Mumbai: India has set an ambitious goal to eliminate TB by 2025 five years ahead of the global goal of 2030, but several years of progress made in the elimination of tuberculosis (TB) have come undone due to the disruption caused by the ongoing COVID-19 pandemic. For the first time in over a decade, mortality due to TB has increased worldwide, and there are indicators that the incidence may have increased as well. The disruptions caused by COVID caused individuals to avoid contact with healthcare, and this delayed health-seeking and stigma have possibly contributed to the same.
The COVID-19 pandemic has “reversed years of progress made in the fight to end TB,” says the World Health Organisation (WHO). COVID-19 and TB are both infections that affect the lungs. COVID-19 being an acute infection that also affects the immune system can result in the reactivation of latent infections including TB. The prevalence of TB among COVID-19 patients is 0.37 – 4.47 per cent in different studies. The WHO estimates that these COVID-19-related disruptions in access to TB care could cause an additional half a million TB deaths. During the lockdown, in the first quarter of 2020, reporting of TB cases was reduced by 26 per cent as reported by the health authorities. This has been a major setback for the National TB Elimination Programme.
The pandemic has not only been a disruptor but also an enabler, one of the key learnings from COVID was the impact of technology in accelerating equitable access to quality healthcare. The tremendous scale-up of genome sequencing and knowledge sharing enabled greater and faster discoveries, including the democratisation of molecular diagnostics like RT-PCR, which before COVID was held by a few multinational companies. It is also evident that bacterial infections like TB and fungal infections, which are known to be secondary to viral infections, can become difficult to treat in absence of accurate diagnostics, especially with the increase in drug resistance. It is also clear that no health problem can be related to only a ‘poor world’ problem. In the era of global travel, infectious diseases, and antimicrobial resistance is indeed a global issue, which can potentially derail any success made in other health conditions.
Digital technologies facilitating TB diagnosis
Online consultations have made access to doctors easier, especially when distances have been prohibitive. Rapid turnaround times, with new-age diagnostics tools, have made treatment initiation quicker. Tests such as radiographs can be digitised and reported remotely. All of these also dependent on internet connections, ease of transporting specimens and overall access, and a lot of work needs to be done to make these universal.
As there are two forms of TB, pulmonary, which affects the lungs and extrapulmonary which affects the other organs. There is a wide range of tests available for diagnosis. This spectrum ranges from the visualisation of the bacteria in a specimen to the demonstration of the DNA and whole genome sequencing of the bacterial genome. There are supplementary tests like ADA, IGRAs and other simple blood tests like ESR, that can be used to assist in the diagnosis of extrapulmonary TB. “The complexities of clinical presentations and the wide range of diagnostic tests available highlight the role of artificial intelligence (AI) and machine learning (ML) tools to support the National Tuberculosis Elimination Programme. Selection of the right test/s for the prevailing clinical situation and the appropriate interpretation of the test results is vital,” remarked Dr Rohini Kelkar, Senior Consultant, Infectious Diseases, Clinical Microbiology and MolecularMicrobiology, Metropolis Healthcare Ltd.
With widespread growth in the area of digital technologies to facilitate TB diagnosis. Timely medical intervention with the help of telemedicine has changed the scenario, especially in rural areas. “Mobile diagnostic labs equipped with digital diagnostic tools have paved the way to enhanced access to healthcare facilities. Moreover, rapid molecular testing kits can detect the presence of drug-resistant strains with high precision in diagnosing TB. Using digital X-rays with computer-aided detection (CAD) also reduces the chances of human error and therefore misdiagnosis,” voiced Raghavendra Goud Vaggu, Global CEO, EMPE Diagnostics.
Speaking on the role of digital technologies aiding in TB detection, Anirvan Chatterjee, Co-Founder and CEO, HaystackAnalytics, shared, “AI in radiology, rapid molecular assays and compressive screening for drug resistance using genome sequencing are the current disruptions which will upend the entire paradigm of TB diagnosis and treatment. Genomics provides the opportunity to enable personalised treatment for every TB case, basis which there is expected to be a reduction in the incidence of drug resistance TB, which will be critical for TB elimination. With access to whole genome sequencing in the public and private health sectors, nationwide, the existing infrastructure will be able to provide these tests for all strata of society.”
Challenges in diagnosing TB
TB remains one of the world’s top infectious killers and has aptly been labelled ‘Captain of the men of death’. Without a rapid and accurate diagnosis, it can be mistaken for other conditions. TB mimics several conditions including cancer, hence a high degree of suspicion is required.
TB diagnosis is exacerbated by a multitude of challenges. While the stigma attached to the disease continues to be a significant contributor among people failing or delaying seeking timely medical help, there are other significant challenges as well. “Another challenge faced are the time-consuming tests. As the growth of the bacteria on culture remains the ‘gold standard’ for diagnosis followed by testing the growth on culture for susceptibility to different antimicrobials. This is referred to as phenotypic testing. These tend to be time-consuming because Mycobacterium tuberculosis the organism that causes TB is extremely slow growing,” shared Dr Kelkar.
Sharing his views on the challenges in diagnosing TB, Dr Lancelot Pinto, Consultant Pulmonologist and Epidemiologist, PD Hinduja Hospital & MRC, Mahim, “A majority of patients with the disease seek help in the private sector. Diagnosis and treatment in the private sector are often non-standardised. The quality of care often tends to be suboptimal. There is a need for education of private practitioners to recognise the disease early, ask for newer molecular tests which have significantly higher accuracy than the conventional sputum smear microscopy, and start treatment as soon as the diagnosis is made. The overreliance on chest radiography and under-utilisation of molecular tests for diagnosis are often the single leading cause of diagnostic delays. Multidrug-resistant tuberculosis, which is a significant contributor to the burden of disease can only be recognised if appropriate testing is done, and practitioners need to be educated about the same.”
Detecting pulmonary TB, that is, TB infection in the lungs in adults is less of a challenge any longer, but there still exists some challenges in detecting paediatric TB and extrapulmonary TB (TB infection in organs other than lungs). However, these are likely to get resolved with current updates in the diagnostic systems. “The greatest challenge still is the availability of universal drug susceptibility test (Universal DST– testing to know among all available drugs which will work and which will not) for all patients. Current microbiological methods for drug susceptibility cannot be scaled, and remain unaffordable. Not only is the technology non-scalable, but it is also unreliable for several drugs and remains a high biohazardous workflow,” stated Chatterjee. He further added, contrary to this, whole genome sequencing is highly scalable, and with increased uptake can be as affordable as an RT-PCR test.
The other crucial aspect that needs immediate attention is the rising burden of drug-resistant TB strains, commenting on this Goud Vaggu added, “Drug-resistant TB strains are on the rise and this makes diagnosis and treatment complicated. In addition, co-infection with other illnesses can impede the treatment plan. Many times, the symptoms of TB overlap with that of other respiratory disorders, therefore, it is tricky to diagnose the disease solely based on symptoms.”
TB misdiagnosis: Technology bridging gaps
There are other ‘Mycobacteria’ referred to as Nontuberculous mycobacteria which can mimic TB. Sometimes infections of the lungs are caused by other bacteria (like nocardiosis) and fungi (histoplasmosis), present like TB. A wrong diagnosis can be disastrous to the patient, hence the need for strong laboratory diagnostic support. “The introduction of nucleic acid amplification tests (NAAT) has been a significant advance in the rapid diagnosis of tuberculosis. These tests are routinely used at most centres in the country. They identify the presence of the DNA of Mycobacterium tuberculosis and can further be used to identify genes indicating resistance to the drugs used for treatment,” observed Dr Kelkar.
Also, the symptoms of TB can often be non-specific. A prolonged cough, fever, weight loss, and loss of appetite can mimic multiple different diseases. Patients often shop from doctor to doctor and unless the prolonged nature of the symptoms is recognised, each doctor often treats the patient in isolation. This leads to misdiagnosis very often, multiple courses of antibiotics, and delays in diagnosis. To improve the diagnostics of TB, one needs to have a very low threshold for suspecting the disease, especially in a country such as India which is endemic for TB.
Dr Pinto added, “Newer molecular diagnostic tests have become cheaper over the years, more accessible, and have a quick turnaround time. Practitioners need to be sensitised about the superiority of such tests and should be incentivised and encouraged to ask for such newer molecular tests rather than conventional sputum microscopy. We need to improve access to such tests, even in rural India, if we want to eradicate the disease.”
Bridging the gap to limit the misdiagnosis of TB is non-negotiable. In several pockets, the extent of drug resistance is so high, the success of the TB elimination programme is being undermined. For every misdiagnosed TB case there are multiple secondary cases of drug-resistant TB, which means less number of drugs are available to treat the patient. “A therapy driven by universal DST is going to be critical for reducing misdiagnosis in TB. This will help in prescribing the right medication for the right drug resistance profile, hence earlier treatment and lesser transmission,” remarked Chatterjee.
Misdiagnosis of TB is a serious concern. False-negative results are a major player in leading to a diagnostic error. Misdiagnosis not only leads to delayed treatment, but it can also at times be fatal for the patient. Goud Vaggu stated, “The gap can be bridged with the use of AI and ML as these technologies enhance the accuracy of diagnosis. Healthcare professionals can evaluate the results of diagnostic tests such as X-rays or molecular tests with the help of AI, thus lowering the likelihood of a misdiagnosis. In addition, AI and ML have significantly contributed to the development of personalised medicine. These algorithms help in predicting the best treatment regimen for a particular population of patients.”
In March 2018, Prime Minister Narendra Modi committed to eliminating TB in India by 2025. On World TB Day while inaugurating the One World TB Summit the PM once again emphasised the need for a collective approach to eliminating this age-old disease. The ongoing pandemic has undone years of progress made in TB elimination but deploying technology in detection, diagnosis and treatment could bolster the fight against TB. With increasing awareness through campaigns and advertisements the stigma related to the disease needs to be done away with as it remains one of the major deterrents in people seeking treatment infected by the disease.