Tuberculosis

Tuberculosis

Tuberculosis in the Lungs
Tuberculosis is a leading threat to global health, infecting one-third of the world’s population. Nearly 2 billion people are infected with the TB bacteria.

Every year an additional 30 million people are infected with the bacterium and 8 million people develop the active disease. TB takes the lives of nearly 6,000 people a day. It kills young and middle-aged adults faster than other disease apart from AIDS. It also is the leading cause of death of HIV-positive people worldwide. The incidence of the disease is rising yearly. Although TB is treatable, current drugs have limitation that are contributing to the spread of the disease.

To control the TB epidemic more effectively, new drugs are urgently needed: new compounds that (1) shorten the duration of treatment to 2 months or less and/or significantly reduce the number of doses needed to be taken under DOTS supervision, (2) improve treatment of multidrug-resistant strains, and (3) provide a more effective treatment of latent TB Infection (LTBI) to prevent the progression from infection to disease. (see page EX-4)

Despite this need, no new class of anti-TB drug has been introduced in over 30 years, and TB has been a neglected disease.

Source: Executive Summary for The Economics of TB Drug Development, The Global Alliance for TB Drug Development 2001

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The Spread of Tuberculosis

Tuberculosis, first recorded in ancient Egypt, shows no signs of disappearing, and has become a scourge of modern day society in some developing countries. Today, the tuberculosis organism (Mycobacterium tuberculosis) affects at least two billion people, one in three of the world’s population.

AstraZeneca and the EU Sixth Framework Programme

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Tuberculosis in Ghana

New treatments are badly needed, as today’s strains have become resistant to existing treatments, first developed some forty years ago, says Professor Stewart Cole, of the Institut Pasteur and Chair of the NM4TB Steering Committee. Higher potency treatments are needed to shorten the treatment time; new treatments that may be used for multidrug resistant (MDR) and now, extensively drug resistant (XDR) strains which are rampant in Africa and parts of Eastern Europe must also be identified.
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Currently, treatment regimens last at least six months, and it is difficult for some patients to comply, especially if their lifestyle is not conducive to taking an assortment of pills. In some developing or insufficiently-resourced countries, in Africa, Asia and Eastern Europe, there may not be sufficient drugs for patients to complete the course. Second-line treatments may be problematic and can be accompanied by severe side-effects.
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Why Is TB So Hard To Kill?

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  • The first line of lung cellular defense against bacterial invasion/infection are the alveolar (lung) macrophages.
  • Multiple researchers have shown that the normal killing mechanism employed by the macrophages after ingesting the bacteria is accomplished through NO.
  • Mycobacterium tuberculosis circumvents the macrophage normal killing mechanism.
  • This manipulation enhances Mycobacterium tuberculosis survival within the host macrophage, leading to increased morbidly and mortality.

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Laboratory reasearch has demonstrated that nitric oxide therapy kills the Mycobacterium tuberculosis bacteria.

The current anti-TB drugs, although effective when properly administered, ultimately cannot win the fight against the tuberculosis epidemic.

Directly Observed Treatment, Short-Course (DOTS)

Global efforts to control TB were reinvigorated in 1991 when a World Health Assembly (WHA) resolution recognized TB as a major global public health problem. In 1994 the internationally recommended control strategy later named DOTS was launched. The DOTS framework has subsequently expanded and implemented in 182 countries. The five elements of DOTS are: 1. Political commitment with increased and sustained financing, 2. Case detection through quality-assured bacteriology, 3. Standardized treatment, with supervision and patient support, 4. An effective drug supply and management system, 5. Monitoring and evaluation system, and impact measurement. DOTS implementation has helped countries to improve national TB control programs and make major progress in TB control. By 2004 more than 20,000,000 patients had been treated. However, DOTS is cumbersome, labor intensive, and expensive, particularly for such a long treatment regiment.

To control the TB epidemic more effectively, new drugs are urgently needed: new compounds that (1) shorten the duration of treatment to 2 months or less and/or significantly reduce the number of doses needed to be taken under DOTS supervision, (2) improve treatment of multidrug-resistant strains, and (3) provide a more effective treatment of LTBI to prevent the progression from infection to disease. Despite this need, no new class of anti-TB drug has been introduced in over 30 years, and TB has been a neglected disease.

Source: Executive Summary for The Economics of TB Drug Development, The Global Alliance for TB Drug Development 2001

Although TB is treatable, current drugs have limitations that are contributing to the spread of the disease:

  • A treatment duration of at least 6 months is required.
  • The most effective strategy for treating TB—DOTS (directly observed treatment, short-course)—is cumbersome, labor intensive, and expensive, particularly for such a long treatment regimen.
  • Strains of TB that are resistant to more than one of the first line of anti-TB drugs—that is, multidrug-resistant TB (MDR-TB)—have become more prevalent in recent years, and second-line drugs are not as effective as the standard therapy and are more toxic and expensive.
  • It is important to treat latent TB infection (LTBI)—that is, infection with Mycobacterium tuberculosis but not active disease—in certain high-risk patients, such as those co-infected with HIV; however, the standard LTBI treatment regimen lasts from 2 months to 12 months, depending on the medicines used.

Source: Executive Summary for The Economics of TB Drug Development, The Global Alliance for TB Drug Development 2001
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The Stop TB Strategy

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Since the implementation of DOTS (read more about DOTS in the section above), WHO and its partners have worked on strategies to address the major constraints to achieving global TB control. One of its partners, the Global Alliance for TB Drug Development, is a public-private partnership established by a wide range of stakeholders to bring together public and private sector TB drug R&D resources and expertise. Its vision is the provision of new medicines with equitable access for the improved treatment of TB. Its mission is to accelerate discovery and/or development of cost effective new anti-TB drugs that will shorten or simplify TB treatment, provide for more effective treatment of MDR-TB, and/or improve the treatment of latent TB infection (LTBI).

In October 2001 the Global Alliance For TB Drug Development, a not-for-profit organization created to accelerate the discovery and development of new drugs to fight TB, published The Economics of TB Drug Development, a comprehensive breakthrough on new drug development outlining the potential market for the cost of developing a new TB drug.

Stop TB Partnership Targets

By 2005: At least 70% of people with infectious TB will be diagnosed (under the DOTS strategy), and at least 85% of these patients will be cured.

By 2015: The global burden of TB (disease prevalence and deaths) will be reduced by 50% relative to 1990 levels. Specifically, this means reducing prevalence to 155 per 100,000 per year of lower by 2015 (including TB cases co-infected with HIV). The number of people dying from TB in 2015 should be less than about 1 million, including those co-infected with HIV.

By 2050: The global incidence of TB disease will be less than 1 case per million population per year.

Prevention and Control of Multidrug-Resistent TB (MDR-TB)‏

Evidence shows that MDR-TB, resistant to more than one of the first line of anti-TB drugs, is a threat to global TB control. This is aggravated by inadequate treatment of those already affected with MDR-TB; the rise in drug resistance resulting from the widespread misuse of second-line anti TB drugs; and the absence of new effective drugs to treat TB. Global surveillance of anti-TB drug resistance indicates that drug-resistant TB is present everywhere and that it is especially severe in parts of China and in countries of the former Soviet Union. If MDR-TB is not properly addressed in these areas, TB cannot be controlled. This means that every patient with MDR-TB should be diagnosed and receive adequate treatment with second-line anti-TB drugs. Increasing evidence shows that management of MDR-TB under programmatic conditions is feasible, effective and cost-effective when implemented in the context of a well-functioning DOTS program and based on WHO’s DOTS-Plus policy guidelines for MDR-TB.

Source: World Health Organization The Stop TB Strategy Stop TB Partnership 2006

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