40 per cent of Indians are already infected with TB bacilli in the form of latent TB
The WHO estimates that TB, one of the oldest and deadliest diseases, kills 1.4 million people a year and costs the global economy nearly $12 billion in lost productivity and wages – with India and China making up half the burden. Shalini Gupta finds out more in an interview with L Masae Kawamura, Senior Director, Medical and Scientific Affairs, QuantiFERON Global
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| L Masae Kawamura |
While medical discovery has reduced TB from a death sentence to upto two million deaths per year, the development of MDR TB and XDR TB, which account for one fourth of treatment costs, highlights the importance of adherence to disease treatment. Your comments.
The treatment of TB is long and complex, and is extremely labour intensive, resembling treating a curable yet infectious cancer. A normal TB drug regimen generally varies between six to nine months, as patients gradually feel better, they may not stick to the regimen, and this is where the journey of drug resistance begins. Management errors by doctors not expert at treating TB and ignorance of providers and patients on the nature of TB are also reasons why drug resistance spreads. Patients with partial drug resistance are very prone to MDR-TB, even with the WHO recommended regimens. This is because drug susceptibility testing as per WHO is not universal for all cases of TB and is recommended for only relapsed cases or patients failing treatment. This is a big gap, since there is no confirmation on whether some or all of these medicines will work, hence failing treatment is the only way to drug susceptibility.
Treating MDR TB takes 1.5 to two years in the US, is expensive with frequent toxicity that is much worse and therefore, it is important to get it right the first time when the disease is easier to treat and cure. XDR treatment is much longer and even more complicated. Hence, adherence, education, appropriate provider care and monitoring is the key to preventing MDR-TB in a patient with regular TB and all the costly downstream financial, societal and human consequences. The patient and doctor also need to know the drug susceptibility pattern from the start.
How much of a public health challenge is TB? What factors further complicate it in India?
TB is a huge public health challenge. India accounts for more than two million active TB cases, which is ~20 per cent of the world’s regular and MDR-TB. 40 per cent of Indians are already infected with TB bacilli in the form of latent TB. For a normal person there is 5-10 per cent lifetime chance of conversion from latent TB to active TB. And although this 10 per cent risk may not seem so bad, the sheer magnitude of the problem and dangerous co-factors that exists in India literally guarantees future TB and MDR-TB a big comfortable home in India. Diabetics are thrice likely to break down with active TB malnutrition (including lack of balance diet), HIV and consumption of new biologic agents for autoimmune diseases or immunosupressants for organ transplants are some more causes. Given the ease of airborne transmission in the crowded cities of India, this vast reservoir of silent carriers will continue to grow and future TB cases are guaranteed unless transmission is stopped through screening and more is done to prevent TB among the most vulnerable.
How much of a threat is latent TB and how could diagnosis address transmission?
Individuals with latent TB silently carry the bacteria that cause TB in their body, but show no symptoms. They are neither sick nor contagious. While not all people with latent TB will develop active TB, all active TB patients progress from latent TB at some point (10 per cent). In addition, immuno-compromised patients such as those with HIV, diabetes, end stage renal disease, silicosis, patients on steroid therapy, TNF alpha therapy and cancer chemotherapy etc. and people with weaker immune systems such as children, the elderly, malnourished, heavy smokers, and drug abusers, have a much higher chance of progressing from latent to active TB.
For major impact on TB disease rates we must address latent TB infection. Previously, the only tool available for identifying latent TB infection was the Tuberculin Skin test (TST) or Mantoux, invented in 1907. It has many limitations, especially in countries that routinely vaccinate with BCG vaccination. This is where the new Interferon –gamma release assays (IGRAs) come in. Not only can they distinguish between TB and BCG as well as common environmental mycobacteria, it requires only one patient visit to get a result instead of two for the Mantoux. Best of all, IGRAS provides an objective laboratory result using a specialised and calibrated instrument, unlike the subjective interpretation of reading the bump on the arm from the Mantoux, which can be highly variable based on the skill and training healthcare worker. Screening high risk populations for TB symptoms and using tools like the QuantiFERON TB-Gold, in conjunction with other tests have been very effective in other countries for this purpose.
In my city of San Francisco, I definitely saw the impact of targetted screening and preventive treatment of latent TB. This is a strategy that reduced the rate and burden of TB by two-thirds over two decades by comprehensively cutting the line of transmission and killing the seeds of future TB by treating both active and latent TB. QuantiFERON TB-Gold was focussed on the homeless and BCG-vaccinated populations beginning 2003 and was well accepted by providers and patients. In the Indian scenario it would be impractical to screen and treat the entire population; however, like other countries, in the beginning India should focus on screening high risk groups, those vulnerable to TB disease development and those in high-transmission environments. This would help reduce the amount of people who will develop active TB and, therefore, help disrupt the ongoing cycle of spread of TB infection in India.
FDA recently approved the first drug to treat MDR TB. How will such medicines impact treatment?
We are finally seeing breakthroughs in drug development for TB, however, if adherence to treatment cannot be assured, these drugs will be squandered like our current second line agents as patients develop resistance to them. The infrastructure that provides patient-centred DOT, contact investigation, prevention, expert care, oversight of care being provided in the community, and patient/community education is what really needs focus. The new pharmaceuticals, tools and technologies would only serve to enhance this infrastructure and ability to cure patients. That said, there are newer shorter regimens for MDR-TB that are being studied that we hope will help in preventing XDR-TB and its subsequent forms.
What corrective and preventive steps are needed in order to control the transmission of TB?
The WHO has acknowledged that the current practice of treating cases that are passively found is not giving the desired results of reducing cases. Patients present themselves with symptoms before a diagnostic work up having already transmitted TB to an estimated 8-10 people, while their disease may have advanced beyond full recovery or may result in life long debilitation. What needs to be urgently addressed is “active case finding”, TB education of private providers, prevention of disease in those with TB co-factors and infection control at health care facilities. “Active case finding” helps find cases early before broad transmission or none and consists of screening high risk groups for TB. This includes examining the contacts of TB cases or the screening of individuals with TB co-factors (risks) like HIV, diabetes, end stage kidney disease and those placed on medicines that suppress the immune system. Screening of people and employees in congregate settings, such as homeless shelters, dialysis rooms, healthcare facilities, schools, colleges, and densely populated work sites with poor ventilation is another high impact area.
TB algorithms integrate processes cross several platforms. What criteria need to be kept in mind while designing an algorithm?
Algorithms are nice because they can align different groups quickly, however, there is the danger of people to stop thinking or become confused when there are scenarios that do not fit the algorithm. With technology changing so quickly in the field of diagnostics for TB, flexibility will need to be built in around clear goals and outcomes. Algorithms need to be realistic, scalable and feasible to implement in different settings without compromising on quality and effectiveness.
How do you see the Indian Government’s Revised National TB Programme (RNTCP)?
In India, even though the incidence of TB hasn’t changed, the steps taken by the Indian government for the treatment of TB has significantly decreased the number of deaths caused by the disease. That’s a huge achievement by itself. However, the prevention of the disease among those with latent TB infection with some exception of child contacts and HIV infected persons hasn’t really been addressed as the RNTCP must focus on detecting and treating all cases of active pulmonary TB. This is of course appropriate, given the limited budget.
We, at QIAGEN, believe that a possible way forward to address the prevention of TB disease is to adopt a public and private sector partnership with the private sector taking the lead on effective screening and prevention. Finding cases earlier and latent TB treatment, could dramatically help decrease the rate of TB.
What could be the future roadmap to TB control?
TB is a long-term problem that needs huge investment and social mobilisation. The current investment in TB control infrastructure in India has greatly improved but in my opinion, remains woefully inadequate to match the scope of the problem and the interventions needed. As one example, universal drug susceptibility testing on every TB case to avoid” treatment in the dark” and active case finding will require massive scale up of laboratory infrastructure and public education. Also, the private sector needs to be fully engaged in true partnership in developing its role of screening, treatment and prevention. Funding, knowledge and commitment are the key drivers here. Technologies for diagnosis and new drugs will help but its impact will be limited if the system and partners are inadequately equipped to use them, or are unwilling to pay them, and policies are not developed to facilitate proper use.
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