India: TB catch-all strategy rings alarm

New Delhi, Feb. 1: Doctors in India have detected what they say is a disturbing rise in the proportion of patients with tuberculosis resistant to second-line drugs that are used only when key first-line medicines have failed.

Their findings underscore India's slow progress in building the laboratory facilities needed to provide every patient suffering from multidrug-resistant (MDR) TB the correct diagnostic strategy to give each one of them the best chance to be cured. The findings also highlight the threat such infections pose to patients and others in their communities.

The doctors from eight hospitals in Mumbai have observed increases in MDR-TB resistant to three second-line drugs called fluoroquinolones - moxifloxacin, ofloxacin, and ethionamide - among patients from the greater Mumbai metropolitan area.

But their findings could be relevant to cities across India that share the medical practices that may have spawned the germs and the living conditions that may help them spread.

"We're seeing a steady worsening of patterns of TB resistant to second-line drugs," Alpa Dalal, a respiratory medicine specialist at one of the hospitals, told The Telegraph. "The existing policy of providing patients with MDR-TB a standard treatment regimen needs to change fast."

Dalal and her collaborators, who analysed drug-resistance patterns in a small sample of 340 patients with MDR-TB, say their results highlight the need for the national TB control programme to shift from the current "standardised" treatment to "individualised" treatment tailored for each patient with MDR-TB.

Their study has found that the proportion of patients with resistance to at least two key first-line drugs, one oral fluoroquinolone and one injectable second-line drug was about 56 per cent while 30 per cent were infected by MDR-TB.

The study, just published in the journal PLOS One, also observed rises in the proportions of patients resistant to the fluoroquinolones - moxifloxacin resistance rose from 60 to 69 per cent, ofloxacin resistance rose from 57 to 73 per cent, and ethionamide resistance more than doubled from 24 to 52 per cent, between the periods 2005 to 2007 and 2011 to 2013.

The national TB control programme provides standardised treatment regimens - a fixed combination of six drugs - to patients with MDR-TB without appropriate laboratory tests to determine whether each drug would actually work for every patient.

The programme, which treats about 1.5 million TB patients each year, has estimated that India had about 64,000 patients with MDR-TB in 2012, among whom 21,000 were first-time patients. The other 43,000 had received first-line drugs that had failed to cure them.

During 2013, the programme treated 20,763 MDR-TB patients across the country, including 1,284 in Bengal.

Programme managers in Mumbai decided last month to offer each patient with MDR-TB an expanded - but still not ideal - drug susceptibility test to determine the most suitable combination of second-line drugs to prescribe a tailored, or individualised, treatment regimen to each patient.

"This policy needs to expand across the country," said Pralhad Prabhudesai, a respiratory medicine specialist at another hospital that participated in the study. "We're being penny-wise pound-foolish not to offer drug susceptibility tests to every MDR-TB patient right at the start."

Such a test, he said, typically costs about Rs 8,000. "But not giving MDR-TB patients an effective combination of drugs will only create extreme drug resistance which is even more expensive and even harder to treat than MDR-TB."

Senior health ministry officials managing the TB control programme have conceded that delivering high-quality diagnosis and appropriate treatment to patients with MDR-TB is among the "challenges" faced by the programme.

The programme had five accredited laboratories - in Bangalore, Chennai, Delhi, Mumbai and Kerala - to conduct drug susceptibility tests for second-line drugs by December 2013. That number has grown but, the doctors say, the pace of expansion has not matched the scale of the problem.

The doctors say the growing resistance to fluoroquinolones is rooted in the widespread abuse of these antibiotics. Several earlier studies have suggested that a "chaotic and unregulated" private health sector may be contributing to drug resistance by abusing fluoroquinolones.

"Our findings suggest the standardised regimens may not work on nearly half the MDR-TB patients in Mumbai," said Dalal, who works at a private hospital but has helped manage TB patients in a government hospital in Mumbai since 2005. "When such treatments do not work, it's terrible for patients, but they can also spread the multi-drug-resistant bacilli to others around them," she said.

The TB control programme currently recommends second-line drug susceptibility testing only to patients already receiving treatment for MDR-TB who do not respond to treatment after six months of therapy. But, doctors say, these patients can spread MDR-TB through the community during that period.

A 20-year-old engineering student in Mumbai who had no history of family or close contact with TB patients was recently diagnosed with extreme drug-resistant TB, his doctor said. "He must have picked up the infection from the community," the doctor said.

A senior epidemiologist cautioned that the Mumbai study is based on a small sample of patients and the patterns of resistance may not genuinely reflect MDR-TB across the community.

"Every single patient with TB deserves a complete drug-sensitivity test," said Madhukar Pai, associate professor at McGill University in Canada, who was not associated with the Mumbai study. "Otherwise, doctors may inadvertently give the incorrect regimen and make a bad situation worse."

Drug resistance increases the duration and cost of treatment and reduces the chance of recovery. Therapy with first-line drugs costs about Rs 4,000 and lasts six months, Dalal said. Treatment with second-line drugs is likely to cost at least Rs 1.2 lakh and last two years, she said. Patients with extreme drug resistant TB also need therapy for two-and-a-half years that could cost over Rs 3.6 lakh and may require surgery too.

Source: The Telegraph

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By G.S. Mudur

Published: Feb. 7, 2015, 1:10 p.m.

Last updated: Feb. 7, 2015, 2:12 p.m.

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