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

Galleria mellonella - a novel infection model for the Mycobacterium tuberculosis complex

“…The close association of tuberculosis with the human immunodeficiency virus (HIV) pandemic, and the rising problem of multi-drug and extreme drug resistance have created difficulties for tuberculosis control programs worldwide [2,3]. There is thus an urgent need for a greater understanding of host and M. tuberculosis interactions, improved vaccines to prevent infection, and novel therapies to shorten the duration of treatment and target latent tuberculosis infection (LTBI), however this has in part been hampered by the current inadequate, costly and time-consuming in vivo infection models for tuberculosis.…”

The tip of the iceberg: Alarming increase in the detection of MDR-TB

“…[2] More recently, this has been supplanted by an increasing burden of extensively drug-resistant TB (XDR-TB), [3] and resistance beyond XDR-TB. [3] The problem of programmatically incurable TB and its spread, in our communities, from home-discharged index cases has recently been highlighted. [4] In their study, Narsingh et al [1] found that almost 11% of patients assessed, had MDR-TB.…”

Why Phenotypic Drug Susceptibility Testing of Mycobacterium tuberculosis to First-Line Drugs is not Sufficient for Proper Management of Drug-Resistant and Multidrug-Resistant tuberculosis?

“…The widespread occurrence of drug-resistant (DR)-TB, MDR-TB and XDR-TB strains of M. tuberculosis is a serious threat to global TB control efforts [5,7]. In 2016, an estimated 600 000 new TB cases were resistant to rifampicin of which 490 000 cases were resistant to both, rifampicin and isoniazid (MDR-TB) [2].…”

“…It is also estimated that nearly 10% of all MDR-TB cases now have XDR-TB which is often fatal. Several countries, including India, Iran and South Africa, have also reported totally drug-resistant (TDR)-TB strains that are apparently resistant to all tested first-line, second-line and third-line anti-TB drugs [7,8]. However, this (TDR-TB) disease entity is currently not endorsed by WHO since drug susceptibility testing (DST) for many second-line/third-line drugs are poorly reproducible (ranging from 50% to 80%), the number of drugs tested varies among reference laboratories and the existing category of XDR-TB already encompasses extensive drug resistance to most active anti-TB drugs [9].…”

“…Compared to fully drug-susceptible (pansusceptible)-TB, treatment of patients with DR-TB and MDR-TB is much more difficult due to lengthy (9-24 months), more expensive and more toxic drug regimens and the patients often experience clinical failure or disease relapse [5,7,10]. The WHO has further categorized infection with M. tuberculosis strains resistant only to rifampicin and isoniazid without additional resistance to other first-line drugs as uncomplicated MDR-TB.…”