A Microbiological Revolution Meets an Ancient Disease: Improving the Management of Tuberculosis with Genomics

Abstract

SUMMARY Tuberculosis (TB) is an ancient disease with an enormous global impact. Despite declining global incidence, the diagnosis, phenotyping, and epidemiological investigation of TB require significant clinical microbiology laboratory resources. Current methods for the detection and characterization of Mycobacterium tuberculosis consist of a series of laboratory tests varying in speed and performance, each of which yields incremental information about the disease. Since the sequencing of the first M. tuberculosis genome in 1998, genomic tools have aided in the diagnosis, treatment, and control of TB. Here we summarize genomics-based methods that are positioned to be introduced in the modern clinical TB laboratory, and we highlight how recent advances in genomics will improve the detection of antibiotic resistance-conferring mutations and the understanding of M. tuberculosis transmission dynamics and epidemiology. We imagine the future TB clinic as one that relies heavily on genomic interrogation of the M. tuberculosis isolate, allowing for more rapid diagnosis of TB and real-time monitoring of outbreak emergence.

Methodological and Clinical Aspects of the Molecular Epidemiology of Mycobacterium tuberculosis and Other Mycobacteria

“…When the same strains that were subjected to WGS were examined by traditional methods, they were, in part, wrongly clustered. By disclosing superspreaders, WGS allows prediction of undiagnosed cases and therefore early administration of proper treatment to newly infected individuals (55-57, 215,228,229). However, it was also observed that strains that were clustered by WGS were not necessarily linked by patient interview data.…”

Accelerating tuberculosis elimination in low-incidence settings: the role of genomics

“…Chief amongst these is that just as early MTB genomic efforts led to new molecular diagnostic tools based on a handful of sequenced genomes [9], the generation and sharing of thousands of MTB genomes will likely lead to new molecular tools for use in higher-incidence settings. Genomics is stimulating TB research and reinvigorating a community that has experienced de-prioritisation (area 1), potentially leading to renewed political interest in TB control and the specialised training and creation of central repositories.…”

“…We applaud this framework and the recognition that elimination in low-incidence countries is a unique problem, where infection occurs amongst the most difficult-to-reach individuals. Although "new research and tools" is one of the framework's areas, it overlooks an important new technology that is changing our understanding of TB and our approaches to diagnosis, phenotyping, and treatment -whole genome sequencing (WGS) of Mycobacterium tuberculosis (MTB) isolates from cases of active TB [3,4].…”

“…The recently issued WHO guidelines on the programmatic management of latent TB infection (LTBI) raised the issue of the current diagnostic gaps for both LTBI and TB diseases, which could be filled by modern, rapid, and easy-to-use molecular-and biomarker-based techniques [3].…”

Accelerating tuberculosis elimination in low-incidence settings: the role of genomics

“…migrants) also [1,8]. Within the spirit of the new WHO End TB Strategy and the perspective to achieve TB elimination the different stakeholders (including donors and scientific societies) need to collaborate in promoting the translational research activities necessary to improve diagnostic and treatment tools available for TB patients and their families [9]. Linezolid in drug-resistant tuberculosis: haste makes waste…”