Implementation of Bacterial Detection Methods into Blood Donor Screening – Overview of Different Technologies

Abstract

Background: Through the implementation of modern technology, such as nucleic acid testing, over the last two decades, blood safety has improved considerably in that the risk of viral infection is less than 1 in a million blood transfusions. By contrast, the residual risk of transfusion-associated bacterial infection is stable at approximately 1 in 2,000 to 1 in 3,000 in platelets. To improve blood safety with regard to bacterial infections, many countries have implemented bacterial screening methods as part of their blood donor screening programmes. Methods: Bacterial detection methods are clustered into three groups: i) culture methods in combination with the ‘negative-to-date’ concept, ii) rapid detection systems with a late sample collection, and iii) bedside screening tests. Results: The culture methods are convincing because of their very high analytical sensitivity. Nevertheless, false-negative culture results and subsequent fatalities were reported in several countries. Rapid bacterial systems are characterised as having short testing time but reduced sensitivity. Sample errors are prevented by late sample collection. Finally, bedside tests reduce the risk for sample errors to a minimum, but testing outside of blood donation services may have risks for general testing failures. Conclusion: Bacterial screening of blood products, especially platelets, can be performed using a broad range of technologies. Each system exhibits advantages and disadvantages and offers only a temporary solution until a general pathogen inactivation technology is available for all blood components.

Diagnostic Methods for Platelet Bacteria Screening: Current Status and Developments

“…If the result status changes from negative to reactive, physicians have to be informed immediately and products need to be recalled. If PCs were already transfused a look-back procedure has to be initiated [25]. The sample collection at an early stage of shelf life exhibits a high risk of sampling error in the range 1:14,000-1:50,000 [5], due to the low number of contaminating bacteria at the beginning of PC shelf life, particularly when slow-growing bacteria are involved in the contamination.…”

“…The BacT/Alert is by far the most common in reports and has been cleared for this application by the Food and Drug Administration (FDA) [18,25,28]. It monitors CO 2 production due to bacterial growth, which changes the color of a gas-permeable sensor at the bottom of the culture bottle from grey to yellow [25]. The Bactec system is very similar to the BacT/Alert system but uses a fluorimetric instead of the colorimetric detection principle [18].…”

“…Bacterial contamination is assumed if the O 2 reading is less than 12.5%, which is the cut-off value between a positive and negative reading [28,32]. Using this technology only bacteria that are able to grow under aerobic conditions will be detected, which confers a risk for false-negative screening results [25]. The sensitivity of the Pall eBDS system is similar to the BacT/ALERT system in the order of 1 CFU/ml [33].…”

“…The analytical sensitivities vary from 5 to 50 CFU/ml. However, the main drawback of these assays is amplification of background signals originating from the utilized PCR reagents, in particular from polymerases since these were produced in bacteria and are, therefore, not free of contaminating bacterial genomic DNA originating from the host [25]. Numerous attempts have been made to reduce background amplification, e.g.…”

“…The test principle of the FDA-licensed, qualitative PGD (Verax Biomedical Inc., Worcester, MA, USA) assay is based on a lateral-flow immunoprecipitation of bacterial cell wall antigens (lipopolysaccharide or lipoteichoic acid), which are present at high copy numbers (>200,000 copies/cell) [25]. The short hands-on time and the minimum requirement for laboratory instrumentation provide the opportunity for a point-of-issue bacterial detection test immediately before transfusion of PCs [42].…”