“Many of the patients enrolled in the trial had either not undergone any testing or not completed the long-duration treatment… Most of the patients enrolled in the trial had extensive disease affecting both their lungs,” Dr. C Padmapriyadarsini, Director of the Chennai-based National Institute for Research in Tuberculosis (NIRT) and the trial coordinator of the modified BPaL regimen, told The Hindu. People with TB not being tested on time and developing severe diseases is not peculiar to this trial.
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According to the WHO Global TB report 2022, over 40% of 10.6 million people globally who developed TB in 2021 were not diagnosed. India along with Indonesia and the Philippines accounted for a 67% drop in the number of people with TB being diagnosed in 2020. The COVID-19 pandemic was responsible for the steep fall in the number of people diagnosed in 2020 and 2021.
However, in India, the gap between the estimated number of people who developed TB and the number of newly diagnosed cases each year has been huge even prior to the pandemic. According to the National TB prevalence survey in India 2019-2021 report, nearly 64% did not get tested for TB. It varied from 46% in the case of Kerala to 88% in Haryana.
Can India “eliminate” TB by 2025?
In 2020, India renamed RNTCP as the National TB Elimination Program (NTEP) to underscore India’s goal to eliminate TB by 2025
Worse, even when people finally get tested for TB, sputum smear microscopy with about 50% sensitivity has been used for diagnosis in a majority of the cases in India, thus leading to a huge number of missed TB cases. Besides lower sensitivity, smear microscopy is ill-equipped to diagnose rifampicin resistance.
Way back in 2014, the WHO guidelines clearly stated that “GeneXpert may be used rather than conventional microscopy and culture as the initial diagnostic test in all adults suspected of having TB”.
Molecular tests are not only more sensitive than smear microscopy, they also help identify rifampicin resistance at the outset. Yet, India has been overly relying on smear microscopy for the initial diagnosis. Even in 2015, the Joint monitoring mission report had criticised the national TB programme for heavily relying on smear microscopy and for the “slow uptake of the new molecular test”. The rapid molecular diagnostic machines have been scaled up from 40 in 2014 to 5,090 in 2022.
As per the National Strategic Plan for TB Elimination 2017-2025 report, the number of presumptive TB patients to be offered sputum smear microscopy should have reduced from over 9.1 million in 2015 to 5.8 million in 2022, while the number of molecular tests should have increased from 40,000 in 2015 to over 13.4 million in 2022. Thus, the share of smear microscopy should have steadily reduced while molecular tests should have accounted for the bulk of all testing. But in reality, the trend has been completely opposite even in 2022. As per the India TB report 2023, even last year, 77% (13.9 million) of presumptive TB cases were examined using smear microscopy and just 23% (4.1 million) with a molecular test.
The presumptive TB case examination rate (PTBER) is a good indicator of the efforts to detect and diagnose TB cases. In 2022, the rate of presumptive TB per 100,000 population was 1,281. Of this, 988.6 were examined using smear microscopy and just 292.7 were tested using molecular testing.
Early diagnosis of all TB patients is further complicated by the absence of symptoms such as cough. According to the 2019-2021 TB prevalence survey report, nearly 43% of the TB cases in the survey would have been missed if a chest X-ray was not included. “In the case of sub-clinical TB, patients may show no clinical symptoms but may still be infectious,” says Dr. Soumya Swaminathan, former Chief Scientist at the WHO. According to an Opinion piece in The Lancet, “50% of all people with bacteriologically confirmed tuberculosis have no symptoms and by the time symptoms develop, transmission has probably already occurred”.
As per a paper in the American Journal of Respiratory and Critical Care Medicine, “both subclinical and active TB states may be infectious and that infectiousness is likely to increase with more advanced disease, although the degree of correlation is uncertain”. However, as per the WHO, people infected with TB bacteria but not yet ill with the disease cannot transmit the bacteria.
There is emerging evidence that TB may not fall under a binary of latent infection (asymptomatic and non-infectious) and active disease (symptomatic and infectious). Instead, TB may be a spectrum of disease, including incipient and subclinical stages. A study in China found that of the 380 patients, 81.8% had active TB, whereas the balance 18.2% were subclinical TB cases.
In 2020, the RNTCP was renamed as the National TB Elimination Program (NTEP) to underscore India’s goal to eliminate TB in the country by 2025, five years ahead of the Sustainable Development Goals. Can India achieve this ambitious goal with its continued over-reliance on a century-old smear microscopy?