In , we can no longer hide from this worrisome problem because Hr-TB is much more common than RR and could seriously jeopardize progress in the fight against TB. This is confirmed by an analysis of aggregated drug resistance data from to across countries presented in the accompanying research study by Anna Dean and colleagues in PLOS Medicine , showing that—on average—7. The analysis by Dean and colleagues highlights major flaws in national surveillance systems, which go hand in hand with limited laboratory capacity.
The small sample sizes available from some countries make national prevalence estimates imprecise. Furthermore, the diversity of detection methods employed across settings along with the widespread lack of quality control underscores the need for improved surveillance by countries. From a clinical standpoint, if INH resistance is not detected, new patients are managed as if they had pansusceptible TB, with a substantially increased risk of treatment failure or relapse and a greater propensity to acquire further resistance [ 4 ].
This means that hundreds of thousands of patients with Hr-TB are staying in the shadows, not receiving appropriate care, and all too often ending up developing MDR-TB.
Thankfully, some progress has been made in the last couple of years. This recommendation is reflected in the updated guideline for DR-TB jointly released in by the American Thoracic Society, Centers for Disease Control and Prevention, European Respiratory Society, and Infectious Disease Society of America, which also suggests reducing the duration of pyrazinamide to 2 months in case of noncavitary and lower-burden disease or if a high risk of pyrazinamide-induced toxic effects are anticipated [ 7 ].
However, high-TB-burden countries will struggle to routinely implement these new guidelines for Hr-TB because easy access to INH-resistance testing is a challenge. Although there are WHO-endorsed technologies such as line-probe assays and liquid cultures that can detect INH resistance, these tools are limited to centralized or reference laboratories [ 8 ].
The TB diagnostics pipeline also includes several next-generation, high-throughput molecular tests that are able to simultaneously detect rifampicin and INH resistance in centralized laboratories [ 11 , 12 ]. Whole-genome sequencing WGS data continue to shed light on the wide range of mutations associated with drug resistance, thus not only improving our understanding of transmission dynamics but also helping to refine therapeutic choices for the individual patient [ 13 ].
Importantly, a deeper examination of the genotypic diversity of INH resistance would be of great benefit to inform treatment guidelines that are currently based on low-quality evidence [ 6 ]. At present, nationwide scale-up of WGS for routine TB diagnosis may not seem within reach in most high-TB-burden countries owing to cost and infrastructure requirements.
However, this technology is becoming cheaper and easier and offers an incredible opportunity to generate better quality information on INH resistance, thanks to its ability to detect clinically relevant mutations that are not captured by conventional rapid tests, which usually target only the most common katG and inhA mutations [ 13 , 14 ]. Related Links. To receive email updates about this page, enter your email address: Email Address.
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