Resilient TB Strains Thrive in Kyrgyzstan
Unsound medication practices are creating increasingly incurable strains of tuberculosis, in a society ill-equipped to cope.
Resilient TB Strains Thrive in Kyrgyzstan
Unsound medication practices are creating increasingly incurable strains of tuberculosis, in a society ill-equipped to cope.
If you catch tuberculosis in the Kyrgyz capital Bishkek, the risk is higher than anywhere else in the world that it is a strain resistant to the best drugs available.
The main sources of drug-resistant TB strains in the world – abbreviated therapy and insufficient medication – have become almost routine practice in the Kyrgyz healthcare system. The resulting hardier strains of TB become extremely difficult to treat and spread in the community.
“I am pretty much immune to all of the drugs I am taking now, except Kanamycin,” said Mikhail, 38, one of an estimated 1,300 to 3,500 people in Kyrgyzstan now suffering from drug-resistant or even multi-drug resistant (known as MDR) tuberculosis.
After ten years of donor engagement, Kyrgyzstan is slowly getting the upper hand in the battle against the standard tuberculosis. These efforts have stabilised and brought down the annual incidence of new cases from 128 per 100,000 people to 109 over a period of seven years.
But according to the preliminary findings of a World Health Organisation, WHO, committee, 26 per cent of the new cases recorded in Bishkek in 2007 were resistant to at least the two most powerful TB drugs — Isoniazid and Rifampicin.
This statistic is the worst ever recorded for drug-resistant TB. A recent WHO report listed Azerbaijan's capital Baku and Moldova as having the highest incidence of MDR strains, at 22 and 19 per cent, respectively. Several countries were left out of the study due to lack of reliable data.
What is more, the special drugs needed to treat MDR strains have always been absent or extremely scarce in Kyrgyzstan, due to the complexity and expense of the cure.
In the three-room flat he shares with his parents, Mikhail rummages through a plastic bag full of vials and pill boxes. He improvises his own treatment, with drugs he gets from contacts in Kazakhstan and Russia.
The alternative is grim — without medication, half of tuberculosis sufferers will die within two years, experts say, and the chances are even worse for MDR patients.
However, do-it-yourself treatments also risk killing the patient, and can give the TB greater immunity.
Every day, Mikhail takes four tablets of Pyrazinamide, one of five drugs that are routinely combined in a six-month therapy to treat ordinary TB. He also takes the antibiotics Kanamycin and Ofloxacin.
These are classed as “secondary” drugs, used when one or several of the standard substances are useless. But therapy with these less effective drugs may take 24, possibly up to 36 months, and it can also set off severe adverse effects requiring supervision and individual care.
The subsidised world market price for a full standard course of treatment for drug-resistant strains is presently 4,600 US dollars compared with some 50 dollars for the treatment of ordinary TB.
Certain drugs are inexpensive — Ofloxacin costs 600 soms or 15 dollars for a month-long supply — and available without prescription in Kyrgyz pharmacies, to people such as Mikhail.
”To be honest, I have lost confidence in the doctors. If I were to follow their advice, I would have been long gone. So I improvise a treatment according to what feels good for me,” he said.
But treating TB with too few medicines, or with types that are not effective against a particular strain, as Mikhail is doing, is precisely what breeds drug-resistant TB in the first place. The normal bacteria are killed while those which have accidentally mutated to a resistant form survive, multiply and become the dominant strain in the patient.
Doing this repeatedly can create further resistance to the point where no drugs are effective. A laboratory in Germany recently identified the first ever Kyrgyz case of this kind, defined as “XDR”.
XDR is increasingly feared in developed countries. While TB is a social disease which mainly threatens people with ailing immune systems in developing countries or among risk-groups, XDR TB can be impossible to treat wherever it is found.
CHAOTIC TREATMENT METHODS
It is not just patients who are creating ad hoc treatments and thereby unwittingly generating MDR strains. Not far from Mikhail’s home in a southern suburb of Bishkek, the country’s foremost TB experts have been doing much the same for years.
Kyrgyzstan’s National TB Centre consists of a cluster of pink stone buildings surrounded by a park. Here, Doctor Atyrkul Toktogonova is responsible for treating the country's MDR TB population.
It was not until November 2005 that she was given the range of medicines she needed, under a project funded by the Global Fund to Fight AIDS, Tuberculosis and Malaria, a part-public, part-private body. Even then, it was only a pilot project covering 100 patients, a number which doctor Toktogonova was able to stretch to 154.
With nothing left over for the thousands others needing help, she started treating them with whatever appropriate medicines she could find, hoping they might be enough for a cure or at least to prolong the patient’s life.
”We are doctors and if a patient looks at us with hope and asks for help, well, we put in what we can,” she said, closing the door to her office.
In the hallway outside, coughing men and women from all over the country were gathered in hope for treatment.
Outside the pilot project, she was only able to obtain two out of the four or five substances needed, and even these came in such small quantities that she could help only a few patients, 313 since 2004, and only for six months, instead of 24. The patients were encouraged to buy more medicines themselves to obtain the right combinations of drugs for the full period of treatment.
”Sure, we have violated the treatment principles a bit,” said Dr Toktogonova. “We know that to get good results, we should put in a minimum of four or five new substances. But for the sick, life is going by. And we have to save them.”
Dr Toktogonova says some of the people she treated by this method are now cured, but she admits many will have developed further resistance and died.
From a public health perspective, these ”budget” therapies are a catastrophe.
Dominique Lafontaine, until recently in charge of a Doctors Without Borders, MSF, team working on the TB epidemic in Kyrgyzstan's prison system, acknowledges there is an ethical dilemma here, but insists nevertheless that improvised treatments are wrong.
”Don't start any antituberculosis programme, if you are not sure to do a good programme. You will select those [bacteria] which are resistant to these drugs, and then you will spread this strain in the community,” said Lafontaine.
DOCTORS BREAK THEIR OWN RULES
The dangers were recognised in an order issued by Kyrgyzstan’s National TB Programme Director Aftandil Alisherov in May 2006, instructing doctors to refrain from "chaotic prescription and use of second-line TB drugs in the treatment of chronically ill TB patients”.
Alisherov is aware the treatment at the TB centre is wanting. arding responsible treatment.
"We give full treatment to only about 100 people. For some of the rest, we buy two or three substances from the budget. Those who wish buy other substances, for their own money…. And they write complaints to the ministry, and we have to explain that the state lacks the funds," he told IWPR.
Alisherov did not comment on how these practices fit with his own prohibition of such treatment.
IWPR approached his second-in-command, Bakyt Myrzaliev, who said he was unaware of these "budget" therapies and said they would be unlawful.
"The purchase of second-line substances alongside official supply lines is forbidden,” he said.
Oskon Moldokulov, the WHO representative in Bishkek, said he had heard about the partial treatments, but that he “did not think it involved this many patients”. He promised to take a closer look at the situation and take it into account when future decisions were being made on WHO support.
“Such treatment is an enormous risk. You can create virtually incurable diseases,” he said.
HUMAN ERROR ADDS TO THE RISKS
In April or May, Kyrgyzstan is expecting the first major shipment of high-quality second-line drugs, enough for some 1,780 MDR TB patients over five years.
"We are waiting, and the patients are too. As soon as these drugs arrive, we will be able to convert all insufficient therapies into adequate ones," said Dr Toktogonova.
Once these pharmaceuticals start arriving, they will theoretically wipe out the backlog of MDR TB patients as well as the new 560 cases believed to arise annually.
The challenge will be to ensure that the correct drugs are used properly. In the first two years of the MDR TB pilot project, only 60 per cent of patients actually completed the full length of treatment, Dr Toktogonova said.
One problem is the shortage of trained medical staff, as many leave the country in search of a better wage than the 90 dollars a month an experienced family doctor can expect to earn in Kyrgyzstan.
“There is a brain drain of TB personnel,” said Maxim Berdnikov of the International Committee of the Red Cross in Kyrgyzstan. “In Kazakhstan and Russia, the salaries are five to ten times higher. In some places in the south, there are no lab technicians left to diagnose the disease, and hospitals are running empty.”
Another obstacle will be patient motivation. Shamyrza Amankulov, a 52-year old resident of the Issyk-Kul region, has interrupted and resumed his treatment more times than doctors can count.
IWPR interviewed him in the MDR ward at the National TB Centre, where he had been transferred after many months of treatment.
He believes he knows better than the doctors at times. “I have left treatments when I have thought they give me the wrong treatment. Last winter ,they gave me first-line medication for four months — that was completely wrong,” he said.
As for others who disrupted their treatment, he explained, “Maybe people don't understand fully that this is a serious disease. Some people say you get better if you eat dog or badger meat.” Amankulov tried such folk-medicine methods himself but admitted they did not help.
In early April, following this interview, Amankulov again broke off his treatment.
Dr Toktogonova has had difficulty in making even the lucky few patients who were included in the pilot project stay on the treatment.
During the interview, she received a phone call from a 22 year old man who wanted to come back after stopping his treatment just two months before full recovery.
”His relatives didn't do anything about it and his district doctor had quit, so none could find him,” she said. ”His lungs are not yet destroyed. But he must begin the entire treatment again, and perhaps for 36 months instead of 24.”
Toktogonova says TB can return and further resistance can develop when therapy is halted prematurely.
”It always comes back, of course — stronger and with resistance to second-line medicines. Then we have nothing left to treat with, and then the patients die,” she said.
She has launched a series of seminars to teach medical staff all over the country about the dangers of mistreatment.
“I am in a state of terror as I watch how our doctors prescribe substances and create XDR,” she says.
The National TB Programme has recognised the danger of poor adherence to treatment and is scrambling to improve matters in time for the arrival of quality drugs.
To minimise the number of drop-outs, Toktogonova said, treatment has been reformed into a four-stage model with six months each spent in intensive care, a rehabilitation home outside the city, an open ward near Lake Issyk-Kul and finally treatment at home.
"This has already brought the number of therapy violations down from some 24 every month to a mere four," she says, commenting on the reform’s impact on the existing MDR pilot project.
Other measures may include food packages for TB patients and better pay for doctors. The National TB Programme headed by Alisherov has applied to the Global Fund to Fight AIDS, Tuberculosis and Malaria for 40 million dollars, half of it to pay for food packages that would be distributed to patients every day they show up for their medication, and the rest to go on raising health service salaries.
If approved, the money will not arrive until the summer of 2009.
Despite all the investment and effort, Alisherov says only rising living standards in Kyrgyzstan will ultimately decide the battle against the TB pandemic.
”If the economy stays at this level, we won't beat TB. I say this openly. It will remain where it is now. Perhaps the numbers will go down a little, but it will remain,” Alisherov concludes.
Andreas Hedfors is a freelance journalist in Bishkek.
The main sources of drug-resistant TB strains in the world – abbreviated therapy and insufficient medication – have become almost routine practice in the Kyrgyz healthcare system. The resulting hardier strains of TB become extremely difficult to treat and spread in the community.
“I am pretty much immune to all of the drugs I am taking now, except Kanamycin,” said Mikhail, 38, one of an estimated 1,300 to 3,500 people in Kyrgyzstan now suffering from drug-resistant or even multi-drug resistant (known as MDR) tuberculosis.
After ten years of donor engagement, Kyrgyzstan is slowly getting the upper hand in the battle against the standard tuberculosis. These efforts have stabilised and brought down the annual incidence of new cases from 128 per 100,000 people to 109 over a period of seven years.
But according to the preliminary findings of a World Health Organisation, WHO, committee, 26 per cent of the new cases recorded in Bishkek in 2007 were resistant to at least the two most powerful TB drugs — Isoniazid and Rifampicin.
This statistic is the worst ever recorded for drug-resistant TB. A recent WHO report listed Azerbaijan's capital Baku and Moldova as having the highest incidence of MDR strains, at 22 and 19 per cent, respectively. Several countries were left out of the study due to lack of reliable data.
What is more, the special drugs needed to treat MDR strains have always been absent or extremely scarce in Kyrgyzstan, due to the complexity and expense of the cure.
In the three-room flat he shares with his parents, Mikhail rummages through a plastic bag full of vials and pill boxes. He improvises his own treatment, with drugs he gets from contacts in Kazakhstan and Russia.
The alternative is grim — without medication, half of tuberculosis sufferers will die within two years, experts say, and the chances are even worse for MDR patients.
However, do-it-yourself treatments also risk killing the patient, and can give the TB greater immunity.
Every day, Mikhail takes four tablets of Pyrazinamide, one of five drugs that are routinely combined in a six-month therapy to treat ordinary TB. He also takes the antibiotics Kanamycin and Ofloxacin.
These are classed as “secondary” drugs, used when one or several of the standard substances are useless. But therapy with these less effective drugs may take 24, possibly up to 36 months, and it can also set off severe adverse effects requiring supervision and individual care.
The subsidised world market price for a full standard course of treatment for drug-resistant strains is presently 4,600 US dollars compared with some 50 dollars for the treatment of ordinary TB.
Certain drugs are inexpensive — Ofloxacin costs 600 soms or 15 dollars for a month-long supply — and available without prescription in Kyrgyz pharmacies, to people such as Mikhail.
”To be honest, I have lost confidence in the doctors. If I were to follow their advice, I would have been long gone. So I improvise a treatment according to what feels good for me,” he said.
But treating TB with too few medicines, or with types that are not effective against a particular strain, as Mikhail is doing, is precisely what breeds drug-resistant TB in the first place. The normal bacteria are killed while those which have accidentally mutated to a resistant form survive, multiply and become the dominant strain in the patient.
Doing this repeatedly can create further resistance to the point where no drugs are effective. A laboratory in Germany recently identified the first ever Kyrgyz case of this kind, defined as “XDR”.
XDR is increasingly feared in developed countries. While TB is a social disease which mainly threatens people with ailing immune systems in developing countries or among risk-groups, XDR TB can be impossible to treat wherever it is found.
CHAOTIC TREATMENT METHODS
It is not just patients who are creating ad hoc treatments and thereby unwittingly generating MDR strains. Not far from Mikhail’s home in a southern suburb of Bishkek, the country’s foremost TB experts have been doing much the same for years.
Kyrgyzstan’s National TB Centre consists of a cluster of pink stone buildings surrounded by a park. Here, Doctor Atyrkul Toktogonova is responsible for treating the country's MDR TB population.
It was not until November 2005 that she was given the range of medicines she needed, under a project funded by the Global Fund to Fight AIDS, Tuberculosis and Malaria, a part-public, part-private body. Even then, it was only a pilot project covering 100 patients, a number which doctor Toktogonova was able to stretch to 154.
With nothing left over for the thousands others needing help, she started treating them with whatever appropriate medicines she could find, hoping they might be enough for a cure or at least to prolong the patient’s life.
”We are doctors and if a patient looks at us with hope and asks for help, well, we put in what we can,” she said, closing the door to her office.
In the hallway outside, coughing men and women from all over the country were gathered in hope for treatment.
Outside the pilot project, she was only able to obtain two out of the four or five substances needed, and even these came in such small quantities that she could help only a few patients, 313 since 2004, and only for six months, instead of 24. The patients were encouraged to buy more medicines themselves to obtain the right combinations of drugs for the full period of treatment.
”Sure, we have violated the treatment principles a bit,” said Dr Toktogonova. “We know that to get good results, we should put in a minimum of four or five new substances. But for the sick, life is going by. And we have to save them.”
Dr Toktogonova says some of the people she treated by this method are now cured, but she admits many will have developed further resistance and died.
From a public health perspective, these ”budget” therapies are a catastrophe.
Dominique Lafontaine, until recently in charge of a Doctors Without Borders, MSF, team working on the TB epidemic in Kyrgyzstan's prison system, acknowledges there is an ethical dilemma here, but insists nevertheless that improvised treatments are wrong.
”Don't start any antituberculosis programme, if you are not sure to do a good programme. You will select those [bacteria] which are resistant to these drugs, and then you will spread this strain in the community,” said Lafontaine.
DOCTORS BREAK THEIR OWN RULES
The dangers were recognised in an order issued by Kyrgyzstan’s National TB Programme Director Aftandil Alisherov in May 2006, instructing doctors to refrain from "chaotic prescription and use of second-line TB drugs in the treatment of chronically ill TB patients”.
Alisherov is aware the treatment at the TB centre is wanting. arding responsible treatment.
"We give full treatment to only about 100 people. For some of the rest, we buy two or three substances from the budget. Those who wish buy other substances, for their own money…. And they write complaints to the ministry, and we have to explain that the state lacks the funds," he told IWPR.
Alisherov did not comment on how these practices fit with his own prohibition of such treatment.
IWPR approached his second-in-command, Bakyt Myrzaliev, who said he was unaware of these "budget" therapies and said they would be unlawful.
"The purchase of second-line substances alongside official supply lines is forbidden,” he said.
Oskon Moldokulov, the WHO representative in Bishkek, said he had heard about the partial treatments, but that he “did not think it involved this many patients”. He promised to take a closer look at the situation and take it into account when future decisions were being made on WHO support.
“Such treatment is an enormous risk. You can create virtually incurable diseases,” he said.
HUMAN ERROR ADDS TO THE RISKS
In April or May, Kyrgyzstan is expecting the first major shipment of high-quality second-line drugs, enough for some 1,780 MDR TB patients over five years.
"We are waiting, and the patients are too. As soon as these drugs arrive, we will be able to convert all insufficient therapies into adequate ones," said Dr Toktogonova.
Once these pharmaceuticals start arriving, they will theoretically wipe out the backlog of MDR TB patients as well as the new 560 cases believed to arise annually.
The challenge will be to ensure that the correct drugs are used properly. In the first two years of the MDR TB pilot project, only 60 per cent of patients actually completed the full length of treatment, Dr Toktogonova said.
One problem is the shortage of trained medical staff, as many leave the country in search of a better wage than the 90 dollars a month an experienced family doctor can expect to earn in Kyrgyzstan.
“There is a brain drain of TB personnel,” said Maxim Berdnikov of the International Committee of the Red Cross in Kyrgyzstan. “In Kazakhstan and Russia, the salaries are five to ten times higher. In some places in the south, there are no lab technicians left to diagnose the disease, and hospitals are running empty.”
Another obstacle will be patient motivation. Shamyrza Amankulov, a 52-year old resident of the Issyk-Kul region, has interrupted and resumed his treatment more times than doctors can count.
IWPR interviewed him in the MDR ward at the National TB Centre, where he had been transferred after many months of treatment.
He believes he knows better than the doctors at times. “I have left treatments when I have thought they give me the wrong treatment. Last winter ,they gave me first-line medication for four months — that was completely wrong,” he said.
As for others who disrupted their treatment, he explained, “Maybe people don't understand fully that this is a serious disease. Some people say you get better if you eat dog or badger meat.” Amankulov tried such folk-medicine methods himself but admitted they did not help.
In early April, following this interview, Amankulov again broke off his treatment.
Dr Toktogonova has had difficulty in making even the lucky few patients who were included in the pilot project stay on the treatment.
During the interview, she received a phone call from a 22 year old man who wanted to come back after stopping his treatment just two months before full recovery.
”His relatives didn't do anything about it and his district doctor had quit, so none could find him,” she said. ”His lungs are not yet destroyed. But he must begin the entire treatment again, and perhaps for 36 months instead of 24.”
Toktogonova says TB can return and further resistance can develop when therapy is halted prematurely.
”It always comes back, of course — stronger and with resistance to second-line medicines. Then we have nothing left to treat with, and then the patients die,” she said.
She has launched a series of seminars to teach medical staff all over the country about the dangers of mistreatment.
“I am in a state of terror as I watch how our doctors prescribe substances and create XDR,” she says.
The National TB Programme has recognised the danger of poor adherence to treatment and is scrambling to improve matters in time for the arrival of quality drugs.
To minimise the number of drop-outs, Toktogonova said, treatment has been reformed into a four-stage model with six months each spent in intensive care, a rehabilitation home outside the city, an open ward near Lake Issyk-Kul and finally treatment at home.
"This has already brought the number of therapy violations down from some 24 every month to a mere four," she says, commenting on the reform’s impact on the existing MDR pilot project.
Other measures may include food packages for TB patients and better pay for doctors. The National TB Programme headed by Alisherov has applied to the Global Fund to Fight AIDS, Tuberculosis and Malaria for 40 million dollars, half of it to pay for food packages that would be distributed to patients every day they show up for their medication, and the rest to go on raising health service salaries.
If approved, the money will not arrive until the summer of 2009.
Despite all the investment and effort, Alisherov says only rising living standards in Kyrgyzstan will ultimately decide the battle against the TB pandemic.
”If the economy stays at this level, we won't beat TB. I say this openly. It will remain where it is now. Perhaps the numbers will go down a little, but it will remain,” Alisherov concludes.
Andreas Hedfors is a freelance journalist in Bishkek.
