Without whole-genome sequencing, a treatable TB epidemic is a challenge

HaystackAnalytics, an IIT Bombay-incubated company working in the area of genomics using big data has created a comprehensive drug resistance test for tuberculosis (TB). In an emailed interview with Sohini Das, Dr Chaitali Nikam, Director-infexn, HaystackAnalytics, explains why whole-genome sequencing is critical for eliminating TB from India. Edited excerpts.
 

Why is whole-genome Sequencing (WGS) critical for tackling the TB crisis in India?

TB is not only a global public health concern, with an estimated 10 million people suffering from the disease and 1.4 million people having died in 2019, but it also has societal consequences. India has the highest TB burden in the world, with an estimated incidence of 2.64 million in 2019. India contributes to one-fourth of the global burden of multidrug-resistant tuberculosis (MDR-TB) with inadequate diagnostic infrastructure for drug susceptibility testing (DST). A survey of anti-TB drug resistance demonstrates high rates of resistance to first-line and second-line anti-tubercular drugs in new and previously treated cases of TB in India.

Analysing the genomic data of the organism is essential, as WGS is increasingly gaining traction as an important molecular tool for TB surveillance and detecting resistance. Effective use of WGS technology would allow rapid identification of the origin and drug resistance (DR) profile of TB strains in the patients, which, in turn, would facilitate treatment strategies for better control of TB transmission to reduce the disease burden.

In a high TB burden country like India, with one of the world's highest burdens of DRTB, a large proportion of the patients are being treated with ineffective therapy, despite being part of one of the world's longest-running and largest public health programs for a disease. For every DRTB patient that has been treated incorrectly, there is a high risk of transmission of DRTB. Thus, a treatable epidemic will be replaced by a difficult-to-treat and more expensive epidemic.

How important is detecting latent TB (LTB) infections for ensuring a reduction in transmission?

The post-2015 World Health Organisation global tuberculosis strategy recognises that elimination requires a focus on reducing the pool of latently infected individuals, an estimated 30 per cent of the global population, from which future TB cases would be generated. Tackling latent tuberculosis infection requires the identification and treatment of asymptomatic individuals to reduce the risk of progression to active disease. Current treatment requires the use of antibiotics for at least three months.

By evading both innate and adaptive immunity, bacteria of the MTC (mycobacterium tuberculosis complex, which causes TB) are able to persist in a dormant phase for several decades or even for the lifetime of the host.

In about 10 per cent of all infected individuals, a LTBI will progress to active replication and cause TB disease. Given the small proportion of LTBI-positive individuals who develop active TB, the imperfect effectiveness of LTBI treatment and associated side effects, it's critical to know who should be targeted for treatment. This question is pertinent because none of the tests currently available can accurately predict future progression. It is widely recognised that the risk of progression is highest in young children, the immunosuppressed, and shortly after infection.

Has Covid-19 increased the risk of contracting TB, as it lowers immunity?

Coronavirus disease 2019 (Covid-19) co-infection with other respiratory pathogens poses a serious concern that can complicate diagnosis, treatment, and prognosis. Since Covid-19 and TB are both severe respiratory infections, their symptoms may overlap and even increase mortality in case of co-infection. The simultaneous prevalence of tuberculosis among patients with Covid-19 was 1.1 per cent in general. According to the investigations, it was found that the simultaneous infection of TB and Covid-19 has been observed in Africa, Asia and America. Furthermore, TB infection may also increase mortality in Covid-19 patients. Based on different evaluated studies, various drug treatments were performed in Covid-19 patients with TB, and antibacterial drugs were the most used.

Are TB-related deaths increasing in India; if so, why?

Among various infectious diseases, TB has a high mortality risk of 4 per cent. Globally, this translates to 1.5 million deaths a year (for comparison, the coronavirus has claimed 6 million lives so far). In India, the death rate has remained the same from 2017 to 2019, with a steep rise in deaths in 2018, followed by a simultaneous increase in TB cases and a subsequent drop. Karnataka stands out in the steep rise in the death rate from 2.5 per cent in 2020 to 7 per cent in 2021. Gujarat, Andhra Pradesh, and Jammu & Kashmir are the only three states that show a fall in the death rate from 2020 to 2021. States such as Tripura report good health facilities, yet show high deaths and cases. On the other hand, states such as Himachal Pradesh report high deaths despite good facilities. Bihar reports both low death rates and low notification rates.
 

Funding for Covid in the span of two years has been exponentially higher than what has been catered to TB research and medication over many years. To add to the woes of poor financing, drug-resistant TB — where bacteria become resistant to the drugs used to treat TB — has been on the rise along with inadequate drug supply, which is the major cause of deaths in India.

What proportion of TB patients in India are suffering from drug-resistant TB?

According to the government’s latest report in March 2021, the estimated number of MDR/RR-TB cases in India is 124,000 (9.1 per 100,000 population). The level of drug-resistant TB may hamper India's progress towards the target of TB elimination by 2025.