Whole genome sequencing for molecular characterization of Mycobacteria tuberculosis MDR/XDR strains from Georgia
Project Status: 3 Approved without Funding
Duration in months: 24 months
Objective
Over the past two decades Tuberculosis (TB) has reemerged as a major public health problem worldwide. Pandemic of human immunodeficiency virus (HIV) infection and interaction between TB and HIV infection exacerbates this problem. The emergence and worldwide spread of multidrug-resistant tuberculosis (MDR TB), and more recently extensively drug -resistant tuberculosis (XDR TB), represent a serious threat to public health and TB control programs. In 2015, a total of 10.4 million new TB cases were reported worldwide, and 1.8 million died from the disease, 0,4 million death were attributed to the people with HIV [1]. MDR TB is now considered a Category C Biological Agent that could be used in possible bioterrorist attacks [2].
TB is widespread in the republics of the former Soviet Union, including Georgia. Although there has been a small decline in TB rates in Georgia over the last few years, TB remains an enormous public health problem in Georgia and TB case rates remain high. WHO assigns Georgia to countries with high burden of TB and MDR TB. In 2015, a total of 3,611 TB cases were reported in Georgia; the incidence and prevalence of TB was 74.7cases and 97.1 cases per 100,000 population, respectively [3]. Prevalence of MDR-TB was11, 6% among new sputum smear positive TB cases and 38.8% among previously treated TB cases [3].
This study will build on the success of previous research projects (BTEP #12 G-610), has examined the prevalence and risk factors for drug resistant TB including MDR-TB and the molecular epidemiology of drug resistant TB in Georgia using IS6110-based insertion sequence restriction length fragment polymorphism (RFLP) analysis. In the frame of previously funded CRDF project in Georgia (CRDF # 2935) Molecular Genetic Assay Genotype MTBDRplus (HAIN Lifescience) for rapid testing of MDR-TB was successfully implemented. ISTC funded project (ISTC#G- 2100) aimed to study risk factors for developing XDR TB in Georgia and molecular epidemiology of MDR/XDR TB on the basis of combination of different molecular techniques - IS6110 RFLP analysis, spoligotyping and 24-locus Mycobacterial Interspersed Repetitive Unit –Variable number of tandem repeat (MIRU-VNTR) typing.
We propose two year project to characterize Mycobacteria tuberculosis (MTB) MDR/XDR clinical isolates on the basis of whole genome sequencing and to develop laboratory biosafety manual for handling MDR/XDR strains of MTB in clinical and research laboratories. In our work, we will investigate MDR/XDR clinical isolates of MTB stored in the repository of NCDC LCPHR, as well as DNAs of resistant clinical isolates of MTB which are stored in Molecular Epidemiology Laboratory of the LCPHR. These materials were collected during the past decade from different regions of Georgia (Western and Eastern Georgia), their phenotypic resistance patterns is already known. Proposed project will give the ability to study genetic diversity and phylogeny of isolates, evaluate the type and prevalence of resistance associated mutations in MDR/XDR clinical isolates of MTB, assess distribution of these mutations in different regions of Georgia, define whether and/or how distinct groups of MTB from diverse geographic locations differ in their genetic patterns of resistance and on the basis of obtained results, evaluate potential utility and reliability of these mutations as possible diagnostic markers for our setting. Ultimately, knowledge of allelic polymorphisms in various MDR/XDR strains from different geographic regions of the world improves our understanding of resistance mechanisms.
Implementation of the proposed study will enhance the ability of public health institutions in Georgia to identify and control drug-resistant TB. The project will be carried out in Molecular Epidemiology Laboratory of LCPHR, NCDC.
Participating Institutions
COLLABORATOR
U.S.Centers for Disease Control and Prevention
COLLABORATOR
The Research Institute of Tuberculosis
LEADING
National Center for Disease Control and Public Health (NCDC)
