New era in drug-resistant TB management powered by NGS

Tuberculosis (TB) remains a global health challenge, affecting millions each year. In 2023, an estimated 10.8 million people contracted TB, with 1.25 million deaths, according to the World Health Organization (WHO) most recent data. The emergence of drug-resistant TB has further complicated treatment efforts, underscoring the urgent need for more precise diagnostic tools. Genetic sequencing is one of the most promising advancements in TB management, which allows for early detection, personalized treatment, and better public health strategies.

On March 24, we mark the 30th World Tuberculosis Day. This year's theme, as set by the World Health Organization, is "Yes! We Can End TB: Commit, Invest, Deliver." The aim is to raise awareness about how new genetic sequencing technology can support disease management and help achieve the WHO's ambitious targets of a 90% reduction in the number of people suffering from TB and a 95% reduction in TB-related deaths by 2035.

Targeting Drug Resistance with Genetic Sequencing

Drug-resistant TB poses a growing threat, with only 44% of affected patients receiving treatment in 2023. The key to tackling this issue lies in genetic sequencing, which can identify mutations that make TB bacteria resistant to specific medications. By understanding these mutations, healthcare providers can select the most effective drugs for each patient, improving survival rates and preventing the spread of drug-resistant strains.

TB drug resistance occurs when mutations in the bacterial DNA interfere with antibiotic action. These mutations are clustered in specific genes or spread across the bacterial genome. Cutting-edge sequencing technologies can detect these mutations with high precision, allowing for targeted treatment plans.

With advances in next-generation sequencing (NGS), scientists and clinicians can analyze multiple genes simultaneously, providing a faster and more comprehensive picture of TB resistance. This approach shortens the time to diagnosis and helps develop new drugs to combat emerging resistant strains.

A Global Effort to Improve Diagnosis

Recognizing the potential of genetic screening, WHO and its partners have introduced several initiatives to improve TB diagnosis. In 2018, WHO published a series of technical guidelines, including:

- A guide on using next-generation sequencing for identifying drug resistance in M. tuberculosis.

- A manual for molecular line probe assays, which help detect drug-resistant TB faster.

- A technical manual for drug susceptibility testing, ensuring standardized testing worldwide.

"Innovations in basic science and new platforms for testing are elevating our understanding of TB drug resistance," said Dr. Tereza Kasaeva, Director of the WHO Global TB Program. "We know more about TB drug resistance than ever before, thanks to molecular science and the ability of innovators to transform such findings into modern technologies for rapid diagnosis."

Patient Story: From Uncertainty to Recovery

For Aisara, a mother from Kazakhstan, TB was an unexpected and frightening diagnosis. In August 2023, she began experiencing persistent fatigue and coughing. After visiting a clinic, a sputum test and chest X-ray confirmed the worst: she had multidrug-resistant TB (MDR-TB).

As Kazakhstan is among the top 30 MDR-TB burden countries, treatment needed to begin immediately. Partners In Health (PIH) Kazakhstan provided a series of tests, using gene sequencing technology, and precision medicine solutions to help her detect drug resistance and personalize treatment.

"I didn't understand how I got tuberculosis or where I got infected," she recalled. "There was a time when I cried and couldn’t accept my illness. But the doctors explained everything—about the disease, the medications, and the treatment process." With financial and psychological support, she completed her treatment and recovered.

Genetic sequencing in TB diagnostics

"Genetic sequencing allows us to pinpoint drug-resistant TB strains with unprecedented accuracy, ensuring patients receive the most effective treatment from day one," says Dr. Pavel Tarlykov, Head of Mass Spectrometry Lab at the National Center for Biotechnology, Kazakhstan.  

As a researcher involved in molecular testing of TB resistance, Dr. Tarlykov further explained, "NGS-based testing detects resistance mutations to new drugs, including Bedaquiline, Linezolid, and Pretomanid, that are not detectable with other methods. This personalized approach not only improves patient outcomes but also helps prevent the spread of resistant strains in the community."

Several studies on Epidemiology and Infection and Frontiers in Immunology have found that certain genetic variants and microRNA (miRNA) biomarkers are associated with a higher likelihood of latent TB infection (LTBI) progressing to active TB. By detecting these biomarkers early, healthcare providers can offer preventive treatments, stopping TB before it has a chance to develop.

BGI Genomics' PTseq™ Pathogen Targeted Sequencing based targeted next-generation sequencing (tNGS) technology enables accurate identification of TB bacteria by sequencing target genes. It helps the detection of drug resistance genes. With rapid and precise detection, clinicians can tailor personalized treatment regimens, minimize drug resistance, and improve patient outcomes.

The integration of genetic sequencing into TB diagnostics marks a turning point in global health. By enabling early detection, targeted treatment, and proactive prevention, these technologies offer a powerful weapon against one of the world’s deadliest infectious diseases.

"Increasingly, precision medicine is guiding the diagnosis of drug-resistant TB, ensuring appropriate treatment for all patients," said Dr. Karin Weyer, Coordinator of TB Diagnostics at WHO.

About PTseq™ Pathogen Targeted Sequencing

PTseq™ Pathogen Targeted Sequencing is based on ultra-multiplex PCR and targeted next-generation sequencing technology (tNGS). It specifically amplifies target genes and performs sequencing on a high-throughput sequencing platform. Through database comparison and bioinformatics algorithm analysis, it can quickly identify 274 common clinical pathogenic microorganisms, drug-resistant genes, and virulence genes, thereby significantly improving the positive rate of pathogen diagnosis, assisting clinicians in formulating personalized anti-infection treatment regimens, reducing the risk of drug resistance, and aiding in precise diagnosis and treatment of infections.

About BGI Genomics

BGI Genomics, headquartered in Shenzhen, China, is the world's leading integrated solutions provider of precision medicine. Our services cover more than 100 countries and regions, involving more than 2,300 medical institutions. In July 2017, as a subsidiary of BGI Group, BGI Genomics (300676.SZ) was officially listed on the Shenzhen Stock Exchange.