The PARR-TB Study: Unlocking the power of next-generation sequencing (NGS) in the fight against drug-resistant TB
Despite significant progress over the last few decades, tuberculosis (TB) continues to be the world’s leading infectious disease, claiming over 1 million lives each year. Though TB is typically considered a treatable disease, drug-resistant tuberculosis (DR-TB) is a growing public health concern. When the disease does not respond to standard antibiotics – such as rifampicin, for example – treatment becomes longer, more complex, and often leads to poorer health outcomes for patients. Every year, 0.5 million people are affected by DR-TB, making it a major contributor to antimicrobial resistance globally. To stay one step ahead of the disease, better diagnostic and treatment solutions are urgently needed.
The GenPath Africa project aims to address the growing danger of DR-TB through the Precision Action for Rifampicin-Resistant TB (PARR-TB) study. The study brings together researchers from the University of Antwerp and Stellenbosch University who seek to unlock the full potential of next-generation sequencing (NGS) to address the rising threat of rifampicin-resistant TB (RR-TB) in the Western Cape Province of South Africa.
The growing danger of rifampicin-resistant TB (RR-TB)
Rifampicin resistance is an invariably complex issue, notes Prof Rob Warren, co-principal investigator of the PARR-TB study. Treating patients with RR-TB can be extremely complicated: “Until recently, treating TB caused by rifampicin-resistant Mycobacterium tuberculosis (Mtb) required 18 months or more, with many side effects and a high risk of poor treatment outcomes,” he says. A newer, more efficient treatment in the form of the BPal regimen (a combination of the antibiotics bedaquiline, pretomanid, and linezolid) is now available but resistance to this treatment is already emerging. “Resistance testing is not always conducted, and when it is, current methods may not reliably detect resistance due to a lack of standardisation or gaps in our understanding of the exact mechanisms that confer resistance. Comprehensive resistance testing is essential to ensure that people suffering from drug-resistant TB receive the most effective treatment as early as possible.”
Unlocking the power of next-generation sequencing (NGS)
As part of the PARR-TB study, our researchers will increase comprehensive resistance testing by conducting NGS of TB-pathogens in the context of the BPal regimen administered to TB-patients in the South African region. Leveraging the power of NGS will generate more comprehensive resistance profiles of drug-resistant pathogens than standard diagnostic methods can currently provide. “A single NGS test can detect resistance to nearly all TB drugs, helping to identify the most effective treatment for each case,” shares PARR-TB’s principal investigator Prof Annelies Van Rie. If integrated into routine healthcare, NGS can enable healthcare workers to tailor treatment based on the specific genetic makeup of pathogens and thus deliver the exact treatment individual patients affected by rifampicin resistance need.
NGS, adds Prof Warren, could also be the key to understanding resistance patterns and fighting DR-TB spread on a larger scale: “Genome sequencing of TB pathogens provides insights into drug resistance, transmission patterns, and bacterial evolution. This information can improve surveillance, guide treatment strategies, and contribute to the development of new drugs and diagnostics. With broader implementation, NGS has the potential to transform TB control efforts and move closer to ending the disease.”
The PARR-TB study has the potential to impact public health strategies far beyond individual patient care, affirms Prof Van Rie. The large-scale resistance data generated through the study can lay the foundation for precision public health strategies that will enable us to fight the spread of DR-TB on a much larger scale. “This information will help track emerging resistance trends, refine TB treatment guidelines, inform preventative therapy decisions and guide targeted interventions to curb TB transmission and improve long-term control strategies,” she says. “Ultimately, it can help reduce the burden of drug-resistant TB in Africa.”
