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Drug-resistant 'white plague' lurks among rich and poor

On New Year's Eve 2004, after months of losing weight and suffering fevers, night sweats and shortness of breath, student Anna Watterson was taken into hospital coughing up blood.
/ Source: Reuters

On New Year's Eve 2004, after months of losing weight and suffering fevers, night sweats and shortness of breath, student Anna Watterson was taken into hospital coughing up blood.

It was strange to be diagnosed with tuberculosis (TB)- an ancient disease associated with poverty - especially since Watterson was a well-off trainee lawyer living in the affluent British capital of London. Yet it was also a relief, she says, finally to know what had been making her ill for so long.

But when Watterson's infection refused to yield to the three-pronged antibiotic attack doctors prescribed to fight it, her relief turned to dread.

After six weeks of taking pills that had no effect, Watterson was told she had multi-drug resistant TB, or MDR-TB, and faced months in an isolation ward on a regimen of injected drugs that left her nauseous, bruised and unable to go out in the sun.

"My friends were really shocked," Watterson said. "Most of them had only heard of TB from reading Victorian novels."

Tuberculosis is often seen in the wealthy West as a disease of bygone eras - evoking impoverished 18th or 19th century women and children dying slowly of a disease then commonly known as "consumption" or the "white plague".

But rapidly rising rates of drug-resistant TB in some of the wealthiest cities in the world, as well as across Africa and Asia, are again making history.

London has been dubbed the "tuberculosis capital of Europe", and a startling recent study documenting new cases of so-called "totally drug resistant" TB in India suggests the modern-day tale of this disease could get a lot worse.

"We can't afford this genie to get out of the bag. Because once it has, I don't know how we'll control TB," said Ruth McNerney, an expert on tuberculosis at the London School of Hygiene and Tropical Medicine.

International alarm

TB is a bacterial infection that destroys patients' lung tissue, making them cough and sneeze, and spread germs through the air. Anyone with active TB can easily infect another 10 to 15 people a year.

In 2010, 8.8 million people had TB, and the Geneva-based World Health Organization (WHO) has predicted that more than 2 million people will contract multi-drug resistant TB by 2015. The worldwide TB death rate currently runs at between two and three people a minute.

Little surprise, then, that the apparently totally untreatable cases in India have raised international alarm.

The WHO has convened a special meeting on Wednesday to discuss whether the emergence of TB strains that seem to be resistant to all known medicines merits a new class definition of "totally drug-resistant TB", or TDR-TB.

If so, it would add a new level to an evolution over the years from normal TB, which is curable with six months of antibiotic treatment, to the emergence of MDR-TB, then extensively drug-resistant TB (XDR-TB).

What's so frustrating about that progression, says Lucica Ditiu of the WHO's Stop TB Partnership, is that all drug-resistant TB "is a totally man-made disease".

Like other bacteria, the TB bug Mycobacterium tuberculosis can evolve to fight its way past antibiotic medicines. The more treatment courses patients are given and fail to complete, the stronger and more widespread the resistance becomes.

"The doctors, the healthcare workers, the nurses, entire healthcare systems have produced MDR-TB. It's not a bug that has come from nature. It's not a spontaneous mutation. It came about because patients were treated badly -- either with poor quality drugs, or not enough drugs, or with insufficient observation so the patient didn't finish the treatment course," said Ditiu.

Ditiu is somewhat reassured that the WHO is meeting to look at recent extreme cases of drug-resistance, which will at least throw a spotlight on this often-forgotten disease. But she says while definitions are central to international guidelines and treatment protocols, they make little difference to sick people.

"What is much more important is the drama and tragedy of the human beings. Whether it's MDR, XDR or TDR TB, it doesn't make much difference to the patients. A lot of them will face a very, very unfortunate fate."

When the drugs don't work

The situation in India is a case in point.

Dr Zarir Udwadia, a tuberculosis specialist at the Hinduja National Hospital in Mumbai, published a paper in the Clinical Infectious Diseases journal late last year documenting four cases of TDR-TB. He told Reuters he has now identified 12 cases for which he has all but run out of treatment options. Three are already dead.

He has tested one powerful anti-TB drug after another on samples cultured from these patients - including first-line treatments like isoniazid, rifampicin and streptomycin, and a range of second line drugs like moxifloxacin, kanamycin and ethionamide. Each medicine failed.

"If you add it all up, they were resistant to 12 drugs in total," he said.

Like others, Udwadia blames poor medical practice.

Non-prescription and over-the-counter antibiotic use is rife in India and it may be no coincidence that the country now has one of the highest burdens on MDR-TB in the world, with more than 100,000 cases.

Udwadia's team conducted a recent study in Mumbai, home to more than 12 million people often living in harsh and overcrowded conditions, and found in one district only five out of 106 doctors in the unregulated private sector could give a correct prescription for a hypothetical patient with MDR-TB.

Most of the prescriptions were "inappropriate" and would only have made the patient worse - driving the conversion of MDR tuberculosis to XDR and then to TDR tuberculosis.

The Mumbai findings show that totally drug-resistant TB "was an accident waiting to happen," Udwadia said.

"To get to this stage, you have to have amplified resistance over years, with loads of misuse of (antibiotic) drugs. And no other country throws around second-line drugs as freely as India has been doing."


That might suggest countries that use antibiotics more prudently should be less vulnerable. Experts are not convinced, and history suggests otherwise.

One of the biggest difficulties in tackling TB is the ease and speed with which it spreads. When patients cough, sneeze or spit, they propel thousands of germ-carrying droplets into the air around them. With people travelling the world in confined spaces, a disease like TB can easily hitch a ride.

A good example is extensively drug resistant TB, which first hit world headlines during an outbreak in South Africa in 2006. Barely four years later in 2010, the WHO said drug-resistant tuberculosis was at "record levels" worldwide and a total of 58 countries had reported at least one case of XDR-TB.

Ditiu fears a similar pattern could emerge with TDR-TB.

"It is spreading, it's spreading as we speak right now," she said. "The situation is extremely worrying."

Anna Watterson, who took 19 months "out of normal life" for her MDR-TB to be successfully treated but still qualified as a barrister and now works in London's law courts, can't be sure where she picked up her infection.

At the time she was living in the northwest borough of Brent, an area of London with a large immigrant community and pockets of poverty. Like millions of others in the British capital, she commuted on the Tube underground train system most days.

Watterson had also travelled to India a couple of years earlier, and since TB can lie dormant for long periods, it's also possible she may have contracted it there.

"You can't be isolated from the rest of the world," she said. "We've become too complacent about TB, thinking that it's gone away. But the reality is that until it goes away in the developing world, it's not going away anywhere."