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Arboviruses pose a significant global public health threat, with Ross River virus (RRV), Barmah Forest virus (BFV), and dengue virus (DENV) being among the most common and clinically significant in Australia. Some arboviruses, including those prevalent in Australia, have been reported to cause transfusion-transmitted infections. This study examined the spatiotemporal variation of these arboviruses and their potential impact on blood donation numbers across Australia. Using data from the Australian Department of Health on eight arboviruses from 2002 to 2017, we retrospectively assessed the distribution and clustering of incidence rates in space and time using Geographic Information System mapping and space-time scan statistics. Regression models were used to investigate how weather variables, their lag months, space, and time affect case and blood donation counts. The predictors' importance varied with the spatial scale of analysis. Key predictors were average rainfall, minimum temperature, daily temperature variation, and relative humidity. Blood donation number was significantly associated with the incidence rate of all viruses and its interaction with local transmission of DENV, overall. This study, the first to cover eight clinically relevant arboviruses at a fine geographical level in Australia, identifies regions at risk for transmission and provides valuable insights for public health intervention.

Background: Australia is theoretically at risk of epidemic chikungunya virus (CHIKV) activity as the principal vectors are present on the mainland Aedes aegypti) and some islands of the Torres Strait (Ae. aegypti and Ae. albopictus). Both vectors are highly invasive and adapted to urban environments with a capacity to expand their distributions into south-east Queensland and other states in Australia. We sought to estimate the epidemic potential of CHIKV, which is not currently endemic in Australia, by considering exclusively transmission by the established vector in Australia, Ae. aegypti, due to the historical relevance and anthropophilic nature of the vector., Methodology/principal Findings: We estimated the historical (1995-2019) epidemic potential of CHIKV in eleven Australian locations, including the Torres Strait, using a basic reproduction number equation. We found that the main urban centres of Northern Australia could sustain an epidemic of CHIKV. We then estimated future trends in epidemic potential for the main centres for the years 2020 to 2029. We also conducted uncertainty and sensitivity analyses on the variables comprising the basic reproduction number and found high sensitivity to mosquito population size, human population size, impact of vector control and human infectious period., Conclusions/significance: By estimating the epidemic potential for CHIKV transmission on mainland Australia and the Torres Strait, we identified key areas of focus for controlling vector populations and reducing human exposure. As the epidemic potential of the virus is estimated to rise towards 2029, a greater focus on control and prevention measures should be implemented in at-risk locations., Competing Interests: The authors have declared that no competing interests exist.

Background: Since 2015, Zika virus (ZIKV) outbreaks have occurred in the Americas and the Pacific involving mosquito-borne and sexual transmission. ZIKV has also emerged as a risk to global blood transfusion safety. Aedes aegypti, a mosquito well established in north and some parts of central and southern Queensland, Australia, transmits ZIKV. Aedes albopictus, another potential ZIKV vector, is a threat to mainland Australia. Since these conditions create the potential for local transmission in Australia and a possible uncertainty in the effectiveness of blood donor risk-mitigation programs, we investigated the possible impact of mosquito-borne and sexual transmission of ZIKV in Australia on local blood transfusion safety., Methodology/principal Findings: We estimated 'best-' and 'worst-' case scenarios of monthly reproduction number (R0) for both transmission pathways of ZIKV from 1996-2015 in 11 urban or regional population centres, by varying epidemiological and entomological estimates. We then estimated the attack rate and subsequent number of infectious people to quantify the ZIKV transfusion-transmission risk using the European Up-Front Risk Assessment Tool. For all scenarios and with both vector species R0 was lower than one for ZIKV transmission. However, a higher risk of a sustained outbreak was estimated for Cairns, Rockhampton, Thursday Island, and theoretically in Darwin during the warmest months of the year. The yearly estimation of the risk of transmitting ZIKV infection by blood transfusion remained low through the study period for all locations, with the highest potential risk estimated in Darwin., Conclusions/significance: Given the increasing demand for plasma products in Australia, the current strategy of restricting donors returning from infectious disease outbreak regions to source plasma collection provides a simple and effective risk management approach. However, if local transmission was suspected in the main urban centres of Australia, potentially facilitated by the geographic range expansion of Ae. aegypti or Ae. albopictus, this mitigation strategy would need urgent review., Competing Interests: The authors have declared that no competing interests exist.

Allogeneic blood transfusion (ABT) is associated with transfusion-related immune modulation (TRIM) and subsequent poorer patient outcomes including perioperative infection, multiple organ failure, and mortality. The precise mechanism(s) underlying TRIM remain largely unknown. During intraoperative cell salvage (ICS) a patient's own (autologous) blood is collected, anticoagulated, processed, and reinfused. One impediment to understanding the influence of the immune system on transfusion-related adverse outcomes has been the inability to characterize immune profile changes induced by blood transfusion, including ICS. Dendritic cells and monocytes play a central role in regulation of immune responses, and dysfunction may contribute to adverse outcomes. During a prospective observational study ( n = 19), an in vitro model was used to assess dendritic cell and monocyte immune responses and the overall immune response following ABT or ICS exposure. Exposure to both ABT and ICS suppressed dendritic cell and monocyte function. This suppression was, however, significantly less marked following ICS. ICS presented an improved immune competence. This assessment of immune competence through the study of intracellular cytokine production, co-stimulatory and adhesion molecules expressed on dendritic cells and monocytes, and modulation of the overall leukocyte response may predict a reduction of adverse outcomes ( i.e., infection) following ICS.

Background: A fatal case of autochthonous Babesia microti infection was reported in Australia in 2012. This has implications for Australian public health and, given that babesiosis is transfusion transmissible, has possible implications for Australian blood transfusion recipients. We investigated the seroprevalence of antibodies to B. microti in Australian blood donors and in patients with clinically suspected babesiosis., Study Design and Methods: Plasma samples (n = 7,000) from donors donating in at-risk areas and clinical specimens from patients with clinically suspected babesiosis (n = 29) were tested for B. microti IgG by immunofluorescence assay (IFA). IFA initially reactive samples were tested for B. microti IgG and IgM by immunoblot and B. microti DNA by polymerase chain reaction., Results: Although five donors were initially reactive for B. microti IgG by IFA, none was confirmed for B. microti IgG (zero estimate; 95% confidence interval, 0%-0.05%) and all were negative for B. microti DNA. None of the patient samples had B. microti IgG, IgM, or DNA., Conclusions: This study does not provide evidence for widespread exposure to B. microti in Australian blood donors at local theoretical risk, nor does it provide evidence of B. microti infection in Australian patients with clinically suspected babesiosis. Given that confirmed evidence of previous exposure to B. microti was not seen, these data suggest that transmission of this pathogen is currently uncommon in Australia and unlikely to pose a risk to transfusion safety at present., (© 2019 AABB.)

Background: Zika virus (ZIKV) is transfusion-transmissible. In Australia the primary vector, Aedes aegypti, is established in the north-east, such that local transmission is possible following importation of an index case, which has the potential to impact on blood transfusion safety and public health. We estimated the basic reproduction number (R 0 ) to model the epidemic potential of ZIKV in Australian locations, compared this with the ecologically similar dengue viruses (DENV), and examined possible implications for blood transfusion safety., Study Design and Methods: Varying estimates of vector control efficiency and extrinsic incubation period, "best-case" and "worst-case" scenarios of monthly R 0 for ZIKV and DENV were modeled from 1996 to 2015 in 11 areas. We visualized the geographical distribution of blood donors in relation to areas with epidemic potential for ZIKV., Results: Epidemic potential (R 0 > 1) existed for ZIKV and DENV throughout the study period in a number of locations in northern Australia (Cairns, Darwin, Rockhampton, Thursday Island, Townsville, and Brisbane) during the warmer months of the year. R 0 for DENV was greater than ZIKV and was broadly consistent with annual estimates in Cairns. Increased vector control efficiency markedly reduced the epidemic potential and shortened the season of local transmission. Australian locations that provide the greatest number of blood donors did not have epidemic potential for ZIKV., Conclusion: We estimate that areas of north-eastern Australia could sustain local transmission of ZIKV. This early contribution to understanding the epidemic potential of ZIKV may assist in the assessment and management of threats to blood transfusion safety., (© 2019 AABB.)

Backgroud: Primate erythroparvovirus 1 (B19V) is a globally ubiquitous DNA virus. Infection results in a variety of clinical presentations including erythema infectiosum in children and arthralgia in adults. There is limited understanding of the seroprevalence of B19V antibodies in the Australian population and therefore of population-wide immunity. This study aimed to investigate the seroprevalence of B19V antibodies in an Australian blood donor cohort, along with a cohort from a paediatric population., Methods: Age/sex/geographical location stratified plasma samples (n = 2221) were collected from Australian blood donors. Samples were also sourced from paediatric patients (n = 223) in Queensland. All samples were screened for B19V IgG using an indirect- enzyme-linked immunosorbent assay., Results: Overall, 57.90% (95% CI: 55.94%-59.85%) of samples tested positive for B19V IgG, with the national age-standardized seroprevalence of B19V exposure in Australians aged 0 to 79 years estimated to be 54.41%. Increasing age (p < 0.001) and state of residence (p < 0.001) were independently associated with B19V exposure in blood donors, with the highest rates in donors from Tasmania (71.88%, 95% CI: 66.95%-76.80%) and donors aged 65-80 years (78.41%, 95% CI: 74.11%-82.71%). A seroprevalence of 52.04% (95% CI: 47.92%-56.15%) was reported in women of child-bearing age (16 to 44 years). Sex was not associated with exposure in blood donors (p = 0.547) or in children (p = 0.261) screened in this study., Conclusions: This study highlights a clear association between B19V exposure and increasing age, with over half of the Australian population likely to be immune to this virus. Differences in seroprevalence were also observed in donors residing in different states, with a higher prevalence reported in those from the southern states. The finding is consistent with previous studies, with higher rates observed in countries with a higher latitude. This study provides much needed insight into the prevalence of B19V exposure in the Australian population, which has implications for public health as well as transfusion and transplantation safety in Australia.

Background: Emerging transfusion-transmissible pathogens, including arboviruses such as West Nile, Zika, dengue, and Ross River viruses, are potential threats to transfusion safety. The most prevalent arbovirus in humans in Australia is Ross River virus (RRV); however, prevalence varies substantially around the country. Modeling estimated a yearly risk of 8 to 11 potentially RRV-viremic fresh blood components nationwide. This study aimed to measure the occurrence of RRV viremia among donors who donated at Australian collection centers located in areas with significant RRV transmission during one peak season., Study Design and Methods: Plasma samples were collected from donors (n = 7500) who donated at the selected collection centers during one peak season. Viral RNA was extracted from individual samples, and quantitative reverse transcription-polymerase chain reaction was performed., Results: Regions with the highest rates of RRV transmission were not areas where donor centers were located. We did not detect RRV RNA among 7500 donations collected at the selected centers, resulting in a zero risk estimate with a one-sided 95% confidence interval of 0 to 1 in 2019 donations., Conclusion: Our results suggest that the yearly risk of collecting a RRV-infected blood donation in Australia is low and is at the lower range of previous risk modeling. The majority of Australian donor centers were not in areas known to be at the highest risk for RRV transmission, which was not taken into account in previous models based on notification data. Therefore, we believe that the risk of RRV transfusion transmission in Australia is acceptably low and appropriately managed through existing risk management, including donation restrictions and recall policies., (© 2018 AABB.)

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., (© 2017 International Society of Blood Transfusion.)

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.

The contribution of two unrelated Aeromonas hydrophila beta-haemolytic toxins to virulence was assessed in a suckling mouse model. The first haemolysin gene, isolated from an A. hydrophila A6 cosmid bank, encoded a potential gene product of 621 amino acids and a predicted molecular size of 69.0 kDa. The inferred amino acid sequence showed 89% identity to the AHH1 haemolysin of A. hydrophila ATCC 7966, and 51% identity to the HlyA haemolysin of Vibrio cholerae EI Tor strain O17. The second haemolysin gene (designated aerA), which encodes aerolysin, a pore-forming toxin, was partially cloned by PCR for the purpose of mutant construction. This PCR product was a 1040 bp fragment from the C-terminal region of aerA. It is proposed that the 69.0 kDa V. cholerae-HlyA-like haemolysin gene be termed hlyA to contrast with the aerA terminology for the aerolysin. A suicide vector was used to inactivate both the hlyA and aerA genes in A. hydrophila A6. When assessed in the suckling mouse model, only the hlyA aerA double mutant showed a statistically significant reduction in virulence--a 20-fold change in LD50 (Scheffe test, P < 0.05). Cytotoxicity to buffalo green monkey kidney cell monolayers and haemolysis on horse blood agar were eliminated only in the hlyA aerA double mutants. This is the first report of cloning and mutagenesis of two unrelated haemolytic toxin genes in the same strain of a mesophilic aeromonad. For A. hydrophila, a two-toxin model provides a more complete explanation of virulence.