Treatment of Multidrug-Resistant Tuberculosis (MDR-TB)

Multidrug-resistant tuberculosis (MDR-TB) is difficult to treat and there exists a dearth of information about this infectious disease. The World Health Organization (WHO) developed the Stop TB Strategy and guidelines on how to prevent, control and treat MDR-TB by using available data worldwide.

Guidelines, however, are theoretical knowledge that is not easily transferrable into actual practice. The WMA therefore volunteered to produce a learning programme for the MDR-TB Guidelines. The course was updated together with the new WHO MDR-TB strategy in 2010.

This MDR-TB online course exists as a free self-learning online tool in English and Mandarin Chinese allowing physicians worldwide to learn and test their knowledge about MDR-TB. It is accredited by the South African Medical Association and the Norwegian Medical Association and therefore will be recognised in whole Europe.

A tablet application of the MDR TB course was developed to globally scale-up education and skills of health care workers to detect, treat and care for MDR-TB patients. Especially in low-resource countries internet access is not always available or stable to access the MDR-TB online course. The Android and iTune apps can be downloaded and viewed offline and is mainly created for use on tablet computers. This application of the MDR-TB course was developed with the support of the Stop TB Department of the World Health Organization (WHO).

To increase the access to MDR-TB training globally a PDF version of the course is translated into French, Spanish, Mandarin Chinese and Azeri. The course is written by the New Jersey Medical School Global Tuberculosis Institute and supported by the MDR-TB partnership.

Training Material Multidrug-Resistant Tuberculosis (MDR-TB)

Multidrug-resistant (MDR) tuberculosis is defined as disease caused by strains of Mycobacterium tuberculosis that are at least resistant to treatment with isoniazid and rifampicin; extensively drug-resistant (XDR) tuberculosis refers to disease caused by multidrug-resistant strains that are also resistant to treatment with any fluoroquinolone and any of the injectable drugs used in treatment with second-line anti-tuberculosis drugs (amikacin, capreomycin, and kanamycin). MDR tuberculosis and XDR tuberculosis are serious threats to the progress that has been made in the control of tuberculosis worldwide over the past decade.1,2

In 2008, an estimated 440,000 cases of MDR tuberculosis emerged globally.1 India and China carry the greatest estimated burden of MDR tuberculosis, together accounting for almost 50% of the world’s total cases. More than three quarters of the estimated cases of MDR tuberculosis occur in previously untreated patients. The proportion of MDR cases among new cases and previously treated cases of tuberculosis reported globally from 1994 through 2009 ranged from 0 to 28.3% and from 0 to 61.6%, respectively (Figure 1FIGURE 1 Distribution of the Proportion of Cases of MDR Tuberculosis among New Cases of Tuberculosis, 1994–2009.

). The highest proportions of MDR cases, and the most severe drug-resistance patterns, appear in the countries of the former Soviet Union. By 2009, a total of 58 countries had reported at least one case of XDR tuberculosis. In eight countries, reported cases of XDR tuberculosis account for more than 10% of all cases of MDR tuberculosis, and six of these countries were part of the former Soviet Union. By far the largest number of cases of XDR tuberculosis has been reported from South Africa (10.5% of all cases of MDR tuberculosis in that country), owing to rapid spread among people infected with the human immunodeficiency virus (HIV).

National programs are failing to diagnose and treat MDR tuberculosis. Globally, just under 30,000 cases of MDR tuberculosis were reported to the World Health Organization (WHO) in 2008 (7% of the estimated total), of which less than one fifth were managed according to international guidelines. The vast majority of the remaining cases probably are not diagnosed or, if diagnosed, are mismanaged. This problem remains despite the evidence that management of MDR tuberculosis is cost-effective3 and that treatment of MDR tuberculosis, and even treatment of XDR tuberculosis, is feasible in persons who are not infected with HIV.4,5

In some countries, the incidence of tuberculosis is rising, and the incidence of MDR tuberculosis appears to be rising even faster (e.g., in Botswana and South Korea).6 However, in Estonia, Hong Kong, the United States, and Orel and Tomsk Oblasts (in the Russian Federation), the incidence of tuberculosis is falling, and the incidence of MDR tuberculosis appears to be falling even faster. 1,6 This trend is the result of high-quality care and control practices that result in high rates of case detection and cure, drug-susceptibility testing for all patients, and the provision of appropriate treatment for all patients carrying drug-resistant strains. In short, preventing initial infection with MDR tuberculosis and managing the treatment of existing cases appropriately are the keys to containing the spread of this disease.

The WHO-recommended Stop TB Strategy7 provides the framework for treating and caring for those who are sick and controlling the epidemic of drug-susceptible and drug-resistant disease. The DOTS approach, which underpins the Stop TB Strategy, calls for political commitment to national programs designed to control disease by means of early diagnosis with the use of bacteriologic testing, standardized treatment with supervision and patient support, and provision and management of the drugs used in treatment; the approach also includes the monitoring of treatment and evaluation of its effectiveness. Between 1995 and 2008, a total of 36 million people were treated successfully with the use of the DOTS approach, and 6 million lives were saved.8 Specific guidelines for controlling drug-susceptible and drug-resistant disease already exist,9,10 and the Global Plan to Stop TB, 2006 through 2015, developed by the Stop TB Partnership, specifies the scale at which these interventions need to be funded and implemented to achieve global targets.11 However, to date, planning, funding, and implementation are falling far behind the milestones that have been set.

Prompted by concern that political support for the management of MDR tuberculosis is insufficient, WHO, the Bill and Melinda Gates Foundation, and the Chinese Ministry of Health organized a ministerial conference in Beijing in April 2009.12 The report from the conference in Beijing and the subsequent resolution (number 62.15) approved by the World Health Assembly in May 2009 state that significant changes in several components of the health care system must be made if MDR tuberculosis is to be eliminated.13,14 This review assesses the critical factors impeding control and discusses the solutions required to address them.

The World Medical Association has realized that there is an urgent need to support physicians in their daily work with TB and MDR-TB patients by developing TB and MDR-TB training material. Since 2005, we have provided the MDR-TB online course and in 2011 we have completed the TB refresher course. Both courses are available free of charge from our webpage as online courses and as PDF for download. They are translated into several languages, and there will be more of them.

Teaching styles have changed and there is an increasing demand for interactive e-Learning methods.

Together with New Jersey Medical School and their Global Tuberculosis Institute, and INMEDEA, a company creating interactive software for medical professionals, WMA has developed as training material 2 interactive patient cases based on the existing TB and MDR-TB cases. Due to the use of new multimedia technology and the web, the user has the impression to solve a real patient case when doing anamnesis, physical examination, making the diagnosis and deciding on a treatment plan. This does not replace the online courses, which are more textbook based, but it is a complement to the existing courses and helps to check whether the learned content is really understood.

Brief introduction to how to solve the patient cases and how to navigate through the system is available through this link.

1st Patient Case:

Rafael Cordero is a 30 year old man who was born in Ecuador and immigrated to the US. He was admitted to a local hospital for night sweats, a 6 week history of productive cough, weight loss of 10 kg, fatigue, and hemoptysis. The patient had no other significant past medical history. The patient’s TST was negative and repeat testing also revealed negative results….

To enter the patient case please click: Rafael Cordero

2nd Patient Case:
Sandra Fisher, a German 34 year old female social worker presents to the clinic with cough of unknown origin with slightly bloody sputum (hemoptysis). She reports that, after a severe cold last winter, shortness of breath and dry cough have remained, now being accompanied by slightly bloody sputum. Also, she feels persistently tired what she always thought was due to spring time. She is lethargic, breaks often out in night sweats and has unintentionally lost 5 kg of weight during the last 2 months. Mrs. Fisher reports that she must often go to the homes of fellow citizens she must look after…

To enter the patient case please click: Sandra Fisher
Visit MDR-TB online course
Visit TB refresher course

Drug Resistance by MDR-TB

Multidrug-resistant TB (MDR-TB) is defined by resistance to the two most commonly used drugs in the current four-drug (or first-line) regimen, isoniazid and rifampin. WHO treatment standards require that at least four drugs be used to treat TB in order to avoid the development of further resistance. The stories of those living with drug-resistant TB are harrowing.

According to the WHO, Eastern Europe’s rates of MDR-TB are the highest, where MDR-TB makes up 20 percent of all new TB cases. In some parts of the former Soviet Union, up to 28 percent of new TB cases are multidrug-resistant. Among previously treated cases in the same region, reported rates of drug resistance are commonly above 50% and as high as 61%. During the late 1980s and early 1990s, outbreaks of MDR-TB in North America and Europe killed more than 80% of those who contracted the disease. During a major TB outbreak in New York City in the early 1990s, one in 10 cases proved to be drug-resistant. Today, drug-resistant TB is also quite common in India and China — the two countries with the highest MDR-TB burdens.

Treatment for MDR-TB consists of what are called second-line drugs. These drugs are administered when first-line drugs fail. Treatment for MDR-TB is commonly administered for 2 years or longer and involves daily injections for six months. Many second-line drugs are toxic and have severe side effects. Further, the cost of curing MDR-TB can be staggering — literally thousands of times as expensive as that of regular treatment in some regions — posing a significant challenge to governments, health systems, and other payers.

The complexity and prohibitive cost of MDR-TB treatment means that fewer than 20 percent of the world’s MDR-TB patients receive proper treatment. Without a significantly simpler, faster cheaper, oral treatment for MDR-TB, countries cannot scale up treatment to serve their populations. The World Health Organization has issued a target of treating 80% of MDR-TB cases by 2015. Without new, simple, and affordable treatments for MDR-TB, this is not realistically possible. – See more at: http://www.tballiance.org/why/mdr-xdr.php#sthash.BXxGxfnZ.dpuf

Multidrug-Resistant Tuberculosis (MDR-TB)

Multidrug-resistant (MDR) tuberculosis is defined as disease caused by strains of Mycobacterium tuberculosis that are at least resistant to treatment with isoniazid and rifampicin; extensively drug-resistant (XDR) tuberculosis refers to disease caused by multidrug-resistant strains that are also resistant to treatment with any fluoroquinolone and any of the injectable drugs used in treatment with second-line anti-tuberculosis drugs (amikacin, capreomycin, and kanamycin). MDR tuberculosis and XDR tuberculosis are serious threats to the progress that has been made in the control of tuberculosis worldwide over the past decade.

The emergence and spread of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) are major medical and public problem, threatening the global health.

Facts about Multidrug-Resistant Tuberculosis (MDR-TB) and Extensively Drug-Resistant Tuberculosis (XDR-TB)

The emergence and spread of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) are major medical and public problem, threatening the global health.
MDR-TB is defined as TB caused by bacteria that are resistant to at least rifampicin (RMP) and isoniazid (INH) – the two most important first-line anti-TB drugs. The annual global MDR-TB burden is estimated at around 425.000 cases or 5% of the global tuberculosis burden. Multidrug-resistant tuberculosis is a challenge to TB control due to its complex diagnostic and A fast and reliable resistance testing is essential to cut transmission paths and to change treatment to effective antibiotics of the second line. Treatment for MDR-TB is cost-intensive, time-consuming (minimum 18 months) and must be undertaken by a physician experienced in therapy of MDR-TB.

XDR-TB is currently defined as TB caused by bacteria that are resistant to rifampicin and isoniazid as well as resistant to any one of the fluoroquinolones (e.g. ofloxacin and moxifloxacin) and to at least one of the injectable second-line drugs (capreomycin, viomycin, kanamycin or amikacin).

XDR-TB is currently defined as TB caused by bacteria that are resistant to rifampicin and isoniazid as well as resistant to any one of the fluoroquinolones (e.g. ofloxacin and moxifloxacin) and to at least one of the injectable second-line drugs (capreomycin, viomycin, kanamycin or amikacin).

XDR-TB emerges like MDR-TB through mismanagement of treatment. XDR-TB is already spread throughout all regions of the world. In some countries more than 20% of all multidrug-resistant TB cases are XDR.!

GenoType MTBDRplus and GenoType MTBDRsl allow for rapid and reliable detection of MDR/XDR-TB.