Transfusion-transmissible infection surveillance in Australia

Erratum for 2020 TTI Surveillance report

After first publication on March 22, an error was discovered relating to the total number of tested donations for HTLV and syphilis. The reported total tested figure of 793,113 was underreported, actual figure 809,607. This error also influenced the New and Repeat donor totals and led to slightly over reported HTLV and syphilis prevalence rates. None of the required corrections in the 27 April update of the report have impacted the trend analyses for HTLV or syphilis.

Transfusion-transmissible infections surveillance reports

In 2011, Lifeblood and the Kirby Institute published a comprehensive surveillance report for transfusion-transmissible infections (TTIs) - Safe blood – a focus on education, epidemiology and testing. This report analysed surveillance data for the period 2005–2010 and was the preface to planned annual TTI surveillance reports, with the first annual report being published the following year in 2012.

Lifeblood regularly reviews and updates the donor interview and selection process, taking into consideration local and overseas research studies, international best practice, literature reviews and analysis of surveillance data such as that included in this report.

The 2020 transfusion-transmissible infections in Australia surveillance report has now been published and the major findings and Lifeblood responses are as follows:
 

1. Supporting the effectiveness of donor education and selection, the prevalence of transfusion‑transmissible infections is substantially lower among first‑time blood donors (13-36 times) than in the general population in 2018/2019, and with the exception of potentially infectious syphilis, shows a stable or declining trend over the period 2010-2019. While remaining low (64 per 100,000), an increase in HCV prevalence in first‑time donors was recorded in 2019. 

Despite the recent increase, the prevalence of active/potentially infectious syphilis in first‑time donors has shown no statistically significant change over time in the past ten years, 2010‑2019, or in the past five years, 2015‑2019.The recent increase among blood donors mirrors that in the general population, where syphilis notifications have been trending upward. 
 
The increase in HCV prevalence among new donors in 2019 is likely to be a result of two factors. Firstly, there was an increase in the number of prospective donors with ‘resolved’ HCV (HCV antibody positive/RNA negative) presenting to donate subsequent to successful treatment, presumably on the assumption they were now eligible to donate. While these individuals are clinically ‘cured’, they remain ineligible as donors because they maintain HCV antibodies and therefore test anti-HCV positive on Lifeblood tests. Regulations preclude acceptance of such individuals as donors and Lifeblood is legally required to notify public health authorities in such cases. Secondly, a change to the blood donation eligibility policy for IDU, from indefinite exclusion to a five‑year postponement from last injection, might have led to an increase in newly eligible donors with undiagnosed HCV.

2. The prevalence of transfusion‑transmissible infections among first‑time donations was much higher than the prevalence among all donations, highlighting the importance of promoting donor education of potential new donors and ensuring first‑time donors read the pre‑donation information and understand the importance of ‘self‑deferral’.  

Lifeblood focuses on education of all donors, particularly first- time donors, including providing a specific blood safety brochure highlighting the pivotal role of accuracy and honesty in answering the standard questionnaire.
In accordance with state and territory laws, there are penalties including fines and imprisonment for anyone providing false or misleading information. 

While every effort is made to maximise donor retention, there is a fundamental requirement for continuing recruitment of new donors: firstly, to replace existing donors who can no longer donate (e.g. due to age and/or medical ineligibility) and secondly, to meet the growing demand for some blood products. 

Lifeblood considers the current proportion of first-time donations (7% in 2019) to be acceptable, noting that this proportion is at the lower end of the range among internationally comparable blood services (7–25%). Importantly, achieving a lower proportion of first-time donors whilst maintaining fresh blood product sufficiency and expanding plasma donations is a positive outcome.    

3. The incidence of newly acquired infection measured by the rate of incident donors is also much lower than results from specific at‑risk populations in Australia. This supports the general effectiveness of the donor questionnaire and specifically that repeat donors generally understand what constitutes ‘risk behaviour’ for acquiring transfusion‑transmissible infections.

4. Infective risk factors identified in blood donors with transfusion‑transmissible infections closely parallel those for the general population with no ‘unique’ risk factors identified to date among blood donors.

5. The non‑compliance rate among TTI-positive donors in 2019 was 19%, slightly lower than the 20% observed in 2018, but within the range of 15-25% observed in the last decade. The current rate highlights the importance of promoting donor education to ensure that the potential donors understand the importance of ‘self‑deferral’ to reduce the risk of collecting blood from a potentially infected donor whose infection may not be detected by testing.

6. While non‑compliance among positive donors has been routinely monitored since 2000, the rate among TTI test‑negative donors is more difficult to track.

Results from a large national survey conducted in 2012-2013 showed a comparatively low rate of reported non-compliance (in the range 0.05 to 0.29%) among TTI test-negative donors for several sexual activity-based donor deferrals. The study included a multivariate analysis of factors influencing non-compliance, which suggested that the use of a computer-assisted structured interview (CASI) might lead to further improvement in the overall compliance rate.

Lifeblood has fully implemented an electronic donor questionnaire (eDQ) at all blood collection sites. Planning for a follow up compliance study among test-negative donors is underway. While the results will inform the current compliance rate, the study will not be capable of measuring the direct impact of the eDQ on compliance because the previous study was conducted close to a decade ago and thus many factors other than the eDQ could have impacted.   

Non-compliance to screening questions remains an ongoing concern despite existing donor education initiatives targeting the importance of complete accuracy and honesty in answering the donor questionnaire. 

As noted, it is pleasing that the results of the national survey showed a comparatively low rate of reported non-compliance (in the range 0.05 to 0.29%) among TTI test-negative donors for several sexual activity-based donor deferrals. 

While it is reassuring that Australian rates in 2012-13 were lower than comparable overseas rates, Lifeblood remains committed to seeking further improvement. The planned non-compliance survey will provide an indication of the trend since the previous study.

One potential strategy to improve compliance is optimising the communication of the rationale underpinning deferral policies. Lifeblood continues to engage externally regarding initiatives to improve communication. Recommendations include optimising the use of social media, developing new education resources and refining current education resources. 

Furthermore, the donor compliance study identified a correlation with non-compliance and concerns over ‘privacy’ of disclosure, which might be partially alleviated by the use of a ‘computer-based’ donor questionnaire. As noted in the response to Q6 above, Lifeblood has now fully implemented an electronic donor questionnaire at all collection sites. Preliminary post-implementation results indicate that this initiative has improved both the donor experience, as well as reducing procedural (‘human’) errors, thus enhancing overall system safety. As noted above, its impact on the non-compliance rate is unknown but is predicted to lead to a lower rate.

7. The estimated residual risk of transmission for HIV, HCV, HBV, HTLV and syphilis in Australia is very low – less than one in one million per unit transfused. This supports the claim that Australia’s blood supply is among the safest worldwide in respect of transfusion‑transmissible infections for which testing is conducted. Despite this, there remains a minimal but real risk of transfusion‑transmissible infections that must be carefully considered before any transfusion.

8. Bacterial screening of 120 591 platelets identified 115 (0.10%) as confirmed positive. The majority of organisms identified were slow‑growing anaerobic skin flora not usually associated with post‑transfusion septic reactions. However, a minority of platelets grew clinically significant organisms that were likely to have been due to transient or occult bacteraemia in the donor and could have led to potentially serious septic transfusion reactions in the recipient. During 2019, there were two confirmed cases of transfusion‑transmitted bacterial infections.

Septic transfusion reactions associated with platelet transfusion in Australia are rare with the last case occurring in 2016. Based on Lifeblood data from May 2008 – June 2020, the risk of transfusion-transmitted bacterial infection from a platelet transfusion is calculated to be 0.47 per 100,000. This compares favourably with US data indicating a rate of 0.9 per 100 000 platelet units.

The two septic transfusion cases reported in 2019 were the subject of comprehensive investigation including root-cause analysis. The implicated donors in both cases were healthy and remained well post-donation. No issues associated with the collection, manufacture, testing, storage or transportation processes were identified. All quality requirements were met. The recalled blood components associated with the platelet donations were cultured and remained negative. A source of the bacterial contamination was not identified. Regarding the implicated organisms (Staphylococcus aureus and Group G Streptococcus), it is reported in the literature that Staphylococcus aureus and some Streptococcal species are associated with false negative results using current bacterial contamination screening (BCS) systems.

 

While the risk of septic reactions associated with platelet transfusion in Australia is already remote, Lifeblood has recently implemented additional measures designed to reduce it further.

1. Since April 2008, all platelets produced by Lifeblood have been screened for bacterial contamination. Until late November 2019, BCS utilised the automated BacT/ALERT 3D system. This was replaced by the BacT/ALERT VIRTUO system – which has demonstrated marginally improved bacterial detection performance. 
2. The efficacy of the BacT/ALERT VIRTUO system correlates with the volume of the platelet component cultured in the anaerobic and aerobic culture bottles. In September 2020, Lifeblood has increased the target volume (from 7 to 9mL) cultured per bottle. In addition, the number of culture bottles for double and triple apheresis platelets were doubled, and tripled respectively.

While these measures applied from late 2019 (after the two reported cases of transfusion-transmitted sepsis) and are aimed at further reducing the risk of such events, it is not expected they will eliminate the risk. Therefore, the guiding principle of minimising transfusions (patient blood management) remains paramount.

9. In addition to established transfusion‑transmissible infections, emerging infectious diseases continue to demand vigilant surveillance and risk assessment. The ongoing risk from SARS‑CoV‑2, local dengue outbreaks, seasonal West Nile virus outbreaks in Europe, outbreaks of hepatitis A virus and Zika virus was monitored during 2019‑2020. The risk to the blood supply posed by donors returning from Zika virus outbreak areas has been managed by deferring donation (or restricting to plasma for fractionation) for an appropriate period. Lifeblood continues to monitor hepatitis A virus, hepatitis E virus and Parvovirus B19 in Australia and a significant change in the risk profile has not occurred since the risk assessments were performed

Lifeblood maintains surveillance for emerging infections through close liaison with government communicable disease control units, CSL Behring, membership of international medical/infectious disease groups and active horizon scanning. 

Potential threats are regularly reviewed by Lifeblood’s Donor and Product Safety Committee and Clinical, Quality and Research Governance Committee, and risk assessment performed in the event that a threat is identified as a clear and present threat to the safety of the blood supply. Where appropriate, this will be performed in collaboration with CSL Behring (in their capacity as national plasma fractionator) and the Therapeutic Goods Administration.

Lifeblood has a comprehensive epidemic management plan - which was activated in response to SARS-CoV-2 (the novel virus causing COVID-19) in early 2020. Based on the epidemiology of known coronaviruses (SARS and MERS-CoV), the risk of transfusion transmission was assessed as low when the virus first emerged. The cumulative data, including over 100 million cases worldwide (at February 19, 2021) without a reported case of transfusion-transmission, supports that the risk is extremely low and currently ‘theoretical’.