New approaches in the diagnosis and treatment of susceptible, multidrug-resistant and extensively drug resistant tuberculosis

ABSTRACT

Tuberculosis [TB] is killing nearly two million people worldwide every year. The current global burden of TB is mainly due to the expanding human immunodeficiency virus infection and its association with active TB disease and increasing resistance of Mycobacterium tuberculosis strains to most-effective [first-line] anti-TB drugs. Incomplete/ improper treatment of TB patients leads to evolution of drug-resistant M. tuberculosis strains as a result of chromosomal mutations in genes encoding drug targets. Sequential accumulation of mutations in target genes generate multidrug-resistant [resistant atleast to rifampin and isoniazid] M. tuberculosis [MDR-TB] and extensively drug-resistant [additionally resistant to fluoroquinolones and an injectable anti-TB agent] M. tuberculosis [XDR-TB] strains. While proper treatment of susceptible TB has > 95% cure rate, effective treatment of MDR-TB is difficult in developing countries as it is heavily dependent on rapid diagnosis, supervised aggressive therapy with several [5 - 6] expensive, toxic and less efficacious drugs for 18 - 24 months and regular monitoring for bacteriological and clinical improvement. Treatment of XDR-TB is far more difficult even in developed countries. Several anti-TB drugs with novel mechanism of action are under clinical development, which may shorten treatment duration of susceptible TB to around three months and also help in effective treatment of MDR-TB / XDR-TB