Evolution of Drug Resistance in Mycobacterium tuberculosis : Clinical and Molecular Perspective

The epidemiology, pathogenesis, transmission, diagnosis, and management of multidrug-resistant, extensively drug-resistant, and incurable tuberculosis

“…Unlike other bacteria that often acquire resistance through promiscuous gene transfer systems such as plasmid exchange, changes in the genomic DNA of M tuberculosis usually result from single-nucleotide polymorphisms (SNPs), indels, or, more rarely, large deletions. 14 In principle, the effect of drug treatment is to diminish the pool of susceptible bacteria, which enables the clonal expansion and enrichment of resistant bacteria and the emergence of a strain able to withstand drug treatment. Sequential mutations in additional genes can lead to resistance to additional drug targets and the emergence of strains resistant to multiple drugs.…”

“…Several studies in individual patients who have developed progressive drug resistance over time have documented the initial acquisition of isoniazid resistance as a result of one or more mutations, followed by acquisition of resistance to rifampicin or ethambutol (or both), pyrazinamide, and finally, the second-line and third-line drugs. [15][16][17] The order in which resistance is acquired might reflect the number of different mutations that lead to resistance to a specific drug, 14 the relative fitness costs associated with specific mutations (ie, mutations might lead to less successful survival and reproduction of the organism), 18 or phenotypic changes following an initial drug-resistance mutation that might facilitate the acquisition of further mutations. 19 When resistance to one or more drugs is acquired in this way, it is referred to as secondary resistance.…”

Tuberculosis in Trinidad a Small Developing Country: Will we Reach the Millennium Development Goal 8 (MDG8) as we Countdown to 2015?

“…In fact in 2010 Trinidad ranked first among the top 10 countries in the Pan American Health Organization (PAHO) with an estimated prevalence of HIV of 30% among incident TB cases [8]. HIV coinfection increases the likelihood of progression to active TB after primary infection and reactivation of latent TB infection [24][25][26]. The immunocompromised state increases the mycobacterial burden of disease and enhances the evolution of drug resistant TB [27,28].…”

The changing face of tuberculosis: Trends in tuberculosis-associated skeletal changes

“…[8][9][10][11] TB remains a major health concern, such that it was declared a global emergency in 1993 by the WHO, 12 as at the time it was estimated that half of all individuals that developed the disease died within six to 24 months. 13 Knowledge of past incidences and signs as well as the spread of TB can inform our understanding of this condition and health practices of today.…”