In a widely publicised statement the World Health Organization recently announced what they termed a major breakthrough in the battle against tuberculosis. The key is implementation of a system referred to as directly observed therapy, short-course (DOTS), which entails a regimen of three or four drugs over 6—9 months, with monitoring by a health worker or other volunteer to verify that each dose of medicine is taken. By ensuring that all patients with tuberculosis are provided with appropriate treatment and supervision, WHO projects that the annual number of tuberculosis cases will be halved in the next decade. The WHO press release did not mention a need for better tools or further research in this disease.
DOTS can certainly provide very high cure rates for most patients who are reached by such programmes, and the widest possible implementation of DOTS should be among the top priorities on the world's health-care agenda. However, should we feel reassured by the WHO prediction of a rapid decline in case rates with existing measures? Such optimistic predictions are not without precedent. True breakthroughs in the 1950s and 1960s gave us powerful drugs, two of which, isoniazid and rifampicin, continue to be the key elements of the DOTS strategy. It was widely assumed then that the availability of effective treatment would end the scourge of tuberculosis, and that BCG vaccine would prevent and control the disease throughout the world. A consequence of these assumptions was the almost total cessation of research efforts during the 1970s and 1980s, resulting in no new drug being developed for tuberculosis control since 1967, and no new vaccine since 1921. Today, with the global incidence of tuberculosis increasing, only 5—10% of patients are being reached by DOTS, and there is an ominous increase in drug-resistant strains.
The re-emergence of tuberculosis in the industrialised countries, and the efforts of WHO in raising public awareness of the global problem, have contributed to a reawakening of biomedical research over the past 5 years. It is imperative that these efforts are not dissipated. While we hope that the optimistic estimates provided by WHO prove correct, we should bear in mind the past history of the disease.
The opportunities for major scientific breakthroughs in tuberculosis research are greater now than ever in the past. The powerful discipline of modern molecular genetics is being applied to the tubercle bacillus, with a tuberculosis genome project releasing an unprecedented flow of new information. With improved techniques for diagnosis of the disease the time needed to identify lethal multidrug-resistant isolates has been cut from several months to days. Potential targets for new drugs are being identified. Development of an effective drug that kills latent bacilli would profoundly accelerate the control of the disease, as would a vaccine that prevents infection, disease, or transmission. At least one major pharmaceutical company has instituted a wide-ranging academic-industrial programme to promote research into tuberculosis, and several other concerns have made major commitments to research and development of new drugs, diagnostics, and vaccines. Recognition and support of such research programmes should be an integral part of any but the most short-sighted control strategy.
We have been lulled into a false sense of security about tuberculosis. It is essential that we avoid the temptation of thinking, like our predecessors, that we have all the answers and means we need to control this disease now and in the future. The tubercle bacillus kills more people today than does any other infectious agent. DOTS is the best help we have—but it is uncertain that it is sufficient to reduce tuberculosis incidence appreciably on a global scale. It would be unconscionable to wait another 20 years to learn whether or not the optimistic predictions prove justified. We believe that, in a responsible and farsighted approach, WHO should provide leadership in promoting effective use of today's medicines, while ensuring that scientific opportunities for developing new and better ways to control tuberculosis are promoted. Both approaches are vital.