declines in ferritin concentration. CONCLUSION: Trade-offs between cost, complexity, uptake, and effectiveness must be considered in the implementation of postdonation iron supplementation.

Hepatitis E virus infections in travellers: assessing the threat to the Australian blood supply.

BACKGROUND: In many developed countries hepatitis E virus (HEV) infections have occurred predominantly in travellers to countries endemic for HEV. HEV is a potential threat to blood safety as the virus is transfusion-transmissible. To minimise this risk in Australia, individuals diagnosed with HEV are deferred. Malarialdeferrals, when donors are restricted from donating fresh blood components following travel toanareain which malaria is endemic, probably also decrease the HEV risk, by deferring donors who travel to many countries also endemic for HEV. The aim of this study is to describe overseas-acquired HEV cases in Australia, in order to determine whether infection in travellers poses a risk to Australian blood safety. MATERIALS AND METHODS: Details of all notified HEV cases in Australia from 2002 to 2014 were accessed, and importation rates estimated. Countries in which HEV was acquired were compared to those for which donations are restricted following travel because of a malaria risk. RESULTS: Three hundred and thirty-two cases of HEV were acquired overseas. Travel to India accounted for most of these infections, although the importation rate was highest for Nepal and Bangladesh. Countries for which donations are restricted following travel due to malaria risk accounted for 94% of overseas-acquired HEV cases. DISCUSSION: The vast majority of overseas-acquired HEV infections were in travellers returning from South Asian countries, which are subject to donation-related travel restrictions for malaria. This minimises the risk HEV poses to the Australian blood supply.

Hepatitis E virus RNA in Australian blood donations.

BACKGROUND: Hepatitis E virus (HEV) poses a risk to transfusion safety. In Australia, locally acquired HEV is rare and cases are mainly reported in travelers returning from countries endemic for HEV. The risk posed by HEV to transfusion safety in Australia is unknown; therefore, we aimed to measure the rate of current HEV infection in Australian blood donations. STUDY DESIGN AND METHODS: A total of 14,799 blood donations were tested for HEV RNA by transcription-mediated amplification, with confirmatory testing by reverse transcription-polymerase chain reaction. Viral load quantification and phylogenetic analysis was performed on HEV RNA-positive samples. RESULTS: One (0.0068%; 95% confidence interval [CI], 0.0002%-0.0376%) sample was confirmed positive for HEV RNA, resulting in a risk of collecting a HEV-viremic donation of 1 in 14,799 (95% CI, 1 in 584,530 to 1 in 2,657). The viral load in this sample was approximately 15,000 IU/mL, and it was determined to be Genotype 3. DISCUSSION: Our finding of 1 in 14,799 Australian donations positive for HEV RNA is lower than that from many other developed countries; this is consistent with the relatively low seroprevalence in Australia. As this HEV RNA-positive sample was Genotype 3, it seems likely that this infection was acquired through zoonotic transmission, either within Australia or overseas in a developed nation. HEV has the potential to pose a risk to transfusion safety in Australia; however, additional, larger studies are required to quantify the magnitude of this risk.

Hepatitis E virus: do locally acquired infections in Australia necessitate laboratory testing in acute hepatitis patients with no overseas travel history?

Hepatitis E virus (HEV) is emerging as a global public health threat. Water-borne HEV outbreaks are common in developing countries and are associated with genotypes 1 and 2. In industrialised countries, sporadic cases of zoonotic transmission associated with genotypes 3 and 4 are increasingly being reported. Transfusion- and transplantation-transmitted HEV have been documented, although ingestion of contaminated food is thought to be the major transmission route. Severe disease is possible and chronic hepatitis infection occurs in solid-organ-transplant recipients and in patients with immunosuppressive disorders. In Australia, HEV cases are mainly travellers returning from disease endemic countries. Indeed, there are few reported cases of locally acquired HEV. Pigs in Australia have been shown to be infected with HEV, which indicates the possibility of zoonotic transmission. The extent of locally acquired infection is not known, however it may be greater than expected and may necessitate laboratory testing in patients reporting no overseas travel.

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.

Understanding noncompliance with selective donor deferral criteria for high-risk behaviors in Australian blood donors.

BACKGROUND: Using a predonation screening questionnaire, potential blood donors are screened for medical or behavioral factors associated with an increased risk for transfusion-transmissible infection. After disclosure of these risks, potential donors are deferred from donating. Understanding the degree of failure to disclose full and truthful information (termed noncompliance) is important to determine and minimize residual risk. This study estimates the prevalence of, and likely reasons for, noncompliance among Australian donors with the deferrals for injecting drug use, sex with an injecting drug user, male-to-male sex, sex worker activity or contact, and sex with a partner from a high-HIV-prevalence country. STUDY DESIGN AND METHODS: An anonymous, online survey of a nationally representative sample of Australian blood donors was conducted. Prevalence of noncompliance with deferrable risk categories was estimated. Factors associated with noncompliance were determined using unadjusted and adjusted odds ratios. RESULTS: Of 98,044 invited donors, 30,790 donors completed the survey. The estimated prevalence of overall noncompliance (i.e., to at least one screening question) was 1.65% (95% confidence interval CI, 1.51%-1.8%). Noncompliance with individual deferrals ranged from 0.05% (sex work) to 0.54% (sex with an injecting drug user). The prevalences of the disclosed exclusionary risk behaviors were three to 14 times lower than their estimated prevalence in the general population. CONCLUSION: The prevalence of noncompliance is relatively low but our estimate is likely to be a lower bound. The selected high-risk behaviors were substantially less common in blood donors compared to the general population suggesting that self-deferral is effective. Nevertheless, a focus on further minimization should improve the blood safety.

An 8-week course of 45 mg of carbonyl iron daily reduces iron deficiency in female whole blood donors aged 18 to 45 years: results of a prospective randomized controlled trial.

BACKGROUND: Blood donation is known to contribute to iron deficiency in regular blood donors. This study investigated the safety and efficacy of postdonation iron replacement to mitigate iron deficiency in blood donors. STUDY DESIGN AND METHODS: A total of 282 female whole blood donors aged 18 to 45 were prospectively randomized in a double-blinded placebo controlled trial to receive an 8-week postdonation course of carbonyl iron (45 mg daily) or placebo. The primary endpoint was prevalence of iron deficiency (ferritin < 15 ng/mL) at 12 weeks postdonation. Secondary endpoints were eligibility to donate based on capillary hemoglobin (Hb) and incidence of gastrointestinal (GI) complaints. RESULTS: Ferritin levels at Week 12 were significantly higher in donors receiving carbonyl iron (17.0 ± 10.9 ng/mL) compared with those receiving placebo (10.6 ± 8.4 ng/mL; p < 0.001). The proportion of iron-deficient donors was significantly lower in the carbonyl iron group (51.9%) compared to the placebo (80.5%; p < 0.001). The mean Hb level in the carbonyl iron group (134.6 ± 8.7 g/L) was significantly higher than in the placebo arm (130.0 ± 9.9 g/L; p < 0.001), significantly improving eligibility to donate at Week 12. Significantly more donors receiving carbonyl iron had at least one GI side effect (p < 0.001). Importantly, 86.7% of donors receiving carbonyl iron indicated that they would take iron on an ongoing basis. CONCLUSION: An 8-week postdonation course of 45 mg of carbonyl iron significantly reduced iron deficiency and was well tolerated in female whole blood donors. Postdonation iron replacement may have a role in a broader strategy to optimize donor iron status.

Hemoglobin and iron indices in nonanemic premenopausal blood donors predict future deferral from whole blood donation.

BACKGROUND: Iron deficiency anemia is an important reason for blood donor deferral. We prospectively determined whether screening donors with hemoglobin (Hb) and iron indices before donation can predict subsequent deferral due to anemia. STUDY DESIGN AND METHODS: We recruited premenopausal, eligible (nonanemic) female donors. Hb, ferritin, soluble transferrin receptor (sTfR), and hepcidin were measured, and the sTfR/(log)ferritin (sTfR-F) index was calculated. After 6 months, the donor database was reviewed and whether donors had returned and undergone successful donation was recorded. RESULTS: Of donors, 59 of 261(22.6%) were iron depleted (ferritin < 15 ng/mL). Iron-depleted donors had donated more often in the previous year, were younger, and had lower Hb. After a minimum of 6 months, 145 eligible donors had returned; of these 10 (6.9%) were deferred for anemia. Donors who developed anemia had significantly lower Hb, ferritin, and hepcidin and higher sTfR and sTfR-F at baseline. The area under the receiver operating characteristic curve for Hb as a predictor of deferral was 0.86, and for ferritin was 0.88. Hb of less than 130 g/L and ferritin of less than 10 ng/mL combined had sensitivity 80% and specificity 96% in predicting deferral. CONCLUSION: Screening with Hb and iron indices enables prediction of donors at risk of subsequent anemia and who would most benefit from prevention strategies.

No evidence of a significantly increased risk of transfusion-transmitted human immunodeficiency virus infection in Australia subsequent to implementing a 12-month deferral for men who have had sex with men.

BACKGROUND: Male-to-male sex is the predominant route of human immunodeficiency virus (HIV) transmission in Australia and since the early 1980s blood services in Australia have deferred donors for this practice for at least 5 years. This retrospective analysis assesses the impact on HIV prevalence of implementing an abridged 12-month deferral for male-to-male sex. STUDY DESIGN AND METHODS: The prevalence of HIV among blood donors for 5-year periods before (Period 1) and after (Period 2) implementing the revised 12-month deferral was compared. Using deidentified data from postdonation interviews with HIV-positive donors the proportion disclosing male-to-male sex as a risk factor was compared for the two periods. RESULTS: Twenty-four HIV-positive donations were identified among 4,025,571 donations in Period 1 compared with 24 among 4,964,628 donations in Period 2 (p=0.468). The proportion of HIV-positive donors with male-to-male sex as a risk factor in Period 1 was 2 in 15 (13.3%), which was not significantly different from the proportion in Period 2, 5 in 16 (31.25%; p=0.22). All five men who have sex with men risk HIV infections during Period 2 were from donors whose risk was within the 12-month criterion for acceptability, who would have been deferred had they provided a complete history. CONCLUSIONS: We found no evidence that the implementation of the 12-month deferral for male-to-male sex resulted in an increased recipient risk for HIV in Australia. The risk of noncompliance to the revised deferral rather than its duration appears to be the most important modifier of overall risk.

Can blood tranfusion transmit cancer? A literature review.

Blood services around the world face increasing challenges in recruiting voluntary blood donors. With increasing donor restrictions and ageing populations, it is essential to look for any existing restrictions that may be relaxed in the light of currently available evidence. We propose that one such restriction is the exclusion of blood donors with a history of a malignancy. Most blood services apart from the United States and Australia continue the historical precaution of permanently excluding donors with a history of cancer, despite the absence of any convincing reports of cancer transmission among the millions of allogeneic blood transfusions performed since the advent of blood banking. In 2007, workers in Scandinavia published convincing data from the SCANDAT (Scandinavian Donations and Transfusions) database that showed no increase in cancer risk among recipients of blood from "precancerous" donors (ie, donors who were later diagnosed with cancer within 5 years of donating) vs recipients of blood from other donors. This review aims to reconcile this finding with other data available in the published literature that is pertinent to the risk of transmitting cancer via blood transfusion, with a view to establishing that there is now sufficient evidence to support the acceptance of carefully selected blood donors with a history of malignant disease.

Relapsing vivax malaria despite chemoprophylaxis in two blood donors who had travelled to Papua New Guinea.

Two Australian blood donors were diagnosed with relapsing Plasmodium vivax malaria 5 and 15 months, respectively, after their most recent travel to a malaria-endemic country. Common features included travel to Papua New Guinea (specifically, the Kokoda Trail); full compliance with recommended malaria chemoprophylaxis; and negative results on malaria antibody testing at the time of donation. Although all fresh blood components from the two donors issued on the basis of these negative results were recalled before transfusion, these cases underscore the increased potential for relapse of P. vivax in donors returning from malaria-endemic countries, as well as the inability to identify the potential for relapse using current malarial screening tests.

The risk of dengue transmission by blood during a 2004 outbreak in Cairns, Australia.

BACKGROUND: Dengue virus (DENV) is a Flavivirus transmitted by the Aedes mosquito. The related arbovirus, West Nile virus, has been shown to be transfusion transmitted, which, added to the four recorded dengue transfusion-associated cases, indicates that DENV is also transfusion transmitted. The purpose of this study was to assess the risk of transfusion-transmitted DENV during a 2004 outbreak in the Australian city of Cairns. STUDY DESIGN AND METHODS: A mathematical model was constructed to estimate the risk of transfusion-transmitted dengue. The model's central premise is that the transmission risk is proportional to the frequency of dengue-viremic donations and correlates with the incidence of asymptomatic dengue viremia among the population at large. RESULTS: The modeling predicted that the total number of DENV infections (clinical plus subclinical) among the population at large during the entire outbreak ranged from 156 to 569 with the epidemic peak occurring between February 8 and March 6, 2004. The overall transmission risk during the entire outbreak was estimated as 1 in 19,759 (range, 1 in 3404 to 75,486) peaking at 1 in 5968 (range 1 in 1028 to 22,800). CONCLUSION: By use of the most conservative estimates for key variables, the risk of collecting a viremic donation could have been as high as 1 in 1028 during the peak of the 2004 outbreak. The model can be used to determine transfusion transmission risk levels during DENV outbreaks and inform decisions as to when fresh component restriction measures are required to minimize transfusion transmission risk.

Emerging viral threats to the Australian blood supply.

OBJECTIVES: To assess the risk to the Australian blood supply posed by emerging or re-emerging viral infections. METHOD: A review was undertaken of the English-speaking literature on the potential for emerging viral threats to human health in Australia, the future implications of virus ecology, climate change and population movement and the implications for blood transfusion. RESULTS: Published data confirm that Australia's blood supply is among the safest in the world for currently screened viral pathogens as a result of rigorous surveillance, donor selection and state-of-the-art processing and laboratory testing. However, Australia has a number of other viral pathogens with the potential to threaten the safety of the blood supply such as the Ross River, Barmah Forrest, Kunjin, Japanese Encephalitis, Murray Valley Encephalitis and dengue viruses. Of these, dengue is currently of most concern to blood safety because; it can cause fatalities, there are regular seasonal outbreaks in Northern Australia and, in contrast to other viruses mentioned above an overseas case of transfusion transmission has already been documented. Notably, despite the lack of a suitable dengue screening test the ARCBS already implements supplementary measures to protect the blood supply during outbreaks. CONCLUSION: Current interventions have proven extremely effective in minimising transfusion transmission in Australia of recognised viral pathogens. The threat posed by emerging viral pathogens to the safety of blood transfusion emphasises the need for global collaboration and consideration of further intervention strategies on a country by country basis including options such as nucleic acid testing and pathogen reduction technologies.

Reducing the risk of transfusion-transmissible viral infection through blood donor selection: the Australian experience 2000 through 2006.

BACKGROUND: Selection of voluntary donors who are at low risk of transfusion-transmissible viral infection (TTVI) is central in maintaining the safety of the blood supply. Evaluation of its effectiveness and the dynamics of the process may offer opportunities to further improve transfusion safety. STUDY DESIGN AND METHODS: The impact of donor selection on prevalence of TTVI was analyzed in all allogeneic donations in Australia between July 2000 and June 2006 by interviewing donors found to have a TTVI. The presence and disclosure of infective risks was reassessed. RESULTS: A total of 6.3 million donations were tested; of these, 1,449 (0.02%) were repeat-reactive for a TTVI and were discarded. This comprised 605 (42%) positive for the presence of hepatitis B, 818 (56%) positive for the presence of hepatitis C, 18 (1%) positive for the presence of human immunodeficiency virus, and 20 (1%) positive for the presence of human T-cell lymphotropic virus-I and/or -II (HTLV-I/II). This prevalence was 50 to 350 times lower than in the Australian population. In 1,158 cases (80%), an infective risk was identified; 509 donors (44%) had more than one. The most common identified were country of birth and parental ethnicity (n = 682, 26% of risks), tattoos and/or piercings (n = 448, 18%), and intravenous drug use (n = 302, 12%). In 302 cases (21%) disclosure at predonation screening would have resulted in deferral. Factors influencing nondisclosure included temporal remoteness and perceptions that laboratory testing rendered disclosure unnecessary. CONCLUSION: These findings affirm the effectiveness of current stringent donor selection criteria in reducing the residual risk of TTVI. Ongoing donor education regarding the importance of risk disclosure is required.

Comparison of two automated nucleic acid testing systems for simultaneous detection of human immunodeficiency virus and hepatitis C virus RNA and hepatitis B virus DNA.

BACKGROUND: Recently developed nucleic acid testing (NAT) assays incorporating simultaneous detection of human immunodeficiency virus (HIV), hepatitis C virus (HCV), and hepatitis B virus (HBV) have made HBV NAT screening more feasible for blood services. This study compared the performance of two "multiplex" NAT assays and their automated testing platforms. STUDY DESIGN AND METHODS: The HBV NAT yield rate was estimated by testing 10,397 Hong Kong (HK) donor samples concurrently on the PROCLEIX ULTRIO (Ultrio) assay as individual donor samples with the TIGRIS and on the cobas TaqScreen multiplex (cobas MPX) test in pools of 6 with the cobas s 201. Analytical sensitivity was assessed by probit analysis of diluted international standards and operational performance was compared. RESULTS: Each system detected two different HBV NAT yield samples for a combined rate of 0.04 percent. One additional sample was reactive on the cobas MPX test but remained unresolved. The 95 percent detection limits for HIV-1, HBV, and HCV were 42.2, 12.2, and 2.0 IU per mL, respectively, for Ultrio and 50.5, 8.4, and 6.0 IU per mL for the cobas MPX. The invalid test and failed run rates were 0.05 and 2.92 percent, respectively, for the TIGRIS and 2.39 and 5.53 percent for the cobas s 201. CONCLUSION: Clinical sensitivity for HBV in HK blood donors was equivalent, as was the analytical sensitivity for HIV-1 and HBV; however, the Ultrio assay had a higher analytical sensitivity for HCV. Despite a shorter downtime and mean time of repair for the cobas s 201, the TIGRIS demonstrated better overall operational performance.

Assessing the accuracy of three viral risk models in predicting the outcome of implementing HIV and HCV NAT donor screening in Australia and the implications for future HBV NAT.

BACKGROUND: Risk modeling is now the most practical method of estimating the residual risk of viral transmission in developed countries. One method of assessing the accuracy of a risk model is to measure the observed against the predicted outcome after implementing a new screening method. The primary objective of this paper is to assess the accuracy of three published models in predicting the impact of implementing HIV and HCV NAT in Australia. STUDY DESIGN AND METHODS: Viral screening data on Australian donors for 2000 and 2001 were retrospectively analyzed. The data were applied to the three models to estimate the risk of transmission and predicted NAT yield for HIV, HCV, and HBV. RESULTS: The median risk estimates for the three models were 1 in 3,415,000 for HIV NAT, 1 in 911,000 for HCV NAT, and 1 in 483,000 for HBsAg. The predicted NAT yield for the three models ranged from 0.17 to 0.30 per million donations for HIV, 1.20 to 5.55 for HCV, and 0.47 to 1.01 for HBV. The observed NAT yield was not significantly different from the expected yield with any of the three models for either HIV or HCV. CONCLUSIONS: First, the residual risk in Australian donors is small in comparison with other transfusion complications and comparable to or lower than the risk in US and European nonremunerated donors. Second, mathematical risk modeling has sufficient precision to be used as a predictive tool for risk-benefit assessments of novel screening procedures. Finally, in relation to the case for implementing HBV NAT and/or anti-HBc in Australia, we conclude that at present, there is inadequate information about our donor population to perform an evidence-based risk-benefit analysis.