Investigator(s)
| Submitter |
Thinley Dorji The Peter Doherty Institute for Infection and Immunity, University of Melbourne Thinley Dorji 
|
| Principal Investigator |
Thinley Dorji The Peter Doherty Institute for Infection and Immunity, University of Melbourne Thinley Dorji
|
| Co-Investigator(s) |
Sonam Lhamo National Tuberculosis Reference Laboratory, RCDC Sonam Lhamo
|
| Co-Investigator(s) |
Karchung Tshering National Tuberculosis Reference Laboratory, RCDC Karchung Tshering
|
| Co-Investigator(s) |
Patiyan Andersson Peter Doherty Institute of Infections and Immunology, University of Melbourne Patiyan Andersson
|
Title(s) and abstract
| Scientific title | Assessment of the suitability of Xpert MTB/XDR using whole genome sequencing for the detection of drug resistance mutations in Mycobacterium tuberculosis in Bhutan. |
| Public title | Assessment of the suitability of Xpert MTB/XDR using whole genome sequencing for the detection of drug resistance mutations in Mycobacterium tuberculosis in Bhutan. |
| Background | Despite the End TB Strategy’s target to reduce global tuberculosis (TB) incidence by 80% by 2030 compared with 2015, TB remains a major public health problem. In 2023, an estimated 10.8 million people developed TB worldwide [1]. Of these, about 400,000 cases were multidrug-resistant or rifampicin-resistant TB (MDR-TB/RR-TB), defined by resistance to rifampicin and isoniazid, the two most effective first-line drugs. MDR-TB accounted for 3.2% of new TB cases and 16% of previously treated cases [2]. Management of MDR-TB requires prolonged treatment with expensive and toxic second-line drugs and carries a high risk of additional drug resistance. Early diagnosis and prompt treatment are therefore essential to improve patient outcomes and limit transmission. A key challenge in TB control is delayed diagnosis caused by the slow growth of Mycobacterium tuberculosis. Phenotypic drug susceptibility testing (pDST), including the mycobacterial growth indicator tube (MGIT) system, remains the gold standard but typically requires 6–8 weeks to yield results. To address this delay, the World Health Organization (WHO) has endorsed rapid molecular assays such as Xpert MTB/RIF and line probe assays (MTBDRplus and MTBDRsl) for early detection of drug resistance. However, line probe assays require polymerase chain reaction–based DNA amplification. The Xpert MTB/XDR assay enables rapid detection of resistance to isoniazid, ethionamide, fluoroquinolones, and second-line injectable drugs, with high sensitivity and specificity, except for ethionamide [3]. In Bhutan, Xpert MTB/XDR is being introduced for the diagnosis of MDR-TB and second-line drug resistance. While the assay targets globally common resistance mutations, locally emerging or novel mutations may not be detected. Whole genome sequencing (WGS), validated using the WHO mutation catalogue, offers comprehensive detection of resistance-associated mutations [4]. This study therefore aims to evaluate the diagnostic accuracy of Xpert MTB/XDR by comparing its resistance profiles with WGS data from MDR-TB isolates in Bhutan. |
| Objectives | • To assess the concordance between drug resistance profiles obtained using the Xpert MTB/XDR, pDST and WGS for first-line drugs. • To evaluate the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the Xpert MTB/XDR for key first- and second-line drugs. • Monitor and describe the drug-resistance mutations to the second-line TB drugs since the implementation of the BPaLM regimen. |
| Study Methods | The study will involve the detection of variants in the ONT reads for resistance to all first-line and second-line TB drugs. These results will be compared with the phenotypic DST and genotypic test results obtained from the Xpert MTB/XDR assay. Additionally, we will also be using demographic features such as age, gender and type of TB to determine if there was any correlation among these features. |
| Expected outcomes and use of results | This study will assess the performance of Xpert MTB/XDR using pDST (for first-line drugs) and WGS as gold standards. These findings will provide evidence-based results on the suitability of the Xpert MTB/XDR for use in the Bhutanese population. |
| Keywords | Xpert MTB/XDR assay. ONT sequencing, variant calling, MDR-TB |
Research Details
| Student research | No |
| Start Date | 30-May-2026 |
| End Date | 30-Dec-2028 |
| Key Implementing Institution | University of Melbourne |
| Multi-country research | No |
| Nationwide research | Yes |
| Research Domain(s) | Communicable Disease Research |
| Research field(s) | Tuberculosis |
| Involves human subjects | No |
| Data Collection | Primary and secondary data |
| Proposal reviewed by other Committee | No |