Search PubMed⌕ Search

PubMed · 12435756

Can tuberculosis be controlled?

Abstract

BACKGROUND: Tuberculosis (TB) is nearly 100% curable. However, the ability of medical and public health interventions to control TB, particularly in developing countries, is often doubted. METHODS: We reviewed data for the amenability of TB to control. We considered separately control of deaths, prevalence, rate of infection and incidence. RESULTS: Tuberculosis mortality can be reduced by more than 80% in less than 5 years. The prevalence of TB can be reduced by 30% or more annually; sustained annual decreases of 17% have been documented in a developing country. The TB infection rate can be reduced by 15% annually. In the absence of human immunodeficiency virus (HIV), TB incidence can be decreased by as much as 25% per year and up to 10% annually in developing countries. A high prevalence of untreated HIV infection in the adult population of a developing country will inevitably result in a significant increase in TB incidence despite optimal use of currently available technologies. CONCLUSIONS: Tuberculosis can be controlled if appropriate policies are followed, effective clinical and public health management is ensured, and there are committed and co-ordinated efforts from within and outside the health sector. However, in the context of a large epidemic of AIDS, TB incidence will inevitably increase. By 2001, less than 30% of global TB cases were reported to have received effective diagnosis, treatment and monitoring. Rapid expansion of effective TB control services is urgently required, both to avert the continued high burden of morbidity and mortality from TB and because of the HIV pandemic.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Thomas R Frieden. 2002. Can tuberculosis be controlled?. https://doi.org/10.1093/ije%2F31.5.894

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

Mechanism of thioamide drug action against tuberculosis and leprosy.

Thioamide drugs, ethionamide (ETH) and prothionamide (PTH), are clinically effective in the treatment of Mycobacterium tuberculosis, M. leprae, and M. avium complex infections. Although generally considered second-line drugs for tuberculosis, their use has increased considerably as the number of multidrug resistant and extensively drug resistant tuberculosis cases continues to rise. Despite the widespread use of thioamide drugs to treat tuberculosis and leprosy, their precise mechanisms of action remain unknown. Using a cell-based activation method, we now have definitive evidence that both thioamides form covalent adducts with nicotinamide adenine dinucleotide (NAD) and that these adducts are tight-binding inhibitors of M. tuberculosis and M. leprae InhA. The crystal structures of the inhibited M. leprae and M. tuberculosis InhA complexes provide the molecular details of target-drug interactions. The purified ETH-NAD and PTH-NAD adducts both showed nanomolar Kis against M. tuberculosis and M. leprae InhA. Knowledge of the precise structures and mechanisms of action of these drugs provides insights into designing new drugs that can overcome drug resistance.

Antitubercular Agents↗

EthA, a common activator of thiocarbamide-containing drugs acting on different mycobacterial targets.

Many of the current antimycobacterial agents require some form of cellular activation unmasking reactive groups, which in turn will bind to their specific targets. Therefore, understanding the mechanisms of activation of current antimycobacterials not only helps to decipher mechanisms of drug resistance but may also facilitate the development of alternative activation strategies or of analogues that do not require such processes. Herein, through the use of genetically defined strains of Mycobacterium bovis BCG we provide evidence that EthA, previously shown to activate ethionamide, also converts isoxyl (ISO) and thiacetazone (TAC) into reactive species. These results were further supported by the development of an in vitro assay using purified recombinant EthA, which allowed direct assessment of the metabolism of ISO. Interestingly, biochemical analysis of [(14)C]acetate-labeled cultures suggested that all of these EthA-activated drugs inhibit mycolic acid biosynthesis via different mechanisms through binding to specific targets. This report is also the first description of the molecular mechanism of action of TAC, a thiosemicarbazone antimicrobial agent that is still used in the treatment of tuberculosis as a second-line drug in many developing countries. Altogether, the results suggest that EthA is a common activator of thiocarbamide-containing drugs. The broad specificity of EthA can now be used to improve the activation process of these drugs, which may help overcome the toxicity problems associated with clinical thiocarbamide use.

Antitubercular Agents↗