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Potential Australian blood donors are deferred indefinitely if they report a history of injecting drug use (IDU), or for 12 months if they report having engaged in sexual activity with someone who might have ever injected. Given incremental improvements in blood safety, this study sought to examine whether Australia's IDU-related eligibility criteria reflected current scientific evidence, were consistent with international best practice and, if current IDU-related policies were to be changed, how this should happen.An expert committee was formed to review relevant literature with a focus on issues including: the epidemiology of IDU in Australia and key transfusion-transmissible infections (TTIs) among Australian people who inject drugs (PWID); and, 'non-compliance' among PWID regarding IDU-related blood donation guidelines. International policies relating to blood donation and IDU were also reviewed. Modelling with available data estimated the risk of TTIs remaining undetected if the Blood Service's IDU-related guidelines were changed.Very few (1%) Australians engage in IDU, and IDU risk practices are reported by only a minority of PWID. However, the prevalence of HCV remains high among PWID, and IDU remains a key transmission route for various TTIs. Insufficient data were available to inform appropriate estimates of cessation and relapse among Australian PWID. Modelling findings indicated that the risk of not detecting HIV becomes greater than the reference group at a threshold of non-admission of being an active PWID of around 1.8% (0.5-5.1%). Excluding Japan, all Organisation for the Economic Co-operation and Development member countries permanently exclude individuals with a history of IDU from donating.Numerous research gaps meant that the study's expert Review Committee was unable to recommend altering Australia's current IDU-related blood donation guidelines. However, having identified critical knowledge gaps and future areas of research, the review made important steps toward changing the criteria.

Background and Objectives Universal testing of blood donations for human T-cell lymphotropic virus (HTLV) in Australia may no longer be appropriate given the low prevalence of HTLV infection and the mitigating effect of universal leucodepletion for cellular components. This study aimed to determine the most appropriate HTLV testing strategy using the Risk-Based Decision-Making Framework for Blood Safety. Materials and Methods The risk of HTLV transfusion–transmission using three testing strategies (universal, new-donor and no testing) and cost-effectiveness of the first two strategies were assessed using adaptations of published mathematical models. Results The overall prevalence for 2004–2014 was three HTLV-positives per million donations. It was estimated that annually, universal testing incurred a cost of approximately AUD $3 million and prevented 83 HTLV-positive cellular components from being issued, and new-donor testing cost approximately $225 000 and prevented 81 components. The number of cases of transfusion-transmitted HTLV and HTLV-associated disease prevented per year by universal and new-donor testing was essentially equivalent. According to preset risk thresholds, the risk of transfusion–transmission was negligible for universal and new-donor testing, and minimal without testing. Conclusion Transfusion–transmission of HTLV is a minimal risk in Australia even without testing. However, any revision of testing strategy must consider not only risk and cost-effectiveness, but also stakeholder, ethical and regulatory perspectives. Considering all relevant criteria, new-donor testing is judged the optimal strategy because it is able to achieve almost the same outcomes as universal testing, at a fraction of the cost.

Background and objectives Ross River virus (RRV) is an enveloped, RNA alphavirus in the same antigenic group as chikungunya virus. Australia records an annual average of 5000 laboratory-confirmed RRV infections. While RRV is currently geographically restricted to the Western Pacific, the capacity of arboviruses for rapid expansion is well established. The first case of RRV transfusion-transmission was recently described prompting a comprehensive risk assessment. Materials and methods To estimate the RRV residual risk, we applied laboratory-confirmed RRV notifications to two published models. This modelling generated point estimates for the risk of viraemia in the donor population, the risk of collecting a viraemic donation and the predicted number of infected components. Results The EUFRAT model estimated the risk of infection in donors as one in 95 039 (one in 311 328 to one in 32 399) to one in 14 943 (one in 48 593 to one in 5094). The point estimate for collecting a RRV viraemic donation varied from one in 166 486 (one in 659 078 to one in 49 158) (annualized national risk) to one in 26 117 (one in 103 628 to one in 7729) (area of high transmission). The modelling predicted 8–11 RRV-infected labile blood components issued in Australia during a 1-year period. Conclusion Considering the uncertainty in the modelled estimates, the unknown rate of RRV donor viraemia and the low severity of any recipient RRV infection, additional risk management for RRV in Australia will initially be restricted to strengthening the messaging to donors regarding prompt reporting of any postdonation illnesses.

Background and Objectives Cytomegalovirus poses a risk to transfusion safety as its transmission to an immunocompromised recipient may lead to significant clinical sequelae. Once infection is established, it is lifelong and generally asymptomatic. Strategies to reduce the risk of transfusion-transmitted CMV (TT-CMV) include donor serological testing and blood component leucodepletion to deplete the transmissible reservoir. We estimate the residual risk for non-CMV antibody screened, leucodepleted (LD-only) fresh blood components. Materials and Methods We established an approach to estimate the risk of TT-CMV under various scenarios. We estimated the probability of an infectious component, for both red cells and platelets, as a function of the observed WBC filter failure rate and the probability that such a unit was also contaminated with infectious virus. Results Using this model, the estimated combined residual risk of LD-only red cell and platelet units was very low, 1 in 13 575 000 (95%CI:1 in 1 344 167 000–1 in 1 730 000) as was the individual residual risk estimate for LD-only red cells, 1 in 7 790 000 (95%CI: 1 in 771 307 000–1 in 993 000) and LD-only platelets, where a zero risk was estimated (95%CI: 0–1 in 1 074 000). Conclusion We describe a novel approach to assess the residual risk of LD-only components. This can be applied generally using local data. Our risk estimate for LD-only blood components in Australia is below the threshold of 1 in 1 million, generally considered negligible. This provides a useful indicator of the relative safety of LD-only components to assist clinical decisions when serologically screened inventory is unavailable.

Summary 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.

Background and Objectives Australia introduced bacterial contamination screening (BCS) for platelet components in April 2008. This study presents analysis performed to assess the efficacy of testing. Materials and Methods Seven-day aerobic and anaerobic culture is performed using the BacT/ALERT 3D system. Following an initial machine positive (IMP) flag, all associated components are recalled, and/or clinicians treating already transfused patients are notified. IMPs are categorized as ‘machine false positive’, ‘confirmed positive’ or ‘indeterminate’ depending on culture results of initial and repeat samples. Results Between 2010 and 2012, 1·1% of platelet donations tested IMP; since 2013, this rate has fallen to 0·6% through improved instrument management, reducing false-positive IMPs but maintaining sensitivity for cultures yielding bacterial growth. On average, 66% of confirmed positive and indeterminate platelet units had been transfused at the time of detection. The majority (95%) of these grew Propionibacterium sp., a slow-growing organism that rarely causes sepsis in the transfusion setting. The incidence of reported transfuion-transmitted bacterial infection (TTBI) has fallen since the introduction of BCS, with a 4·2-fold [0·5, 28·2] lower rate from platelets. Conclusion BCS has been successful in detecting platelet units containing pathogenic bacteria. The incidence of TTBI from platelets has fallen since the introduction of BCS, but the risk has not been eliminated due to rare false-negative results. In the absence of a pathogen inactivation system for red blood cells, BCS provides ‘surrogate’ testing of red blood cells from which platelets have been manufactured.

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.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.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.Trade-offs between cost, complexity, uptake, and effectiveness must be considered in the implementation of postdonation iron supplementation.

Background and Objectives We previously published a model to estimate the residual risk (RR) for occult hepatitis B infection (OBI) in the absence of universal anti-HBc testing. To incorporate new information on the epidemiology of OBI, we describe model refinements and estimate a more accurate HBV RR due to OBI in Australia. Materials and Methods In our original model, the OBI risk, p(OBI), was defined by the rate of ‘non-detection’ by the HBV DNA screening test in use, p(NAT non-detection), and the average infectivity of blood components from OBI donors, p(transmission). We revised the model by integrating three refinements: that donations with anti-HBs levels of >10 IU/l, or donations solely for manufactured plasma products, be excluded from the risk calculation, and an updated estimate of p(transmission). Results Refining our OBI RR model resulted in a more than 10-fold reduction in the reported RR risk to recipients from OBI in our donor population. Based on the use of a common data set, the mean OBI RR risk decreased from 1 in 374 354 donations (95% CI: 1 in 191 940–1 072 681) to 1 in 3 984 033 (95% CI: 1 in 1 146 188–65 268 257) for the refined model. Conclusion Our model refinements provide a more realistic measure of the HBV RR in the donor population. Unlike the previous model, the new model demonstrates that the risk of HBV due to OBI in the Australian blood donor population is negligible, and further potentially cost-ineffective risk management strategies are not currently warranted.

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.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.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.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.

Background Currently used indicators of iron status have limitations. Hepcidin, a key regulator of iron metabolism, is reduced in iron deficiency. We sought to determine the properties of hepcidin as a diagnostic test of iron deficiency.Design and Methods Sera from female, non-anemic, whole blood donors were analyzed for hepcidin (enzyme-linked immunosorbent assay), ferritin, soluble transferrin receptor and C-reactive protein. Iron deficiency was defined as (i) serum ferritin less than 15 ng/mL or (ii) soluble transferrin receptor /log(ferritin) index greater than 3.2 if the C-reactive protein concentration was less than 10 mg/L, or greater than 2.2 if the C-reactive protein concentration was greater than 10 mg/L). Receiver operating characteristic curves were plotted to determine the overall utility and identify optimal cut-points of hepcidin as a test of iron deficiency.Results In 261 blood donors the prevalence of iron deficiency defined by ferritin concentration was 59/261 [22.6% (17.5, 27.7)], whereas defined by soluble transferrin receptor/log(ferritin) index it was 53/261 [20.4% (15.4, 25.2)]. The 95% reference range of hepcidin concentration in the iron-replete population was 8.2–199.7 ng/mL. The area under the receiver operating characteristic curve for hepcidin compared with ferritin concentration less than 15 ng/mL was 0.87 (0.82, 0.92), while that compared with the soluble transferrin receptor /log(ferritin) index was 0.89 (95% CI 0.84, 0.93). For a diagnosis of iron deficiency defined by the soluble transferrin receptor/log(ferritin) index, hepcidin less than 8 ng/mL had a sensitivity of 41.5% and a specificity of 97.6%, while hepcidin less than 18 ng/mL had a sensitivity of 79.2% and a specificity of 85.6%.Conclusions Serum hepcidin concentration may be a useful indicator of deficient iron stores. Further studies are required to evaluate the role of hepcidin in the diagnosis of iron deficiency in other groups of patients.

To the Editor: Hepatitis E virus (HEV) is an emerging public health concern for industrialized countries (1). Although HEV infection has been associated with travel to countries where the virus is endemic, cases of autochthonous HEV are increasing (2). Detection of HEV RNA in blood donations in the United Kingdom, Germany, the Netherlands, Japan, and China and accumulating reports of HEV transmitted through blood transfusion highlight the potential risk this virus poses to blood supply safety (1–4). In Australia, where most HEV infections are associated with travel (5), an average of 25 HEV cases occurred each year during 1999–2013 (http://www9.health.gov.au/cda/source/rpt_3.cfm). HEV infection is nationally notifiable in Australia, but the presence of subclinical infections and the lack of recent seroprevalence studies have prevented the accurate estimation of HEV incidence and population exposure. Thus, we examined HEV seroprevalence in a cohort of Australian blood donors, assessed risk factors for exposure, and used the data to examine the effectiveness of current blood safety strategies for the management of HEV in Australia. Plasma samples (n = 3,237) were collected from donors during August–September 2013. Information on age, sex, state of residence, new/repeat donor status, and overseas travel disclosure was obtained. Details of any relevant blood donation deferral (malaria, diarrhea) applied on previous donation attempts were also collected. Application of a specific malaria deferral code is routine for donors disclosing travel to a malaria-endemic country, and a diarrhea deferral applies when a donor reports having had diarrhea (of viral or unknown cause) 1 week before any attempted donation. All samples were tested for HEV IgG by using the Wantai HEV-IgG ELISA (Beijing Wantai Biologic Pharmacy Enterprise Co., Ltd, Beijing, China). Positive samples were tested for HEV IgM by using the Wantai HEV-IgM ELISA and for HEV RNA by using a prototype transcription-mediated amplification assay (Hologic Inc., San Diego, CA, USA). Of 3,237 samples, 194 (5.99%) were positive for HEV IgG (95% CI 5.18–6.81). Compared with estimates from previous studies that used the Wantai ELISA (6–9), our estimate is comparable to those reported from Scotland (4.7%) and New Zealand (4.2%) but lower than those from the United States (18.8%) and southwestern France (52.5%). Considerable debate exists regarding the sensitivity and specificity of HEV detection methods (2,10); however, on the basis of studies in France and the United Kingdom (9,10), we believe that the measured seroprevalence in our study is accurate. Our findings showed an increased seroprevalence of HEV associated with previous malaria deferral, diarrhea deferral, and age (multivariate logistic regression) (Table), the latter of which is consistent with previous findings (9). IgG seropositivity was also higher (7.73%) in donors who had traveled to a malaria-endemic country. HEV is often endemic to malaria-endemic countries (http://wwwnc.cdc.gov/travel/yellowbook/2014); however, the HEV exposure status of travelers is unknown before departure, so the exact place of exposure cannot be determined. Furthermore, 3.37% of donors in our study had evidence of previous HEV exposure; these donors had not reported travel outside Australia, so they may have acquired HEV locally. Because subclinical HEV infection is possible, persons infected locally may not be identified by the current donor screening questionnaire and thus pose a potential risk to blood supply safety. Table HEV (IgG) seroprevalence, and risk factors for exposure, in Australian blood donors* Detection of HEV IgM in 4 (2.06%) of the 194 samples from IgG-positive donors indicates the donors had been recently exposed to HEV (95% CI 0.06–4.06). All 4 donors had traveled overseas; 3 reported travel to malaria-endemic countries. HEV RNA was not detected in any of the HEV IgG–positive samples. Although it is encouraging that HEV nucleic acid was not detected, the sample size is insufficient to accurately determine the true rate of HEV RNA carriage among donors in this study; a larger study is planned. Management strategies to safeguard the Australian blood supply against transfusion-transmitted HEV are based on donor selection guidelines. To identify donors with possible bacteremia/viremia, including HEV, blood donation staff members ask donors several medical, behavioral, and travel-based questions before donation. These include questions relating to general wellness, sex practices, gastric upset, diarrhea, abdominal pain, and vomiting within the previous week. In addition, for 4 months after a donor’s return from travel to a malaria-endemic country, donations are restricted to plasma for fractionation. Some protection against blood donations from HEV-infected persons may occur because HEV and malaria are co-endemic to many countries. Our findings showed a higher HEV seroprevalence among donors with prior malaria or diarrhea deferrals; thus, malaria- and diarrhea-related screening questions may reduce contributions from donors with travel-associated HEV infection. Our findings showed HEV exposure in travelers and nontravelers, suggesting the possibility of imported and locally acquired HEV in Australia. Prior HEV exposure was higher in donors who were temporarily excluded from donating blood on previous donation attempts, suggesting the current management strategy in Australia is partially effective in minimizing any risk of HEV transmission through blood transfusion. However, the presence of HEV IgG in donors who reported no overseas travel and/or no prior related deferrals, coupled with the knowledge that asymptomatic infection is possible, suggests that additional safety precautions may be warranted.

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.

summary A blood donor questionnaire and declaration, with deferral of potential donors at a higher risk of blood-borne infections, was introduced in Australia in the mid-1980s to reduce the risk of donation of HIV-infected blood. However, the absolute risk of HIV transmission through blood donation from high-HIV-risk donors has not been estimated. This study presents a new method of assessing the risk posed to the blood supply by selected HIV risk behaviours. A model was developed to estimate the probability of blood donation during the window period for HIV infection. Five scenarios for blood donors were considered: (1) men who have sex with men (MSM), (2) men who have sex with women in Australia, (3) women who have sex with partners from countries with a high HIV prevalence, (4) men who have sex with commercial sex workers in Australia and (5) people injecting drugs used once in a year. Those estimated to be at highest risk of becoming infected and donating in the window period were MSM. Women who have sex with men from countries of high HIV prevalence are at greater risk than men who have sex with female sex workers from Australia. These three groups under current Australian guidelines are deferred from donating blood for 12 months. In Australia, a single episode of injecting drug use is associated with very low risk of HIV transmission. The model presented in this study can be used to assess the impact of selected individual risk behaviours on the safety of the blood supply.

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.

Background and objectives Previous studies have demonstrated that transfusedblood components from donors with occult hepatitis B virus infection (OBI) arepotentially infectious. This study reports the results of an Australian lookback pro-gramme for the period subsequent to the commencement of individual donationHBV NAT in July 2010 and estimates the HBV transmission rate for componentsfrom two categories of donors, confirmed OBI and HBV inconclusive (anti-HBcreactive with non-discriminated NAT result).Materials and methods Using the results of lookback investigations, weestimated HBV transmission rates by donor category and type of componenttransfused based on the prevalence of antibodies to HBV core antigen (anti-HBc)in recipients adjusted for the estimated prevalence in the general population.Results After subtracting the background anti-HBc rate, we derived an adjustedtransmission rate (all components) with lower and upper bounds as follows:0 85% (0 00–2 35%) for OBI donors, 2 83% (1 23–4 33%) for inconclusive donorsand 1 81% (0 21–3 31%) for total (OBI and inconclusive) donors. The medianadjusted transmission rate for total donors was higher (but not statistically) forplasma (3 01%) than RCCs (2 86%), but there was no evidence of transmissionfor cryoprecipitate or platelets (0% for both components).Conclusion Our lookback study suggests a low (0 2–3 3%) but measurable rateof HBV transmission in Australia associated with donors with OBI and sup-ports published evidence that at least some blood component types from OBIdonors, including a proportion undetectable by ID-NAT can transmit HBV bytransfusion.Keywords: Hepatitis B virus, Lookback, NAT testing, transfusion transmission.

Whole blood for transfusion was initially collected in glass bottles, but these are fragile, heavy to transport and prone to bacterial contamination. After the Second World War, Carl Walter experimented with plastics for collection and storage of blood, and found that di-ethylhexyl phthalate (DEHP) as plasticizer for polyvinyl chloride (PVC) had the most favourable properties [1, 2]. The breakage rate of frozen plasma in DEHP PVC is low, and the better storage properties of red cell concentrates in DEHP PVC are explained by leaching of plasticizer into the lipid bilayer of these cells, thereby improving membrane stability resulting in lower haemolysis rates [3]. However, ever since the 1970s, scientific and public concern has been raised on the toxicity of DEHP for transfused patients [4, 5]. DEHP and its metabolite mono ethylhexyl phthalate (MEHP) are associated with impairment of reproduction in animal models, resulting in testicular dysgenesis syndrome in (male) rodents, as reviewed in depth elsewhere [6], and particularly, neonates are susceptible to the risks of high exposure to DEHP. Due to the omnipresence of phthalates (not only DEHP), and some important differences in DEHP metabolism between animal models and humans [6], it is difficult to estimate the effect of DEHP toxicity in humans. A study of 234 young men showed no effect of MEHP in urine on their reproductive function [7], but others showed that DNA damage in sperm was associated with the MEHP concentration (after adjustment for other DEHP oxidative metabolites) [8]. In vitro human testis explants incubated with DEHP or MEHP showed that both significantly inhibited testosterone production [9], and a study of 881 men showed a 9% lower free androgen index between the lowest and the highest quartile of the proportion DEHP excreted as MEHP (P = 0.02) [10]. Also, an association was found between urinary MEHP concentrations and lower free T4 and lower total T3 thyroid hormones in adult men [11]. In addition to these effects on hormonal level in adult males, DEHP and its metabolites can have an effect on fetal development, with a shorter anogenital distance associated with higher metabolite concentrations in urine samples collected during pregnancy [12]. Others found no difference in T4 and testosterone levels, as well as no effect on phallic length in 13 male adolescents 14– 16 years of age that had underwent ECMO treatment in their neonatal period, as compared to ageand sexmatched controls [13]. Also, DEHP/MEHP exposure (as detected in cord blood) was significantly associated with a shorter pregnancy duration [14]. Despite these associations, they should be interpreted with care. DEHP is not the only phthalate that may cause these effects; studies that showed no association may not have been published; DEHP administered through the intestinal tract is converted to MEHP in a higher degree as by intravenously [15]; and because phthalates are everywhere in our environment, comparisons are less versus more, rather than absent versus present. DEHP-plasticized PVC has long been used as standard material for a wide range of applications, like packing foil (including food), building material, toys and plastic devices. DEHP is considered to be a ubiquitous environmental contaminant and is present in air, dust, water, soil and food. The latter is considered to be the main source of DEHP intake for the general population. The current daily intake is estimated to be between 2 and 5 lg/kg for adults and between 4 to 8 lg/kg for children [16, 17]. Various measures to reduce the use of DEHP-plasticized PVC have indeed resulted in a 2-times lower exposure to DEHP in the general population over the last two decades [18]. DEHP is applied in many medical devices, and depending on the procedure, patients can be exposed to high (peak) concentrations of DEHP, in the order of 1 mg per kg of bodyweight. One of the sources of DEHP exposure is the leaching from the blood bags into the content of the container, particularly into lipophilic solutions such as plasma [19], but also red cells. Therefore some patient groups, including pregnant or nursing women and children, are considered to be most at risk of possible harmful effects attributable to DEHP exposure by medical treatments. DEHP is broken down into various metabolites. First, it is hydrolysed to MEHP and then further oxidized to mono-(2-ethyl-5-hydroxyhexyl) phthalate (5OH-MEHP)

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.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.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.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.

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.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.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.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.

Background and Objectives In Australia since 2000, donors are deferred for12 months since last male-to-male sexual contact. There is no estimate of theprevalence of non-compliance (i.e. failure to disclose a risk during the predona-tion interview which would lead to deferral) with the policy in Australia; how-ever, published studies elsewhere indicate a range of 0 8–11%. We investigatedthe rate of, timing and motivation for non-compliance.Materials and Methods A nationally representative sample of donors who hadmade a recent donation negative for transfusion-transmissible infection testingwas surveyed using an anonymous, online instrument. Non-compliance was con-sidered as a ‘yes’ response to the current screening question. Non-compliers wererequested to define the timing of the last sexual contact relevant to their mostrecent donation. Univariate and multivariate regression analyses were used todefine factors associated with non-compliance.Results Of 14 476 responses from male donors, 34 (0 23%, 95% CI: 0 16–0 33%)were non-compliant of whom 24 (0 17%, 95% CI: 0 11–0 25%) had contactwithin 6 months of donation. Factors significantly associated with non-compli-ance included: multiple sexual partners, history of injecting drug use, perceptionof a lack of privacy during interview and preference for a computer-based ques-tionnaire.Conclusion Our study confirms high compliance (>99 7%) to the 12-month defer-ral for male-to-male sex in Australia providing reassuring evidence for the effi-cacy of the screening question. Issues of ‘privacy’ and ‘discomfort’ associated withdisclosure suggest the use of validated audio computer-assisted structured inter-view as a possible option for improving compliance with the donor questionnaire.Key words: donors, epidemiology, transfusion-transmissible infection.

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.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 (ferritin15 ng/mL) at 12 weeks postdonation. Secondary endpoints were eligibility to donate based on capillary hemoglobin (Hb) and incidence of gastrointestinal (GI) complaints.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.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.

OBJECTIVE To evaluate the risk of post-transfusion and postoperative non-A non-B hepatitis in Australia immediately before the introduction of screening for hepatitis C. DESIGN Retrospective testing of blood samples from a prospective study of cardiac surgery patients. Samples were taken from transfusion recipients and non-transfused controls at regular intervals for 12 months after surgery during 1987-1989. For all donor, recipient and control samples, alanine aminotransferase (ALT) levels were measured and tests for antibody to hepatitis B (anti-HBc, anti-HBs) and, when available, to hepatitis C (anti-HCV) were performed. SETTING Cardiac surgery units. PARTICIPANTS Participants were included if they lived in the metropolitan area, and had not had a transfusion in the past year. MAIN OUTCOME MEASURES Post-transfusion hepatitis (two consecutive samples showing raised ALT levels, > 90 IU/L with no other known cause); hepatitis C infection and carriage (antibody to hepatitis C). RESULTS Post-transfusion hepatitis occurred in 1.1% of 736 recipients of blood not screened for hepatitis C (i.e., two cases per 1000 unscreened units given). No hepatitis occurred in 514 controls. Seven of the eight patients with post-transfusion hepatitis seroconverted to hepatitis C virus infection. Seven of the 26 anti-HCV-positive donations transmitted hepatitis C, six of these were positive by recombinant immunoblot assay (RIBA) (one by second generation testing only) and one was RIBA indeterminate. Nineteen were RIBA non-reactive; one transmitted hepatitis but the recipient did not develop anti-HCV, although hepatitis C RNA was detected in the donation. Serum ALT was raised in four of the six infective donations. CONCLUSIONS Hepatitis C virus infection accounted for almost all cases of non-A non-B post-transfusion hepatitis. First generation anti-HCV tests detected about 85% of infective donations. Surrogate testing of donations by ALT or anti-HBc offers no additional advantage.

The frequency of infection with the six classified major genotypes of hepatitis C virus (HCV) was investigated in 447 infected volunteer blood donors from the following nine countries: Scotland, Finland, The Netherlands, Hungary, Australia, Egypt, Japan, Hong Kong, and Taiwan. Viral sequences in plasma from blood donors infected with HCV were amplified in the 5'-noncoding region and were typed by restriction fragment length polymorphism analysis. Electrophoresis of DNA fragments produced by cleavage with HaeIII-RsaI and ScrFI-HinfI allowed HCV types 1 (or 5), 2, 3, 4, and 6 to be identified. Further analysis with MvaI-HinfI allowed sequences of the type 5 genotype to be distinguished from sequences of the type 1 genotype. Types 1, 2, and 3 accounted for almost all infections in donors from Scotland, Finland, The Netherlands, and Australia. Types 2 and 3 were not found in the eastern European country (Hungary), where all but one of the donors were infected with type 1. Donors from Japan and Taiwan were infected only with type 1 or 2, while types 1, 2, and 6 were found in those from Hong Kong. HCV infection among Egyptians was almost always by type 4. Donors infected with HCV type 1 showed broad serological reactivity with all four antigens of the second generation Chiron RIBA-2 assay (Chiron Corporation, Emeryville, Calif.), while infection with divergent HCV genotypes elicited antibodies mainly reactive to c22-3 and c33c. Reactivities with antibodies 5-1-1 and c100-3 were infrequent and were generally weak, irrespective of the geographical origin of the donor. Because the envelope region of HCV is even more variable than the NS-4 region, it is likely that vaccines based on these proteins need to be multivalent and perhaps specifically adapted for different geographical regions.

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.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.Of donors, 59 of 261(22.6%) were iron depleted (ferritin15 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.Screening with Hb and iron indices enables prediction of donors at risk of subsequent anemia and who would most benefit from prevention strategies.

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.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.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.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.

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.

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.

Udgivelsesdato: 2008-Apr

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, 1449 (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 1158 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. T he freedom of the blood supply from transfusion-transmissible infection (TTI) is protected by a combination of measures, including the use of voluntary, nonremunerated donors; donor education and careful donor selection; and sensitive laboratory screening of donated blood. 1 Together, these measures have resulted in an extremely low residual risk of transfusion-transmitted viral infections (TTVIs). 2

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.

Background and Objectives The two key objectives of the study were, first, to evaluate the sensitivity and specificity of a recombinant antigen-based malarial enzyme-linked immunoassay (EIA) and, second, to estimate the risk associated with implementing this test with a shortened cellular component restriction period (6 months rather than the standard 12–36 months) for blood donors with a malarial risk exposure. Materials and Methods Blood donors were recruited into four distinct groups [non-exposed (control), malarial area ‘visitors’, ‘residents’ and ‘previous infection’) and screened by using the Newmarket malarial antibody EIA. Assay specificity was evaluated in unexposed blood donors, and sensitivity was determined in acute clinical samples. Results No parasitaemic donors were detected amongst 337 malarial ‘visitors’ who had returned from a malaria-endemic area less than 6 months previously, or for 402 ‘visitors’ or ‘residents’ who had returned from a malaria-endemic area more than 6 months previously. The incidence of malarial antibodies within the exposed blood donor groups was 1·33% (10/751). In acute clinical non-donor samples, the Newmarket EIA detected 106/108 (98·1; 93·5–99·5%) ‘film’ positive Plasmodium falciparum infections and 12/12 (100, 75·7–100·0%) P. vivax infections. The estimated additional risk exposure of the proposed new strategy was one infectious P. falciparum donation per 175 years or 1 per 4·2 years for P. vivax. Conclusions The study findings support the efficacy and safety of a targeted screening strategy combining antibody screening with a 6-month cellular component restriction period for donors with a declared malarial risk.

OBJECTIVE To describe the results of human immunodeficiency virus type 1 (HIV-1) antibody testing of blood donations in Australia. DESIGN Blood transfusion services tabulated the number of HIV-1 antibody tests carried out on blood donations and the number of donations found to be positive, from 1985 to 1990. SETTING All blood transfusion services in Australia. PARTICIPANTS All donors of blood in Australia from 1 May 1985 to 31 December 1990. OUTCOME MEASURES The proportion of blood donations found to have HIV-1 antibody, according to State or Territory, year of donation and, when available, age, sex and donation status (repeat or first-time) of the donor. RESULTS To the end of December 1990, 5,367,970 donations had been tested for HIV-1 antibody, and 46 were found to have the antibody, giving an overall prevalence rate of 0.86 per 100,000 donations. The highest rate was recorded in New South Wales, followed by Western Australia, and four of eight Australian States and Territories reported no donors with HIV-1 antibody. There has been no clear trend with time, but the rate is about 20% higher for 1989-1990 than for 1985-1986. Of donors found to have HIV-1 antibody, 67% were male and 33% female, and 41% reported no known or potential exposure to HIV-1 other than heterosexual contact. Among blood donors in two major Australian cities, the overall prevalence of HIV antibody was higher in those who were male, younger, and first-time donors. There has been a recent increase in the number of blood donors with HIV-1 antibody who were women reporting heterosexual contact as their only potential exposure. CONCLUSION The rate of HIV-1 antibody in Australian blood donations remains very low and shows no clear temporal trend, but specific donor characteristics define higher rates of antibody prevalence.

Health care workers in the Royal Newcastle Hospital, in surrounding hospitals and pathology services, and in a large mental institution were surveyed to determine the prevalence of hepatitis B markers. The aim of the study was to identify the groups of workers at particular risk of contracting hepatitis B in order to determine which workers would benefit most from a programme of vaccination against hepatitis B. Although the prevalence of hepatitis B markers in the Newcastle health care workers was higher than that in the control subjects, this rate did not approach the high rates previously reported in overseas studies.