‘Preventing drug-resistant TB in India’

Madhukar Pai

March 24 is World TB Day, and a good time to take stock of progress in tuberculosis (TB) control in India, the country with the largest number of TB cases. Yet, most people in India probably think that TB is a disease from their grandparents’ era. They are seriously mistaken. TB is an enormous problem, even today. Every year, India reports over 2 million TB cases, although the true numbers may be much higher. It is only in 2012 that the Government of India made it mandatory for the private healthcare sector in India to notify all TB cases to local health authorities. So, the true magnitude of the TB problem in India will become clear only when we precisely count the number of TB cases managed in the private sector which accounts for a majority of healthcare delivery in the country.

The scary truth about TB is that everyone is at risk. TB is an airborne infection that is spread when infected people cough and release droplets with TB bacteria in the air. As in the case of any airborne infection, we are all vulnerable. TB anywhere is TB everywhere!

As India witnesses increasing cases of multidrug-resistant (MDR) TB, the disease is now becoming increasingly difficult to diagnose and treat. A 2011 Global TB Report by the World Health Organization estimated that approximately 64,000 cases of MDR-TB emerge annually from the notified cases of pulmonary TB in India. This number may not seem large. However, for a moment, consider the TB burden of India. Then consider the quality of care that is accessible to most patients. Now consider the possibility that many more can become drug resistant in India in the coming years.

TB control in India is at a decisive juncture. Unless we invest more in TB control, we will see an increasing number of cases in the future. What is MDR-TB? If TB strains become resistant to isoniazid (INH) and rifampicin (RMP), the most critical first-line TB drugs, this is called MDR-TB. If the treatment of people with TB is incorrect, interrupted or not completed, the TB bacteria can become resistant to the common TB drugs that are used. Also when doctors prescribe the wrong treatment, the incorrect dose, or duration of treatment, the patient can easily become drug resistant. Counterfeit TB drugs can also result in drug-resistance and poor outcomes, and this is a growing concern with all drugs in India.

Analysis of sputum smears of TB patients

Why should we be concerned about MDR-TB? The answer is simple. MDR-TB requires extensive treatment (for two years) with multiple, toxic drugs and outcomes are poor. Treatment of MDR-TB is also very expensive. And MDR-TB can progress into even worse forms of TB such as extensively drug-resistant TB (XDR-TB).

The rise of MDR-TB in the recent past in India is worrying. Recently, Hinduja Hospital in Mumbai reported cases of ‘totally drug-resistant tuberculosis’ (TDR-TB) – suggesting that this form of TB was incurable because of resistance to all the TB drugs tested. WHO has not accepted or endorsed the definition of TDR-TB.

How has India controlled the problem of TB? India’s Revised National Tuberculosis Control Programme (RNTCP) is a globally lauded success in the area of TB control. It expanded basic diagnostic and treatment services to cover 100 per cent of the Indian population. And yet, TB continues to be a huge public health challenge. It is important to consider what we can do to go beyond extending basic TB services.

Early diagnosis and treatment of patients with MDR-TB is one area that RNTCP needs to improve. Currently, most TB patients in the public sector receive only sputum smears as the diagnostic test (see image: Analysis of sputum smears of TB patients). While most patients eventually get free TB treatment in the public sector, they first seek care at chemist and drug shops and visit informal and unqualified providers. All of this can result in long delays before TB treatment is started. While sputum smears are rapid, inexpensive and do help identify the most infectious cases, the technology lacks sensitivity, and cannot detect MDR-TB. So, unless patients fail first-line TB drug therapy or have been previously treated for TB, they generally do not get tested for MDR-TB in the public sector.

Xpert analysis in progress

The RNTCP needs to consider providing a large section of the patients with adequate drug-susceptibility testing and second-line drug treatment. New, fast and WHO-approved molecular tests such as Xpert MTB/RIF (GeneXpert platform by Cepheid Inc, Sunnyvale, California) can now give drug-susceptibility results within hours and such technologies need to be urgently scaled-up to detect more MDR-TB cases and initiate them on second-line drug therapy.

A Cochrane systematic review, published on January 31, 2013, showed that the Xpert assay (see image: Xpert analysis in progress) is highly accurate with a sensitivity of 88 per cent and specificity of 98 per cent, when compared to culture. The test is significantly more sensitive than sputum smear microscopy. Furthermore, the Xpert assay can detect resistance to rifampicin with as sensitivity of 94 per cent and specificity of 98 per cent. Recent initiatives by donors have successfully reduced the price of Xpert test cartridges to under $10 for the public sector, but the test continues to be expensive for the private sector in India. This may soon change with the impending launch of a Consortium of private labs in India that will offer WHO-endorsed tests like Xpert at affordable prices.

We need many more such efforts to engage the private sector. India’s private sector, which diagnoses and treats more than half of all TB patients, has been a source of mismanagement of TB and hence, drug resistance. This includes the use of incorrect diagnostics, incorrect regimens and lack of supervision to ensure all TB patients complete treatment.

What can patients do to prevent drug-resistant TB? To begin with, all individuals with cough for more than two weeks must get their sputum tested for TB. Sputum testing is available free via thousands of microscopy centres run by the RNTCP, and ad campaigns such as Bulgam Bhai (see image:Bulgam Bhai ad campaign, Source: Project Axshya) have been focused on encouraging patients with chronic cough to seek sputum testing. If patients seek care in the private sector, they must demand sputum testing over blood tests for TB. There is no accurate blood test for TB. If TB is diagnosed, the most important thing a person can do to prevent MDR-TB is to take medications exactly as prescribed. No doses should be missed and treatment should not be stopped early, even if symptoms improve. Patients who cannot afford to buy drugs must seek treatment in the public sector where TB drugs are given free. Initiatives are also underway to provide free TB drugs to patients in the private sector, and such an effort can make a big difference in India, where even the really poor patients often seek care in the private sector and pay out-of-pocket for medical care.

Bulgam Bhai ad campaign, Source: Project Axshya

Doctors, healthcare providers, pharmacies, and laboratories have a critical role to play in preventing MDR-TB. They must ensure quick and accurate diagnosis, follow recommended treatment guidelines, monitor patients’ response to treatment, and make sure therapy is completed is the key to prevention. If TB is confirmed, they should start treatment promptly and follow WHO or RTNCP guidelines. Efforts are underway to develop the ‘Indian Standards for TB Care’ that both public and private sectors can agree on and adhere to.

The Indian government recently banned the use of antibody blood tests for diagnosing TB, and leading newspapers carried ads on the ban (see image: Reproduction of RNTCP ad released in newspapers). This is a welcome development as blood antibody tests are known to be highly inaccurate and misleading (see story “Beyond the Ban” published in Express Pharma, 1-15 July, 2012 : http://bit.ly/11KFsOz). Other blood tests such as QuantiFERON-TB Gold (marketed in India as ‘TB-Gold’) are not meant to diagnose active TB. They are meant to detect latent TB infection and one in three Indians is latently infected. So, doctors should not use such blood tests to start treatment for active TB. Laboratories should stop the use of inaccurate blood tests for TB and instead prioritise sputum tests.

Reproduction of RNTCP ad released in newspapers

Also, it is critical that pharmacies and drug stores do not dispense TB drugs without a valid allopathic doctor’s prescription. This is mandated by law (i.e. Schedule H) but rarely implemented or enforced. It’s important to remember TB is not an ordinary cough and TB drugs are not cough syrups that can be handed out. Over-the-counter use of TB antibiotics without adequate supervision can foster drug resistance. Indeed, prescription audits have shown widespread use of irrational TB drug prescriptions which might partially explain the emergence of MDR and XDR-TB in India. The Indian government must do a better job of regulating the sale of TB drugs in India. Indeed, all antibiotics must be regulated to prevent their widespread abuse.

As the lead agency for TB control in India, the RNTCP’S role is pivotal in preventing MDR-TB. The RNTCP has just announced its National Strategic Plan (NSP), for the period 2012 – 2017, with its new objective of ‘universal access’ for quality diagnosis and treatment for all TB patients in the community. A transformational change in the relationship between the RNTCP and the private health sector is critical for the success of all the major areas of the NSP (universal access, early diagnosis, interruption of transmission, prevention or management of MDR-TB). While the RNTCP must work harder to partner with the private sector, the private sector also has a responsibility towards public health in India. TB control in India cannot succeed without both sectors joining forces.