International Activity Report 2004
Running out of breath?
Tuberculosis control in the 21st century
By Sally Hargreaves and Laura Hakokongas for the MSF Campaign for Access to Essential Medicines

Treatment of patients with tuberculosis (TB) is at a crossroads. Care providers are forced to use decadesold, difficult-to-use medicines because there are no new, improved drugs and diagnostic tools available. In addition, current treatment strategies focus on reaching those who are easiest to treat while a growing number of people are infected with resistant strains or suffer from another life-threatening illness such as HIV/ AIDS. To counter this reality, MSF is calling for a revised global TB treatment strategy and much more effort to expand options for diagnosis and treatment.

Until the 1990s, management of TB was disorganised and ineffective. Treatment regimens varied widely; ambulatory non-observed treatment was common, and reporting mechanisms were largely absent. There was little interest in TB from the international community, including the World Health Organization (WHO), which only allotted US$10 million for TB in 1992-93.

A variety of factors, including an outbreak of multidrug-resistant TB in New York in 1991-93, and growing evidence of the link between TB and HIV/AIDS, began to change this situation. The WHO and the International Union Against Tuberculosis and Lung Disease started to raise the profile of TB as a global crisis and to develop a new global approach to it. Directly Observed Treatment, Short-course (DOTS), was launched in 1994 as a public healthbased management strategy aimed at controlling the disease.

DOTS focuses on identification of the most infectious (smearpositive) patients. This approach was partly based on evidence that detecting 70 percent of smear-positive patients and curing 85 percent of them could reduce TB incidence by 6 percent per year – effectively halving the incidence in 10 years. Yet it is accepted that diagnosis and reporting based on the existing smear-microscopy test, which can only pick up smear-positive patients, represents only 45 to 60 percent of TB patients overall, and therefore reliance on DOTS cannot curb TB globally. DOTS was not only conceived as a medical approach but also as a brand, designed to convince Western donors and developing country policy makers. The message was that DOTS – and only DOTS – could deliver global TB control.

However, WHO's decision to back DOTS as the answer to TB was questioned by the medical, academic and scientific communities. There were widespread objections in industrialized countries to WHO's conservative decision to build its TB strategy around existing TB tools rather than developing more effective diagnostics, vaccines and drugs. WHO and its supporters, on the other hand, argued for "restraint in the adaptation of new technologies by non-industrialized nations". They noted that "new technologies are expensive and there is a danger that their introduction would divert attention and money away from the real issues ... the global challenge of TB lies in the implementation of old, tried and tested technologies." Others were troubled by DOTS' simplified "one size fits all" strategy, noting that it was based on pilot studies in nine developing countries, and that the results – particularly the failures (Senegal, Mali and Yemen) – had not been properly analyzed. The debate over DOTS has calmed down during the past five years. Critics have learned to appreciate DOTS' good points and WHO has toned down what some saw as an inf lexible approach to implementation. Multilateral funding has also increased, with new Global Fund and World Bank money becoming available, although WHO still reports serious shortfalls in funds available to DOTS programs.

Although DOTS has many shortcomings, and the normal scientific process of scrutinizing and testing its premises and principles was cut short by its launch as a brand, specialists agree that it can and does work in "normal settings". That is, in the absence of HIV or multidrug-resistant TB (MDR-TB), where targeting the most infected patients can deliver six to ten percent annual declines in TB incidence.

Room for improvement

TB kills roughly two million people every year. Around 95 percent of all patients with active TB live in the developing world, where 99 percent of TB deaths occur. Improving DOTS is crucial if we are going to try to effectively treat the growing number of patients with the disease.

MSF has had first-hand experience of the current WHO-recommended strategy to control TB. In 2003, MSF's medical staff treated 20,000 TB patients in MSF projects across 21 countries. While most MSF and other experts agree that DOTS is the best approach we have, DOTS has demonstrated serious limitations in its nearly decade-long existence in the kinds of settings in which MSF works. The greatest challenge to TB control is HIV/AIDS. An estimated 12 million people are now co-infected with HIV and TB, a rapid increase in recent years. More than two-thirds of them live in sub- Saharan Africa. DOTS was not designed to address the specific context of HIV/AIDS and TB and a major re-think is required here if we are to treat these patients. Even in MSF's programs, only 4 of the total 25 HIV/AIDS programs directly provide TB treatment in sub-Saharan countries although TB is the most important opportunistic disease affecting HIV/AIDS patients. Most patients are referred to national tuberculosis programs that are often unable to treat co-infected patients.

In addition, far too few patients have access to second-line treatment for MDR-TB. Defined as resistance to at least rifampicin and isoniazid, the two most powerful TB drugs, this strain might be spreading as fast as by 250,000-400,000 new cases each year. Vigorous action for improved, more inclusive DOTS and for resources to develop new tools to fight TB is needed. Improving and expanding DOTS to address "low-priority" patients – those who are not detected as smear-positive with the tests currently available – is crucial if we are going to try to treat effectively the growing number of TB patients. New, shorter treatments need to be developed as the old ones are cumbersome to administer and treatment courses take months to complete. The development of new diagnostic tests and ensuring research and development of new drugs is now urgent. Investment into new tools is critical if we are to have any hope of tackling the global burden of TB. It is critical that the most promising diagnostic tools are prioritized and that their development is properly resourced. Most novel drugs are still on the bench, months if not years away from early trials, and their development should be promoted.

MSF believes that the global TB strategy needs to be revised. WHO should lead the process of adequately addressing the HIV/AIDS pandemic and its consequences for TB care. Access to treatment for smear-negative patients must be ensured. Innovative means of improving treatment adherence must be found, including reduced need for direct observation.

More resources must be brought together to develop new tools to fight TB within resource-poor settings. The development and validation of new diagnostic tools need to become a priority. There is also a need to quicken the pace of developing new, easier-to-use drugs and make them available at affordable prices. WHO and governments must work together to develop and fund an essential TB clinical research agenda, ensuring that needed clinical trials take place. The agenda should consist of developing new tuberculosis treatments among both existing drugs and new compounds.

Governments should insist that companies which make compounds that could be used to help treat TB in the future make them available to those willing to develop them into drugs. When commercial interests hamper the development of a potential tuberculosis treatment, governments need to intervene.