Assessing Tuberculosis Transmission Dynamics, Drug Resistance and Recurrence Using Whole Genome Sequencing in Pune, India

Tuberculosis (TB) is the top killer from an infectious disease pathogen. The disproportionate burden of TB in low- and middle-income counties (LMIC) has been attributed to both reactivation of latent TB infection (as in China) as well as to active TB transmission (as in Sub-Saharan Africa) in high TB burden countries. A complex interaction between host, pathogen and environmental factors including virulence and infectivity influences TB transmission in community settings, particularly, the TB strain type (Beijing vs. East Indian strains). Social networks as well as casual contacts have been implicated in TB transmission, however, data are limited on the role of these factors on TB transmission dynamics in India, a country with world’s highest burden of TB. We hypothesize that active TB transmission, rather than reactivation of TB infection, contributes to high TB burden in India, influenced likely by the TB strain type. Advanced molecular epidemiologic tool- whole genome sequencing (WGS), has been increasingly utilized to understand TB transmission in high TB burden countries. In this proposal, we aimed to describe the TB transmission dynamics using combined geospatial, and genotyping methods in a hyperlocal region of Pune City in Western India. A tuberculosis relational sequencing data platform (ReSeqTB) has been established and generated drug resistance mutation list. Using this, we will aim to assess the lineage and sub-lineage of samples as well as assess drug resistance among circulating TB strains in the community. 

Objectives

1. 
   To identify the prevalent TB strain types in Pune city, a high TB burden region of Maharashtra. 
2. 
   To characterize the lineage and sub-lineage of samples as well as assess drug resistance using the ReSeqTB endorsed drug resistance mutation list.
3. 
   To assess the geospatial clustering of cases with genotype clustering and demographic, socioeconomic, and TB risk-factor information.