TB Challenges
Our Need for a New, Effective Tool Box

by Mark Walport
May 1, 2009

This essay by Mark Walport, Director, The Wellcome Trust, is a part of the “2009 Summit Challenge—MDR-TB: Overcoming Global Resistance.”

The tools we currently possess to respond to the TB burden are inadequate. We are still using antiquated diagnostic and treatment regimes for control and management, and these are only effective in optimal conditions. With the emergence of TB strains resistant to all anti-TB drugs, we are greatly in need of a more effective tool box. The gathering of top leaders from science, industry, and policy at the Pacific Health Summit showcases the commitment from the world’s top institutions and organizations to develop and deliver such tools.

Approximately one-third of the world’s population has latent TB, with approximately 10 percent of infected individuals going on to develop active TB. Our understanding of TB latency and reactivation is still rudimentary, with neither host nor bacterial factors adequately understood. Surmounting basic research roadblocks such as these will be crucial to achieving worldwide control of the disease.

While TB is traditionally associated with poverty and overcrowding, the recent emergence of co-infection with HIV is a lethal combination, and HIV has caused TB incidence in sub-Saharan Africa to escalate since the 1990s. In some countries, 80 percent of TB patients are co-infected with HIV.

Diagnosing TB in resource-poor settings relies mainly on the use of smear microscopy of sputum samples, a very labor-intensive process with low sensitivity. Diagnosis of TB needs to be fast, sensitive, and accurate at the point of care&#8212discriminating between drug-resistant strains and allowing rapid commencement of appropriate antibiotics. As if this were not enough of a challenge, treatment regimes are currently complex, lengthy, and expensive.

Even so-called ‘short-course’ standard TB treatment lasts six to nine months, while drug-resistant TB is much harder to cure and may require treatment for up to two years or more. Compliance with treatment regimes can therefore be poor, and patients may abandon treatment for a variety of reasons&#8212because they feel better or because they can no longer afford the drugs, for example. However, stopping treatment early means that many still harbor viable bacteria, which may in turn cause a relapse.

The WHO’s currently recommended DOTS regime has successfully treated many patients, but it is human resource intensive and inaccessible for many patients. Even treatment of uncomplicated TB requires four different drugs.

Beyond compliance, the reliability of the drug supply chain in many countries is a real issue. New drugs allowing shorter, simpler, and cheaper treatment regimes should be a primary research and development priority. We have a pressing need for drugs targeting mycobacteria during their long dormant phase. National TB control programs require more resources and better tools to achieve success. While there is a role for the private sector in TB control, this must be supportive of, and consistent with, government services.

There are new TB vaccines in development. Encouraging results have been achieved in safety and immunogenicity trials for some, and crucial efficacy trials are now underway. An important challenge will be to characterize specific protective responses that can be used as immune correlates of efficacy for the new generation vaccines. Key to this is the capacity of health systems to undertake appropriate clinical trials. Building this vital infrastructure and this new tool box will have a health impact far beyond TB.

This essay is a part of the 2009 Summit Challenge – MDR-TB: Overcoming Global Resistance. To learn more about the 2009 Pacific Health Summit on MDR-TB, visit the Pacific Health Summit.