Research Project
9619330
Abstract The NIAID is part of a global research community that is committed to finding new ways to eliminate the global scourge of tuberculosis. One critical component of this mission is the ability to accurately diagnose the disease, which guides treatment and prevention of antibiotic abuse. The ability to achieve this in a pediatric population is especially critical, as evidenced by recent focused RFA's announced by the agency for precisely that purpose. This project aims to address this critical gap by developing a novel, empirical, blood-based biomarker approach for the diagnosis of both pulmonary and disseminated active TB in children. We propose to achieve this by exploiting a novel Lipoprotein Capture assay and an ultra-sensitive biosensor platform that were developed at the Los Alamos National Laboratory, and integrating them with a well characterized clinical cohort of pediatric samples that are being collected from children in Siaya, Kenya, as a part of an ongoing study. The Lipoprotein Capture assay utilizes the interaction of Lipoarabinomannan secreted by the pathogen with host lipoproteins to quantitatively measure the biomarker in blood for the very first time. This effort is strengthened by the expertise of our collaborations ? pediatric clinical study and co- morbidities (University of New Mexico), Lipoarabinomannan chemistry and the microbiology of tuberculosis (NIAID), clinical and pediatric tuberculosis expertise (Johns Hopkins University) and extensive statistical analysis (LANL). Indeed, by exploiting over 12 years of clinical expertise in Siaya, Kenya, we are able to obtain microbiologically characterized, longitudinal sequel of pediatric samples and systematically probe the issues with pediatric TB diagnostics. We will also study the change in LAM concentrations in these patients over a period of 1 year, and the interdependencies of HIV co- infection, therapy, and nutrition on the assay outcomes. We will validate our methods in blinded pediatric samples, providing empirical data to guide further development. Taken together, these findings promise a path forward for pediatric TB diagnosis from blood, and enhance our understanding of host-pathogen biology during M. tuberculosis infection.
