Tuberculosis Phenotypic and Genotypic Drug Susceptibility Testing and Immunodiagnostics: A Review

Abstract

Tuberculosis (TB), considered an ancient disease, is still killing one person every 21 seconds. Diagnosis of Mycobacterium tuberculosis (M.tb) still has many challenges, especially in low and middle-income countries with high burden disease rates. Over the last two decades, the amount of drug-resistant (DR)-TB cases has been increasing, from mono-resistant (mainly for isoniazid or rifampicin resistance) to extremely drug resistant TB. DR-TB is problematic to diagnose and treat, and thus, needs more resources to manage it. Together with+ TB clinical symptoms, phenotypic and genotypic diagnosis of TB includes a series of tests that can be used on different specimens to determine if a person has TB, as well as if the M.tb strain+ causing the disease is drug susceptible or resistant. Here, we review and discuss advantages and disadvantages of phenotypic vs. genotypic drug susceptibility testing for DR-TB, advances in TB immunodiagnostics, and propose a call to improve deployable and low-cost TB diagnostic tests to control the DR-TB burden, especially in light of the increase of the global burden of bacterial antimicrobial resistance, and the potentially long term impact of the coronavirus disease 2019 (COVID-19) disruption on TB programs.

Tuberculosis in an Aging World

“…Although there is no diagnostic gold standard test to detect latent-TB infection in the elderly, IGRA tests have been used for the detection of IFN-γ production (in response to specific peptides from M.tb ) over the tuberculin skin test (TST), due to its increased sensitivity [ 125 ]. Phenotypic and genotypic testing have been implemented for the rapid diagnosis of M.tb infection, especially in low- and middle-income countries with high burden disease rates [ 126 ], as these tests are urgently needed, especially after the emergence of multi-drug resistant (MDR) strains. Due to the challenges of diagnosis and treatment of TB in the elderly we should focus our attention on (1) determining mechanisms to reduce inflammation levels at an appropriate time to avoid TB progression, and (2) determining methods to prevent adverse drug effects to ensure successful TB treatment outcomes in this fragile and compromised population.…”

Machine learning and phylogenetic analysis allow for predicting antibiotic resistance inM. tuberculosis

“…Three feature sets were used for our ML models: (1) all SNPs selected as described above; (2) 30% features with highest PRPS; (3) 30% features chosen randomly from all features. The 30% threshold was chosen, since it consistently delivered best performance for the PRPS-ranked features (data not shown).…”

Advancements in Tuberculosis Diagnostics: A Comprehensive Review of the Critical Role and Future Prospects of Xpert MTB/RIF Ultra Technology

“…Comparison with phenotypic drug susceptibility testing (DST): The gold standard for DST has always been traditional phenotypic DST, which involves cultivating M. tuberculosis and measuring growth when medicines are present. When it comes to identifying rifampicin resistance, Xpert MTB/RIF Ultra exhibits similar sensitivity and specificity to phenotypic DST, with the added advantage of yielding data in a much shorter amount of time [ 11 ].…”

“…Advantages over conventional methods: Xpert MTB/RIF Ultra offers several advantages over conventional DST methods, including a reduced turnaround time, lower technical expertise requirements, and the ability to detect resistance directly from clinical specimens. The system's ability to function without the need for bacterial culture is especially valuable in settings with limited laboratory infrastructure [ 11 ].…”

“…Despite these advancements, the need for more reliable and rapid diagnostic tools became increasingly evident, particularly with the emergence of drug-resistant tuberculosis strains. This realization prompted a shift towards molecular diagnostics, leading to the development of the Xpert MTB/RIF Ultra system, a groundbreaking technology designed to address the limitations of traditional methods [ 11 ].…”