Multi-Drug and Extra Drug Resistance of M.Tuberculosis
Studying of mutations leading to Multi-Drug and Extra Drug Resistance of M.Tuberculosis in Kyrgyz Republic
Tech Area / Field
- MED-DID/Diagnostics & Devices/Medicine
3 Approved without Funding
National Center of Cardiology and Internal Medicine / Institute of Molecular Biology and Medicine, Kyrgyzstan, Bishkek
- Anti Tuberculosis city hospital, Kyrgyzstan, Bishkek
- National Reference Center (NRC) for Mycobacteria and antituberculous drug resistance, France, Paris
Project summaryTuberculosis is one of the world leader diseases in term of mortality and morbidity.
Its active transmission is both due to the pathogenicity of the causing bacteria, Mycobacterium tuberculosis, and its specific resistance to common antibiotics. Decades of tuberculosis treatment failures led to acquired resistance to the first-line antituberculous drugs, isoniazid and rifampicin, resulting in multidrug resistant tuberculosis (MDR-TB). These latter cases of MDR-TB can be hopefully treated by second-line drugs which included at least one fluoroquinolone such as levofloxacin or moxifloxacin), one aminoglycoside such as amikacin, kanamycin or capreomycin, and ethionamide. These treatments are long-term (24 months at least) and possibly deleterious (injections, toxicity) and and failure is observed in 20 to 50% cases . Failure is often linked with acquisition of resistance to these second-line drugs. This was brought up some years ago as extensively drug resistance tuberculosis (XDR-TB). XDR tuberculosis cases may represent about 3 to 10% of MDR cases in endemic countries such as Kyrgyz Republic (300 to 400 MDR cases a year). Moreover the use of fluoroquinolones and aminoglycosides, which are commonly prescribed for urinary tract and respiratory infections, might also select for XDR TB in an endemic tuberculosis setting. Beyond the untreated communicable disease which brings a real threat for contact living populations, these XDR cases need to be rapidly detected to eventually benefit of recently developed antituberculous drugs (8,9,10).
In identification of microorganisms, including of Mycobacterium tuberculosis, the polymerase chain reaction (PCR) of molecule-and-biological technique is becoming the most frequently used one within the territory of CIS. Being included into the list of clinical laboratory examinations and effectively combining with it, it makes a good contribution to the traditional diagnosing. The PCR technique is constantly modified, but it has disadvantage as lack of classification of mycobacterium population by types, and credibility of that analysis is only 45%.
Culture examination remains as a commonly accepted “golden standard” for testing drug susceptibility of MT WHO now recommends to use also molecular techniques to detect for resistance since, culture examination is laborious, takes much time and does not enable to get information quickly consequently, this complicates timely performance of chemoprophylaxis and chemotherapy.
At present, molecular-genetic methods as an alternative technique are widely used along with culture examinations to test MT susceptibility to antibiotics. Starting in 2001, the Engelhardt Institute (Moscow, Russia) has developed a novel biochip technology potentially adapted to the detection of a large number of mutations in a clinical TB isolate. The biochip technique differs from cultural examination not only by a rapid obtaining of results, but by identification of mutation types in genes rpoB, katG, inhA, ahpC and gyrA. The principle advantage of the biochip analysis compared to culture examination is a direct detection of MT DNA and an opportunity to get results within 3 days.
The present project aims to develop a method for rapid detection of Multi-Drug and Extra Drug Resistance in M.Tuberculosis. The new biochip method should have a high sensitivity for detecting resistance to moxifloxacin, amikacin and ethionamide resistance on the basis of new data on resistance mechanisms and their correlation with antibiotic resistance phenotype. Compared to the existing techniques (line probe kit and home PCRs), the biochip would provide a more accurate result with an easy-to handle device and commercially available standardized kit. This will allow detecting in less than a day XDR cases who required special isolation measures and an inpidualized long-term treatment with directly observed therapy (DOTS+). This will also provide a surveillance tool for assessing XDR rates per place, region and countries.
Because tuberculosis is still expanding in countries of the former Soviet Union, contrarily to the European countries, the collaboration between two endemic countries such as Kyrgyz Republic and the NRC France might be fruitful. In case of success, this opens perspective to a global expansion of such a standardized test, especially in endemic regions.
The International Science and Technology Center (ISTC) is an intergovernmental organization connecting scientists from Kazakhstan, Armenia, Tajikistan, Kyrgyzstan, and Georgia with their peers and research organizations in the EU, Japan, Republic of Korea, Norway and the United States.
ISTC facilitates international science projects and assists the global scientific and business community to source and engage with CIS and Georgian institutes that develop or possess an excellence of scientific know-how.