[Epidemiology of tuberculosis: a global, European and Polish perspective].
ABSTRACT Tuberculosis (TB) still remains a significant global health problem. At present, it has been estimated that one-third of the world's population is infected with Mycobacterium tuberculosis, the causative agent of TB. A total of 8-9 million new cases and 2 million deaths are recorded annually, ranking TB as the leading cause of morbidity and mortality from infectious diseases. According to the World Health Organization, by 2015 almost 1 billion people will become newly infected, about 200 million will develop the disease, and 35 million will die of TB, if the current trends continue. A number of factors have contributed to the global TB crisis, among which low case detection rates, the emergence of drug-resistant M. tuberculosis strains, coinfection with HIV, increased influx of immigrants from countries with a high incidence of TB, socioeconomic decline and deterioration of health care services seem to be most crucial. Although TB occurs predominantly in low-income and middle-income countries that account for as much as 95% of all new cases and 98% of all TB deaths, the disease persists in the populations of the developed countries, posing a potential risk for its resurgence. This review provides an update of the epidemiological situation of TB in the world, Europe, and Poland.
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ABSTRACT: Thymidine biosynthesis is essential in all cells. Inhibitors of the enzymes involved in this pathway (e.g. methotrexate) are thus frequently used as cytostatics. Due to its pivotal role in mycobacterial thymidylate synthesis dUTPase, which hydrolyzes dUTP into the dTTP precursor dUMP, has been suggested as a target for new antitubercular agents. All mycobacterial genomes encode dUTPase with a mycobacteria-specific surface loop absent in the human dUTPase. Using Mycobacterium smegmatis as a fast growing model for Mycobacterium tuberculosis, we demonstrate that dUTPase knock-out results in lethality that can be reverted by complementation with wild-type dUTPase. Interestingly, a mutant dUTPase gene lacking the genus-specific loop was unable to complement the knock-out phenotype. We also show that deletion of the mycobacteria-specific loop has no major effect on dUTPase enzymatic properties in vitro and thus a yet to be identified loop-specific function seems to be essential within the bacterial cell context. In addition, here we demonstrated that Mycobacterium tuberculosis dUTPase is fully functional in Mycobacterium smegmatis as it rescues the lethal knock-out phenotype. Our results indicate the potential of dUTPase as a target for antitubercular drugs and identify a genus-specific surface loop on the enzyme as a selective target.PLoS ONE 05/2012; 7(5):e37461. · 3.53 Impact Factor
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ABSTRACT: Tuberculosis (TB) is a health public problem and a long combination therapy is necessary to treat patients. In recent years, some drugs, not routinely used in treatment of TB, have appeared as promising new anti-TB therapies in patients with resistance to classical drugs. The aim of this study was: (i) to evaluate a modified checkerboard assay, Resazurin drugs combination microtiter assay (REDCA) to detect drugs interaction in Mycobacterium tuberculosis; (ii) to evaluate the interaction between isoniazid (INH) or ethambutol (EMB) with levofloxacin (LEVO) in susceptible and resistant M. tuberculosis Brazilian clinical isolates. M. tuberculosis H37RV ATCC 27294 and 19 clinical isolates (10 resistant and 9 susceptible) were tested. The fractional inhibitory concentration index (FICI) ≤ 0.5 was considered synergistic. Synergism in M. tuberculosis H37RV and resistant M. tuberculosis Brazilian isolates was observed with EMB vs. LEVO. No synergism was observed with INH vs. LEVO by both assays. No statistical difference was observed by the two assays studied. REDCA showed to be a simple assay for detecting synergism between drugs in M. tuberculosis. The results with EMB vs. LEVO are promising and it can be a new option in future investigations of drugs interactions against M. tuberculosis with the view to reduce EMB adverse effects.Tuberculosis (Edinburgh, Scotland) 09/2013; · 2.54 Impact Factor