Tuberculosis - an old plague comes back stronger
By Honor Mahony
Over the course of two weeks in 2011, Stefan Radut lost seven kilos in weight. He coughed constantly, was chronically tired and had difficulty sleeping. His girlfriend finally persuaded him to go to a doctor.
That's when he discovered he had tuberculosis (TB) - an illness he thought belonged to the history books.
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“I didn’t know anything about this disease. I thought it was eradicated,” says Stefan
But there was a nastier surprise still to come. Stefan, a 24-year old university graduate from Romania, did not just have a normal version of the bacterial lung disease. He had a drug-resistant strain. The first line of antibiotics did not work.
Instead he had to be hospitalised for several months and take a cocktail of drugs which are less effective and which have distressing side effects.
Stefan’s initial reaction to tuberculosis is common. But the Great White Plague - normally associated with 19th century workhouses - was never fully beaten.
And now several eastern European countries are fighting an epic battle against a tuberculosis that has mutated into a more deadly form.
That they succeed in this battle is of direct relevance to all Europeans. And in some countries, success is not guaranteed.
Collapse of the Soviet Union
The seeds that enabled Stefan to catch drug-resistant TB were probably sown just over 20 years ago, when the Soviet Union collapsed.
The world watched in amazement as 15 countries emerged from the Soviet yoke. But the liberation was matched by a complete breakdown in the public health care system.
This breakdown triggered a sharp rise in TB cases.
Normal TB is almost always treatable (left untreated it kills around half of those it infects), although it is crucial to stay the six-month course of treatment.
But in the territories of the former Soviet Union there was suddenly no nurses to chivvy people into taking the full course of antibiotics. Unregulated pharmacies sold the expensive drugs without prescriptions and in dubious combinations.
TB patients simply stopped taking the pills when they felt better - long before the half-year treatment time was up. Or they took the wrong medication from the beginning.
This allowed naturally-mutating bacteria to evolve to fight the drug. When patients fell ill with TB for a second time, it was with a resistant strain.
This toxic combination of circumstances took the three Baltic states to the brink of an uncontrollable outbreak towards the end of the 1990s.
Outside help as well as commitment at home have recently seen the countries - particularly Estonia and Latvia - make headway with the problem.
“Although the Baltics are politically well-committed we are still paying for the mistakes of the past,” says Giovanni Battista Migliori, director at the World Health Organisation (WHO) Collaborating Centre for TB and Lung Diseases in Italy.
The misuse of antibiotics has led not only to a TB that is resistant to some forms of drugs but also to an extreme drug-resistant version, able to fight off almost all the weapons in the anti-TB war-chest.
Multi-drug-resistant TB (MDR-TB) is resistant to at least two first-line drugs - isoniazid and rifampicin. Extreme drug-resistant TB (XDR-TB) is resistant to those two drugs as well as fluoroquinolones (broad-spectrum antibiotics) and one of three injectable antibiotics.
All types are caught the same way - through the air.
Stefan and Andreea
That it has been eradicated is one part of the myth surrounding TB. Another is that only poor people get it.
The disease is not choosy. All that is needed is enough time in a badly ventilated room with a TB sufferer.
Stefan does not know where he got it. “I breathe and so I contracted it,” he says.
He was first diagnosed with normal TB. But some time later he was called back to the clinic and told that he had a resistant strain. This led to a three and half month stay in hospital with a daily regime of 18 tablets and an injection.
He has to steel himself each time. Going to sleep at night is a relief because it means being one day closer to the end of treatment.
“The side-effects are harsh headaches, joint pains, feelings of paranoia, nausea and irreversible hearing damage," Stefan says.
His treatment will continue until May this year. After this he will try to pick up the threads of his life again - getting married and trying to find a job.
Andreea Vladoi has a similar story. Also Romanian, the 24-year-old used to be a professional gymnast. She went to college, graduated, worked in a circus. At some stage, the bacterium found its way into her body.
Like Stefan, she was initially treated for normal TB. She was in her words a “conscientious” patient. She finished the treatment after six months but soon started coughing again.
“The doctor said to me that maybe I had MDR-TB from the beginning but she didn’t know. I had to start the treatment again for two years,” she says.
“It was much harder this time round. I thought I would die taking the pills. The body does not get used to it. For two or three hours after taking them I couldn’t walk. I would sit and watch the wall. I didn’t dare to move in case I threw up the treatment. You can’t understand it if you haven’t taken it yourself,” she adds.
Both Andreea and Stefan consider themselves relatively lucky. They had some financial support and, almost as important, some loved ones to help them through the harsh treatment.
Romania - “medical urgency”
This contrasts with many other Romanian TB suffers.
The country has the highest number of TB cases in the EU. And the highest number of drug-resistant cases, with about 1,000 to 1,200 diagnosed every year.
“Almost every second TB patient in the EU is from Romania,” notes Dara Masoud, Europe advisor on TB for the WHO.
Meanwhile, fewer than two out of 10 patients are cured of the multi-drug-resistant strain, even after undergoing the full course of treatment.
Gina Popescu, head of Romania’s TB programme, says the issue is one of “medical urgency.”
She notes that 27-28 percent of patients suffering from drug-resistant TB abandon their treatment early. One TB sufferer, if left untreated, can infect up to 15 people in one year.
Compounding the problem is the fact it takes months - rather than the days in other member states - to get the right diagnosis.
Even with a correct diagnosis, the money is sometimes missing to supply the right drugs.
“It costs $50 to $60 per month to treat TB,” says Masoud. With MDR-TB (muti-drug-resistant TB), this can become $7,000 dollars.
Extreme drug-resistant TB can cost up to $20,000 a month.
The lack of money produces a lottery effect when it comes to treatment in Romania. You may be lucky and get the right drugs. But then again you may not be.
“This is a death sentence,” says Cataline Constantin, whose association (ASPTMR) looks after MDR patients, including Stefan.
“Because if we don’t have enough drugs for the treatment, who chooses who is living and who is dying?” she asks.
A regular complaint is that the Romanian authorities are not taking the problem seriously enough. They have been told in as many words by outside experts. Their own experts say the same.
“They are not aware of the seriousness of the problem,” says Popescu.
Doesn’t affect me, or does it?
If the Romanian political class does not get the seriousness of having a rising number of patients with an antibiotic-resistant disease, then it could, given time, become everyone’s problem.
Because people travel.
Half of drugs-resistant TB patients in the Netherlands are from Romania, says Popescu.
Guido Groenen, who deals with multi-drug-resistant tuberculosis in Belgium, notes that patients with drug-resistant TB in the EU capital are generally from eastern Europe, particularly Chechnya.
“In the former Soviet Union, they have been using all kinds of drugs for 10 or 20 years. So they have, more or less, created this problem," he notes.
Migliori, the Italian WHO expert, says: “Every year we have three or four people coming to Italy and dying. The cases are completely unmanageable - resistant to all drugs.”
He adds: “On their way here, they take a flight, a train and then they are in the hospital and sometimes they escape from hospital. So in a couple of years we will see other migrants or Italians appearing with this strain. At the moment this is sporadic, but it is happening in a consistent manner.”
A tale of two TBs
For the EU it is a tale of two TBs. The number of cases of normal TB is declining steadily each year, according to the European Centre for Disease Prevention and Control (ECDC), an EU body monitoring the 27 member states.
But the proportion of multi-drug-resistant TB, though still negligible in western Europe, is going up. In 2008, 23 of the 30 ECDC states registered MDR-TB cases. Of the 27 high-burden countries listed by the WHO, 15 are in Europe, a loose category that includes Kazakhstan, Russia and Belarus. Four are in the EU.
“I think the problem we see in European states is that we are able to control normal TB quite reasonably. But we see an increase in cases of MDR-TB and XDR-TB in areas where there are hardly any drugs to treat people,” says Gerard de Vries, from KNCV, a Dutch Tuberculosis foundation.
His own country sees about 15 multi-drug-resistant cases each year.
Meanwhile, if certain EU states - the Baltic countries, Bulgaria and Romania – worry tuberculosis experts, counties bordering the EU make them blench.
Belarus, running alongside Poland, has the highest rate of drug-resistant tuberculosis in the world. There, nearly one in two TB patients has the more virulent strain.
In Ukraine it is one in five. In Moldova, according to WHO estimates in 2010, there are 1,700 cases of drug-resistant TB. But less that half are being treated. In Russia, it is estimated there are 31,000, with just 13,700 getting treatment.
“It is imperative that we invest in the countries that are on the border now,” says Migliori.
“Without investment in proper health care infrastructure, there is a risk that at a certain moment, this will be come unmanageable,” he adds.
The re-emergence of TB
The disease itself has been around for many hundreds of years. It is one of the world’s leading killers, taking 1.4 million lives in 2011.
Around a third of the world’s population is estimated to have a latent form of the disease.
The first modern TB epidemic occurred during the Industrial Revolution in the 1700s. The great urban migration, where people flocked to cities to find work created the ideal conditions - people with malnutrition living in cramped spaces - for the disease to spread.
Numbers went down with increased hygiene practices and better medicine.
By the mid-1980s, policy-makers in the West were talking about its eradication.
But then came HIV. People with latent TB are up to 30 times more likely to develop full-blown TB if they are HIV positive. The number of TB cases shot up. Treatment mismanagement led to the resistant strains.
In 1993 the WHO labelled tuberculosis a global emergency. The European Centre for Disease Prevention and Control, for its part, started monitoring and collecting TB data from its member states in 2008.
But although health experts were agitated about the disease, vaccines, treatments and diagnostics remained decades-old - in large part due to the fact that pharmaceutical companies see it as a disease with little profit potential.
Drugs introduced over 50 years ago still form the basis of treatments today.
The vaccine - Bacillus Calmette-Guerin (BCG) - was first used in the 1920s (it is effective mainly against childhood TB.)
“Vaccines are extremely difficult to make. The BCG is almost 100 years old. That’s incredible when you think about it. But TB is one of those really difficult diseases,” says Hannu Laang, from the European Commission’s research department.
He notes that the EU is the global leader in vaccine research. Still, the recent results of highly-anticipated vaccine trial in South Africa, led by Oxford University researchers, was a disappointment.
There are drugs – three at clinical phase - in the pipeline. But without fixing the health infrastructure, so that TB sufferers get the correct treatment and keep taking it to the end, then in places like Belarus strains resistant to these drugs will build up very quickly
“In 10 years we will lose resistances to these three new drugs too and then for another 20 years we won’t have anything,” points out Migliori.
There is never a good time to make the case that politicians should be spending more money on public health care, and allowing free treatment for everyone, including migrants, for the greater good of society.
Right now, in the midst of an economic crisis, this is truer than ever
But the cuts in public spending in several EU countries have already got TB experts worried.
“We are looking closely at all the countries that suffer most in the economic crisis, so the southern European countries - Greece, Spain, Italy and Portugal,” says Marieke van der Werf, head of the tuberculosis programme, at the European Centre for Disease Prevention and Control.
She notes that they have data from 2010. The financial crisis really started in 2008. “For TB you do expect that it takes a couple of years before you really see something,” she adds. New data will be released in March this year.
Andra Cirule, a pulmonologist at the TB and lung disease clinic in Latvia, which implemented some of the harshest austerity measures in the EU, shares the same concern.
“People are poor. They don’t go to doctors because they think it is necessary to pay for a visit. But for TB, it’s not,” she says.
She has noticed a slight increase in cases when she compares data from this year with the same period last year.
“I think this is because of the economic crisis. I thought to myself two years ago already, there will be an increase in TB,” she notes.
Van der Werf says that surveillance data from 2010 does not show an increase. This can be down to two things.
“Either it is due to good news and there really is no increase and they are still keeping up their TB-control activities. The other explanation could be that the health system has really collapsed,” she adds.