Molecular epidemiology of "mycobacterium tuberculosis" in the country of Georgia

Tuberculosis (TB), an infectious disease caused by Mycobacterium tuberculosis (MTB), is one of the major contributors to human mortality globally. Being attributable to several socio-economic factors, national TB control programs still struggle to prevent transmission and treat active cases of the disease. In order to achieve sustainable development goal for ending TB in 2030, The World Health Organization (WHO) has endorsed the recommendations for prompt diagnosis and integrated molecular surveillance of TB. Molecular typing of MTB is progressively used for strengthening disease surveillance. However, in most limited-resources settings such as low/middle income countries, implementation of the typing methodologies is challenging.
In the first part of the thesis, we implemented a genotyping tool at the National Reference Laboratory (NRL) in Georgia, aiming to support disease surveillance at the molecular level. We took advantage of the isolate biobank, containing MTB isolates from 2009, and performed genotyping for the recurrent TB cases (chapter 3). The generated results gave the opportunity to customize and develop more practical application of MIRU-VNTR typing. The stepwise MIRU-VNTR typing approach described in chapter 4 represents a simplified and less time/cost/workload consuming way of the typing, which can be easily customized for different settings, thereby enhancing the usage of molecular typing for the TB control and surveillance.
Despite of being an ancient disease, treatment of TB remains to be complex, especially throughout evolution of the drug resistant variants, requiring treatment with toxic and expensive medications. Drug resistance is still hindering TB control strategies in Georgia.
Moreover, resistance to the novel, promising medications, such as bedaquiline, bears utmost importance. Since 2019, bedaquiline has been used as the backbone for the treatment regimens for MDR, preXDR and XDR TB. However resistance has already been detected in vivo, translated into 22 (6.9%) of resistant cases in 2020-21 in Georgia. While transmission of resistant MTB strains is threatening TB control, the data for developing molecular test-systems for prompt
detection of such cases is still lacking. This requires collated information of precise phenotypic information associated with corresponding sequencing data. In our second part of the thesis, we combined evidence of any influence between the genomic variants of bedaquiline resistance associated genes and minimum inhibitory concentration values. Simultaneously, we looked for samples identified as phenotypically resistant using single, critical concentration (CC) provided by WHO, and correlated genomic information for those isolates. Herein, the chapter 5 provides valuable and essential data for the further developmental implications.