Whole genome sequencing emerges panacea to prevent TB outbreak

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With the rise in drug resistant tuberculosis cases, whole genome sequencing (WGS) has emerged as a panacea to prevent the outbreak of the disease by identifying drug resistant TB at genetic level, region of mutation, level of resistance of a specific medicine.

WGS relies on direct sequencing of DNA obtained from sputum to detect and characterise the bacteria that cause TB doing away with culture of bacteria in the laboratory. Laboratory diagnosis of TB using traditional methods is a tardy process, which takes weeks or months.

PD Hinduja Hospital in Mumbai where the burden of drug resistant TB is high has started mycobacterium TB WGS since January this year. WGS helps identify drug resistant TB and transmissibility of lineages of TB that will help rein in its outbreak. “Our aim is to establish fast drug susceptibility test to improve TB treatment outcome which is possible through WGS”, said Dr Camilla Rodrigues, consultant microbiologist and chairperson of Infection Control Committee, Hinduja Hospital.

She said “We are using the latest sequencing technologies and bioinformatics which allows us to detect and characterise the bacteria that cause TB in a day or two, without growing the bacteria. It gives us crucial details into their genome sequences and the lineages that come from.”

Hinduja Hospital is one of the 12 centres spanning over 8 countries to conduct WGS of TB samples. Led by Oxford University researchers, the global study titled “Comprehensive Resistance Prediction for Tuberculosis: an International Consortium (CryPTIC)” aims at speeding up diagnosis and treatment of TB.

“We are conducting WGS of 6,000 TB samples in parallel with drug-resistance testing to provide patients with personalized treatment”, she said. WGS of 6,000 TB samples are part of 100,000 samples to be tested from across the world.

Each site will conduct drug-resistance testing on the samples in parallel with whole genome sequencing and the Oxford team will assemble these results into a single open-access database. These data will be compared to a library of other TB bacteria with known drug-resistance to identify genes associated with resistance to certain treatments. Such large numbers are required to find nearly all the changes in the germs’ genetic code that could cause drug-resistance, including very rare ones and this large amount of genetic data will be analysed to accurately predict drug-resistance in new TB infections. This will allow future TB cases to be treated with the best drugs faster, increasing the chance of curing individual patients’ infections and will help control its spread, thus contributing to TB elimination.

Oxford researchers received $2.2m (£1.53m) grant from the Bill & Melinda Gates Foundation and a £4m ($5.75m) grant from the Wellcome Trust and MRC Newton Fund for the study.

TB bacterium’s WGS seems far better than four TB tests approved by WHO: LED Microscope, Liquid Culture and two molecular tests – Gene Xpert and Line Probe Assay.

The rise of multidrug resistant (MDR) and extensively drug-resistant (XDR) TB threatens to reverse decades of progress in treating and preventing the disease. In India MDR and XDR TB cases constitute 10 per cent of total TB cases.

Until recently, it was believed that drug resistant strains were less transmissible and that MDR and XDR-TB was mainly acquired by individuals as a result of poor compliance to treatment. However recent molecular and epidemiological studies have challenged this belief. In most regions of the world, drug resistant TB is now caused by transmission. An estimated 95.5% of new MDR TB cases are due to transmission.

One in five cases of TB are now resistant to at least one major antibiotic. The mortality rate is high at around 40% for patients with MDR and 60% for patients with XDR TB, and the disease is very expensive to treat.

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