An innovative study using whole genome sequencing (WGS) has revealed significant genetic diversity among rifampicin-resistant Mycobacterium tuberculosis (M. tb) strains in Botswana. These findings offer crucial insights that could shape future strategies for combating drug-resistant tuberculosis (TB).
The study, “Whole Genomic Analysis Uncovers High Genetic Diversity of Rifampicin-Resistant Mycobacterium tuberculosis Strains in Botswana”, led by Tuelo Mogashoa, was published in Frontiers in Microbiology on February 11, 2025. Mogashoa, is a TB researcher at Botswana Harvard Health Partnership (BHP) and also a PhD candidate at Stellenbosch University, under the Trials of Excellence in Southern Africa (TESA). She is a Fellow under the TESA Addressing Gender and Diversity Regional Gaps in Clinical Research Capacity (TAGENDI) fellowship programme.
In an interview with The BHP Insider, Mogashoa noted that “Drug-resistant TB remains a major public health threat and understanding the genetic diversity of circulating strains is critical for developing effective treatment strategies.”
The study analyzed 202 stored M. tb isolates from individuals diagnosed with rifampicin-resistant TB (RR-TB) between January 2016 and June 2023. WGS revealed a high prevalence of multidrug-resistant TB (MDR-TB) (57.9%), with 16.8% classified as pre-extensively drug-resistant (Pre-XDR), 20.2% as RR-TB, and 0.5% as high-level isoniazid-resistant TB (HR-TB).
Mogashoa noted that Botswana harbors a complex and evolving TB epidemic, with three dominant lineages: lineage 4 (60.9%), lineage 1 (22.8%) and ineage 2 (13.9%).
“This genetic diversity influences how the disease spreads and responds to treatment,” she explained.
The study also identified key drug resistance mutations, including:
- rpoB S450L for rifampicin (28.6%)
- katG S315T for isoniazid (60.5%)
- embA_c.-29_-28delCT and embB Q497R for ethambutol (31.7%)
- gyrA A90V for fluoroquinolones (79.4%)
Encouragingly, no resistance-associated mutations were found for newer TB drugs such as bedaquiline and delamanid, a promising sign for treatment options in Botswana.
“This study reinforces the need for continuous genomic surveillance of TB in Botswana,” Mogashoa stated. “By identifying drug resistance patterns early, we can improve treatment regimens and slow the spread of resistant strains.”
With Botswana’s commitment to eliminating TB, these findings highlight the urgent need for routine genomic monitoring and targeted interventions. As BHP expands its research on pathogen genomic surveillance, this study marks a crucial step toward improving TB control strategies and guiding public health policies.
“BHP scientists are committed to working with key stakeholders such as policymakers to ensure that genomic research plays a pivotal role in the fight against TB and antimicrobial resistance in Botswana,” Mogashoa concluded.
