Tackling the new tuberculosis

June 4, 2008

Trials of the first new tuberculosis drug for 40 years are under way in South Africa. Scientists are looking for new compounds to help fight the infectious disease and the first vaccines for decades are being tested on humans. Non-profit organisations, not big pharmaceutical firms, are driving this movement to curb one of man's oldest and deadliest diseases.

Between them they have created the largest TB portfolio in the history of the disease, a list of drugs and vaccines on which they have worked. "TB is back - the truth is it never went away," says Professor John Grange, a TB researcher at University College London's Centre for Infectious Diseases and International Health.

TB still claims 2 million lives a year. It is greatly exacerbated by poverty, overcrowding and inadequate drugs. HIV has made a huge impact, driving up the numbers of people suffering from the disease (about half of those recorded as dying from Aids in sub-Saharan Africa actually die of TB).

New and deadlier strains are appearing. TB develops resistance to some drugs when patients do not complete the full - and onerous - treatment regime (a cocktail of pills must be taken for six months). The results are being felt worldwide. "We have the largest pool of partially treated cases in the world, with no infection control and no isolation," says TB expert Zarir Udwadia, of Hinduja Hospital and Research Centre in India.

Despite this there has been almost no TB research for decades (three of the 1,556 medical advances between 1975 and 2004 were for TB) and doctors rely on decades-old drugs, a 100-year-old diagnosis test and the BCG vaccine that was developed in the 1920s.

Non-profit organisations such as Global Alliance for TB Drug Development (TB Alliance), Aeras Global TB Vaccine Foundation and the Foundation for Innovative New Diagnostics (Find), are filling the gap, acting in lieu of pharmaceutical companies.

Mel Spigelman, the director of research and development at TB Alliance, says that big pharma has ignored TB because it is not seen as a lucrative market. "This is a disease of the poor. We all realise this is the not what commercial pharmaceutical companies go after."

The non-profits' mission is to make better TB drugs, diagnostic tests and vaccines for developing countries by gathering all the skills needed to create products from across the globe. They co-ordinate disparate scientists, contract laboratory research and help prepare for clinical trials.

Find has helped create an affordable microscope and has funded laboratories that will diagnose TB more effectively in sub-Saharan Africa.

A critical role for these non-profits has been to convince pharmaceutical companies to look again at TB by providing incentives such as research funds. A deal struck by TB Alliance compels the German pharmaceutical company Bayer to allow its drug to be made available in poorer countries in return for retaining the exclusive rights to sell the same drug at a higher price in richer countries. The deal was done after it emerged that a Bayer treatment for bronchial and sinus problems in the West might also be a crucial TB drug.

The non-profit model has led to collaborations not only with pharmaceutical companies such as GlaxoSmith-Kline, Novartis and Serum India but also institutions such as the universities of Oxford and Cape Town, St John's Medical College in India and the Kenya Medical Research Institute.

TB Alliance is conducting trials in South Africa with partners including Bayer, British Medical Research and University College London, and has contracted scientists to scrutinise thousands of compounds to find more drugs. It is working with Aeras to trial vaccines on thousands of babies with the disease. Aeras is developing two vaccines in-house and has built a manufacturing plant capable of making enough doses to vaccinate every vulnerable newborn baby worldwide in the course of a year.

But despite donations, health activists say that there are neither sufficient researchers nor funds for what has now become a race against the clock. Extremely drug-resistant TB (XDR-TB), a nearly untreatable form, has now been reported in 45 countries.