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.

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.

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.

Riboflavin and ultraviolet light: impact on dengue virus infectivity.

BACKGROUND: Dengue viruses (DENV 1-4) are emerging across the world, and these viruses pose a risk to transfusion safety. Pathogen inactivation may be an alternative approach for managing the risk of DENV transfusion transmission. This study aimed to investigate the ability of riboflavin and UV light to inactivate DENV 1-4 in platelet concentrates. MATERIALS AND METHODS: DENV 1-4 were spiked into buffy coat-derived platelet concentrates in additive solution (SSP+) before being treated with riboflavin and UV light. Infectious virus was quantified pre- and posttreatment, and the reduction in viral infectivity was calculated. RESULTS: All four DENV serotypes were modestly reduced after treatment. The greatest amount of reduction in infectivity was observed for DENV-4 (1·81 log reduction) followed by DENV-3 (1·71 log reduction), DENV-2 (1·45 log reduction) and then DENV-1 (1·28 log reduction). CONCLUSION: Our study demonstrates that DENV 1-4 titres are modestly reduced following treatment with riboflavin and UV light. With the increasing number of transfusion-transmitted cases of DENV around the globe, and the increasing incidence and geographical distribution of DENV, additional approaches for maintaining blood safety may be required in the future.

Projections of increased and decreased dengue incidence under climate change.

Dengue is the world's most prevalent mosquito-borne disease, with more than 200 million people each year becoming infected. We used a mechanistic virus transmission model to determine whether climate warming would change dengue transmission in Australia. Using two climate models each with two carbon emission scenarios, we calculated future dengue epidemic potential for the period 2046-2064. Using the ECHAM5 model, decreased dengue transmission was predicted under the A2 carbon emission scenario, whereas some increases are likely under the B1 scenario. Dengue epidemic potential may decrease under climate warming due to mosquito breeding sites becoming drier and mosquito survivorship declining. These results contradict most previous studies that use correlative models to show increased dengue transmission under climate warming. Dengue epidemiology is determined by a complex interplay between climatic, human host, and pathogen factors. It is therefore naive to assume a simple relationship between climate and incidence, and incorrect to state that climate warming will uniformly increase dengue transmission, although in general the health impacts of climate change will be negative.

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.

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'.

Seroprevalence of 2009 pandemic influenza A(H1N1) virus in Australian blood donors, October - December 2009.

Assessment of the severity of disease due to the 2009 pandemic influenza A(H1N1) in Australian states and territories has been hampered by the absence of denominator data on population exposure. We compared antibody reactivity to the pandemic virus using haemagglutination inhibition assays performed on plasma specimens taken from healthy adult blood donors (older than 16 years) before and after the influenza pandemic that occurred during the southern hemisphere winter. Pre-influenza season samples (April ­ May 2009, n=496) were taken from donation collection centres in North Queensland (in Cairns and Townsville); post-outbreak specimens (October ­ November 2009, n=779) were from donors at seven centres in five states. Using a threshold antibody titre of 40 as a marker of recent infection, we observed an increase in the influenza-seropositive proportion of donors from 12% to 22%, not dissimilar to recent reports of influenza A(H1N1)-specific immunity in adults from the United Kingdom. No significant differences in seroprevalence were observed between Australian states, although the ability to detect minor variations was limited by the sample size. On the basis of these figures and national reporting data, we estimate that approximately 0.23% of all individuals in Australia exposed to the pandemic virus required hospitalisation and 0.01% died. The low seroprevalence reported here suggests that some degree of prior immunity to the virus, perhaps mediated by broadly reactive T-cell responses to conserved influenza viral antigens, limited transmission among adults and thus constrained the pandemic in Australia.