On World TB Day this year, MSF focusses on the urgent need for TB tests to deliver faster and accurate results, for all patients, even in the remotest settings. Patients from Kenya, India and Georgia tell their stories of how TB tests today are failing them.
Tuberculosis under control? Definitely not
Many people in rich countries think of tuberculosis as a disease of the past. Indeed well until the 1980s, experts thought that tuberculosis (TB) could be eliminated in a matter of decades.1 TB was seemingly under control.
Antibiotics, developed from the 1940s on, appeared to be effective in treating the disease. And as long as the strategy introduced by the World Health Organization (WHO), known as DOTS (Directly Observed Treatment, Short-Course), was correctly and efficiently rolled out, policy makers were convinced that TB would one day be a scourge of the past.
But now the international community recognizes that with around nine million new cases appearing every year, TB is far from defeated. TB is a deadly killer, responsible for 1.7 million deaths in 2006 – that is almost four lives claimed every single minute. The vast majority of TB cases occur in developing countries, with 22 high burden countries (mostly low and middle income countries) carrying approximately 80 percent of the global burden. Two billion people – one third of the world’s population – are infected and carry the tubercle bacillus.2
Worse, this ‘disease of the past’ has returned with new faces that are stretching our capacities to breaking point. The rapid spread of TB among people living with HIV, coupled with the emergence and spread of strains of TB that are resistant to the most common and effective drugs used to treat the disease, have led to a situation where far from being contained, TB is in fact spiraling out of control.
After calling victory too early, the world is waking up to the fact that TB has re-emerged as a major threat to global health.
Fueled by the HIV pandemic
People living with HIV are particularly vulnerable to developing TB. For that reason, TB incidence rates have shot up dramatically in the wake of the HIV epidemic, in particular in sub-Saharan Africa.3
In countries characterized by high HIV prevalence, the number of TB cases has almost tripled in the last 15 years. In South Africa, 44 percent of newly detected TB cases are estimated to be HIV positive. Globally, the figure stands at eight percent.4 In developing countries, TB is the leading cause of death among people who are HIV infected.5
In just one generation we have become witnesses to the ravaging of the African continent by the deadly combination of HIV and TB (...). At the same time, in Eastern Europe, multidrug-resistant strains have been created by bad control practices and disseminated all over the former USSR and beyond (…). The global TB incidence rate continues to rise.
Dr. Juliet Melzer
Médecins Sans Frontières, Uzbekistan
Drug-resistant strains spreading globally
We should understand that TB spares no one – there’s no single image today that represents the face of this disease. People think of TB as a disease primarily of men, of older people, of prisoners, but we have all sorts of people being treated here, all ages and from all walks of life, including a number of very young women.
Dr. Mario Raviglione
Director of WHO Stop TB Department
What is TB?
Tuberculosis is a contagious airborne disease, and spreads like a common cold. It is caused by a bacterium called Mycobacterium tuberculosis (or M. tuberculosis) which usually infects the lungs.
Only one in 10 people infected by the bacterium will actually develop the disease, since a healthy immune system will keep the infection dormant. But these infections can be reactivated years, even decades later, if the immune system is weak. This explains why people living with HIV whose immune system has been suppressed by the virus are so vulnerable to TB.
The pulmonary form of TB is characterized by a persistent cough, shortness of breath and chest pain. Each person with the infectious form of TB, if untreated, will go on to infect between 10 and 15 other people each year.
The Mycobacterium can also infect almost any part of the body, such as the lymph nodes, the spine or bones. This is the extra-pulmonary form of TB, and is more common in HIV infected patients and children. Although extra-pulmonary TB may not be contagious, it is equally vital to diagnose and treat it rapidly, as all forms of the disease can be deadly if adequate treatment is not given.
The emergence and geographical spread of strains of TB that are resistant to treatment by the standard anti-TB drugs is a second major concern. Resistance to any one drug is the result of naturally occurring genetic mutation within the Mycobacterium, but resistance to multiple drugs emerges through incorrect, interrupted or frequently repeated treatment.
The WHO estimates that there are now almost 490,000 new cases of multidrug-resistant (MDR) TB every year, and that the amount of drug resistance has been ever-increasing in countries as diverse as Peru, South Africa, China and India.6 An estimated 120,000 people die annually from multidrug-resistant TB.7
Diagnosis, treatment and prevention of drug-susceptible TB are difficult enough. But when it comes to tackling the disease in patients who are also infected with HIV or those with resistant strains of the disease, the medical challenges are multiplied.
In this document, through our work in Africa, the Caucasus and Asia, we illustrate our encounters with the new faces of TB and the tough challenges that we face in treating patients with drug-resistant TB and those infected with both TB and HIV. We also shed light on the limits of our capabilities, specifically linked to the continuing neglect of research into the development of newer and better vaccines, diagnostics and drugs to prevent, detect and treat tuberculosis.
Médecins Sans Frontières (MSF) and TB
We have been treating tuberculosis since our first day of operations more than 30 years ago. Today, MSF – often working alongside national health authorities – treats patients in 31 countries in a wide variety of settings, ranging from ...urban slums to rural areas, prisons or refugee camps.
MSF has been working to integrate care for patients with TB and HIV infection across many of its projects.
MSF has also increased the numbers of people it treats with multidrug-resistant tuberculosis from 11 patients in 2001 to 574 patients in 2007 in 12 different projects in countries including Uzbekistan, Georgia, Armenia, Kenya and South Africa.
In the period between 1999 and 2005, 52 percent of patients with drug-resistant TB under MSF’s care in projects in the Caucasus, Central Asia and Thailand either completed their treatment or were cured. 12 percent died and 18 percent defaulted on their treatment due to its length and toxicity. For the remaining 18 percent, treatment either failed or patients had yet to complete their treatment. These figures illustrate the considerable difficulties of treating drug-resistant TB even when this treatment is provided with considerable support and resources.
HIV/TB co-infection: Fighting a Losing Battle?
Mortality in co-infected patients is much higher than in patients only suffering TB. There’s no time to waste here: it may be only a matter of a few weeks before patients die.
Dr. Eric Goemare
MSF, South Africa
People living with HIV/AIDS, whose immune systems are suppressed, are particularly susceptible to TB. Not only are they much more likely to develop active TB, but the disease also progresses much more rapidly in HIV positive patients. TB causes up to half of all deaths of people with HIV.
This vulnerability caused by weakened immune systems explains why TB has been ripping through the populations in Sub-Saharan Africa where there is a high prevalence of HIV.
In the past 15 years, new TB cases have tripled in such countries.8 In Lesotho, for instance, where MSF runs an HIV care project in a rural health clinic, of the 221 patients started on TB treatment in 2006, 92 percent were also infected with HIV.
Diagnosis: Falling through the net
People infected with both TB and HIV often present unclear clinical symptoms and are frequently missed by existing diagnostic tools.
I remember one young man who was very sick. He had HIV but I couldn't diagnose TB. He was not coughing but he was losing weight fast. We did the TB tests: both sputum test and X-ray were negative. The only thing that made me suspect he had TB was his swollen and fluid-filled abdomen. I wanted to start treating him for TB but because the tests were negative, I wasn’t able to put him on treatment. Eventually, he went to the big city and got a correct diagnosis there. The lack of the right diagnostic tools that could work in our setting caused a treatment delay of two months.
Dr. Charles Ssonko
The most widely used technique for diagnosing TB in developing countries is no more sophisticated than examining a suspected patient’s sputum sample under a microscope to assess whether it contains TB mycobacteria. This method, called sputum-smear microscopy, was developed well over a century ago.
Although relatively fast and easy to implement in resource-limited settings, the method has significant limitations: it detects less than half of all TB cases, and it is, by definition, not able to identify TB in people, such as children or many people living with HIV, who either have difficulties producing enough sputum from their lungs for a sample for analysis, or don’t have sufficient or any mycobacteria in their sputum to be detected under the microscope.9 It also completely misses the extra-pulmonary form of TB.
The other possibility is to X-ray the patient’s chest. But for people living with HIV/AIDS, the X-ray often doesn’t show up the typical changes in the lung associated with TB infection. The result is that TB infection in many patients who are HIV positive goes undiagnosed – they are falling through the net.
The need for speed
We therefore desperately need better diagnostic techniques. Currently, a technique known as culture, also known as “gold-standard”, is considered the best alternative to microscopy. Culture consists of incubating (or ‘growing’) a sputum sample in a reagent or medium to see whether it contains live TB mycobacteria. It gives results that are far more accurate than microscopy. But as the mycobacteria are such slow-growing organisms, it can be up to eight weeks before a result comes through.
Swift diagnosis of tuberculosis is crucial – not only so that the patient can be put on appropriate treatment as soon as possible, but also to prevent the spread of the disease in the community.
Faster culture techniques do exist: one technique, known as MGIT (Mycobacterium growth indicator tube), is based on a liquid culture rather than the usual solid culture medium. Liquid culture methods have been endorsed by the WHO since 2007.10 MGIT, however, requires very skilled staff, a constant power supply and high safety standards to protect the laboratory staff handling the samples from contamination – things that simply do not exist in many of the more remote settings where we work. Getting hold of the component parts – new tubes and liquid reagent – also requires a reliable supply-chain which cannot always be assured.
In a pilot project in Kenya, where up to 80 percent of TB patients are co-infected with HIV, MSF is working with another improved culture medium. Called thin layer agar (TLA), it shortens the time to diagnosis down to eight to 10 days and shows similar accuracy to that achieved by MGIT. TLA is cheaper and less logistically challenging than the MGIT culture technique. Yet although these factors combine to make TLA potentially a very interesting tool for the sustainable scale-up of TB diagnosis, it is still a rather complex technique that has to be carried out in a laboratory with proper staff training and protection.
As close to the bedside as possible
Many of today’s existing tools are excessively complex. The use of culture as the main diagnostic tool – though it gives more accurate results than microscopy – still presents serious drawbacks in many of the settings where we work: access to culture remains very limited as the vast majority of TB patients (an estimated 85 percent) seek care in small clinics and health posts where either no test or only sputum-smear microscopy is available. Only the remaining 15 percent is seen at better equipped health structures, where it is possible to perform TB diagnosis using culture techniques.11
Current diagnostic methods thus need improving – we need tools that give better results, but are also faster, and we need tools that are as low-tech as possible.
Treatment: two diseases, one patient
Current TB treatment is complex and long-lasting, involving a combination of antibiotics that were developed more than 35 years ago. Lengthy treatment timelines (six or eight months of antibiotics therapy) and drug side effects make it difficult for patients to adhere to treatment through to its completion. Currently, the recommended strategy to maintain adherence is Directly Observed Treatment (DOT), where a health worker or a community volunteer supervises the patient taking his or her medication. While this can improve cure rates, it remains highly labor intensive for health staff, and places considerable strain on patients who sometimes have to travel several kilometers, every day for several months, to a health centre in order to receive treatment.12
Treating patients who are infected with both TB and HIV is even more difficult. When the drugs for the two diseases are taken in combination, there can be drug interactions, which may lead to increased side effects or reduce the effectiveness of treatment. For example, one of the main TB drugs, rifampicin, lowers the efficacy of one of the most common antiretrovirals used to treat AIDS, nevirapine. As a result, a more complicated treatment regimen is required. The patient must take a vastly increased number of pills every day, which when taken together can have toxic effects, notably on the liver.
Integrating HIV and TB treatment
The drugs for these two diseases interact. In integrated HIV/TB programs, we can follow this interaction more easily and we know exactly what drugs the patients are on, so if necessary we can take patients off drugs that aren't working for them.
Dr. Gilles Van Cutsem
MSF, South Africa
Given the high risks of co-infection in places where large numbers of people with HIV live, it has become increasingly clear that treatment for the two diseases should be integrated. Treatment integration would allow patients to benefit from early diagnosis of either disease and ensure effective monitoring of the combined treatments.
MSF has worked on setting up ‘one stop shops’, in effect clinics where people are treated for both diseases in one place. This brings benefits to both health care staff and patients – patients are assured swifter diagnosis of the two diseases, and staff can effectively monitor them for both treatments at the same time.
However, despite the clear statement from the WHO and others of the importance of implementing an integrated approach13, in most places TB and HIV programs continue to operate in isolation from each other. In 2006, worldwide less than 1 percent of people living with HIV/AIDS were reported to be also screened for tuberculosis.14
Living with two diseases: HIV/TB co-infection
It’s not easy taking all the drugs. I take two tablets for my TB every morning at 6 am and then for my HIV I take one in the morning and three at night. I get pains in my legs and headaches and sometimes I just don’t want to take the drugs, but I do my best.
Margaret, 40 years old, Nigeria. She is co-infected with TB and HIV.
After being diagnosed as having both diseases, Alison died within six months. She was already too sick for the medicine to help her. When she died, they took five liters of liquid out of her chest. It was a terrible way to die. I think if Alison had been diagnosed earlier and gone to the clinic to get treatment, she would have been alive today. Alison was a good person, I miss her very much. She left behind four children.
Sarah speaks about her sister Alison, 29 years old, who died of HIV and TB co-infection in Zambia.
I am fine now. I have had some tough times, but I survived. When I meet other patients who are reluctant to take a TB or HIV test, I always try to convince them. I give myself as an example. I was once also very sick, but now I am as strong as a horse. I would like to say to other co-infected patients that life is worth living, you should get treatment. You only have one life, you should take this opportunity and get some treatment. Without it you will die. And that is completely unnecessary.
Masautso, 37 years old, Voluntary Community Worker, Zambia. Masautso helps detect and take care of TB and HIV patients. He was previously co-infected with TB and HIV.
I had diarrhea, fever, and my lymph nodes were swollen. I thought it would pass. So I did nothing .But I became weaker and weaker. I suspected it was TB but I could not afford treatment. Then I heard about the MSF clinic where you get treatment for free. The diagnosis was TB and I started treatment. In the beginning I felt a bit giddy and my fingers tingled. When they told me I was also HIV positive, I was in pieces. Every month now I come to the clinic for my pills. If I take my pills it will go fine. I don’t want to think about death. If I take my pills carefully I can do things and care for my children.
Lucy, 32 years old, Myanmar. She is taking antiretrovirals for her HIV infection and finished her TB treatment a month prior to being interviewed.
Drug-resistant tuberculosis: entering the mainstream
What is drug resistance and how does it develop?
In the case of TB, resistance to drugs – when the effectiveness of a drug against a pathogen is reduced – develops through a mutation of genes in the bacteria. Although this is a natural phenomenon, resistant bacteria will only multiply in the presence of the drug in question.
Resistance can also develop if the bacteria are underexposed to drugs, because of under-dosing or if the treatment is interrupted or not continued for long enough. In all of these cases, treatment is likely to fail and the disease will re-emerge in a more resistant form, meaning that fewer drugs will be effective against the bacteria.
But direct infection with resistant strains is also possible. Because TB is an airborne disease, a patient can contract drug-resistant TB directly through contact with another person already ill with the drug-resistant strain. There are concerns that the number of those directly infected this way is rapidly increasing. For instance in Tashkent in Uzbekistan, 15 percent of TB cases who have never been previously treated for TB have MDR-TB, that is to say the resistant strain was caught directly from another person with MDR-TB.15
Diagnosis: establishing which drugs work, and which don’t
Basically with drug-resistant TB, whenever you look for it, you find it. And when you try to deal with it, you inevitably run up against the shortcomings of the available diagnostic tools and treatment. What we are also finding is that more and more patients we see have drug-resistant TB and they come to us with ever more resistant forms of the disease.
Dr. Juliet Melzer
Many countries in the developing world are not aware of the incidence of drug resistance among their populations affected with TB. A major factor is the difficulty associated with diagnosing drug-resistant strains.
Detecting drug resistance means finding out not only whether a person has TB or not, but just as importantly establishing to which drugs the patient’s TB strain has become resistant. For each individual patient, there will be a different pattern of resistance. Some programs provide a standard drug combination to all patients with MDR-TB but to ensure a patient is given the best possible treatment, doctors need to get an accurate profile of the specific drug resistance for each of their patients.
The diagnostic processes that allow medical workers to establish which drugs will work against the particular TB bacilli in a patient, and which won’t, are known as drug sensitivity testing – or DST. Results cannot be achieved with microscopy or by looking at chest X-rays but they can be obtained through certain culture methods.
A sputum sample is cultured a first time to grow the TB mycobacteria – as described in the previous chapter. The bacteria are then exposed to various TB drugs. After a period of time, the bacteria are then re-examined to see which drugs have had an effect. If the mycobacteria have continued to grow then we can conclude that they are resistant to the effects of the drug. If, however, the mycobacteria have been killed, we can conclude the drugs are still effective.
This might allow caregivers to determine a patient’s resistance patterns, but the method comes with all the problems associated with culture described above: it relies on sputum samples, so the technique is of limited use to those unable to produce sputum or with extra-pulmonary TB. It is complex, relying on a well-equipped laboratory and skilled staff, so much so that it is rarely available in developing countries, and not at all in more remote settings. And it is lengthy, taking up to eight to 12 weeks – time that patients needing to start treatment can ill-afford.
More modern techniques that work on analyzing the DNA of the Mycobacterium do address the last problem at least, in that they can give results in less than 48 hours. But they demand highly sophisticated pieces of equipment, meaning that we are still very far from a TB diagnostic tool that can be used as close to the patient’s bedside, however remote the setting, as possible.
Treatment: a terrible burden
I get terrible headaches, dizziness and loss of appetite. It is better now, but there were times in the past when I just wanted to die, I felt so low and depressed. Maybe it was the drugs, or maybe the length of treatment, but it all just seemed too much.
MDR-TB patient, Uzbekistan
Treating drug-resistant TB is notoriously arduous for patients and presents huge difficulties for health programs. Most of the second-line TB drugs used to treat drug-resistant TB are known for their relative ineffectiveness against the bacilli, meaning a lengthy treatment of up to two years. Patients must receive daily injections for up to six months and take a handful of different drugs once or twice a day for a further eighteen months or more. Treatment is also fraught with numerous side effects which require additional medical management.16
Such intense treatment places very big demands on patients. Many have to give up work in order to see their treatment through. Some patients who are hospitalized for periods of their treatment are isolated from their families, which can again give rise to psychological problems and major loss of income.
The toxicity of the drugs is perhaps the most striking feature of drug-resistant TB treatment (see table “The grim reality of DR-TB treatment”). Indeed, the severity of the side effects has been compared to cancer chemotherapy, with the difference that MDR-TB therapy is not administered in cycles, but in a continuum over two years. With a long list of commonly experienced side effects added to such a lengthy treatment, it is not surprising that many patients give up, some considering the treatment worse than the disease.
We explain to patients that to treat MDR-TB, you have to use medicines that will work like a bomb and clean everything out once and for all. That takes time because the bacteria responsible for TB are vicious and can hide anywhere in the body. When they re-emerge, they are even more vicious. But sometimes nothing helps. Inevitably, there will be people who give up treatment. It's a source of enormous frustration for us.
Dr. Adrien Marteau
MSF project data from Georgia, Armenia, Uzbekistan and Thailand show a patient defaulter rate of 18 percent. Faced with these challenges, MSF has tried to improve the situation by introducing ambulatory and outpatient methods of treatment together with offering psychological and some economic support to patients. We have learned that we can often help patients overcome the social and economic barriers to continuing treatment.
Other caregivers experience similar difficulties. The proportion of patients cured and completing their treatment remains below 50 percent in many programs, especially when the patient is HIV/TB-co-infected.17 However, success rates of up to 66 percent have been reported in some programs.
What is particularly concerning is that even when the best treatment is available, some drug-resistant patients will go on to develop yet further resistance to their drugs. Data from our project in Sukhumi, Georgia, show that 13 percent of MDR-TB patients went on to develop extensively drug-resistant TB, or XDR-TB despite all of MSF’s efforts to provide the highest standards of care. Similarly, in Uzbekistan, the analysis of an MSF cohort of MDR-TB patients revealed that six percent of patients developed XDR-TB while under treatment.18
Practical difficulties make expanding treatment challenging
For healthcare programs, there are also logistical difficulties to contend with. Very often there is only one supplier of the second-line drugs used to treat drug-resistant TB. This can mean that caregivers often have to wait for new supplies of a drug and stocks can actually run out – any treatment interruption bringing disastrous consequences for patients and further fuelling resistance.
DR, PDR, MDR, XDR:
the many faces of resistant TB
The term drug-resistant TB, or DR-TB is used to describe those strains of TB which show resistance to one or more of the common first-line drugs.
Patients infected with strains of TB that are resistant to (at least) the two most powerful first-line antibiotics used to treat TB, namely rifampicin and isoniazid, are said to have multidrug-resistant TB, or MDR-TB.
Patients who have MDR-TB and also show resistance to second-line drugs, including at least one from the class known as fluoroquinolones and one of the injectable drugs, are described as suffering from extensively drug-resistant TB or XDR-TB.
All forms of resistance to more than one of the first-line antibiotics and which are neither MDR- nor XDR-TB are defined as polydrug-resistant TB, or PDR-TB.
Patients can be infected with strains with a wide range of possible combinations of resistance to different drugs. Although we categorize them by DR-, PDR-, MDR-, and XDR-TB they are all the same disease but require different medications in order to cure people.
The financial cost of treating drug-resistant TB is also very high compared to treating a patient with drug-susceptible TB. Because the number of drug-resistant patients actually receiving treatment is still quite low, pharmaceutical companies manufacturing the drugs face low demand and do not get the advantage of cutting costs through large volume production. In addition, these drugs are complicated to produce and use expensive raw ingredients.
Some treatment programs have access to quality assured drugs at discounted prices through a WHO-hosted initiative known as the Green Light Committee (GLC). For them, the average cost of a two-year treatment stands at around US$2,000.19 Drugs purchased outside this procedure cost a great deal more: in Cambodia, for example, MSF has paid around US$7,300 for a single patient’s treatment course.
Donor funding is available in principle through the Global Fund to Fight AIDS, TB and malaria but countries need to make the scale-up of MDR-TB treatment a priority.
These factors, taken together, explain why only 10 percent of the estimated new MDR-TB cases are treated each year, and less than two percent are receiving verifiable, quality-assured, second-line anti-TB drugs through WHO’s Green Light Committee mechanism.20
The grim reality of DR-TB treatment
Below are some of the side effects that accompany second-line TB drugs – note that not all of these drugs will be taken at once by DR-TB patients.
Developed in 1946.
Two sachets of granules a day taken with acidic liquid drink.
Para-aminosalicylic acid or PAS is one of the drugs most hated by MDR patients. Many patients experience nausea and vomiting so severe that it can lead to anorexia. In some places, there have been so called ‘PASer strikes’ where patients simply refuse to take the drug.
Developed in 1952.
Two to three capsules a day for a minimum of 24 months.
Cycloserine frequently causes headache and dizziness. But on rare occasions it can even cause changes in personality and lead to aggressive behavior or depression or it may provoke psychotic disturbances. Some patients say they hear voices and hallucinate. On rare occasions, treatment has to be interrupted for fear that a patient may commit suicide.
Developed in 1952.
One intramuscular injection each day for at least six months.
Kanamycin injections are often painful. This is particularly true when the patient is emaciated by their illness and little muscle remains available, a factor which also increases the likelihood of infection from the injection. Occasionally, patients using the drug can also suffer from dizziness and vertigo. Most alarmingly, kanamycin is capable of sending patients irreversibly deaf.
Developed in 1956.
Two to three tablets a day for the whole course of the treatment.
Ethionamide has been known to give patients nausea, diarrhea, vomiting, splitting headaches as well as mouth and gum infections. Taken in combination with PAS, patients can suffer from low blood pressure, leading to feelings of total lethargy, fatigue and weakness. The drug can also lead to occasional bouts of psychotic disturbance.
Developed in 1963.
One injection a day for at least six months.
An alternative to kanamycin that is administered by a painful daily injection, capreomycin can provoke potentially allergic reactions. It can also lead to a loss of hearing resulting in either partial or total deafness.
“If you want to live, you have to finish the whole regimen”
MDR-TB treatment in Armenia
The Caucasus region has one of the highest rates of MDR-TB worldwide, as indicated in WHO’s 2008 drug resistance surveillance report. In September 2005, MSF and the Armenian Ministry of Health opened a treatment program for drug-resistant TB, the first and only one in the capital, Yerevan.
N.L. was the first patient to complete treatment which lasted almost two years.
"At first, I couldn't imagine how difficult it would be," says N.L. "I just wanted to be treated and return home to my family. But it was a long, slow process."
N.L. had been in and out of TB treatment for nearly 15 years. After years of failed attempts to comply with a strict and demanding treatment regimen, the TB bacilli in his system had gradually developed resistance to drugs. Fearing that he might infect his wife and son, N.L. moved out of home. And because of the fierce stigma associated with TB, he didn’t tell his neighbors about his illness. Meanwhile, his condition went from bad to worse.
Still, N.L. was one of the lucky few who were able to start treatment through the MSF program in October 2005.
Treatment at the special drug-resistant TB (DR-TB) unit in the outskirts of Yerevan involves taking a combination of up to 20 pills every day, accompanied by a painful injection in the morning for up to six months.
"When I was three months into the hospital treatment, I began to suffer side effects," says N.L. "Feelings of weakness, dizziness, nausea, fatigue, mood changes, shortness of breath. It was so intolerable that just looking at the drugs was enough to make me nauseous."
There were nearly 20 more months of treatment ahead, and already N.L. was in constant agony. His daily struggle started to overshadow any benefits that treatment could bring.
"N.L.'s main visitor was his son, who helped him a lot to cope with the sense of isolation at the hospital," says an MSF volunteer. "Our team too - social workers, psychologists, doctor and nurse - encouraged him in different ways, and wherever possible."
After seven months in hospital, N.L.’s sputum smears finally became negative. TB bacilli were no longer detected in his body and N.L. was discharged from the hospital. He was not yet cured, but he could now go home, back to his family, and continue ambulatory treatment –or outpatient treatment – at a clinic in Yerevan. However, this was not the end of the story: N. L. started outpatient treatment with great difficulty.
"I was happy to leave the hospital and be reunited with my family. But on top of the side effects going to the clinic every day for many more months, throughout the hot summer and harsh winter was not easy. I thought I would never be able to get through it."
MSF, with the help of N.L.’s son, continued to encourage and emphasize the importance of adherence to the treatment. The MSF team also offered N.L. social support. They provided him food parcels to ensure a balanced diet, transportation allowance to cover the costs of getting to the clinic every day, firewood for the coldest months of winter, and psychological counseling when needed.
After months of strenuous effort on both sides, N.L. started to believe in the effectiveness and benefits of treatment. His attitude changed over time.
"I very much wanted to finish my treatment so I continued to take the drugs regularly. If you want to live, you have to finish the whole regimen."
Right up to the end of his treatment, N.L. visited the clinic every day and never missed a dose.
In Armenia, where health care resources remain among the most limited in former Soviet Union countries, MSF covers the entire cost of treatment. Second-line drugs for treatment of drug resistant TB alone cost over 9,000 euros per DR-TB patient.
MSF has to date enrolled over 160 people with polydrug-resistant, multidrug-resistant or extensively drug-resistant TB in treatment programs in the capital, Yerevan. 20 patients have successfully completed the treatment, 11 have died, and 21 have defaulted on treatment. The rest are still undergoing treatment.
- WHO. Global Tuberculosis Control 2008 - Surveillance, Planning, Financing. Geneva: World Health Organization, 2008.
- WHO. Tuberculosis Fact Sheet. Geneva: World Health Organization, 2007; WHO. Global Tuberculosis Control 2008 - Surveillance, Planning, Financing. Geneva: World Health Organization, 2008.
- Corbett EL, Marston B, Churchyard GJ, De Cock KM. Tuberculosis in sub-Saharan Africa: opportunities, challenges, and change in the era of antiretroviral treatment. The Lancet 2006; 367(9514):926-37.
- WHO. Global Tuberculosis Control 2008 - Surveillance, Planning, Financing. Geneva: World Health Organization, 2008. Available at: http://www.who.int/tb/publications/global_report/2008/pdf/fullreport.pdf; Corbett EL, Watt CJ, Walker N, et al. The growing burden of tuberculosis: global trends and interactions with the HIV epidemic. Archives of Internal Medicine 2003;163(9):1009-21.
- Corbett EL, Watt CJ, Walker N, et al. The growing burden of tuberculosis: global trends and interactions with the HIV epidemic. Archives of Internal Medicine 2003;163(9):1009-21.
- WHO/IUATLD. Anti-Tuberculosis Drug Resistance in the World. Report no.4. Geneva: World Health Organization and International Union Against Tuberculosis and Lung Diseases, 2008.
- Keshavjee S, Seung K. Stemming the tide of multi-drug resistant tuberculosis: major barriers to Addressing the growing epidemic. Harvard Medical School, Partners in Health, Francois-Xavier Bagnoud Center for Health and Human Rights, Brigham and Women's hospital, 2008.
- WHO. Global Tuberculosis Control 2008 - Surveillance, Planning, Financing. Geneva: World Health Organization, 2008.
- Perkins MD, Cunningham J. Facing the crisis: improving the diagnosis of tuberculosis in the HIV era. J Infect Dis 2007;196 Suppl 1:S15-27; Shingadia D, Novelli V. Diagnosis and treatment of tuberculosis in children. The Lancet Infectious Diseases 2003;3(10):624-32.
- WHO. Use of liquid TB culture and drug susceptibility testing (DST) in low and medium income settings. Geneva: World Health Organization, 2007.
- TDR, FIND. Diagnostics for tuberculosis: global demand and market potential. Geneva: World Health Organization Special Programme for Research and Training in Tropical Diseases and Foundation for Innovative New Diagnostics, 2006.
- O'Brien RJ, Nunn PP. The need for new drugs against tuberculosis. Obstacles, opportunities, and next steps. Amercian Journal of Respiratory and Critical Care Medicine 2001;163(5):1055-8.
- WHO. Interim Policy on Collaborative TB/HIV activities. Geneva: World Health Organization, 2004.
- Stop TB Partnership. Facts on HIV/TB. HIV-TB Global Leaders Forum, 2008.
- WHO. Global Tuberculosis Database. Country profile. Geneva: World Health Organization.
- Nathanson E, Gupta R, Huamani P, et al. Adverse events in the treatment of multidrug-resistant tuberculosis: results from the DOTS-Plus initiative. International Journal of Tuberculosis and Lung Disease 2004;8(11):1382-4.
- Suarez PG, Floyd K, Portocarrero J, et al. Feasibility and cost-effectiveness of standardised second-line drug treatment for chronic tuberculosis patients: a national cohort study in Peru. The Lancet 2002;359(9322):1980-9; Park SK, Lee WC, Lee DH, Mitnick CD, Han L, Seung KJ. Self-administered, standardized regimens for multidrug-resistant tuberculosis in South Korea. International Journal of Tuberculosis and Lung Disease 2004;8(3):361-8; Narita M, Alonso P, Lauzardo M, Hollender ES, Pitchenik AE, Ashkin D. Treatment experience of multidrug-resistant tuberculosis in Florida, 1994-1997. Chest 2001;120(2):343-8; Mitnick et al,2008:"Comprehensive Treatment of Extensively Drug resistant Tuberculosis". The new England Journal of Medicine,August 7,2008 Vol.359 No 6.
- Cox HS, Kalon S, Allamuratova S, et al. Multidrug-resistant tuberculosis treatment outcomes in Karakalpakstan, Uzbekistan: treatment complexity and XDR-TB among treatment failures. PLoS ONE 2007;2(11):e1126.
- MSF calculation on the basis of Green Light Committee prices for a patient weighing 50kg for a regimen of pyrazinamide, prothionamide, levofloxacin, cycloserine and capreomycin as an injectable.
- Keshavjee S, Seung K. Stemming the tide of multi-drug resistant tuberculosis: major barriers to addressing the growing epidemic. Harvard Medical School, Partners in Health, Francois-Xavier Bagnoud Center for Health and Human Rights, Brigham and Women's hospital, 2008.
Related News & Publications
Be part of MSF
Our supporters, donors and fundraisers are a vital part of the MSF movement.
Find out how you can support MSF's lifesaving work.