contribution of new cases from the pool of previously infected individuals. Obstacles to effective chemotherapy include non adherence with treatment which has been, to a large extent, overcome with directly observed treatment, and resistance of the bacteria to the chemotherapeutic agents. It is now clearly demonstrated that where patients are resistant to both of the most powerful chemotherapeutic agents (isoniazid and rifampicin), their clinical course is no different than if no chemotherapy was given at all134 135.
If chemotherapy is only haphazardly applied, the prevalence of tuberculosis may actually increase due to the fact that patients' lives are saved while the patients are not cured45 152. This may actually enhance the transmission of Mycobacterium tuberculosis.
There is a clear and important impact of the use and type of chemotherapy (notably the length of treatment) on the probability of becoming once again contagious after having become no longer contagious with tuberculosis39. This was shown to be an important contributor to the rapid decline of tuberculosis in Inuit who experienced one of the highest rates of tuberculosis ever recorded81.
Improper chemotherapy (principally an incorrect combination of medications resulting in "effective" monotherapy) also may lead to the emergence of resistance to the medications used in the treatment136 through selection of the existing subpopulation of mutant bacilli occurring naturally in large populations, notably in smear positive pulmonary cases. These cases (with acquired resistance due to improper treatment) may infect others who, when they develop disease, have micro organisms with primary resistance.
The impact of chemotherapy on tuberculosis infection has been less frequently demonstrated13. Imprecise estimations have been reported15 but these are hampered by the "averaging" inherent in the process of deriving incidence from prevalence. A study of Aboriginals in Canada showed a marked reduction in prevalence of infection in children born after the introduction of chemotherapy for cases of tuberculosis81.
4. Eradication of tuberculosis
Because of the inefficiency of transmission of tuberculosis, the disease should, theoretically, be eradicable137. With the tools currently available, however, it will only be fully eradicated once the last heavily infected generation has died. The impact of the HIV epidemic, the emergence of substantial numbers of drug-resistant incurable cases and the dismantling of health service structures through the process of Health Sector Reform, are serious setbacks to progress toward eradication.
Stages along the road to eradication have been defined138. As tuberculosis declines, it becomes increasingly sequestered in hard-to-reach subsets of the population139 where the level and characteristics of tuberculosis are often similar to the situation in low income countries and the disease can re-enter the general population at any moment when the social and epidemiological conditions are advantageous.
A number of communities are now approaching the elimination phase of tuberculosis. This must be the aim for all of society. However, success carries with it the dangers of complacency140. Unless improved tools are developed, it will be difficult to maintain political commitment at a sufficient level for the generation required to finally achieve eradication.
