Tuberculosis genome sequencing gives hope for improved diagnostic and therapeutic approaches
Latest WHO Global Tuberculosis Report points out that 26 per cent of new TB cases are from India, which is the highest among high TB burden countries.
BHUBANESWAR: In a major step towards elimination of tuberculosis, scientists at the Institute of Life Sciences (ILS), Bhubaneswar have conducted sequencing of tuberculosis genomes which will help predict drug-resistant TB and improve diagnostic and therapeutic approaches.
Conducted in collaboration with Regional Medical Research Centre (RMRC), Bhubaneswar for the first time in Odisha and North East states, the study on genetic diversity, evolution, transmission pattern and drug resistance development provides molecular-level insight into Mycobacterium tuberculosis (MTB) strains of eastern region in comparison with Indian and global perspective.
With the Covid-19 pandemic disrupting progress made for TB diagnosis in recent years and reducing access to TB treatment, the most visible impact was observed: the drop in the number of newly diagnosed and reported TB cases. A sharp decline of 18 per cent (pc) has been observed from the data collected up to June 2021.
Although the drug-susceptible cases had a higher treatment success rate, the multi-drug resistance (MDR) and extensively drug-resistant TB (XDR TB) cases have a treatment success rate of only 54 pc and 30 pc, respectively.
The major challenge with the current TB diagnostic strategies are the time required for culture-based tests (three to six weeks) and commercially available molecular diagnostics fail to account for novel compensatory mutations leading to drug resistance development.
In the recent study, scientists sequenced 118 culture-positive MTB whole genomes, which include seven follow-up samples, collected from 111 patients in Odisha, Sikkim and Meghalaya. While the samples from Odisha mostly consist of drug-susceptible samples, those from the northeast were a mix of MDR and XDR samples as Fluoroquinolone resistance is highly prevalent in the region.
The researchers extensively studied the genomic diversity of Fluoroquinoloneresistant Lineage 2 strains along with Lineage 1 and Lineage 3 strains. They detected a total of 12926 high-quality single nucleotide variants and observed a drastic difference between the lineage distribution of MTB in the northeast region and Odisha.
Lineage-1, also known as Indo Oceanic lineage, is more prominent in Odisha and Lineage-2 also known as Beijing lineage has a very dominant presence in the northeast. A very diverse representation of MTB strains was observed and all three lineages prevalent in the country were found in the State. Lineage 1 is the dominant followed by lineages 3 and 2.
A senior scientist of ILS Dr Sunil Raghav said the study that examined the transmission patterns of MDR strains and their mutation acquisition patterns apart from the performance of drug resistance phenotype prediction has provided a great opportunity for developing and improving diagnostic and therapeutic approaches.
"The State also sees a prevalence of lineage 3, also known as Central-Asian lineage.
We checked the distribution of lineages among different districts to further understand the most affected areas and found that southern districts of Odisha are mostly affected by lineage-1 whereas central and eastern districts show a mixed presence of all three lineages," he said.
Of the 48 samples sequenced from Odisha, 39 were drug-susceptible and two samples were classified as mono resistant and the rest seven as MDR. The median age of patients enrolled in the study is 32 years consisting of 57 men and 44 women.
Although Odisha has less burden of drug-resistant TB the number of reported cases are also less due to lack of health facilities in close vicinity, and poor lifestyle choices, found the study.
Dr Raghav said large scale genomic studies are required to understand the dynamics of the highly diverse MTB population in India to devise better region-specific diagnostics methods.
"Sequencing on a large scale will also help improve already available low cost molecular diagnostic tests. Targeted panels can be developed using the studies for prediction of drug resistance phenotypes directly from sputum samples in a short period of time using a massively parallel sequencing approach," he added.
According to the latest WHO Global Tuberculosis Report, 26 pc of new TB cases are from India, which is the highest among high TB burden countries followed by China with nine pc of thy new cases reported. India has the second-highest incidence of MDR cases with the highest mortality rate.