Challenges of Tuberculosis Treatment with DOTS: An Immune Impairment Perspective

Abstract

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.

Poor treatment outcomes and its determinants among tuberculosis patients in selected health facilities in East Wollega, Western Ethiopia

“…It typically affects the pulmonary system (pulmonary TB) and occasionally any other anatomic site (extrapulmonary TB) of the body. The disease is mainly transmitted by inhaling droplet aerosols from lungs with active lung disease [ 1 – 4 ].…”

“…Early diagnosis, effective treatment and timely identification of rifampin resistance are crucial for controlling and eventual elimination of the disease. It is diagnosed by rapid molecular tests, sputum smear microscopy and culture-based methods [ 4 , 7 ].…”

“…Ethiopia implemented DOTS strategy as pilot programmes in Arsi and Bale zones since 1997. Currently, the DOTS strategy has been subsequently scaled up throughout the country and implemented at national level [ 4 , 14 , 15 ].…”

Challenges in Drug Discovery against Tuberculosis

“…Due to the diversification and complexity of the infection for M tuberculosis, no model can completely define the in-vivo conditions in which mycobacteria are found in Tuberculosis patients and there is no sole standard detection condition for generating successful compounds for tuberculosis drug development. Recent efforts have focused on the development of whole-cell screening trials because objectivebased biochemical screens of inhibitors over the past two decades have not provided new tuberculosis drugs [68]. There are significant challenges in the discovery of antituberculosis drugs due to the nature of the causative bacteria.…”

“…At present treatment of tuberculosis requires more than one antibiotic with prolonged combination therapies to eradicate the infection and prevent resistance [58] and the standard therapy may include 4 antibiotics i.e., Isoniazid & Rifampicin (most effective drugs and these are given for six months and thus these two helps in killing the bacteria), Pyrazinamide & Ethambutol (given for first two months only) [67,68]. During treatment antibiotics are required for a long period, the minimum treatment period is six months and if the patient is having CNS or bone disease it often goes on for at least 12 months [69].…”