New Testing and Diagnostic Methods for Tuberculosis

Tuberculosis (TB) is not an ordinary disease. It emanates a level of panic that goes beyond the usual concerns. It has been highlighted in medical history for centuries as the "killer disease". Way back in 5000 B.C., history reveals that the evidence of TB was found in the spines of Egyptian mummies. Ever since then, this disease remains immortal. After the discovery of antibiotics for the disease in the 20" century, the causative agenttubercle bacilli developed strategies for its survival by making itself drug resistant. At it's worst, the social stigma associated with it not only envelopes the affected ones, but their entire family as well .

Like it was very recent, when I visited a family with my sister. While we were there, they asked us for water. The father gave me a glass of water, but my sister stopped me from drinking it. This confused me a little and really upset the man. We said nothing about it, but when we left, my sister told me that people suspected he had Tuberculosis, and touching the glass might have given me Tuberculosis.

In many countries, the public is not very well informed, and there are many myths about how TB is passed on. As a result many people believe that it is hereditary or can be spread through food or water. In developing countries, a major effect of the resulting stigma and discrimination can be the complete isolation of patients, both within and outside the family. Within the family, patient may be forced to eat and sleep separately due to the fear of transmission. Patients may even isolate themselves to avoid infecting others.

Here, education needs to be a major part of Tuberculosis prevention.

It is important to know that Tuberculosis is a lung infection caused by the tubercle bacilli- Mycobacterium tuberculosis. It can also infect other parts of the body including kidney profile test, spine or brain, in which case it is known as Extrapulmonary Tuberculosis. This infection can either be active or latent; active infection shows symptoms and is infectious whereas latent infection remains hidden without showing symptoms for a long time. Latent infections can revert back into active ones.

Several new Tuberculosis diagnostics have made an appearance in the market and many have also been policy-endorsed by World Health Organization (WHO) and other agencies. These new diagnostics include GeneXpert MTB/RIF, Line Probe Assays (LPA) , urine lipoarabinomannan antigen Detection Test , liquid cultures , and interferon-Gamma Release Assays (IGRA)

Although it is widely known that rapid and accurate diagnosis is critical for timely initiation of anti-TB treatment, many people with TB (or symptoms of TB) struggle to access an adequate initial diagnosis. This is emphasized by the fact that an estimated 41% of about 1.04 crore new cases globally are either undiagnosed or not reported.These "missing" 43 lakh people with Tuberculosis, contribute to the ongoing Tuberculosis transmission, which also includes the transmission of Multidrug-Resistant TB (MDR-TB).

Even if people are diagnosed with Tuberculosis, access to universal Drug-Susceptibility Testing is far from reality for most patients. Even among previously treated patients at risk of drug-resistance and mortality, nearly 40% are not tested for drug resistance.

To detect these cases of drug-resistant Tuberculosis, the Indian government has invested in GeneXpert (CB-NAAT) and LPA, tests that allow different types of drug- resistant TB to be quickly and correctly identified. The government has 1,180 CB-NAAT machines and 51 laboratories equipped for second-line LPA across the country. This miracle machine GeneXpert, also resolves a long-standing problem of Tuberculosis diagnosis in children, which was complicated due to challenges associated with sample collection and poor sensitivity of tests. It is three times as effective as sputum tests, with a quick turnaround time for receiving results (90% of the results are available in less than 24 hours). This becomes critical for the children, for whom delay in diagnosis are usually longer, and more dangerous, than for adults.

Overall, the TB burden in India is highest in Uttar Pradesh, India's largest state, accounting for 17% of the country's population, contributed 20% of total Tuberculosis notified patients. So, how is India handling the 27.5 lakh TB-affected people and many thousands more that remain undiagnosed? A programme on World TB Day 2017, was launched to eliminate TB deaths by 2025. However, this path to eliminate Tuberculosis is long and brimming with challenges, but technology is being harnessed to give a big boost to the Tuberculosis response. India is closer now than ever before towards ending Tuberculosis. There are series of innovations that revolutionized Tuberculosis response, including GeneXpert, the new TB drugs bedaquiline and delamanid, and wirelessly observed treatment (like DOTS).

However, bedaquiline and delamanid are still undergoing clinical trials. Yet, to ensure that access to treatment is not denied in the meantime to patients with drug-resistant TB, a strong drug safety monitoring mechanism is being put in place by Revised National Tuberculosis Control Programme (RNTCP) and Challenge Tuberculosis. This mechanism allows those administering these drugs to screen for warning signs and prevent adverse reactions.

To achieve its goal of eliminating the TB epidemic by 2025, India would have to reduce new TB cases by 95% over the next decade. In comparison, India had reduced TB cases by 22% between 2005 and 2015, and 2.7% between 2015 and 2016, the new report showed.

Game-Changing Diagnostics in India In the journey towards a cure for this archetypal disease, India remains conscious about how to better implement the test procedures and improve patient care, how these tests can impact patient outcomes and how these issues vary from different settings. India has introduced daily treatment strategies such as electronic treatment monitoring system, universal drug sensitivity testing, new drugs, children friendly 'flavored' tablets, and regimen for treating drug resistant patients, as well as active case finding to reach the unreached, which are "excellent steps" for better diagnosis and treatment for all TB patients.

While there has been interest in deploying GeneXpert in peripheral laboratories (as in PHCS), its decentralization may be limited by infrastructure requirements, including continuous electricity power supply and air-conditioning.

How do you test for tuberculosis?
True Nat is a new chip-based, micro real-time Polymerase Chain Reaction (PCR) test that detects tubercle bacilli in sputum samples in approximately one hour. Upon receiving a positive test result, an "add-on" chip can be used to detect RIF-resistance, adding another one hour of test time. It is an indigenously developed technology under the "Make in India initiative. It is designed for situations where there may not be electricity and where the need is for one test to be done at a time. This marks the further decentralization and increased access to highly sensitive molecular tests with augmented capacity for resistance testing at the peripheral level. TrueNat is not meant to replace GeneXpert, rather it is designed to be used in different circumstances.

Mobile X-ray van another exciting shift in diagnostics for providing a technical assistance against TB. On average, someone with symptoms of TB takes one- and-a-half months to get diagnosed, mainly because very few smaller Primary Health Centres (PHC) have X-ray machines, and only half the TB cases are detected through the usual sputum test. The other half that go undiagnosed, can infect others and even succumb to the infection. Under "Mission TB-Free Haryana", mobile X-ray vans travel the last mile to PHCs and share X-rays with radiologists for a quick diagnosis. So far, with just two vans, this project has identified 1,100 missed cases of TB since 2015.

99DOTS... a solution if one forgets to take medicines- Drug side-effects, confusing medications and long-term treatment regimen causes patients to drop out from the treatment course, making the disease worse. A simple yet innovative tool is 99DOTS (Directly Observed Treatment, Short course), which is a low-cost, mobile phone-based technology, first introduced by the RNTCP under the national programme in 2015. It makes big waves at present, where a patient receives a phone number in the blister pack under each pill, and gives a missed call to that number noting that the pill was taken. Free dial-in adherence counselors are also available through this innovation. It is an effective approach for improving TB medication adherence, thereby increasing the compliance to TB treatment. It will be helpful for easy access of treatment to patients from remote areas, improving notification of patients from private practitioners, and enable differentiated care.

NIKSHAY portal... Tracking diagnosis and treatment in real-time-To keep a track of the TB patients across the country, the Government of India has introduced a system called NIKSHAY. The word is combination of two Hindi words Ni and KSHAY meaning Eradication Of Tuberculosis. NIKSHAY (www.nikshay.gov.in) is a web enabled application, that facilitates monitoring of universal access to TB patients data by all concerned. Once diagnosed, patients' are registered and tracked through the NIKSHAY portal. The upcoming upgrade of NIKSHAY is slated to allow treatment outcomes including recovery, mortality and relapse which is to be monitored in real-time."

These new diagnostics have proved to be the game changers for promptly picking up the patterns of resistance to different TB drugs and identifying patients who are eligible for different treatment regimens for drug-resistant TB, with or without use of new drugs, thereby improving chances of better treatment outcomes.

But despite these innovations, technology cannot replace human interface. REACH, a Chennai-based organization, has built networks of survivors across India, to make the survivor's voice heard from panchayat to ministry level.These 'TB Champions' support those undergoing treatment or seeking diagnosis, and tackle stigma head-on by speaking about their experience with their communities.

There are more innovations that aim to end TB in India, some in design phase, others in pilot and a few are ready to scale. But with innovation must come investment. Both public and private sectors need to invest and do so wisely to eliminate TB. Delays and inaction will be costly. A detailed description about the government control strategy is explained in the Article 6.

Access to sophisticated diagnostic technologies and high quality treatment comes as a costly affair for most TB patients. This leads to inconsistencies in proper follow-up of this disease, in turn leading to uneven patient care and under-diagnosis.

Thyrocare has joined the Initiative for Promoting Affordable and Quality TB Test (IPAQT) as a partner laboratory. This initiative has made all WHO- endorsed TB tests available at affordable costs in the private sector.

Focus TB, a brand powered by Thyrocare Technologies Limited, focuses on affordable and quality TB diagnostics. It follows a roadmap for strengthening TB laboratory and aims at ensuring quality TB diagnosis within the framework of National Laboratory strategic plans. It offers TB testing using both, phenotypic testing that includes Microscopy, MGIT culture with Drug Susceptibility Testing, and genotypic testing that includes Line Probe Assay, GeneXpert, TB PCR and Book TB whole genome sequencing profile.

Standing as Nation Against TB! Despite these challenges, it is clear that improvements in diagnostics are driving a feedback loop in Indian health care. The promise of improved tests drives their uptake, their uptake results in better health outcomes, improved outcomes attract more funding for health care systems and better- funded systems are an incentive to the development of even better technologies. We are particularly optimistic about the potential role of our government in the execution of the strategy and implementation. We now have the capacity to develop low-cost generic or novel assays adapted to local framework and incorporate that scale-up in both, National Tuberculosis-Control Programs and private laboratories, supported by a successful public-private partnership. It would not be wrong if we say, that if we tackle our own TB problems successfully, the elimination of TB by 2025 might become a reality!