Project Details

Early Career

Status: Funded - Open

Investigating the use of next generation sequencing on stool to detect Mycobacterium tuberculosis heterogeneity in children with pulmonary tuberculosis

Tara Ness, MD, MPH

Summary

BACKGROUND: As culture-based drug susceptibility testing takes significant time and has limitations due to sample collection when used in small children, other avenues, such as next-generation sequencing (NGS), are being investigated for identifying resistance patterns. Of particular interest is the concept of mixed infections, or the idea that an individual may harbor more than one strain of Mycobacterium tuberculosis (MTB) and could even have strains that have different resistance patterns, termed heteroresistance. GAP: Our study will be the first to utilize NGS on stool samples to identify mixed infections in children with microbiologically confirmed TB over time and explore whether mixed infections are associated with treatment response. HYPOTHESIS: Stool-based NGS will identify TB mixed infections in a significant (~15.9%) proportion of children at baseline. Persistent mixed infections will be associated with worse treatment response as indicated by delayed clearance of MTB DNA in stool. METHODS: We will utilize an existing biorepository augmented by a prospective cohort of children presenting for routine screening and care at and collect stool samples to undergo NGS to identify drug resistance. Using baseline and serial sequencing results, we will identify and compare strains present within a single individual over time. RESULTS: Pending. IMPACT: NGS has the potential to identify clinically relevant mixed infection. If feasible, the next step would be a clinical trial evaluating NGS-based tailored drug therapy