Challenges of Tuberculosis Treatment with DOTS: An Immune ImpairmentPerspective

The World Health Organization (WHO) estimates that the causative agent of tuberculosis (TB) currently infects one third of the global population and is responsible for about 2 million deaths among those infected annually. Current therapy for TB consists of multiple expensive antibiotics (Isoniazid, Rifampicin, Pyrazinamide, and Ethambutol) and is lengthy, up to six months for drug-susceptible, and nine months or more for drug-resistant variants of TB. Although current TB treatment eradicates M.tb from the host body it also causes severe hepatotoxicity and other adverse side effects, causing a large number of patients to withdraw early from therapy. Additionally, displaying a phenomenon called therapy-related immune impairment; TB-treated patients are vulnerable to reactivation or reinfection of the disease. Once patients start feeling better, they often withdraw from treatment, especially those that live in resource-limited environments. Treatment withdrawal is largely responsible for the generation of drug-resistant variants of M.tb, including multidrug-resistant (MDR) and extremely drug-resistant (XDR) forms of M.tb. Therefore, new treatment approaches that reduce treatment regimen lengths and limit hepatotoxicity and other side effects are urgently needed.