Update on the status of pathogen inactivation methods

Abstract

Background Improvements in donor selection criteria and donor testing have reduced the risks of transfusion-transmitted diseases to remarkably low levels in developed countries. Residual risk remains because of window period donations and the potential for error. Developing countries may not have implemented all these safety measures fully, however. In all countries, tests with limited sensitivity (e.g. for detection of bacterial contamination) and 'emerging' pathogens, for which accurate tests have not been developed, pose continued threats to recipients.Results Pathogen inactivation (PI) has brought a welcome level of safety to plasma derivatives, and an increasing number of techniques are available for labile blood components. The toxicity profile of these techniques appears acceptable. Although the processes inevitably cause a reduction in the content or efficacy of the component, transfusions of the inactivated components appear to provide clinically useful outcomes. Transfusion of pathogen-inactivated plasma components is in widest use across multiple countries, and an increasing number of centres in multiple countries are adopting PI of platelet units as well. Development of techniques applicable to red cell units continues and preliminary success has been claimed. Not all reports of clinical use of PI platelets and plasma have been positive, however. Differences in bleeding rates may be attributable to different approaches to patient evaluation. Some regulatory agencies continue to place emphasis on the potential for pulmonary complications, although reanalysis of previous data indicates no increased risk of pulmonary toxicity. Multiple cost-effectiveness analyses have demonstrated that currently available PI techniques will likely reduce the residual risk of known pathogens by only a small amount and thus have marginal cost-effectiveness ratios in the range of $500 000-1 500 000 ⁄ QALY (this is worse than for most commonly accepted medical procedures but not out-of-line in comparison to other blood safety interventions). The presumed effectiveness of current bacterial detection approaches is central to these analyses as bacteria remain the most frequently transmitted pathogen with culture detecting only 30-50% of contaminated units. An analysis of residual risk indicates that while techniques applicable across all components will be necessary to achieve the desired maximal effect of PI, implementing PI for plasma and platelets with currently available technology would reduce transmissions of both acute and chronic emerging disease agents by 40%. ConclusionsThe decision whether to implement PI is a complex one with ethical, societal and financial aspects. The ability to improve the safety of transfusion for recipients, particularly with respect to bacteria and emerging threats, is an important augmentation to our commitment to patients.

Where do Trypanosoma cruzi go? The distribution of parasites in blood components from fractionated infected whole blood

“…The effectiveness of leukoreduction of blood components in reducing the risk of pathogen transmission has been studied, and pathogen reduction technologies (PRTs) are currently in development. 7 A review of the literature reveals that platelet (PLT) concentrates are the blood component most frequently identified as responsible for the transmission of T. cruzi by transfusion. However, in cases of whole blood (WB) transfusion its responsibility has not been clearly identified.…”

“…Improvements have also been made to reduce adverse reactions to transfusion and decrease the risk of transfusion‐transmitted infections without altering the quality of blood components. The effectiveness of leukoreduction of blood components in reducing the risk of pathogen transmission has been studied, and pathogen reduction technologies (PRTs) are currently in development …”

The importance of hemovigilance in the transmission of infectious diseases

“…Studies carried out in the HRU in 2008 and in a blood bank in São Paulo in 2004 also support the implementation of this method (19,20) . A work published in 2011 also defends the use of increasingly sensitivity and specific serological screening methods in an attempt to increase transfusion safety (21) .…”

Comparative study on the inactivation of MS2 and M13 bacteriophages using energetic femtosecond lasers

“…The need to safely and reliably inactivate or remove viruses is universal in the biomedical manufacturing sector. Conventional pharmaceutical methods for pathogen inactivation are quite useful, but they often involve substantial collateral damage and may have undesirable side effects [1][2][3][4]. Chemical-free viral inactivation methods such as ultraviolet (UV) and gamma-ray irradiation are useful sanitization methods but lack selectivity and can also induce mutations in the pathogen.…”