Abstract
Transfusion-transmitted infections due to contaminated platelet products remain an important and underrecognized healthcare challenge despite existing screening methods and photochemical pathogen-reduction strategies. Investigation of septic transfusion events currently relies on microbial culture, which is time consuming and low yield in the setting of antibiotic use prior to sample collection. Here we report three septic transfusion cases, two of which involved fatalities, where culture-independent metagenomic next generation sequencing (mNGS) of blood products afforded rapid and actionable assessment of pathogen identity, abundance and phylogenetic relatedness. In each case, direct mNGS of clinical specimens permitted longitudinal assessment of pathogen burden, clarified the temporal sequence of events and confirmed occurrence of a transfusion-transmitted infection. Informative data was obtained from mNGS of residual platelet products and leftover blood specimens including those that were either unsuitable or unavailable for culture, or that failed to grow in culture due to antibiotic use prior to sampling. We highlight the utility of mNGS for unbiased pathogen discovery by identifying a novel Acinetobacter species and confirming its role in a septic platelet transfusion event. Lastly, we propose methodology to enhance the accuracy of mNGS-based assessment of transfusion-related pathogens that share taxonomic similarity to background contaminants commonly found in metagenomic sequencing library preparations. Together, these challenging cases demonstrate the potential for mNGS to advance existing methods for investigating transfusion-transmitted infections.