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Overcoming TB Challenges: Targeted NGS for Comprehensive Resistance Detection

NextEdge Admin

26 Apr 2024

2 min 52 sec

In 2022, the World Health Organization (WHO) commissioned a series of systematic reviews, aiming to address the pressing need for expanded access to drug-resistance testing to combat the global tuberculosis (TB) epidemic. Currently, there are no WHO-recommended rapid diagnostics (WRDs) capable of detecting resistance to all drugs in the best available TB treatment regimens in a single test. Additionally, existing WRDs do not cover new and repurposed drugs such as bedaquiline, linezolid, delamanid, and pretomanid. These limitations underscore the necessity for more comprehensive testing methods.

Targeted next-generation sequencing (NGS) technology emerges as a promising solution. By amplifying selected genes and employing next-generation sequencing, targeted NGS can detect resistance to multiple drugs simultaneously, offering potential improvements in accuracy compared to existing WRDs. Moreover, targeted NGS-based tests have the capability to identify mutations associated with resistance, enhancing their diagnostic precision. Notably, these tests can also detect resistance to new and repurposed drugs not covered by current molecular assays.

Cost and cost-effectiveness evaluations of targeted NGS were conducted across different TB epidemiological settings, including Georgia, India, and South Africa. While targeted NGS does not replace more accessible and cheaper WRDs for detecting resistance to certain drugs, it presents an alternative for prioritized patient populations requiring comprehensive drug susceptibility testing (DST) with faster results than phenotypic DST, particularly where access to phenotypic DST is limited.

Although targeted NGS can provide crucial early DST results, its suboptimal sensitivity for some new and repurposed drugs necessitates the continued use of phenotypic DST. It’s important to note that any new in-class product must undergo evaluation by WHO before clinical use. In conclusion, expanding access to drug-resistance testing, including through targeted NGS, is imperative for achieving the goal of ending the global TB epidemic by 2030.