PubMed Health⌕ Search

PubMed · 16567876

Tuberculosis control in Latvia: integrated DOTS and DOTS-plus programmes.

Abstract

From 1991 until the end of 1998, the number of patients with tuberculosis in Latvia increased 2.5 times with a simultaneous increase of drug resistant and multidrug resistant tuberculosis (MDR-TB). Descriptive analysis of different TB programme services, activities and strategies including Directly Observed Therapy Short-course (DOTS) for tuberculosis and treatment of MDR-TB, were performed. Data from the state tuberculosis registry, drug resistance surveillance, and the national MDR-TB database were used. The state-funded national tuberculosis control programme (NTAP, Nacionala Tuberkulozes Apkarodanas Programma), based on WHO recommended DOTS strategy, was introduced in Latvia in 1996. The NTAP includes TB control in prisons. Treatment of MDR-TB using second line drugs was started in 1997. Cure rates for TB patients increased from 59.5% in 1996 to 77.5% in 2003. Between 1996 and 2003, more than 200 patients began MDR-TB treatment each year, and the cure rate was between 66% and 73%. Numbers of MDR-TB patients were reduced by more than half during this period. Treatment results including MDR-TB reached the WHO target, with cure rates 85% of newly diagnosed patients. These results demonstrate that MDR-TB treatment and management using the individualised treatment approach can be effectively provided within the overall TB programme on a national scale, to successfully treat a large number of MDR-TB patients. Rapid diagnostic methods combined with early intensified case finding, isolation and infection control measures could decrease transmission of TB and MDR-TB in hospitals and in the community. Highly important that MDR-TB management follows WHO recommendations in order to stop creating drug resistance to first and to second line drugs.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

V Leimane, J Leimans. 2006. Tuberculosis control in Latvia: integrated DOTS and DOTS-plus programmes.. https://pubmed.ncbi.nlm.nih.gov/16567876/

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↗