Without a magic wand, India cannot eliminate TB by 2025

GeneXpert

Only 93,000 MDR-TB cases have been diagnosed till 2015 in India.

At the end of 50 years of tuberculosis control activities, the disease remains a major health challenge in India. As per new estimates, the number of new cases every year has risen to 2.8 million and mortality is put at 4,80,000 each year. These figures may go up when the national TB prevalence survey is undertaken in 2017-18. Against this backdrop, the Ministry of Health and Family Welfare, in its national strategic plan for tuberculosis elimination (2017-2025), has set a highly ambitious goal of “achieving a rapid decline in burden of TB, morbidity and mortality while working towards elimination of TB by 2025.”

Though the Revised National Tuberculosis Control Programme (RNTCP) has treated 10 million patients, the rate of decline has been slow. Providing universal access to early diagnosis and treatment and improving case detection were the main goals of the national strategic plan 2012-17. But the RNTCP failed on both counts, as the Joint Monitoring Mission report of 2015 pointed out. Going by the current rate of decline, India is far from reaching the 2030 Sustainable Development Goals — reducing the number of deaths by 90% and TB incidence by 80% compared with 2015. Yet, the latest report for TB elimination calls for reducing TB incidence from 217 per 1,00,000 in 2015 to 142 by 2020 and 44 by 2025 and reduce mortality from 32 to 15 by 2020 and 3 per 1,00,000 by 2025.

Incidentally, nearly 50% of people in India are latently infected with TB. According to CDC, 5-10% of infected people will develop TB disease at some time in their lives. “About half of those people who develop TB will do so within the first two years of infection,” the CDC says. With the latently infected people acting as a reservoir, it will be nearly impossible to eliminate TB in India by 2025.

Radical approaches are needed to come anywhere close to reaching these ambitious targets. Most importantly, the TB control programme plans to do away with the strategy of waiting for patients to walk in to get tested and instead engage in detecting more cases, both drug-sensitive and drug-resistant. The emphasis will be on using highly sensitive diagnostic tests, undertaking universal testing for drug-resistant TB, reaching out to TB patients seeking care from private doctors and targeting people belonging to high-risk populations.

The other priority is to provide anti-TB treatment — irrespective of where patients seek care from, public or private — and ensure that they complete the treatment. For the first time, the TB control programme talks of having in place patient-friendly systems to provide treatment and social support. It seeks to make the daily regimen universal; currently, the thrice weekly regimen is followed by RNTCP, and the daily regimen has been introduced only in five States. There will be a rapid scale-up of short-course regimens for drug-resistant TB and drug sensitivity testing-guided treatment. In 2013, India “achieved complete geographical coverage” for MDR-TB (multi-drug-resistant tuberculosis) diagnosis and treatment.  Yet, only 93,000 people with MDR-TB had been diagnosed and put on treatment till 2015; several MDR-TB cases are simply not diagnosed.

What next?

Though Bedaquiline, the drug for people who do not respond to any anti-TB medicine, is provided in six sites in the country, the number of beneficiaries is very small. It has been a battle to get the drug for treatment, as in the case of an 18-year-old who had to approach the Supreme Court for help. Yet, the report envisages a countrywide scale-up of Bedaquiline and Delamanid.

In a marked departure, the report underscores the need to prevent the emergence of TB in susceptible populations. One such segment is those in contact with a recently diagnosed pulmonary TB. Incidentally, active-case finding is already a part of the RNTCP programme but rarely implemented. It wants to increase active case finding to 100% by 2020. Since RNTCP expenditure has increased by 27% since 2012 and is inadequately funded, the Ministry proposes to increase funding to ₹16,500 crore.

Acknowledging that the business-as-usual approach will not get the Health Ministry anywhere close to the goals, it has earmarked critical components that will be addressed on priority. These include sending customised SMSes to improve drug compliance, incentivising private doctors to notify cases and providing free medicines to patients approaching the private sector, facilitating nutritional support to TB patients, including financial support, rewarding States performing well in controlling TB, and using management information systems to monitor all aspects of TB control. “The ultimate impact of this national strategic plan will be transformational improvements in the end TB efforts of India,” the report says. It plans to take a “detect-treat-prevent-build approach” in its war against TB.

Published in The Hindu on March 19, 2017

Indian private sector bears 2-3 times higher TB burden than estimated

GeneXpert

A major revision of the TB burden estimates might be required both for India and the world.

A study has found that in 2014 there were 2.2 million TB patients treated in India’s private sector alone. This is 2-3 times higher than current estimates.

In all probability, the higher TB burden in the private sector might still be an underestimation as drug-resistant TB cases were not taken into account. Thus, the private sector is treating an enormous number of patients for TB, appreciably higher than has been previously recognised. In contrast, the State-run Revised National Tuberculosis Control Programme (RNTCP) treated 1.42 million TB patients in 2014.

According to a 2015 WHO report, six million new TB cases were reported to WHO from across the world in 2014. And India’s TB contribution accounted for 26 per cent of these reported cases. But based on the results of the study, a major revision of the TB burden estimates in India and worldwide might be required. Under-reporting of TB cases could be significantly fuelling drug resistance and have implications for patients across the globe.

More importantly, the results of a study published on August 25 in the journal The Lancet suggests that TB incidence is considerably higher than previously recognised, Prof. Nimalan Arinaminpathy, the first author of the paper from the School of Public Health, Imperial College London, says in an email to me.

India has to redouble efforts to reach patients being treated in the private sector.

Lack of systematic data

Despite the private sector treating more patients than the public sector, systematic data on the private sector was lacking. So the study by Prof. Arinaminpathy looked at the sales of anti-TB drugs containing rifampicin by pharmacists across the country in 2013 and 2014. The team then used this figure to calculate the number of cases. The authors adjusted for TB overdiagnosis in the private sector. There was much variance in the number of patients treated in the private and public sector in different States. For instance, the public sector in Orissa had 1.5-2.8 times the volume of TB medicines prescribed than the private sector but Bihar had three times the volume of TB medicines prescribed in the private sector than public sector. But on a national level, there was nearly twice as much TB treatment in the private sector as in public sector in 2013 and 2014.

The 2.2 million cases treated in 2014 in the private sector was arrived at by considering that TB patients underwent four months of treatment on average and only 50 per cent of TB diagnosis in the private sector was correct. The number of patients treated in the private sector increases when higher accuracy of positive TB diagnosis and shorter average treatment duration were considered.

The results of the study have major implications for TB strategy for India. The disorganised private sector poses several challenges to TB control. Since free TB care is assured even to patients opting for private sector, India has to “redouble efforts to reach patients being treated in the private sector and to deliver the highest possible standards of TB care.”

stethoscope

Indians spent $59 million for TB drugs alone in the private sector in 2014.

Second, surveillance of TB in the private sector has to be strengthened. In 2014, as against 2.2 million cases, only a little over 100,000 cases were notified by doctors in the private sector. “But the government has been making strong progress in engaging with providers in the private sector. There has been a rapid increase of private-sector notifications in the last two years (there were essentially zero in 2011). These are encouraging first steps, and our results show the scale of the challenge ahead,” he says.

 Finally, there is a compelling need to find the true TB burden in the country. “TB burden is typically measured through TB prevalence surveys, the most recent of which was in Gujarat. We may soon see the opportunity to conduct these surveys more broadly across the country, which would cast critical light on the TB burden in India as a whole,” says Prof. Arinaminpathy.

There is an economic cost attached to the disease. Since TB treatment in private sector is met primarily by out-of-pocket expenditure, as no medical insurance in India covers treatment cost, a six-month treatment course for first-line TB drugs would cost $20. The 2.2 million patients seeking care in the private sector would have therefore spent $59 million for drugs alone.

Published in The Hindu on August 25, 2016

TB treatment programme in India may be generating more MDR cases

 

Mycobacterium - Photo -  CDC

The Joint Monitoring Mission has emphasised the need for RNTCP to speed up implementation of the transition to daily dosing. – Photo: CDC

The Joint Monitoring Mission 2015 has come down heavily on the Revised National Tuberculosis Control Programme (RNTCP) and the Ministry of Health and Family Welfare for their inability to handle the MDR-TB crisis in the country. The report released last month reflects on the findings, conclusions, and recommendations made by it in 2012.

Despite its inability to diagnose drug-resistant TB, the national programme’s heavy dependence on the century-old, insensitive smear microscopy as a primary diagnostic tool has been strongly criticised. Besides the lack of sensitivity, the microscopy is ill-equipped to diagnose drug-resistant TB. This is particularly worrying as the number of drug-resistant cases is steadily increasing.

The Standards for Tuberculosis Care in India (STCI) — a document drawn up by the Central TB Division in consultation with the WHO and national TB institutes — advocates drug sensitivity testing for all presumed MDR-TB cases. However, this may not become a reality in the near future. “Progress is threatened by slow uptake of the new molecular test” the JMM says. “Procurement of these tests is unaccountably delayed.”

“The RNTCP currently treats patients without knowing their resistance profile,” states the Joint Monitoring Mission report. This along with its current regimen of thrice weekly drugs even to those with prior resistance has been associated with “failure and amplification” of resistance to rifampicin drug. “It is therefore likely, under programme conditions, to be generating more MDR cases,” it says.

While private doctors treat patients with daily dosing, the RNTCP follows a thrice weekly strategy. The report has emphasised the need to “accelerate implementation of the transition to daily dosing.”

According to the report, turning to “universal drug susceptibility testing and switching to a daily regimen with adherence support” can go a long way in addressing the problem of unwittingly exacerbating TB drug resistance in the country.

According to Dr. Soumya Swaminathan, Director of the Chennai-based National Institute for Research in Tuberculosis, the RNTCP is planning to start daily dosing using fixed dose combination in 5-6 States and then expand it to the rest of the country. “RNTCP is currently procuring drugs to make this shift,” she said.

Another failing of the TB programme pertains to the mandatory TB notification by the private practitioners. “In spite of mandatory notification, TB patients [treated by private doctors] are not notified to the RNTCP,” the report says. It wants the Ministry to develop e-Nikshay, an advanced version to the existing Nikshay system for notifying TB patients.

The national strategic plan (NSP) for TB control for 2012-17 developed by the Union Ministry of Health & Family Welfare had raised the bar for tackling the rapidly growing TB epidemic in the country. The main goals of the strategic plan are to provide universal access to early diagnosis and treatment and improve case detection.

Due to faltering on both counts, the JMM reports that the “implementation of the NSP for 2012-2017 is not on track — projected increases in case detection by the RNTCP have not occurred, vital procurements are delayed and many planned activities have not been implemented.”

Worse, about two-thirds of the recommendations made by the Joint Monitoring Mission 2012 have “not been fully implemented.” For the most part, the Central TB Division has “completed the policy work requested. Work is held up for lack of timely decisions, especially at central level,” it states.

Recommendations

With the cost of treating a person with TB going up to 39 per cent of the household’s annual expenditure, the report has recommended that the Ministry of Health minimises the out-of-pocket expenditure by families by “supporting the cost of TB testing and [providing] free drugs.” It also wants the government to eliminate taxation on TB diagnostics and drugs considering TB as a public health emergency.

In order to ensure that patients receive the standards for TB care for India, the JMM has recommended that the government establishes a “state-of-art TB surveillance system for capturing all TB cases, public and privately-treated.” This is essential for the country to “capture and respond to local and focal epidemics.”

Published in the Hindu on May 7, 2015

One million TB cases in children annually

One million children aged below 15 years are annually diseased with tuberculosis across the world, notes a study published a few days ago in The Lancet . The new estimates are twice the number of children thought to have tuberculosis in 2010 and thrice the number of children who were actually diagnosed that year. The study has also estimated the number of children who were diseased with multidrug-resistant TB (MDR-TB) — in 2010, the number stood at about 32,000.

But there is very high possibility that even the new estimates are way below the actual number of diseased children. “It is certainly possible that the true numbers of children with both TB and MDR-TB will turn out to be higher than what we have estimated,” noted Dr. Mercedes C. Becerra from the Division of Global Health Equity, Brigham and Women’s Hospital, Boston and the Corresponding author of the paper.  “We used two existing sources of information from WHO reports — smear-positive cases reported to WHO from some countries, as well as WHO incidence estimates for all countries.  If those numbers are underestimates of TB, then that underestimation will play through into our child disease estimates.”

In fact, the authors had taken into account the fact that TB notification is way off the mark, and applied an “adjustment that took into account how smear microscopy misses more children than adults.” She, however, notes: “But we did not try to adjust for how the quality of case notification data varies across countries.” Therefore, in the case of India, there is a greater possibility of even the revised numbers being a gross underestimation.

With a huge population below the age of 15 years, and the number of new TB cases being about 2.3 million a year in the case of India, there is greater likelihood of more children being missed out.

Even the not-so-accurate revised estimates by the authors highlight the gross failure of the TB control programme of individual countries to diagnose a vast majority of children with TB and MDR-TB every year.

More reliable estimates of drug-sensitive and drug-resistant TB are essential for several reasons, prioritising government’s efforts to diagnose and treat more children with TB being the most important one. The study used the data available in 97 studies accounting for over 8,000 children who had undergone drug-susceptibility testing. The data was used primarily to “establish the relationship between the proportion of treatment-naive adults with MDR-TB and the proportion of children with MDR-TB” and not to arrive at estimating the total number of those with TB.

The study found that in a specific setting, the risk of MDR-TB was “nearly identical” in both children and adults who were never treated before.

Published in The Hindu on March 27, 2014

Editorial: Missing TB cases in India

Although tuberculosis killed 1.3 million people across the globe in 2012 and nearly 8.6 million developed the disease, the world is on track to reach some important targets of the 2015 Millennium Development Goals. According to WHO’s global tuberculosis report 2013 released recently, the incidence rate has been falling, and the mortality rate since 1990 has been reduced by 45 per cent. Yet, at 37 per cent, the reduction in prevalence during the same period is far below the half-way goal. In all likelihood, India may be responsible for the slow reduction in global TB prevalence. At 2.8 million (26 per cent), the country has the highest caseload. But the true incidence and prevalence would be higher if those approaching the private sector and remain unreported are also taken into account. The government’s landmark decision last year to make TB a notifiable disease by the public and private sectors was meant to correct this anomaly. If implemented in earnest, every case detected would get reported and the actual extent of the disease will become known. Unfortunately, very little has been done to ensure that the private sector complies with the requirement. The government reluctantly made TB a notifiable disease, and has shown little interest in implementing the order.

WHO has taken special note of these missed out people. Globally, three million people who developed TB last year have been missed out by the national notification systems, it notes. If detecting and notifying all adult TB cases is found wanting in India, it is far worse in the case of children below 15 years. WHO has estimated that TB incidence among children is over half a million across the world. But its recently released road map for childhood tuberculosis clearly indicated that the actual burden would be higher. WHO’s 2006 guidance on TB management in children indicated that about one million TB cases the world over occur in children. Though children can contract TB at any age, those under five are especially vulnerable, particularly those from households where an adult has been recently diagnosed with active pulmonary TB. Young children are more susceptible to getting infected and face an increased risk of progression to disease; they also acquire the more severe forms of the disease. It is for these reasons that WHO had recommended contact tracing. Though India’s Revised National TB Control Programme (RNTCP) has also approved contact tracing of young children from such families, its implementation is at best sub-optimal. Thus, while RNTCP estimates children with TB to be 10.2 per cent of the total TB caseload, only seven per cent of the cases were registered in 2011.

Published in The Hindu on November 7, 2013

India’s tuberculosis challenge

Published in The Hindu on October 21, 2012

Mycobacterium - Photo -  CDC

India and China together account for nearly 40 per cent of the global burden. – Photo: CDC

Tuberculosis was declared a global health emergency in 1993, but it has been growing unchecked. Today, TB is causing millions of deaths every year globally. Like any infectious disease, TB is prevalent even in developed countries. But it is a more serious problem in the developing and populous countries.

India and China together account for nearly 40 per cent of the global burden. The World Health Organisation’s Global Tuberculosis Report 2012 reveals the magnitude in the two countries, and why India has the most number of patients . In India, the prevalence is 3.1 million at best and 4.3 million at high. In China, the figures are 1.4 million and 1.6 million respectively. Even in prevalence rate (per one lakh population a year), India is 249 at best and 346 at high. China fares better: 104 at best and 119 at high.

In 2011, India again topped the list for incidence (the number of new cases detected in a year). It had 2 million to 2.5 million, compared with China’s 0.9 million to 1.1 million. If global incidence during 2011 was 8.3 million to 9 million, “India and China accounted for 26 per cent and 12 per cent respectively,” the WHO report notes. Mortality is also high in India. About three lakh people will die this year.

There are other differences between China and India. The percentage of TB patients who are also HIV positive is 6.5 in India; China’s figure is 2.3 per cent. This could be because only 23 per cent of TB patients were tested for HIV in China compared with India’s 45 per cent.

There is a significant, but apparent, reduction in prevalence and mortality when compared with 1990 levels. Increases in treatment success percentages have been registered for new cases — from 25 per cent in 1995 to 88 per cent in 2010.

According to the WHO report, the detection rate for new and relapse cases is almost the same in 1995 and 2011 — 58 in 1995 and 59 in 2011. But it was 71 per cent in 2011 among new sputum positive (NSP) patients alone, notes a May 2012 paper in the Indian Journal of Medical Research .“TB case-finding has stalled,” warns the draft executive summary of the Joint Monitoring Mission.

More than one lakh patients are put on treatment each month. The case detection, incidence, prevalence and treatment success figures are based on data drawn from the Revised National Tuberculosis Control programme (RNTCP). “…Early and effective TB treatment and control is difficult in India with its current tools and systems,” notes an editorial in IJMR (March 2012).

According to the May 2012 IJMR paper, only 30,000 private practitioners and 15 corporate health facilities are providing RNTCP services. Continuing the programme without the participation of all private practitioners has been its weakness. This despite the fact that the government is aware of the reality — private practitioners are the first point of contact for a majority of patients.

But private doctors are ill-equipped to track and follow up all patients and ensure treatment adherence. Resorting to unreliable tests, particularly serological (blood) tests based on antibody response to diagnose active TB, and some doctors relying exclusively on X-rays, have added to the challenge. Finally, the Directly Observed Treatment, Short-course (DOTS) is a passive system: it does not seek out patients but waits for them to walk in and get tested. Delayed diagnosis, faulty treatment, lack of follow-up, use of wrong diagnostic tools by doctors, and giving up on treatment mid-way often result in patients infecting others and developing resistance to drugs.

According to a recently published paper in the journal Health Policy and Planning , drug resistance surveillance surveys undertaken in Gujarat and Chennai indicate that there are “1-3 per cent MDR-TB [multi-drug resistant-TB] among fresh pulmonary cases… and 13-17 per cent among previously treated cases.” If detecting and treating all TB patients who are not drug resistant is challenging enough, detecting and treating drug-resistant TB is riddled with problems.

The government has woken up. After it took some dramatic and bold initiatives over the last one year, TB detection and management is no longer the same. In June 2012, the government banned serological tests. There are plans to go out and test certain target groups. But the landmark decision was making TB a notifiable disease. This has made it mandatory for laboratories, hospitals, nursing homes and doctors, both in the public and private sector, to report every TB case detected. The government system would kick in once a case is notified to ensure correct diagnosis and complete adherence to treatment during the entire duration of treatment. Two important panels have made recommendations to engage the private sector in multiple ways to rein in TB.

The government dragged its feet for too long and remained in a state of denial till the spectre of multi-drug resistant TB, high prevalence and missing out of a huge number of patients made it too difficult to avoid making it a notifiable disease.

As most patients first approach the private sector for treatment, the true incidence and prevalence levels are never known. Evidently the government delayed the decision principally because once TB is made notifiable, and when the requirement is fully and effectively implemented, the true incidence and prevalence of all forms of TB will come to light. As the executive summary notes, “approximately one million TB cases per year are unreported.”

This is where the approaches that India and China adopted to fighting TB diverged. Of the 37 notifiable diseases in China, TB ranks No. 1. It pulled out all the stops by 2000. “The concept of acceptance of the problem, identifying its requirement and the political will of TB eradication has set China on a progressive path,” notes a paper published in the journal Interdisciplinary Perspectives on Infectious Diseases .

Notification and treatment will not have a significant impact until the TB control programme starts using new WHO-approved diagnostic tests. Smear microscopy used for sputum sample study is a 125-year-old method. Aside from its low sensitivity (50 per cent), it cannot determine drug resistance. Xpert MTB/RIF, on the other hand, has 72 per cent sensitivity with one test, and 90 per cent with three tests in the case of smear-negative patients. The sensitivity goes up to 98 per cent in the case of smear-positive and culture-positive patients. Xpert MTB/RIF has 99 per cent specificity. It can turn in results in less than two hours compared with four to six weeks in the case of the culture process.

But the most important advantage is its ability to diagnose rifampicin drug resistance. Rifampicin resistance is a brilliant marker of MDR-TB. Most patients who are resistant to rifampicin are also resistant to isoniazid. Resistance to at least rifampicin and isoniazid are required to classify a person as an MDR-TB patient.

Widespread use of such diagnostic tools that provide quick and accurate results and also indicate drug resistance will go a long way in battling the epidemic.

The diagnostic tool is being used in a couple of pilot test centres. The TB control programme should quickly evaluate its performance and use it more widely after bargaining for a cheaper price. Strengthening the programme to treat more number of drug-resistant patients should go hand in hand with that strategy.

But there is way to go before the challenge is surmounted credibly and effectively.

Editorial: No room for haste

Published in The Hindu on October 2, 2012

The past year has witnessed unprecedented official efforts to rein in the growing tuberculosis epidemic. In 2011 alone, 1.2 million new TB cases were reported while 60,000 patients already inflicted died. In reality, the real incidence, most likely was much higher — the number of new cases diagnosed and treated by private practitioners has not been factored in. It is to change this that TB was made a notifiable disease in May this year. The government had to bite the bullet as effective interventions can be taken only if a system is in place to capture the true incidence and prevalence of the disease, including the drug-resistant cases. Herein lies the biggest challenge — ensuring every new case diagnosed by the private health sector is accounted for. This can be achieved only if the government engages with the private sector by first taking it into confidence. The draft versions of the Joint Monitoring Mission (JMM) and the National Strategic Plan for TB Control, 2012-2017 have made strong recommendations to engage the private health sector to stem the spread of TB. The government, which very recently sent out guidelines on notification, requires every private health institution, including laboratories, to provide the personal details of a patient — name, address, mobile number and unique identification number (Aadhar or driving licence). The objective is to provide a support system to patients seeking private healthcare in terms of treatment initiation, adherence, follow-up and default retrieval — tasks that are beyond the private sector’s capacity.

The goal is laudable but it is quite unlikely that the TB Control programme can achieve all of its highly ambitious objectives in the short term. The most significant obstacle will be the reluctance of patients and some doctors to part with personal data. This despite the fact that such sharing is mandatory in the U.S. and many other developed countries, and that the Medical Council of India’s code of ethics warrants such sharing. Hence, consensus and confidence-building measures have to be undertaken on a massive scale to bring private healthcare providers on board and make them open to the idea of sharing details. According to the draft JMM report, about one million TB cases per year are not reported. While the National Rural Health Mission has found some innovative ways of increasing manpower, urban areas lack the infrastructure to handle additional cases. This needs fixing. Most importantly, the TB control programme, which uses the interrupted regimen, has to show flexibility and allow the private sector to continue following the WHO recommended daily fixed-dose regimen.