Novel and Optimized Diagnostics for Pediatric TB in Endemic Countries

Pediatric TB is underdiagnosed and has a high mortality rate. Promising new diagnostics have been developed but not sufficiently evaluated in children less than 5 years of age, those at greatest risk. We propose a comprehensive study of children from Uganda and Peru suspected to have TB that addresses the most critical challenges and unmet needs in the area of pediatric TB diagnosis by several different, but inherently complementary approaches. The study will concurrently evaluate, optimize and develop more sensitive non-sputum based diagnostics for children < 5 years of age applicable at POC and propose an enhanced reference standard that can be applied to unconfirmed as well as confirmed TB. Moreover, this protocol includes the following design features to enhance the efficiency with which investigational tuberculosis diagnostic assays are formally evaluated, thereby enabling rapid identification of the most promising assays and speeding their movement through the pipeline to tuberculosis patients and programs:
• A continuously enrolling protocol that will a) facilitate rapid evaluation of new investigational tuberculosis diagnostic assays as they become available, thereby allowing the FEND for TB Consortium to respond nimbly to new scientific opportunities, and b) allow for collection of specimens from participants whose tuberculosis status is well characterized, for use in evaluation of new technologies at the study site and at the Analytic Laboratory Core and for use in determining the comparative performance of assays that enter evaluation at different times;
• Potential use of a two-stage study design to allow early but statistically rigorous decisions as to proceed, or not, with continued evaluation of a given investigational assay.