UKZN masters student Mr Kashmeel Maharaj won the first prize of R30 000 for his oral presentation at the College of Health Sciences Research Symposium titled: “Comprehensive Screen to Identify and Confirm M Tuberculosis PNCA Mutations that Confer Resistance”.
Maharaj, who will use the prize money to attend an international conference of his choice, completed his BSc in Bio-Medical Sciences and BMedSc Honours in Human Physiology through UKZN and is currently completing his dissertation for an MSc in Medical Microbiology degree.
He is employed as a Laboratory Technologist in the Pym Lab at the African Health Research Institute, formerly known as the KwaZulu-Natal Research Institute for Tuberculosis and HIV (K-RITH).
Maharaj spent just over two and a half years working as a Laboratory Technician at Lancet’s reference TB diagnostic lab in Richmond, Johannesburg, where he was first exposed to tuberculosis and the public health crisis that it poses, particularly with the emergence of drug resistant Tuberculosis. This inspired him to pursue a career in research in understanding drug resistance in tuberculosis in order to contribute knowledge towards the fight against TB.
Pyrazinamide is a crucial antibiotic in the treatment of tuberculosis as it allows for the shortening of treatment down to the current six-month regimen for drug-susceptible tuberculosis and is also a vital component of new experimental treatment regimens.
The emergence of drug resistant TB is a major public health concern and early detection of drug resistance is paramount in the fight against Tuberculosis as it allows for the customisation of individual patient treatment regimens leading to more favourable outcomes as well as a reduction in the transmission of Tuberculosis.
‘Advances in technology have allowed us to detect drug resistance towards other drugs, such as rifampicin and isoniazid, more rapidly using genetic based approaches which identify “mutations” (alterations of the DNA sequence), in specific “genes” (DNA sequences which code for components of cells), as the specific genes and mutations have been well investigated and characterised,’ said Maharaj.
‘Mutations in the pncA gene of tuberculosis are the primary driver of drug resistance to pyrazinamide, however the full spectrum of mutations which confer resistance is still unknown. Our research utilised genetic manipulation of the tuberculosis bacteria in order to create a “pncA mutant library” or population of bacteria containing every possible mutation in pncA. After screening our mutant library in two separate testing systems, we were able to identify 411 mutations which we predict to confer resistance to pyrazinamide.
‘Selected pncA mutants identified in our screens were tested using current diagnostic tools to validate our results and underwent additional testing to identify the mechanism by which the specific mutations cause the drug to be ineffective. This research represents a massive step towards a genetic based test for pyrazinamide as in combination with the current diagnostic platforms available for other drugs, it will aid in speeding up of diagnosis of drug resistance and lead to more favorable patient outcomes,’ he said.