Tuberculosis stats drive search for new drugs

March 22, 2005

Glaxo and TB Alliance team up to replace old treatments.

Pharmaceutical companies have pledged to redouble their efforts to find drugs to fight tuberculosis. The announcement comes as the World Health Organization (WHO) reports that the situation in Africa is worsening, even as it improves elsewhere.

Tuberculosis, or TB, claims some 2 million lives across the world each year. In most places, that number has steadily declined. The WHO's Global Tuberculosis Control report for 2005, released today, says that the prevalence of the disease has dropped by more than 20% since 1990.

WHO director-general Lee Jong-Wook attributes much of this success to the strengthening of government commitments in parts of Asia. "The news this year is that there was a tremendous improvement in the situation in India and China," he says.

But Lee also acknowledges that the battle against tuberculosis is far from over. "We can rightfully talk about success in other parts of the world, but in Africa we have to face the fact that we have much further to go."

The WHO notes that although TB death rates have fallen worldwide, the situation in Africa is a 'glaring exception' to this trend. Much of this has to do with insufficient health infrastructure to deliver the necessary treatment, a course that involves several drugs over six to nine months.

Important combination

In much of Africa, high HIV infection rates worsen the impact of tuberculosis. This is because HIV sufferers are more vulnerable to infection with Mycobacterium tuberculosis, the bacterium that causes TB. What's more, HIV drugs can cause harmful side-effects when taken together with the TB treatment rifampicin.

Rifampicin, like other existing TB drugs, was introduced decades ago. With drug-resistant TB on the rise, the lack of new options is frustrating health officials. "In most cases, we don't use things from the 1940s and say: 'Oh, that's good enough'," says Gwynne Oosterbaan of the non-profit Global Alliance for TB Drug Development in New York.

Earlier this week, the TB Alliance announced a joint programme with pharmaceutical giant GlaxoSmithKline, headquartered in Middlesex, UK, to promote developments in the TB drug pipeline. The project will explore four different paths to find compounds that attack M. tuberculosis, aiming to shorten the course of TB treatments to as little as two months.

Strength in numbers

One of the most promising leads involves a new class of antibiotics, the pleuromutilins, which should inhibit the growth of M. tuberculosis. Another project will target isocitrate lyase, which is known to be important for M. tuberculosis survival. Researchers will also screen a wide range of compounds to find completely new candidates.

According to Mel Spigelman, director of research and development at the TB Alliance, scientists will test these compounds to make sure they do not disrupt the action of HIV medications.

But drugs and financial commitments alone will not solve the problem, stresses Mario Raviglione, director of the WHO's Stop TB department. He points to the lack of available medical workers in Africa: "You can have, paradoxically, all the finances you need, but if you don't have the people where the patients are, then you are really stuck."