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Wall Street Journal
At Europe's Doorstep, Fierce War Against TB

<p>Gautam Naik</p>


December 31, 2012

TARTU, Estonia - All along the edges of Western Europe, new and hard-to-defeat strains of tuberculosis are gaining a foothold, often moving beyond traditional victims - alcoholics, drug users, HIV patients - and into the wider population.

Which is why Irina Nikolajeva, a petite 34-year-old former furniture saleswoman, spent the better part of four months in virtual lockdown here last year. She was resistant to all but one of 10 TB drugs. Nobody could figure out how she even caught the disease.

"NAKKUSOHT!" declared a bright red sign just steps from her tiny, bare isolation room. "DANGER OF INFECTION!" To see her 18-month-old daughter, she initially needed Skype. "I could see my child running around at home," Ms. Nikolajeva recalled. "She'd say, 'Hello, Mama.' "

Estonia's aggressiveness - and only recently, its success - in turning the corner against drug-resistant TB offers one of the few bright spots globally as the ancient plague mutates into new and more deadly forms. Indeed, experts say the country, with half the population of Chicago, could be a model for others. But there is one catch: It takes years and some pricey treatments just to gain the upper hand.

"The easy ones are treated," said Martin Kadai, a public health adviser at Estonia's ministry of social affairs. The toughest patients, he said, remain.

In Western Europe, drug-resistant strains of TB are starting to make a wider appearance. Last year, Britain reported 421 cases of drug-resistant TB, a 26% jump from the previous year. Most Western Europe cases can be traced to the TB-wracked eastern half of the continent. (In contrast, there were 124 case of drug-resistant TB in the U.S. in 2011.)

Nearby nations, including Serbia, Kosovo, Montenegro and hard-hit areas in Russia, have sought Estonian advice in their own fight against the disease - and they need it. The 15 countries of the former Soviet Union, as well as Romania, Bulgaria and Turkey, together harbor more than 85% of TB cases, and 96% of multidrug-resistant tuberculosis, or MDR-TB, found in Europe, according to the World Health Organization.

"Eastern Europe is in a disastrous situation with MDR-TB and it risks compromising anything you can do" globally, said Mario Raviglione, who has led the WHO's TB program for nearly a decade.

At least 30% of all new TB cases in Eastern Europe are now resistant to key front-line drugs. The equivalent official rate is 6% for China and 2.1% for India, though the latter is probably an underestimate. (In absolute numbers, India and China have far more multidrug-resistant cases because of their larger populations.)

"There are no borders" for tuberculosis, said Masoud Dara, the WHO's TB adviser for Europe, based in Denmark. Several countries in the region lack resources for strong TB programs, he said.

A key part of Britain's response to multidrug-resistant TB is a "virtual electronic committee" that puts the details of newly diagnosed cases on a secure website to be shared with some doctors. Inspired partly by Estonia's approach, the system was crafted by a group of TB experts who became worried about the rise in British TB cases.

The system isn't yet recognized by the U.K.'s National Institute for Health and Clinical Excellence, or NICE, which sets medical guidelines. Because of that, it captures only half of all multidrug-resistant cases in Britain, said Peter Davies, a physician at the Liverpool Heart and Chest Hospital and founder of the MDR-TB committee. "We need NICE to recognize the service," he said. "But I don't see how this is going to happen in the next year or two."

A spokeswoman for NICE said it doesn't usually set guidelines for such projects. In an emailed response, a spokesman for the U.K.'s department of health said that, "despite the rise in cases, drug-resistant strains of TB are still relatively uncommon in the U.K."

Meantime, along the edges of Western Europe, the expansion of TB among low-risk patients - such as Ms. Nikolajeva here in Estonia - is raising alarms. About 40% of Estonians were apparently healthy when they got infected, just as she was.

As part of the country's efforts to rein in the disease, its doctors can under a 2003 law forcibly hospitalize infectious TB patients, which they did about 10 times in 2012. In her case, Ms. Nikolajeva agreed to her hospital stay. She was confined for four months in isolation, in a sparsely furnished room that resembled a prison cell and was painted a gloomy green. Yet it is the country's unusually harsh regimen of confinement and intensive drug treatment that has helped dramatically slash the number of cases of drug-resistant TB here.

Ms. Nikolajeva received up to six drugs a day, including one by injection. During that time, she occasionally did get to see her husband and their infant daughter, but the meetings had to occur away from her room, in the open air. Tuberculosis is most easily transmitted by inhaling the bacteria that cause it.

If doctors hadn't hospitalized Ms. Nikolajeva in isolation, "she could have infected even more people in society," said Manfred Danilovits, a doctor involved in her care and an architect of Estonia's TB strategy.

The effort has helped the tiny nation stage an effective comeback against both regular TB and multidrug-resistant strains. As recently as 1998 Estonia was one of the leading exhibits in TB's global hall of shame, reporting 824 cases of all types of TB, a very high level for a relatively prosperous country of only 1.3 million people.

For 2012, the Baltic nation expects to reduce the number of overall TB cases to fewer than 300, and multidrug-resistant cases to 45 from about 100 in 1998. As a result, Estonia is now on the verge of becoming a "low incidence" TB country, according to criteria set by the World Health Organization.

Estonia's efforts to tame TB are by no means over. About half of the new TB patients each year suffer from alcoholism, drug abuse or HIV, making them the toughest cases.

Nonetheless, "Estonia has done it right," said Lee Reichman, a TB expert and professor of medicine at New Jersey Medical School in Newark, N.J., who has studied the country's TB program. "They made TB a priority."

Some 8.7 million people world-wide fell ill with TB last year and 1.4 million died, the vast majority of them in poorer countries. After HIV, tuberculosis is the second-biggest killer world-wide that can be attributed to a single infectious agent.

While Estonia and other countries in the region were under the boot of the Soviet empire, TB was relatively rare. But after the U.S.S.R. collapsed in the early 1990s, the health system foundered. Many patients stopped following the proper TB-drug regimen. That bred mutant resistant strains. Within a few years, Estonia faced a public-health emergency.

The response got kick-started in the mid-1990s when neighbors including Finland, Sweden, Denmark, Norway and Iceland - fearful that TB would spill into their territory - offered help. Then Estonia embarked on bolder, homegrown initiatives.

Estonia banned pharmacies from selling TB drugs, in order to prevent patient misuse that can fuel drug-resistance. India is now planning a similar strategy to fight its own TB problem.

All TB-related drugs and hospital stays are now provided free to patients by the government. Estonia benefits from a TB drug-purchasing arrangement it has with the WHO, but it still costs up to $5,000 to treat an MDR patient over a two-year period. In countries that don't have such arrangements, the tab can reach $10,000 or more.

Also in place is a WHO-promoted plan that encourages patients to come to clinics and take their daily dose of TB drugs under the watchful eye of a health worker. This is to ensure that people stick to the regimen. Missing even a few treatments can allow drug-resistance to build. A patient who follows the regimen for a week is rewarded with a €10 voucher, worth about $13, that can be used to buy various things (but not alcohol).

One of Estonia's toughest challenges is treating difficult patients who either don't know they are infected or who simply won't follow their drug regimen. About 45% of the country's TB patients, for example, have alcohol or drug problems. So now, when people come in for addiction treatment, they automatically get tested for TB, too, in hopes of catching the sick earlier.

The country has also revamped its creaky Soviet-era lab network with state-of-the-art equipment. On a recent morning, at one of the main TB labs at Tartu University Hospital, a technician used a microscope to study a new patient's sputum sample. A smattering of fluorescent orange spots could be seen, indicating TB.

The sample would later be placed in another machine for testing against a range of drugs. That step would indicate if the patient had regular TB or the drug-resistant variety. The lab boasts a costly machine, GeneXpert, that can diagnose TB and identify a common type of drug resistance in two hours, compared with older systems that take days.

Estonia is ahead of many countries in this regard. In the U.S., for instance, the device doesn't yet have regulatory approval for use on TB. India is only beginning to install GeneXpert machines.

Also central to Estonia's TB effort is the close attention paid to every case. Once a month, a half-dozen TB doctors from across the country gather to discuss patients. Recently, the group assembled in Tartu to go over 35 cases. One was a 51-year-old man with drug-resistant TB. Fed up with being in isolation, he walked away before the treatment was finished.

On a laptop, Dr. Danilovits displayed an X-ray of the man's lung, marked with telltale signs of the disease. The man had been rehospitalized, he said, "But the response hasn't been good so far."

In June of last year, Ms. Nikolajeva, the young woman with the toddler daughter, came down with severe bouts of coughing and a weeklong fever. A friend persuaded her to see a doctor, who suspected pneumonia and prescribed antibiotics.

Ms. Nikolajeva felt no better. Her weight fell to 101 pounds from 114 pounds, according to Lea Pehme, another doctor closely involved in Ms. Nikolajeva's care. In August, after several more tests - X-rays, a skin test and a bronchoscopy - she was finally diagnosed with an especially severe type of multidrug-resistant TB: She was resistant to all but one of 10 drugs.

Her husband and daughter tested negative. "I thought I might not be cured, I might die," said Ms. Nikolajeva.

Her doctors, too, were "pessimistic," said Dr. Danilovits, who oversaw her treatment. If all drugs fail, doctors sometimes have no option but to stop providing them entirely. At that stage, there is almost nothing more that can be done.

Ms. Nikolajeva was sequestered in a tiny room in the 25-bed TB hospital in Tartu. She didn't like the idea of being in isolation. "But I was terrified that if I went home, I would infect my child," she said.

Too unwell to read, Ms. Nikolajeva passed the time watching a small hospital-supplied TV placed on the window sill. After six weeks, Ms. Nikolajeva was allowed a visit with her husband and daughter. They took a walk in a nearby park.

Ms. Nikolajeva received five or six drugs each day. The powerful medications made her weak and nauseated. One powdered medicine she found especially repulsive. "I would put it on the table and stare at it for 15 minutes" before taking the plunge, she recalled.

One day, a new patient arrived in the room next door. She had two children, including a newborn. But her family lived 200 kilometers away.

"I helped her get through the initial shock of being isolated," said Ms. Nikolajeva. "We discussed baby matters."

The new patient taught Ms. Nikolajeva to knit. Ms. Nikolajeva crafted a summer hat for her daughter. "I didn't know the size," she said. "I later found out it was too small."

A year ago in November, Ms. Nikolajeva left the hospital. The TB had largely cleared from her lungs, and she was no longer deemed to be infectious to others. She had regained some weight.

In about three months' time, provided all goes well, she can stop taking the drugs. It will mark the end of a treatment odyssey that will have lasted two years.

On a recent morning, as snow fell in whispers and winter tightened its grip on this northern nation, Ms. Nikolajeva returned to the clinic to take her daily dose of TB medicines. There, she popped a series of pills and signed a register, with a nurse watching on.

"It was great to pack up my things and finally go home," Ms. Nikolajeva said. "But there was no celebration."

Write to Gautam Naik at gautam.naik@wsj.com



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