“Star Wars” or Looking for Trouble?
I always told my kids to be careful turning over rocks - there might be a scorpion there to sting them. The warning came from my clinical experience, watching colleagues test patients for infections that you could tell they did not have after talking to the patient, and coming up with false positive tests to explain away. The pathologists among us (at least those beyond a certain age) will remember "febrile agglutinins" in this context.
More recently, large-scale screenings for prostate-specific antigen and mammography have been criticized because they generate abnormal results in folks for whom they are clinically irrelevant, causing harm from over-diagnosis and treatment. A recent Food and Drug Administration workshop focused on the application of next-generation nucleic acid sequencing as donor testing, which could cause similar problems in our laboratories. These techniques are being developed to find bugs we know cause problems, but also for use in "pathogen" discovery. This is the sensitive identification of previously unknown viruses (or higher organisms) by comparing extensive DNA and RNA sequences found during screening to the human genome and known organisms to find new bugs in the data. If donors are screened with these approaches, we may find an organism that's searching for an illness. Recent examples demonstrate that humans harbor a normal viral flora that does not cause illness, e.g,. TTV and GBV-C, which were initially candidates to explain post-transfusion hepatitis that is not caused by the usual suspects. On July 29, the Journal of Infectious Diseases published a report by Nikolay Popgeorgiev and colleagues, documenting the identification of an apparently non-pathogenic "Marseillevirus" in French blood donors. An editorial comment by Jesse Goodman, former director of FDA's Center for Biologics Evaluation and Research, discusses this finding's potential impact on blood safety. Yin: speedy identification and mitigation of agents that are destined to cause trouble. Yang: finding agents that are harmless, with the thorny issue of explaining the test results to donors when we know little or nothing about the identified agent.
How do we deal with these prospects going forward without sacrificing the power of these techniques to prevent or mitigate the impact of an emerging agent on transfusion safety? The solutions range from robust non-donor surveillance of pathogens and their diseases, unlinked donor-recipient repositories to allow "off line" characterization of opportunities and threats, long-term follow up of blood recipients to recognize adverse outcomes associated with transfusion before we find a pathogen, and (maybe most important) conservative transfusion practices. These methods necessitate research commitments and infrastructure that will require a large and long-term investment from agencies with deep pockets.
Louis Katz, MD, Executive Vice President, Scientific, Medical, Technical, Quality, and Regulatory; LKatz@americasblood.org