Search PubMed⌕ Search
Home/Archive/PubMed

PubMed · 7663613

Tuberculosis in children.

J R Starke
View original source ↗Export metadata ↓

Abstract

The World Health Organization estimates that 90 million cases of tuberculosis will occur throughout the world in the 1990s, and 30 million people will die from the disease. Although traditional epidemiology suggested that 90% of tuberculosis cases arise from reactivation of remote infection, urban studies in the United States using DNA fingerprinting techniques imply that up to 40% of current cases are due to recent acquisition, a finding that will alter some basic approaches to tuberculosis control. Drug resistance is emerging as a major obstacle to tuberculosis control in the United States and the world. New studies focusing on the genetic basis of drug resistance may lead to better diagnostic techniques and new drugs. New trends in treatment center on shorter but more intense and directly observed therapy to maintain adherence. The new emphasis in developed countries is to concentrate control efforts selectively on those individuals, with the greatest risk factors for development of tuberculosis infection and disease.

Explore related subjects

Antitubercular AgentsBCG VaccineChildCross InfectionDNA, BacterialDrug Resistance, MicrobialDrug Resistance, MultipleHumansIncidenceMycobacterium tuberculosisPolymerase Chain ReactionTuberculin TestTuberculosisVaccinationJournal ArticleResearch Support, U.S. Gov't, P.H.S.Review

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

J R Starke. 1995. Tuberculosis in children.. https://doi.org/10.1097/00008480-199506000-00005

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

KEEP EXPLORING

Related citations

PubMed2007

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↗
PubMed2007

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↗