TB turns invincible
In December last, when doctors at Hinduja Hospital in Mumbai raised the alarm over a deadly form of tuberculosis, the Union health ministry was quick to refute the claim. In its press release on January 17, the ministry said the term “totally drug resistant TB” is “misleading”; it is neither recognised by the national programme for TB control nor by WHO. But WHO has received reports of a similar strain of TB bacteria before: first from Italy in 2007 and then from Iran in 2009. With India becoming the third country to have raised the concern, it has now convened a meeting of global TB experts in March to discuss whether the strain should be called totally drug resistant (TDR), or be clubbed under the existing category of extensively drug-resistant TB (XDR-TB), given that advanced drugs are in the making and that it is not possible to test TB bacteria against every possible drug and concentration.
Calling the new TB strain as XDR or TDR, however, does not take away the seriousness of the issue that the Hinduja researchers have highlighted. Inappropriate and irrational treatment is amplifying the resistance of TB bacteria, which have grown resistant to the first-line treatment, and are mutating into difficult-to-cure forms like XDR-TB and TDR-TB, the researchers noted in the study published in Clinical Infectious Diseases on December 21. While they blame the private healthcare sector for abusing precious anti-TB drugs by prescribing irrationally, several public health experts also find fault with the Revised Natio¬nal TB Control Programme (RNTCP).
DOTS fails to cope with mutating TB
It is not clear when India saw its first case of drug-resistant TB, though health experts say its presence has been known from the time anti-TB drugs were introduced about two decades ago. Initially, it was resistant to first-line drugs, including the powerful isoniazid and rifampicin, and hence named multi-drug resistant TB (MDR-TB). To control its spread, India started scaling up DOTS programme, a WHO recommended strategy under RNTCP, to DOTS-Plus in 2006.
By then decades of neglect had made the bacteria stubborn. That year, soon after WHO brought into notice XDR-TB, resistant to second-line treatment as well, India reported its first case of the disease. Hinduja Hospital was the first to report the case. In absence of a universal regime, the only ways to treat a XDR-TB patient are surgery and drugs not tried before. Eight of 10 patients succumb to the illness.
RNTCP did not grow at the pace at which the TB bacteria developed resistance, says Sarabjit Chadha of the International Union Against Tuberculosis and Lung Diseases. He blames the mutation of TB bacteria on insufficient diagnostic facilities. Ideally, doctors should do a drug susceptibility test (DST) before treating a patient who has failed to respond to the first-line therapy or is a dropout and could have developed resistance to certain drugs. The six-week-long test helps doctors decide on the right regime. But in India DST is done only after patients fail to respond to the second-line therapy and develop difficult-to-treat forms like XDR-TB, Chadha adds. RNTCP has just 27 labs, of which four are equipped to test drug resistance in an XDR-TB patient.
“The faster the drug-resistant TB cases are identified, the quicker their treatment can start,” says Jayant Banavaliker of Rajan Babu Institute for Pulmonary Medicine and Tuberculosis run by Delhi’s municipal corporation. “Delay in treatment can amplify resistance.”
Discontinuation of treatment is known as the primary reason for developing drug resistance. But it is not easy to complete second-line therapy, admits Joanna Laomirska of Medicines Sans Frontiers (MSF) India. Patients have to take strong drugs and injections for months. Many suffer from pain in the abdomen and vomiting. Some even commit suicide, she adds, suggesting that DOTS-plus should have provision for counselling the patients.
MAKING OF A STUBBORN TB
- With a fifth of global TB burden, India is TB capital of the world
- 20% of the world’s multi-drug resistant TB are found in India
- DOTS-Plus meant to curb resistant TB has been implemented in only 12 of the 28 states
- 27 labs to test resistant TB; 4 can test XDR-TB
Blessina Kumar, vice-chairperson of Stop TB Partnership, an alliance of non-profits, says the programme should be restructured on the lines of HIV/AIDS programme, which offers counselling as well as treatment. It must rope in non-profits and communities to deliver the benefits to the grassroots level, she adds.
Leena Menghaney of MSF-India agrees. More community-based care for MDR-TB patients supported by trained, supervised, and paid community workers can help check mutation of MDR-TB bacteria. But so far, she adds, RNTCP has initiated such programmes only in two of the 28 states.
Such inadequacy and inflexibility of the government programme often push patients to seek treatment from private healthcare centres, but in vain.
Irrational private care
The Hinduja doctors say three of the 12 TDR-TB patients who succumbed to the disease had received erratic, unsupervised second-line drugs, often in incorrect doses and from multiple private practitioners.
An earlier study by the team in Mumbai’s Dharavi slum had revealed that only five of 106 private practitioners could prescribe a correct prescription for a hypothetical patient with MDR-TB. The vast majority of these unfortunate patients seeks care from private physicians. “This sector of private sector physicians in India is among the largest in the world and these physicians are unregulated both in terms of prescribing practice and qualifications,” they note.
To cure TB faster than a DOTS centre, a private practitioner may prescribe drugs that are not needed, says Kumar. Bad prescriptions coupled with easy availability of precious antibiotics make the situation precarious. Besides, Chadha says, private practitioners hardly check whether the patient is taking the anti-TB drugs as prescribed or not.
Irrational and unmonitored treatment was also the reason behind the emergence of TDR-TB in Italy and Iran.
Italian researchers, who identified the strain resistant to all available anti-TB drugs and named it extremely drug-resistant TB (XXDR-TB), wrote in their paper that the two women diagnosed with XXDR-TB were initially treated in non-specialised TB facilities.
Iranian researchers had documented that all of the 15 TDR-TB patients had past history of TB and were treated with irrational drugs. In Iran, some of the second-line drugs are routinely used for the treatment of respiratory diseases. It is likely that these patients had previously been treated with aminoglycosides and fluoroquinolones in a poorly controlled manner, which led to the mutation of MDR-TB strain, they had noted.
Why India can’t afford resistant TB
Emergence of the stubborn strain in India, the TB capital of the world, is worrying as it could easily spread in the heavily populated country. The finding by the Hinduja doctors could be just the tip of the iceberg. Documentation by St John’s Research Institute in Bengaluru in 2007 shows they had isolated several TDR-TB like strains from limited number of samples. The challenges of increasing drug resistance of TB are “enormous” for the government, says John Kenneth of division of infectious diseases at the institute who led the study.
Banavaliker explains. It takes six months and Rs 600-Rs 800 to treat a patient suffering from drug-sensitive TB. The figures go up to two years and Rs 2 lakh for MDR-TB. The cost of treating an XDR-TB patient is more than Rs 5 lakh.
RNTCP’s budget needs to be greatly increased along with newer WHO-approved molecular tests for TB and drug resistance for rapid diagnosis, says Madhukar Pai, epidemiologist with McGill University in Canada. Pai, who has worked on TB in India, suggests: “We must get doctors, especially in the private sector, to follow international and national guidelines on TB management. Improved regulation of the private health sector is a big part of the solution.”
As far as naming the TB strain is concerned, Bobby John of non-profit Global Health Advocates, says: “Once resistance starts developing in treatable TB, the downfall starts. Whatever you name it after that doesn’t matter.”