Beyond the numbers: India's first anti-TB drug resistance survey reveals the shortcomings of the tuberculosis-control programme
The results of the first anti-tuberculosis drug resistance survey in India indicate that the country’s national tuberculosis-control programme is ill-equipped to detect the drug-resistant strains prevalent in India. The report, which was released in March this year, reveals that nearly a quarter of India’s new tuberculosis patients are resistant to at least one of 13 drugs used for its treatment, whereas the control programme only accounts for resistance to one particular drug. “Resistance to certain drugs such as isoniazid are ignored by the system,” Dr Yogesh Jain, one of the founder members of Jan Swasthya Sahyog, a community health organisation in Bilaspur, in Chhattisgarh, said. “If the objective is to diagnose drug-resistant tuberculosis, then the algorithm used by the programme is inappropriate.”
The health ministry enrolled a total of 5,280 tuberculosis patients—3,240 new patients and 2,040 who were previously treated—for the drug-resistance survey, which was conducted from July 2014 till May 2016. The survey sought to study the proportion of patients suffering from multi-drug resistant tuberculosis, or MDR-TB, among the patients treated under the Revised National Tuberculosis Control Programme—a central-government initiative to arrest the spread of the disease. MDR-TB refers to tuberculosis that does not respond to the two powerful first-line drugs—rifampicin and isoniazid—and a person afflicted with it requires second-line treatment, which comprises drugs that are more aggressive and require a longer regimen.
On 24 March this year, four years after initiating the survey and 11 days after Prime Minister Narendra Modi inaugurated the Delhi END TB Summit, the union health ministry released the report. Several international dignitaries, including the health ministers of over 20 countries, and the WHO director-general, Dr Tedros Adhanom, were in attendance at the summit, where Modi declared, “I am confident that India can be free of TB by 2025.”
The health ministry’s report notes that although the proportion of MDR-TB cases within India’s total cases of tuberculosis is lower than the official global estimates, the absolute number of drug-resistant tuberculosis patients in India is the highest in the world. Of the 27 lakh tuberculosis patients in the country, a 2017 report by the World Health Organisation notes, approximately 1.47 lakh, or 5.44 percent, are cases of MDR-TB. Among those enrolled for the survey, the report noted that 6.19 percent suffered from MDR-TB—including an affliction among 2.84 percent of the new tuberculosis patients, and among 11.60 percent of the previously treated patients. The worldwide estimates, as stated in the survey report, show an affliction of MDR-TB among 4.1 percent of new patients and 19 percent of previously treated patients. But the figures for India arising from the survey are particularly grave given the report’s finding that Indian tuberculosis patients showed a resistance to a wide range of drugs, which the country’s tuberculosis-control programme fails to address.
Drug-resistant tuberculosis can be a result of an infection of drug-resistant bacteria, an incomplete prior treatment, or an irrational use of tuberculosis antibiotics. Its prevalence among new patients, which is termed primary infection, means that they contract the drug-resistant strain directly, without ever being treated for it earlier. This could occur in crowded cities such as Mumbai and Delhi, where drug-resistant tuberculosis cases are high, or through close contact with any patient previously suffering from it.
In India, the chances of these patients getting tested for their resistance to all these drugs up front are currently bleak because the government protocol under the tuberculosis-control programme mandates testing for just one drug—rifampicin. If a patient shows resistance to it, the government then begins treatment for MDR-TB. But a patient may often be resistant to the drugs used to treat MDR-TB, and the control programme’s failure to test the resistance to these drugs may then exacerbate the patient’s condition and suffering. The complexities of drug resistance revealed in the survey also highlight other crucial concerns, including the difficulties posed by the current state of diagnostic infrastructure in India, the absence of regulations guiding private healthcare, and the lack of access to necessary lifesaving drugs.
The failure to test for resistance to multiple drugs very often drives patients with drug-resistant tuberculosis from doctor to doctor—both public and private—in search of the right diagnosis, which, in turn, may likely lead to further drug resistance. For instance, a 24-year-old resident of Ujjain district, in Madhya Pradesh, told me that it took him five years before he received the correct tuberculosis diagnosis. He said, “I just kept taking pills and injections and continued to be sick.”
The 24-year-old first visited a doctor in Ratlam, in Madhya Pradesh, after he began showing symptoms of tuberculosis in 2013. By 2017, he said he was so sick that he had to quit his job in Gujarat and move back to his house in Ujjain. According to the 24-year-old, he was then treated with haphazard regimens by private doctors in Ratlam and Indore. “Not once did they do a sputum test to check what kind of tuberculosis I have,” he told me. A sputum test examines a patient’s sputum under a microscope for tuberculosis bacteria. This year, he was referred to Hinduja Hospital, a private hospital in Mumbai, where the doctors conducted a complete profile of his drug resistance, which showed that he was resistant to some drugs used to treat MDR-TB.
Another case, of a 19-year old woman from Patna who moved the Delhi High Court in December 2016 seeking access to a new tuberculosis drug, bedaquiline, is also illustrative of the lacunae in the control programme’s drug-resistance protocol. Following the protocol, she was tested for resistance to rifampicin and then initiated on treatment for MDR-TB. Within six years, she lapsed into extreme drug-resistant tuberculosis, or XDR-TB—a strain of tuberculosis in which a patient is resistant to first-line and second-line drugs. After the failure of both first-line and second-line treatment, which continued for five years, a complete drug-resistance profile identified the drugs to which she was resistant.
A recent Newslaundry article indicated that the use of bedaquiline in India may be illegal because the drug had not yet cleared phase-three trials—the final stage of clinical trials before any drug is approved. But Anand Grover, the senior advocate who represented the 19-year-old woman, told me, “The Drug Controller of India can waive phase 3 trials in public interest under section 122A of the Drugs and Cosmetics Act”—the section that prescribes the law for importing a new drug. The article also fails to acknowledge that the urgent necessity for bedaquiline arises from the fact that the patients who need are resistant to other tuberculosis drugs. For the same reason, the WHO issued a report on the guidelines for using bedaquiline, in 2016, which also noted that its benefits outweighed the overall harm of the drug. In January this year, the Delhi High Court allowed the 19-year-old woman to receive bedaquiline, following which her condition has reportedly been improving.
Sandeep Ahuja, the founder of the non-profit Operation Asha, which works with tuberculosis patients across India, told me that the current system is geared towards standardised treatment regimens. “The moment a patient is not part of a standard group, the system is not able to respond quickly enough.” The Ujjain and Patna patients could have both benefitted from a complete drug-resistance profile, and probably avoided years of suffering, but the government programme fails to take into account the sheer diversity of the problem of drug resistance.
While the government’s tuberculosis control programme suffers from the inadequate protocols for testing drug resistance, the private sector is not mandated to follow any laid down protocol, including WHO guidelines on treating tuberculosis. In fact, apart from a few experiments in cities such as Mumbai, Mehsana and Patna—where local government bodies have actively worked with private doctors—the government has not adequately engaged with the private sector on the treatment for tuberculosis. As a result, patients often receive incorrect treatment in the private sector that only worsens their condition.
Chapal Mehra, the convener of a support group for tuberculosis patients called Survivors Against TB, expressed the same concern to me over an email correspondence. “We should focus on how drug-resistant TB is diagnosed and treated in the private sector and build capacity amongst those treating a large section of India’s TB-affected population,” Mehra wrote. “Until we do so, we are addressing only half the problem.”
The shortcomings of India’s tuberculosis control programme are further compounded by a lack of infrastructure to efficiently diagnose the drug-resistant strains, and the limited access to the necessary drugs even after a diagnosis. The health ministry’s survey revealed that a frightening number of tuberculosis patients have lapsed into critical levels of drug resistance—the report notes that almost 25 percent of MDR-TB patients are resistant to the very drugs used to treat MDR-TB.
The first stage at which this problem ought to be addressed is during diagnosis. In India, most patients are still diagnosed using sputum microscopy, which fails to identify nearly 50 percent of the cases. Since 2013, the government has been scaling up the availability of the cartridge-based nucleic acid amplification test or CBNAAT, which can detect both tuberculosis bacteria in small samples and smaller amounts of bacteria in samples, for instance in the case of children. But CBNAAT continues to be underused in India. While there are 628 CBNAAT machines across the country, they are predominantly used only in major cities because the machine needs constant air conditioning and electricity, which can be challenging in far-flung districts.
It is important to note that even CBNAAT would be insufficient to understand the medical requirements of tuberculosis patients because the machine only tests for rifampicin resistance. As per the government survey, 11 percent of new tuberculosis patients were resistant to isoniazid. The central government has also noted in a 2017 report, titled “Guidelines on Programmatic Management of Drug-Resistant Tuberculosis in India,” that nearly thrice as many people resistant to rifampicin are independently resistant to isoniazid and other drugs. These patterns of resistance are not picked up by the CBNAAT.
Jain, the founder member of Jan Swasthya Sahyog, expressed grave concerns about the treatment protocol. “We can’t be treating so many patients with this first-line drug, isoniazid and streptomycin, when we do not know the resistance patterns,” he said. “This is the pathway to develop more MDR-TB in the community.”
While the 2017 central government guidelines direct patients whose sputum samples are sensitive to rifampicin to be tested for isoniazid—but not a full drug-sensitivity profile—it may still take time for these guidelines to be implemented, considering the level of infrastructure in the country. For instance, across the Northeast, the Guwahati Medical College is the only institute that provides drug-sensitivity testing for both first and second-line drugs. Similarly, states such as Jammu and Kashmir, Jharkhand and Chhattisgarh have only one centre in each state that is certified to provide this service.
Even after an effective diagnosis, patients may still suffer because of the lack of access to drugs. This becomes particularly difficult in cases of XDR-TB, when a patient is resistant to second-line drugs as well. According to the government survey, 21.82 percent of MDR-TB patients showed additional resistance to fluoroquinolones, a class of second-line drugs, and 3.58 percent were resistant to all second-line injectable drugs. The XDR-TB strain is tougher to treat because the drugs to treat it are available in fewer numbers.
In late March this year, Médecins Sans Frontières India, the Indian wing of an international medical humanitarian organisation, issued a statement in response to the survey report, which noted that the fluoroquinolones resistance “translated to over 30,000 DR-TB patients who need immediate access to better treatment regimens.” It is important to note that this figure does not account for all cases for XDR-TB—but according to the central government’s annual “India TB Report” of 2018, only 2,666 patients were initiated on treatment for XDR-TB, in the previous year.
The MSF India statement expressly noted that the patients with drug-resistant tuberculosis needed access to the “new drugs bedaquiline and/or delaminad.” Bedaquiline has been made available only conditionally in government centres in five cities across the country—Mumbai, Guwahati, Chennai, Ahmedabad and Delhi. Delamanid is still not provided in the government programme, though the government has been planning it since last year. “People who need these drugs are scattered across the country,” Dr Stobdan Kalon, the MSF medical coordinator in India, told me. “We need more centres that can handle these cases across the country.”