War to end a scourge

April 9, 2019 0 By S Harachand

In the year 1821, John Keats, one of the most celebrated English poets, died of consumption at the age of 25. Centuries later, that ‘consumptive disease’ still takes a toll of millions of lives the world over in a more lethal form, despite tremendous strides made by modern medicine to curb diseases caused by bacterial infectious agents.

The history of tuberculosis is, perhaps, as old as humanity itself. Though mankind survived the onslaught of many a foul contagion that threatened to wipe it out through the ages, tuberculosis (TB) turned out to be a particularly resilient adversary.

TB is one of the top 10 causes of death today and the leading cause of death from a single infectious agent. More people die from TB than HIV. In 2017, the infection caused nearly 1.3 million deaths, excluding the 300,000 HIV-positive people who lost their lives to TB that year, according to WHO estimates. Ten million people developed the disease during the year, including 1 million children.

India has the world’s highest burden of TB, accounting for 27 percent of all cases and over 30 percent of all TB-related deaths.

Recognised as the leading infectious killer, TB is now getting unprecedented attention in India. Signalling an increased commitment, the health ministry has announced an ambitious nationwide campaign to end TB by 2025, five years ahead of UN’s Sustainable Development Goals. The National Strategic Plan (NSP) for TB elimination 2017-25, with an estimated cost of Rs 16,649 crore, banks on public-private partnership to ensure that every TB patient has access to quality diagnosis, treatment and support. The NSP provides goals and strategies for the country’s response to the disease during the period.

Missing millions and gaps in reporting
Home to a quarter of the 8.6 million cases of TB that occur worldwide, India also has the dubious distinction of harbouring about a third of the ‘missing 3 million TB cases’ that do not get diagnosed or notified. India, along with Indonesia and Nigeria, accounts for 80% of the global shortfall in the reporting of TB cases.

A study reported in The Lancet in 2016 found that prescriptions and drug sales exceeded the number of cases recorded in the national registry by almost 2 million, clearly indicating improper reporting from the private sector. This failure in reporting continues to hamper an effective implementation of eradication strategies.

As much as 60-70% of patients access private health care providers as the first point of care, including for TB, according to National Sample Survey Office. The majority of the patients take prescriptions from private hospitals due to the dysfunctional public sector.

“A ubiquitous private sector and low notification rates have been one of the major impediments in getting a sense of the magnitude of the TB challenge,” points out Dr Sameer Kumta, Senior Programme Officer, TB, Gates Foundation, India.

Most Indians prefer seeking care from the private sector first, resulting in under-reporting of TB, he adds.

India declared TB a notifiable disease way back in 2012. However, the reporting of the disease is abysmally low from the private health care sector in the northern regions of the country where the incidence of TB is very high.

“The scenario is expected to change as the reporting of TB has been made compulsory,” says Dr George Mothy Justin, Head of the Department, Respiratory Medicine, Medical Trust Hospital, Kochi, India.

Last year, India made non-reporting of TB a punishable offence. Failure to report TB cases can now invite punishment under relevant sections of Indian Penal Code.

Leading pulmonologists like Dr George are sceptical whether India would be able to bring down its numbers within the stipulated timelines, considering the slow pace of diagnosis and unusually protracted treatment regimens practiced in India’s TB hotspots.

Treating latent TB: A daunting task
Also, at 40%, the proportion of people with latent TB is higher in India owing to poor diagnosis and ineffective treatment. People with latent TB infection (LTBI) do not show any symptoms nor do they infect others. The infection, however, won’t go away unless treated along the lines of active TB.

The WHO recommends treating only those with active diseases in high-burden countries like India, a stand criticised by many TB experts. Targeting LTBI, along with the active disease, is important to eliminate TB, they assert.

Recent reports indicate that the government is considering to bring all LTBI patients too under the purview of treatment. Treating asymptomatic TB patients would be a daunting task in India as the numbers can be huge. Policymakers plan to tackle the enormous LTBI population in a phased manner, targeting the high-risk group with priority to achieve the goal.

Among those included in the high-risk group and identified to receive LTBI treatment by the NSP are those on long-term corticosteroids, immunosuppressants, the HIV-infected and juvenile contacts of sputum-positive index cases.\

Since children are more susceptible to develop severe forms of disseminated TB, those above six years of age, who are in close contact of TB patients, will be evaluated. After excluding active TB cases, they will be given 10 mg/kg of isoniazid (INH) administered daily for a minimum period of six months irrespective of their BCG or nutritional status.

INH preventive therapy will also be considered for all HIV infected children, all tuberculin skin test (TST) positives who are receiving immunosuppressive therapy and a child born to a mother who was diagnosed to have TB during pregnancy.

The health ministry is likely to allow the import of rifapentine for the treatment of LTBI, waiving off the local clinical trials requirement that is mandatory for all new drugs introduced in India, according to reports.

A weekly regimen of rifapentine with isoniazid for three months has been found effective in the prevention of active tuberculosis

But the implementation of treating LTBI can still be challenging as people without any obvious symptoms have to adhere to a months-long regimen of multiple pills which often have undesirable side-effects.

“If you start checking, you will come to know that a good proportion of the Indian population has asymptomatic TB. We have systems in place to rapidly detect the disease with nearly 100% accuracy. And we have effective medicines to treat even MDR TB. But the question is, will everybody detected with asymptomatic, latent TB be willing to follow the treatment course,” asks Dr Sunil Nair, Assistant Professor, Pulmonary Medicine, Medical College, Trivandrum. Places like Kerala have brought down TB cases dramatically through effective intervention. The situation, however, is not so in other parts of the country, where the infection is more rampant.

Unlike earlier days, we now have GeneXpert machines in place to quickly diagnose TB in every district. Soon the facility will be brought to the taluk level. Nevertheless, the availability of the diagnostic facility doesn’t mean that everybody goes for testing. If one tests positive for diabetes, he wouldn’t hesitate to share the status with his friends. It is not usually the case with TB. In many cases, the person wouldn’t share the information with even his family members. Tuberculosis, like HIV, still has a lot of stigmas. People may not go forward to test TB as eagerly as they go for other diseases, comments Dr Nair.

Challenge of drug resistant TB
While the increasing number of deaths are attributed to delayed diagnosis and inadequate treatment, the emergence of multi-drug resistant strains presents the most formidable challenge to the efforts of containing TB. Again, India tops the list of the three countries which account for nearly half of the world’s cases of MDR/RR TB. There are around 1.5 lakh cases of MDR TB in India. Of this, nearly 12% are in Mumbai, which is considered the epicentre of the MDR TB. Unlike drug-sensitive TB, the success rate for curing MDR-TB is only 33 percent.

Even though, drugs to treat MDR TB is currently available, not all Indian clinics have access to these novel treatments. Both bedaquiline and delamanid — novel anti-TB drugs — were introduced in India through a conditional access programme and included in the Revised National TB Control Programme (RNTCP). Their availability is limited to a handful of patients from select cities.

For instance, the 400 doses of delamanid that India received from Otsuka Pharma as part of a phase 3 programme were rolled out in seven states in November last year. High costs remain a major barrier to patients accessing these treatments, which are yet to come out with their safety and efficacy data from phase 3 trials.

Even with the latest treatment, India is achieving a cure rate of only around 47% on average at the national level.

India-wide, around 15-20% of MDR TB patients die. There are very few diseases with such a high mortality rate. Many cancers have a better cure rate. This makes TB a big challenge.

TB kills more than 1,400 people every day, or around 480,000 Indians every year, as per official estimates.

India accounts for nearly 10% of the global burden of HIV-associated TB. According to the India TB Report 2018, 87,000 HIV-associated TB patients are being diagnosed annually. HIV prevalence among incident TB patients is estimated to be 4%. The mortality in TB/HIV co-infected patients is very high and 12,000 people die every year from this condition.

Prevention as centrepiece?
Alongside free diagnosis and treatment, the NSP provides an incentive for nutritional support. “In India, undernutrition is a driver of TB,” comments Dr Sameer. Undernutrition and TB have a bidirectional relationship. While undernutrition increases the risk of TB, contracting the disease increases the risk of malnutrition, thereby culminating in an intercausal cycle for the two diseases.

India has practically doubled the budget to meet the target of eliminating TB by 2025. “The government has backed the NSP with a historic resource commitment of Rs 12,000 crores over three years, while it increased investment in research and development to $6 million,” comments Dr Sameer.

Some experts are of the opinion that the current budget allocation may still be way below the actual requirement. Considering the enormity and the urgency of the situation, both the regular, drug-susceptible TB as well as the drug-resistant TB need additional expenditure.

In order to achieve the target of ending TB by 2025, India needs to reduce new TB cases by 10 percent every year. But recent reports indicate that the country is nowhere near the number. Moreover, India needs to pay more attention to a preventive strategy. The goals can’t be translated to reality until prevention becomes the centrepiece of India’s TB policy, warn experts.