Bacteremia is a leading cause of death in sub-Saharan Africa where childhood mortality rates are the highest in the world. The early diagnosis of
bacteremia and initiation of treatment saves lives, especially in high-disease burden areas. However, diagnosing
bacteremia is challenging for clinicians, especially in children presenting with
co-infections such as
malaria and HIV. There is an urgent need for a rapid method for detecting
bacteremia in pediatric patients with co-morbidities to inform treatment. In this manuscript, we have developed and clinically validated a novel method for the direct detection of amphiphilic pathogen
biomarkers indicative of
bacteremia, directly in aqueous blood, by mimicking innate immune recognition. Specifically, we have exploited the interaction of amphiphilic pathogen
biomarkers such as
lipopolysaccharides (LPS) from Gram-negative bacteria and lipoteichoic
acids (LTA) from Gram-positive bacteria with host
lipoprotein carriers in blood, in order to develop two tailored assays -
lipoprotein capture and membrane insertion - for their direct detection. Our assays demonstrate a sensitivity of detection of 4 ng/mL for LPS and 2 ng/mL for LTA using a waveguide-based optical biosensor platform that was developed at LANL. In this manuscript, we also demonstrate the application of these methods for the detection of LPS in serum from pediatric patients with invasive Salmonella Typhimurium
bacteremia (n = 7) and those with Staphylococcal
bacteremia (n = 7) with 100% correlation with confirmatory culture. Taken together, these results demonstrate the significance of biochemistry in both our understanding of host-pathogen biology, and development of assay methodology, as well as demonstrate a potential new approach for the rapid, sensitive and accurate diagnosis of
bacteremia at the point of need.