Tribotronic and electrochemical properties of platinum-nanofluid interfaces formed by aqueous suspensions of 5 and 40 nm TiO2 nanoparticles.

Nanoparticles (NPs) can be highly beneficial as additives to lubricating fluids, and the tribotronic response of charged NPs tuned by external fields represents an area of great technological potential. Tribotronic response, however, is expected to be highly size dependent, which represents a significant design challenge. To explore this issue, quartz crystal microbalance and cyclic voltammetry were employed to characterize nanotribological and electrochemical behavior of platinum-nanofluid interfaces formed by aqueous suspensions of different-sized negatively charged titanium dioxide (TiO2) NPs. Suspensions of 5, 40, and 100 nm NPs were all observed to reduced interfacial frictional drag forces upon introduction into pure water in zero field conditions, with reductions for the 40 nm NPs about twice those of 5 nm particles at comparable concentrations. Suspensions of 100 nm NPs produced even greater reductions, but rapidly precipitated from the suspension when left unstirred. NPs were also driven to and from Pt electrode surfaces by applying external electric fields with varying amplitudes and modulation frequencies. For electric fields of sufficient amplitude and duration, the 40 nm TiO2 nanosuspension exhibited tribological properties consistent with a reversible electrophoretic deposition of the NPs, accompanied by changes in the electrochemical attributes and increasing interfacial drag. The 5 nm NP properties were consistent with progressive reductions in interfacial drag forces at the NP-suspension interface linked to field-induced increases in concentration.

Tuning friction and slip at solid-nanoparticle suspension interfaces by electric fields.

We report an experimental Quartz Crystal Microbalance (QCM) study of tuning interfacial friction and slip lengths for aqueous suspensions of TiO2 and Al2O3 nanoparticles on planar platinum surfaces by external electric fields. Data were analyzed within theoretical frameworks that incorporate slippage at the QCM surface electrode or alternatively at the surface of adsorbed particles, yielding values for the slip lengths between 0 and 30 nm. Measurements were performed for negatively charged TiO2 and positively charged Al2O3 nanoparticles in both the absence and presence of external electric fields. Without the field the slip lengths inferred for the TiO2 suspensions were higher than those for the Al2O3 suspensions, a result that was consistent with contact angle measurements also performed on the samples. Attraction and retraction of particles perpendicular to the surface by means of an externally applied field resulted in increased and decreased interfacial friction levels and slip lengths. The variation was observed to be non-monotonic, with a profile attributed to the physical properties of interstitial water layers present between the nanoparticles and the platinum substrate.

Creutzfeldt-Jakob disease and blood transfusion safety.

Transmissible spongiform encephalopathies (TSEs) are untreatable, fatal neurologic diseases affecting mammals. Human disease forms include sporadic, familial and acquired Creutzfeldt-Jakob disease (CJD). While sporadic CJD (sCJD) has been recognized for near on 100 years, variant CJD (vCJD) was first reported in 1996 and is the result of food-borne transmission of the prion of bovine spongiform encephalopathy (BSE, 'mad cow disease'). Currently, 230 vCJD cases have been reported in 12 countries, the majority in the UK (178) and France (27). Animal studies demonstrated highly efficient transmission of natural scrapie and experimental BSE by blood transfusion and fuelled concern that sCJD was potentially transfusion transmissible. No such case has been recorded and case-control evaluations and lookback studies indicate that, if transfusion transmission occurs at all, it is very rare. In contrast, four cases of apparent transfusion transmission of vCJD infectivity have been identified in the UK. Risk minimization strategies in response to the threat of vCJD include leucodepletion, geographically based donor deferrals and deferral of transfusion recipients. A sensitive and specific, high-throughput screening test would provide a potential path to mitigation but despite substantial effort no such test has yet appeared. The initial outbreak of vCJD appears to be over, but concern remains about subsequent waves of disease among those already infected. There is considerable uncertainty about the size of the infected population, and there will be at least a perception of some continuing risk to blood safety. Accordingly, at least some precautionary measures will remain in place and continued surveillance is necessary.

Emerging infectious disease outbreaks: estimating disease risk in Australian blood donors travelling overseas.

BACKGROUND AND OBJECTIVES: International travel assists spread of infectious pathogens. Australians regularly travel to South-eastern Asia and the isles of the South Pacific, where they may become infected with infectious agents, such as dengue (DENV), chikungunya (CHIKV) and Zika (ZIKV) viruses that pose a potential risk to transfusion safety. In Australia, donors are temporarily restricted from donating for fresh component manufacture following travel to many countries, including those in this study. We aimed to estimate the unmitigated transfusion-transmission (TT) risk from donors travelling internationally to areas affected by emerging infectious diseases. MATERIALS AND METHODS: We used the European Up-Front Risk Assessment Tool, with travel and notification data, to estimate the TT risk from donors travelling to areas affected by disease outbreaks: Fiji (DENV), Bali (DENV), Phuket (DENV), Indonesia (CHIKV) and French Polynesia (ZIKV). RESULTS: We predict minimal risk from travel, with the annual unmitigated risk of an infected component being released varying from 1 in 1·43 million to <1 in one billion and the risk of severe consequences ranging from 1 in 130 million to <1 in one billion. CONCLUSION: The predicted unmitigated likelihood of infection in blood components manufactured from donors travelling to the above-mentioned areas was very low, with the possibility of severe consequences in a transfusion recipient even smaller. Given the increasing demand for plasma products in Australia, the current strategy of restricting donors returning from select infectious disease outbreak areas to source plasma collection provides a simple and effective risk management approach.

Reconsideration of blood donation testing strategy for human T-cell lymphotropic virus in Australia.

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.

Hepatitis E virus RNA in Australian blood donors: prevalence and risk assessment.

BACKGROUND AND OBJECTIVES: Hepatitis E virus (HEV) is a known transfusion-transmissible agent. HEV infection has increased in prevalence in many developed nations with RNA detection in donors as high as 1 in 600. A high proportion of HEV infections are asymptomatic and therefore not interdicted by donor exclusion criteria. To manage the HEV transfusion-transmission (TT) risk some developed nations have implemented HEV RNA screening. In Australia, HEV is rarely notified; although locally acquired infections have been reported, and the burden of disease is unknown. The purpose of this study was to determine the frequency of HEV infection in Australian donors and associated TT risk. MATERIALS AND METHODS: Plasma samples (n = 74 131) were collected from whole blood donors during 2016 and screened for HEV RNA by transcription-mediated amplification (TMA) in pools of six. Individual TMA reactive samples were confirmed by RT-PCR and, if positive, viral load determined. Prevalence data from the study were used to model the HEV-TT risk. RESULTS: One sample in 74 131 (95% CI: 1 in 1 481 781 to 1 in 15 031) was confirmed positive for HEV RNA, with an estimated viral load of 180 IU/ml, which is below that typically associated with TT. Using a transmission-risk model, we estimated the risk of an adverse outcome associated with TT-HEV of approximately 1 in 3·5 million components transfused. CONCLUSION: Hepatitis E virus viremia is rare in Australia and lower than the published RNA prevalence estimates of other developed countries. The risk of TT-HEV adverse outcomes is negligible, and HEV RNA donor screening is not currently indicated.

Blood safety implications of donors using HIV pre-exposure prophylaxis.

HIV pre-exposure prophylaxis (PrEP) is the use of one or more antiretroviral medications (in combination) to prevent HIV infection. The most commonly used PrEP medication (Truvada® , Gilead Sciences, Inc.) acts by inhibiting HIV-1 reverse transcriptase. If someone who is using PrEP unknowingly becomes HIV infected (termed 'PrEP breakthrough infection'), there may be suppressed viral replication resulting in a virus level undetectable by the most sensitive HIV NAT. Failure to seroconvert and seroreversion (loss of previously detectable HIV antibodies) have also both been observed with 2nd, 3rd and 4th generation screening immunoassays, as well as Western blot assays. If such a person was tested in the course of donating blood, the results may therefore be difficult to interpret. The index of suspicion for possible PrEP 'interference' should be highest in the context of concomitant low-level positive or 'greyzone' reactivity on HIV NAT and serological tests, which is an unusual pattern in acutely HIV-infected blood donors. Another possibility is detectable HIV RNA with negative HIV serology (i.e. a potential 'NAT yield' case) but without subsequent HIV seroconversion (or disappearance of HIV RNA). Excluding antiretroviral therapy or PrEP use by the donor in such circumstances would be important. The current rarity of PrEP breakthrough infection indicates that any potential safety risk is likely very small. However, considering the increasing use of PrEP we feel it is prudent for those interpreting HIV donor screening test results to consider the potential for PrEP interference.

Refining the risk estimate for transfusion-transmission of occult hepatitis B virus.

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.

Re-evaluating the residual risk of transfusion-transmitted Ross River virus infection.

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.

The residual risk of transfusion-transmitted cytomegalovirus infection associated with leucodepleted blood components.

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.

Infectivity of blood components from donors with occult hepatitis B infection - results from an Australian lookback programme.

BACKGROUND AND OBJECTIVES: Previous studies have demonstrated that transfused blood components from donors with occult hepatitis B virus infection (OBI) are potentially infectious. This study reports the results of an Australian lookback programme for the period subsequent to the commencement of individual donation HBV NAT in July 2010 and estimates the HBV transmission rate for components from two categories of donors, confirmed OBI and HBV inconclusive (anti-HBc reactive with non-discriminated NAT result). MATERIALS AND METHODS: Using the results of lookback investigations, we estimated HBV transmission rates by donor category and type of component transfused 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 adjusted transmission 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 donors and 1·81% (0·21-3·31%) for total (OBI and inconclusive) donors. The median adjusted transmission rate for total donors was higher (but not statistically) for plasma (3·01%) than RCCs (2·86%), but there was no evidence of transmission for cryoprecipitate or platelets (0% for both components). CONCLUSION: Our lookback study suggests a low (0·2-3·3%) but measurable rate of HBV transmission in Australia associated with donors with OBI and supports published evidence that at least some blood component types from OBI donors, including a proportion undetectable by ID-NAT can transmit HBV by transfusion.

Compliance with the current 12-month deferral for male-to-male sex in Australia.

BACKGROUND AND OBJECTIVES: In Australia since 2000, donors are deferred for 12 months since last male-to-male sexual contact. There is no estimate of the prevalence of non-compliance (i.e. failure to disclose a risk during the predonation interview which would lead to deferral) with the policy in Australia; however, published studies elsewhere indicate a range of 0·8-2.3% [corrected]. We investigated the rate of, timing and motivation for non-compliance. MATERIALS AND METHODS: A nationally representative sample of donors who had made a recent donation negative for transfusion-transmissible infection testing was surveyed using an anonymous, online instrument. Non-compliance was considered as a 'yes' response to the current screening question. Non-compliers were requested to define the timing of the last sexual contact relevant to their most recent donation. Univariate and multivariate regression analyses were used to define 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 contact within 6 months of donation. Factors significantly associated with non-compliance included: multiple sexual partners, history of injecting drug use, perception of a lack of privacy during interview and preference for a computer-based questionnaire. CONCLUSION: Our study confirms high compliance (>99·7%) to the 12-month deferral for male-to-male sex in Australia providing reassuring evidence for the efficacy of the screening question. Issues of 'privacy' and 'discomfort' associated with disclosure suggest the use of validated audio computer-assisted structured interview as a possible option for improving compliance with the donor questionnaire.

A method for estimating the residual risk of transfusion-transmitted HBV infection associated with occult hepatitis B virus infection in a donor population without universal anti-HBc screening.

BACKGROUND AND OBJECTIVES: This report describes a method for estimating the risk of transfusion-transmitted HBV infection attributable to blood components from donors with occult hepatitis B virus infection (OBI) applicable where universal anti-HBc screening is not performed. MATERIALS AND METHODS: In the context of parallel HBsAg and individual donation HBV DNA testing, we developed a mathematical function p(OBI) to estimate the probability of failing to detect [p(NAT nondetection)] a potentially infectious [p(transmission)] donation from a donor with OBI. RESULTS: Among 1 312 451 donations tested for HBsAg and HBV DNA, 29 (from 17 anti-HBc reactive donors classified as OBI) were individual donation NAT negative, giving a p(NAT nondetection) of 2·2096 (95 CI: 1·538-3·173) × 10(-5) . To date, lookback on OBI donors has identified 35 (8·2%) recipients with evidence of current or past HBV infection among 427 tested recipients. After correcting for the background anti-HBc rate in recipients, this results in a p(transmission) of 0·0384 (0·0167-0·0601). The product, pOBI is 1 in 981 920 (95% CI: 437 181-3 223 701). When this is summed with the WP risk for the 2011-2012 period, the overall HBV residual risk estimate is 1 in 538 224 (95% CI: 209 732-1 552 443). CONCLUSION: We estimate the OBI residual risk in Australia is approximately 1 in 982 000 per unit transfused, and this risk represents 55% of the total HBV residual risk and is declining as consequence of ID-NAT identifying repeat donors with OBI.

Malaria antibody persistence correlates with duration of exposure.

BACKGROUND AND OBJECTIVES: In Australia, the risk of transfusion-transmitted malaria is managed through the identification of 'at-risk' donors, antibody screening enzyme-linked immunoassay (EIA) and, if reactive, exclusion from fresh blood component manufacture. Donor management depends on the duration of exposure in malarious regions (>6 months: 'Resident', <6 months: 'Visitor') or a history of malaria diagnosis. We analysed antibody testing and demographic data to investigate antibody persistence dynamics. To assess the yield from retesting 3 years after an initial EIA reactive result, we estimated the proportion of donors who would become non-reactive over this period. MATERIALS AND METHODS: Test results and demographic data from donors who were malaria EIA reactive were analysed. Time since possible exposure was estimated and antibody survival modelled. RESULTS: Among seroreverters, the time since last possible exposure was significantly shorter in 'Visitors' than in 'Residents'. The antibody survival modelling predicted 20% of previously EIA reactive 'Visitors', but only 2% of 'Residents' would become non-reactive within 3 years of their first reactive EIA. CONCLUSION: Antibody persistence in donors correlates with exposure category, with semi-immune 'Residents' maintaining detectable antibodies significantly longer than non-immune 'Visitors'.

Duration of Ross River viraemia in a mouse model--implications for transfusion transmission.

BACKGROUND AND OBJECTIVES: There is little data on the duration of viraemia following infection with Ross River virus (RRV), the most common cause of arbovirus disease in Australia. In particular, no accurate estimate exists for the duration of pre-symptomatic RRV infection, which is important in assessing the potential for transfusion transmission. MATERIALS AND METHODS: We used an established mouse model of RRV infection involving adult Swiss outbred mice to measure viraemia following infection. Applying our experimental data to a published probabilistic model for estimating the risk of dengue transmission by transfused blood, we derived comparable risk estimates for RRV. RESULTS: Ross River virus RNA was measured using highly sensitive real-time PCR in serum samples to determine the duration of asymptomatic viraemia, which typically lasted 5 days, but extended to 9 days in some mice. Assuming the potential for transfusion transmission is proven, the risk of RRV transmission by blood during a 2004 outbreak in Cairns, Australia was retrospectively estimated as 1 in 13,542 (range from 1 in 4765 to 47,563). CONCLUSION: This study provides updated epidemiological data useful to underpin modelling to assess the potential risk of transfusion-transmitted RRV. Using an established model for dengue, the risk estimate for RRV transmission is comparable in the same geographical region. Should transfusion be proven as a route of transmission, this supports consideration of appropriate mitigation strategies to safeguard blood recipients.

Assessing the safety and efficacy of a test-based, targeted donor screening strategy to minimize transfusion transmitted malaria.

BACKGROUND AND OBJECTIVES: In 2005, the Australian Red Cross Blood Service implemented a malaria antibody testing based strategy for donors with a history of travel/residence in a malaria endemic country or a past history of malaria. This report assesses the safety and efficacy of the strategy since inception. MATERIALS AND METHODS: Eligible blood donors were tested using the Newmarket malarial antibody EIA at least 4 months after their last potential exposure. Where EIA non-reactive their quarantined red cells were considered for transfusion and they were re-instated for cellular component manufacture at their next donation. The efficiency and safety of this strategy were evaluated based on the additional number of components recovered for transfusion and the observed incidence of transfusion transmitted malaria (TTM) respectively. RESULTS: Of the repeat reactive donors, 2696 (> 99.99%) were PCR negative whilst one was PCR positive with very low level parasitaemia. The average number of RBCs and platelets recovered per annum was 64 967 and 7398 representing 7.9 and 5.5% respectively of their annual production. No new TTM cases were recorded and the observed TTM rate of zero was consistent with the upper 95% CI for the pretesting TTM incidence of 0.9 per million donations. CONCLUSION: The study findings support the efficacy and safety of a targeted screening strategy combining a sensitive antibody screening test with a 4-month cellular component restriction period for donors with a declared malarial risk. The TTM risk in Australia remains low and did not measurably change after implementing the testing strategy.

Estimating the risk of blood donation associated with HIV risk behaviours.

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.