New Tools for an Old Disease: A Range of Promising New Tools to Prevent, Detect and Cure Tuberculosis (TB), Which Kills Some 1.6 Million People Globally Every Year, Could Soon Be within Reach. but More Funding to Feed the Research and Development (R&D) Pipeline Is Needed If the Reinvigorated Fight against TB Is to Succeed

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An array of new--and a few recombined--compounds and methods hold the potential to revolutionize the way TB is prevented, diagnosed and cured.

Thanks to generous funding from donors, particularly the Bill & Melinda Gates Foundation, three public--private partnerships are among a number of groups working to develop a new generation of diagnostics, medicines and vaccines for TB.

Scientists are researching vaccines that have the potential to be more effective than Bacille Calmette--Guerin (BCG), which was introduced in 1921 and is still the only TB vaccine. Diagnostic tools are being tested that may detect TB in patients more quickly than those used today and that may be used in places where medical staff have little or no laboratory training. And candidate drugs that reduce months-long

treatment regimens may soon be available.

"The new and exciting thing is that for the first time in decades we have a fairly robust clinical drug portfolio being tested," said Dr Melvin Spigelman, director of research and development for one of those public--private partnerships, the Global Alliance for TB Drug Development, known as the "TB Alliance". "But there is a tremendously high attrition rate in developing drugs. You never can count on any one drug or a handful of drugs to be successful. We need to set up a pipeline to continually feed the process."

Arguments for shorter drug treatment regimens abound. Currently, a full course of treatment means taking multiple medicines daily for about six months under the supervision of a health-care worker. Many patients break off treatment once they start feeling better. But failure to complete the full course has encouraged the development of bacteria that are resistant to common drugs, prompting the need for new drugs.

Shortening treatment would result in better patient adherence, reduced transmission of TB and less drug resistance, leading to fewer deaths. It could also save costs for patients and health services.

The not-for-profit TB Alliance has two drugs in clinical trials. Spigelman told the Bulletin that the aim is to produce a drug that reduces treatment duration from the current six-to-nine months down to four and, eventually, to two months. The long-term goal of the TB Alliance is to provide a drug that can cure TB in two weeks or less.

Among the TB Alliance's most advanced candidates is moxifloxacin, which it is developing with Bayer HealthCare AG of Germany. The drug has been used for other respiratory tract conditions since 1999 and is now being tested for use against TB.

Dr Martin Springsklee, vice president of global clinical development for therapy area anti-infectives at Bayer, said that if phase III trials, due to start this year, are successful, moxifloxacin could be available as early as 2010 and could become the first new antitubercular treatment in almost four decades.

Springsklee said there was "no significant commercial value" in the project for Bayer, but that the company had a moral obligation to make any resulting TB drug available to developing countries at affordable prices.

Separately, the TB Alliance has developed an antibacterial agent, called nitroimidazole PA-824, with Chiron Corporation of the USA. The compound is now in phase I clinical development.

The TB Alliance has received around US$ 200 million from donors to fund its projects, including the Gates Foundation as well as the governments of Ireland, the Netherlands, the United Kingdom and the United States of America (USA).

New diagnostics are also desperately needed to speed up the detection of TB. The main method, sputumsmear microscopy, was developed in the 1880s. But this method can take four to six weeks to grow bacteria cultures capable of producing a test result and it is generally not performed on the spot. Results are not always accurate--particularly when the patient is co-infected with HIV--and skilled laboratory staff are not always available in the countries that are worst affected by the disease. …