The frenetic pace of activity in some areas of science is only matched by lethargy in others. A classic case, as Madhukar Pai, renowned researcher on Tuberculosis and Associate Director, McGill International TB Centre, McGill University, Canada, put it in a tweet as a pithy foreword to his article in Nature: “Billions of molecular (PCR) tests were done for Covid-19 Why are we still using century-old microscopy for tuberculosis? We can and must do better!” Accompanied with a messy, unhygienic kitchen sink with racks of slides (presumably for sputum testing, requiring the patient to violently cough up phlegm from the lungs), there could not have been a more convincing argument to change the way testing is being done for Tuberculosis, pronto.
But why has time stood still for TB at what might conveniently be called ancient smear microscopy?
“The simple answer,” Dr. Pai says, “is that few people care about TB, and the investment in R&D has been so little over the past century. The fact that we are still using a century-old BCG vaccine today speaks volumes about the scale of neglect. Investment in Covid-19 vaccines was probably 1000-fold higher! So, it is deeply frustrating that many high-burden countries, including India, are still so heavily reliant on microscopy, when nearly every country, including India, scaled up PCR (molecular) testing for COVID-19.”
Dr. Pai co-authored with Soumya Swaminathan and Puneet K. Dewan, an article arguing fiercely for ‘Transforming tuberculosis diagnosis’ in the May 1 issue of Nature Microbiology. In terms of sheer numbers, TB was the #1 infectious killer of humans until SARS-CoV2 emerged, Dr. Pai says, and as such would have demanded the bulk of the world’s resources. But that did not happen since TB primarily affects poor people and impacts low and middle-income countries. So, unlike infectious diseases like HIV or Covid-19 that also impacted high income countries, TB gets little attention or investment, he explains.
“Interestingly, even when investments were made and good products like CB-NAAT [tests] were developed, many high burden countries have limited their use only to certain special risk groups (people with HIV, people at high risk of drug-resistance, children), instead of replacing microscopy with molecular testing,” Dr. Pai adds.
In the Nature article, the authors go on to describe diagnosis as the weakest aspect of TB care and control, but do not stop there. They further list out seven critical transitions (in a map that has been shared widely since) to close the massive TB diagnostic gap and enable TB programmes worldwide to recover from the pandemic setbacks.
In Nature, the authors recommend using molecular tests with non sputum samples in a decentralised testing facility that can test for multiple conditions, and testing that would focus on yield and population covered, cost lower but have high volumes and possibly manufactured in low and middle-income countries. Even if seems like a test that is ‘less sensitive’, it can nonetheless be very useful if it can reach a much larger population. “COVID RATs and syphilis rapid tests are both good examples. Right now, we do not have a simple, RAT-like rapid test for TB, but efforts are being made to develop such rapid, simpler options. I see the need for scaling up Polymerase Chain Reaction (PCR) testing right away, while we wait for a RAT for TB. When it becomes available, we will need to scale it up, since it can reach more people than regular tests,” Dr. Pai says, speaking to The Hindu.
Not entirely a co-incidence, the World Health Organisation (WHO) has released for the first-time – its standard for Universal access to rapid tuberculosis diagnostics, setting benchmarks to achieve universal access to WHO-recommended rapid diagnostics; increase bacteriologically-confirmed TB; detect of drug resistance; and reduce the time to diagnosis. WHO-recommended rapid diagnostics are highly accurate, cost-effective, reduce the time to treatment initiation, and impact patient-important outcomes.
In another related editorial in a recent issue of the Indian Journal of Medical Research, Dr. Pai and Dr. Swaminathan discuss how India is still too reliant on smear microscopy, but is perfectly poised to lead innovations in the area.
“TB is a priority for the government and the budget has increased in the past few years. Also, India now has its own CB-NAAT, and India also worked hard on manufacturing PCR reagents and buying more molecular systems during this pandemic. So, there is no reason why India cannot replace microscopy with molecular testing in 2023… The intent is there, and execution and scale-up are urgently needed,” he says.