Facts & Figures
TB is a contagious disease and spreads mainly through the air like a common cold. Only one in ten people infected by the germ will actually develop the disease, as a healthy immune system will keep the infection dormant. These infections can reactivate years, even decades later, if the immune system is weak. Poor populations are most at risk to TB due to cramped living conditions, which favour disease transmission and due to weaker immune systems because of less nutritious diets. Mycobacterium tuberculosis usually affects the lungs. Called pulmonary TB, this form of the disease is characterised by a persistent cough, shortness of breath and chest pain. Other symptoms include weight loss, fever and night sweats. Left untreated, each person with active pulmonary smear positive TB will infect on average between 10 and 15 other people every year. The mycobacteria can also infect almost any part of the body, such as the lymph nodes, bones, the brain and heart. This “extrapulmonary” form, most common in HIV coinfection, may not be contagious but is equally vital to diagnose and treat rapidly, as all forms of TB are deadly if left untreated.
Diagnosis
The tools available to diagnose TB have changed little in the last 100 years, due to lack of research and development. The most widely used techniques to examine a suspected patient's sputum sample is using a microscope. Although this means diagnosis is cheap and possible even in remote areas provided you have trained staff, there are serious shortcomings associated with this method. Many people with active TB will not have sufficient TB mycobacteria in their sputum. In some cases, there is no presence of mycobacteria at all. This is especially true for patients su_ering from extra-pulmonary TB and co-infected with HIV. Microscopy is also of limited use for detecting TB in children, because they often do not produce enough sputum to make a reliable sample. Even in the best of hands, microscopy will only detect around half of all TB cases.
Another technique, known as culture, consists of incubating a sputum sample over a few weeks to see whether it contains live TB mycobacteria. Although this is a more sensitive method when performed correctly, it is unfortunately slow, as you need to wait at least three weeks and sometimes up to eight weeks, to be sure no mycobacteria are present. Improvements to culture, such as Thin Layer Agar or MODS (microscopically observed drug sensitivity) are reducing the time to diagnosis and are simplifying the techniques, but culture remains logistically difficult, requiring incubators, a continuous power supply, and skilled sta_. More modern methods such as those relying on DNA tests, for example, are too sophisticated to be used widely in developing countries, precisely where tuberculosis takes its heaviest toll.
Treatment
Although TB can be cured, current treatment is complex, lengthy and involves a combination of antibiotic drugs that were developed over 35 years ago. To prevent the emergence of resistance, the drugs are taken in combination. It is therefore recommended that TB drugs be produced in fixed-dose combinations (different drugs combined in a single pill). Treatment must be continued until all the mycobacteria are dead, which takes at least six months. Interruption of treatment before its completion, an irregular compliance to treatment as well as bad quality or insufficient drugs can trigger the selection of mycobacteria that are resistant to the drugs in use, leading to the development of drugresistant forms of TB (DR-TB) that are more complex and lengthy to treat. The drugs must also be of quality. This is often not the case, as substandard anti-tuberculosis drugs are widely available on the market in many countries. The World Health Organization is currently assessing the quality of drugs produced by different manufacturers, a valuable exercise which should enable developing countries to purchase “WHO pre-qualified” drugs of guaranteed quality. Today, only some first-line drugs for TB are “WHO pre-qualified”. There are no pre-qualified sources of anti-tuberculosis drugs in formulations suitable for children, nor are there any pre-qualified sources of streptomycin, one of the drugs used against TB [2].
Drug-resistant tuberculosis
An inadequate or incomplete treatment course and poor quality drugs are the major factors favouring the emergence of mycobacteria that are resistant to antituberculosis drugs. Drug-resistant TB (DR-TB) has reached alarmingly high levels in many countries around the world and is a serious global health problem. The World Heath Organization estimates that there are around 450,000 new cases of MDR-TB every year and 25,000 of these cases are expected to develop XDR-TB[3]. DR-TB is a particularly pressing emergency in Eastern Europe and Central Asia, but it is also growing in incidence in Africa.
The increasing numbers of MDR-TB cases, and the growing body of data showing the poor outcomes of patients taking inappropriate first-line therapy when they have MDR/XDR-TB, reinforces the urgency for access to good diagnostic tools. It is no longer sufficient to just diagnose TB. We need simultaneous, rapid drug sensitivity information, which is necessary to guide treatment. Without this information, a doctor risks treating a patient with drugs that are ineffective and that further fuel resistance. Treating DR-TB is difficult. Only one of the second-line drugs used against MDR-TB is WHO pre-qualified. There are very few manufacturers of these drugs, and those that exist have a limited production capacity, which endangers the regular supply that is necessary to ensure continuous treatment. MDR drugs are less effective than first-line drugs and must be taken for at least 18-24 months. They are also highly toxic and can cause a range of serious side-effects including hepatitis, depression and hallucinations. The patient is often hospitalised for long periods, in isolation.
In addition, the drugs are extremely expensive: depending on the choice of drugs, a treatment course for MDR-TB can cost up to US$ 15,000 per patient; and sometimes up to 300 times more than a treatment course for standard TB[4]. Finally, because of their limited production and the absence of a central buffer stock, due to their short shelf-life, and given the customs and registration barriers, the supply of second-line drugs is extremely complex and erratic. Although the feasibility and cost-effectiveness of treating patients with MDR-TB in resource-constrained countries is well established, outcomes of MDR-TB treatment remain sub-optimal. MDR-TB can be lethal; 5-20% of HIV-negative patients and 66% of HIV-positive patients die during treatment. The combined frequency of cure and completion often remains below 50%[5]. Moreover, the poor outcomes of current regimens mean that many of those treated will develop chronic, highly resistant forms of TB that have a high mortality rate and can be transmitted to others. XDR-TB has been reported in at least 37 countries, with very poor treatment outcomes.
The need for better tools
TB has suffered from decades of neglect from pharmaceutical companies, researchers and policy makers, because it offered no lucrative rewards and incentives for investment into R&D. Funding has been running at a disgracefully low level: the annual shortfall for TB R&D has recently been estimated at around US$800 million[6]. MSF is calling for governments and international bodies to step up and reinvest in this killer disease. After decades of virtually no TB drug R&D, we welcome today the existence of a TB drug pipeline that counts approximately 40 compounds. But, chances are low that a multiple therapies will emerge from the current pipeline, as only about one compound in 20 successfully emerges from an anti-infective drug discovery programme. Since new drugs for TB should only be used in combination, to prevent resistance, it is necessary to attract approximately 60 new lead compounds into the pipeline as quickly as possible. Nothing less will avert the escalation of what is already a major public health catastrophe. Few of the compounds in the pipeline are in the clinical phase of development. Some of these candidate drugs have been shown to be active against MDR-TB strains in vitro and can be potentiality effective against MDR-TB in human patients. There is an urgent need for innovative thinking in the field of clinical trials for new TB drugs in order to speed up the development of these new tools and accelerate their delivery to patients.
MSF and TB
MSF has fought against tuberculosis since its first day of operations more than 30 years ago and in 2006 treated around 29,000 patients in 40 countries worldwide. The settings in which MSF provides TB care vary widely. They include areas of chronic conflict, such as Chechnya; refugee camps in Chad or Thailand; prison settings as in Kyrgyzstan. The focus of the projects also vary: some concentrate on integrating HIV and TB services, such as in South Africa and Kenya; others offer treatment to patients suffering from drug-resistant tuberculosis, as in Uzbekistan and Georgia; others reach out to particular populations who have little access to medical care, such as migrants in Thailand. MSF is striving to improve diagnosis of all TB patients, by introducing culture and other tools where possible and assessing the feasibility of other diagnostic methods. In terms of treatment, MSF is currently exploring different ways of ensuring patient adherence, and is committed to using fixed-dose combinations and quality-assured drugs in its programmes. MSF also aims to integrate TB and HIV services where possible, and to treat drug-resistant tuberculosis in appropriate settings.
Diagnosis
The tools available to diagnose TB have changed little in the last 100 years, due to lack of research and development. The most widely used techniques to examine a suspected patient's sputum sample is using a microscope. Although this means diagnosis is cheap and possible even in remote areas provided you have trained staff, there are serious shortcomings associated with this method. Many people with active TB will not have sufficient TB mycobacteria in their sputum. In some cases, there is no presence of mycobacteria at all. This is especially true for patients su_ering from extra-pulmonary TB and co-infected with HIV. Microscopy is also of limited use for detecting TB in children, because they often do not produce enough sputum to make a reliable sample. Even in the best of hands, microscopy will only detect around half of all TB cases.
Another technique, known as culture, consists of incubating a sputum sample over a few weeks to see whether it contains live TB mycobacteria. Although this is a more sensitive method when performed correctly, it is unfortunately slow, as you need to wait at least three weeks and sometimes up to eight weeks, to be sure no mycobacteria are present. Improvements to culture, such as Thin Layer Agar or MODS (microscopically observed drug sensitivity) are reducing the time to diagnosis and are simplifying the techniques, but culture remains logistically difficult, requiring incubators, a continuous power supply, and skilled sta_. More modern methods such as those relying on DNA tests, for example, are too sophisticated to be used widely in developing countries, precisely where tuberculosis takes its heaviest toll.
Treatment
Although TB can be cured, current treatment is complex, lengthy and involves a combination of antibiotic drugs that were developed over 35 years ago. To prevent the emergence of resistance, the drugs are taken in combination. It is therefore recommended that TB drugs be produced in fixed-dose combinations (different drugs combined in a single pill). Treatment must be continued until all the mycobacteria are dead, which takes at least six months. Interruption of treatment before its completion, an irregular compliance to treatment as well as bad quality or insufficient drugs can trigger the selection of mycobacteria that are resistant to the drugs in use, leading to the development of drugresistant forms of TB (DR-TB) that are more complex and lengthy to treat. The drugs must also be of quality. This is often not the case, as substandard anti-tuberculosis drugs are widely available on the market in many countries. The World Health Organization is currently assessing the quality of drugs produced by different manufacturers, a valuable exercise which should enable developing countries to purchase “WHO pre-qualified” drugs of guaranteed quality. Today, only some first-line drugs for TB are “WHO pre-qualified”. There are no pre-qualified sources of anti-tuberculosis drugs in formulations suitable for children, nor are there any pre-qualified sources of streptomycin, one of the drugs used against TB [2].
Drug-resistant tuberculosis
An inadequate or incomplete treatment course and poor quality drugs are the major factors favouring the emergence of mycobacteria that are resistant to antituberculosis drugs. Drug-resistant TB (DR-TB) has reached alarmingly high levels in many countries around the world and is a serious global health problem. The World Heath Organization estimates that there are around 450,000 new cases of MDR-TB every year and 25,000 of these cases are expected to develop XDR-TB[3]. DR-TB is a particularly pressing emergency in Eastern Europe and Central Asia, but it is also growing in incidence in Africa.
The increasing numbers of MDR-TB cases, and the growing body of data showing the poor outcomes of patients taking inappropriate first-line therapy when they have MDR/XDR-TB, reinforces the urgency for access to good diagnostic tools. It is no longer sufficient to just diagnose TB. We need simultaneous, rapid drug sensitivity information, which is necessary to guide treatment. Without this information, a doctor risks treating a patient with drugs that are ineffective and that further fuel resistance. Treating DR-TB is difficult. Only one of the second-line drugs used against MDR-TB is WHO pre-qualified. There are very few manufacturers of these drugs, and those that exist have a limited production capacity, which endangers the regular supply that is necessary to ensure continuous treatment. MDR drugs are less effective than first-line drugs and must be taken for at least 18-24 months. They are also highly toxic and can cause a range of serious side-effects including hepatitis, depression and hallucinations. The patient is often hospitalised for long periods, in isolation.
In addition, the drugs are extremely expensive: depending on the choice of drugs, a treatment course for MDR-TB can cost up to US$ 15,000 per patient; and sometimes up to 300 times more than a treatment course for standard TB[4]. Finally, because of their limited production and the absence of a central buffer stock, due to their short shelf-life, and given the customs and registration barriers, the supply of second-line drugs is extremely complex and erratic. Although the feasibility and cost-effectiveness of treating patients with MDR-TB in resource-constrained countries is well established, outcomes of MDR-TB treatment remain sub-optimal. MDR-TB can be lethal; 5-20% of HIV-negative patients and 66% of HIV-positive patients die during treatment. The combined frequency of cure and completion often remains below 50%[5]. Moreover, the poor outcomes of current regimens mean that many of those treated will develop chronic, highly resistant forms of TB that have a high mortality rate and can be transmitted to others. XDR-TB has been reported in at least 37 countries, with very poor treatment outcomes.
The need for better tools
TB has suffered from decades of neglect from pharmaceutical companies, researchers and policy makers, because it offered no lucrative rewards and incentives for investment into R&D. Funding has been running at a disgracefully low level: the annual shortfall for TB R&D has recently been estimated at around US$800 million[6]. MSF is calling for governments and international bodies to step up and reinvest in this killer disease. After decades of virtually no TB drug R&D, we welcome today the existence of a TB drug pipeline that counts approximately 40 compounds. But, chances are low that a multiple therapies will emerge from the current pipeline, as only about one compound in 20 successfully emerges from an anti-infective drug discovery programme. Since new drugs for TB should only be used in combination, to prevent resistance, it is necessary to attract approximately 60 new lead compounds into the pipeline as quickly as possible. Nothing less will avert the escalation of what is already a major public health catastrophe. Few of the compounds in the pipeline are in the clinical phase of development. Some of these candidate drugs have been shown to be active against MDR-TB strains in vitro and can be potentiality effective against MDR-TB in human patients. There is an urgent need for innovative thinking in the field of clinical trials for new TB drugs in order to speed up the development of these new tools and accelerate their delivery to patients.
MSF and TB
MSF has fought against tuberculosis since its first day of operations more than 30 years ago and in 2006 treated around 29,000 patients in 40 countries worldwide. The settings in which MSF provides TB care vary widely. They include areas of chronic conflict, such as Chechnya; refugee camps in Chad or Thailand; prison settings as in Kyrgyzstan. The focus of the projects also vary: some concentrate on integrating HIV and TB services, such as in South Africa and Kenya; others offer treatment to patients suffering from drug-resistant tuberculosis, as in Uzbekistan and Georgia; others reach out to particular populations who have little access to medical care, such as migrants in Thailand. MSF is striving to improve diagnosis of all TB patients, by introducing culture and other tools where possible and assessing the feasibility of other diagnostic methods. In terms of treatment, MSF is currently exploring different ways of ensuring patient adherence, and is committed to using fixed-dose combinations and quality-assured drugs in its programmes. MSF also aims to integrate TB and HIV services where possible, and to treat drug-resistant tuberculosis in appropriate settings.