Extensively Drug Resistant Tuberculosis
Management of Extensively Drug Resistant (XDR) Tuberculosis in Georgia
Tech Area / Field
- BIO-CGM/Cytology, Genetics and Molecular Biology/Biotechnology
- MED-DIS/Disease Surveillance/Medicine
3 Approved without Funding
National Center of Tuberculosis and Lung Disease, Georgia, Tbilisi
- National Center for Diseases Control, Georgia, Tbilisi
- ATCC, USA, VA, Manassas\nForschungszentrum Borstel / Leibniz-Zentrum für Medizin und Biowissenschaften, Germany, Borstel\nPrince Leopold Institute of Tropical Medicine, Belgium, Antwerpen
Project summaryThe emergence of drug-resistant tuberculosis (TB), and in particular, multidrug-resistant tuberculosis (MDR TB) (MDR TB-resistance to at least isoniazid and rifampin) seriously challenges the success of present and future global TB control. In addition to MDR TB, a recent CDC Mortality and Morbidity Weekly Report described the worldwide appearance of Mycobacterium tuberculosis isolates with extensive resistance to at least three of the six classes of existing second-line antituberculosis drugs (XDR TB) as an additional, ominous threat to global TB control.
MDR-TB has been detected in every region of the world, with the highest rates found in countries of the former Soviet Union, including Georgia. According to the World Health Organization (WHO), in 2004, the reported burden of incident TB cases in Georgia was 82/100,000 population/year. The previously funded BTEP projects in Georgia (BTEP #12 G-610, BTEP # 72, A-998) demonstrated the emergence of high rates of MDR-TB (10.5% in newly diagnosed patients and ~50% in retreatment cases). However, the extent of XDR TB in Georgia has yet to be determined.
We propose to study XDR-TB prevalence and and risk factors for the development of XDR TB in Georgia. This is a three-year project proposal that will be pided into four unique projects, each of which is intended to enhance the abilities of the collaborating public health scientists in Georgia to control MDR and XDR tuberculosis, so that appropriate actions can be taken to prevent ongoing M. tuberculosis transmission. In addition to the research objectives proposed, this project will also provide substantial infrastructure development for the Georgian NCTBLD-NTP and NCDC as well as provide training opportunities for Georgian collaborators.
This study will build on the success of the recent country-wide WHO survey and the BTEP #12 G-610, BTEP # 72, A-998 projects (which included collaboration between CDC, NCDC, NCTBLD-NTP and Emory University) and have examined the prevalence and risk factors for drug resistant TB including MDR-TB and the molecular epidemiology of drug resistant TB in Georgia. Currently, M. tuberculosis MDR isolates from these two projects are stored in their National Reference Laboratory and are available for second-line drug susceptibility testing to determine the magnitude of XDR TB in Georgia. In addition, epidemiologic data available on these patients will be further analyzed to identify risk factors associated with XDR TB.
Work done through previous BTEP project (BTEP #12 G-610), the Georgian genotyping program using IS6110-based insertion sequence restriction length fragment polymorphism (RFLP) was established according to the standard fingerprinting methodology. We propose to expand genotyping program in Georgia and introduce a rapid PCR-based method (spoligotyping) that will increase the volume of isolates that can be genotyped, and also increase the sensitivity, specificity and rapidity of genotyping. Spoligotyping method will be useful to increase the discriminatory power for strain typing of, and for determining Beijing family genotypes in M.tuberculosis. Genotyping results may allow for earlier detection and control of TB transmission. The implementation of spoligotyping, and its utility along with the RFLP method in the above region, will allow us to determine i) M. tuberculosis genotypes responsible for TB infections, ii) their genetic persity and population structures, and iii) transmission routes of TB in Georgia.
Assessment of treatment outcomes for XDR TB of patients who are enrolled in this project and are demonstrated to have laboratory confirmed XDR TB will have the impact upon TB control strategies in Georgia.
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