Drug-resistant Mycobacterium tuberculosis isolates (TB) from Sri Lanka and Pakistan

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Tuberculosis (TB) is an infection caused by inhalation of infectious bacteria belonging to Mycobacterium tuberculosis complex when an infected patient coughs, sneezes, sings or talks. The infection predominantly occurs in the lungs. Once a person is diagnosed as TB, he/she is prescribed a 6-month long chemotherapy comprised of four drugs. However, sometimes the patient does not answer to the given drugs (one or many), termed as drug resistance (DR) or multidrug resistance (MDR). One major problem in drug resistant TB diagnostics is the low turnaround time. Hence, new fast and reliable diagnostic methods are a timely requirement. Drug resistance is driven by genetic alterations/mutations in the bacterium. The knowledge on mutations, is necessary to identify them to be used in reliable diagnostics. This study was a collaborative study with Pakistan, intended to identify bacterial mutations that are responsible for drug resistant TB.  The researchers carried out advanced molecular techniques and identified common mutations as well as uncommon mutations that circulated within the two countries that could be responsible for drug resistance. Hence, more attention should be given to improvement of current diagnostics as they are a chance for false negatives. In addition, the genetic alterations in human blood of drug resistant and sensitive patients were compared using advanced molecular techniques. From the Sri Lankan study, a signature panel comprising of 22 markers, majority of which are related to immune functions was identified, implying that the immune system of drug resistant patients signals to activate certain immune functions to fight against drug resistant tuberculosis. These markers should be further tested to understand their potentiality in diagnostics. Further, from Sri Lankan part the team was able to develop a rapid and low-cost real-time multiplex PCR (RT-PCR) technique that can be used in a clinical setting for diagnostic purposes of MDR-TB.