Decentralization of resistant pulmonary Tuberculosis (TB) diagnosis in Pakistan: evaluation of Xpert® MTB/XDR Assay for rapid detection of fluoroquinolones and isoniazid resistant TB

Abstract

Background: Drug resistant Tuberculosis (DR-TB) is a major threat to global health. In high burden DR-TB settings, as Pakistan, decentralization of drug susceptibility testing (DST) is one of the key strategies recommended by WHO to end the TB epidemic. The peripheral rapid DST for isoniazid and fluoroquinolones is now possible as a new molecular assay, Xpert® MTB/XDR (Cepheid, USA) was recently endorsed by WHO. Aim: This study aims to assess the performance of Xpert® MTB/XDR and to evaluate the feasibility of implementing this test in peripheral settings in Pakistan. It also proposed an updated DR-TB diagnostic algorithm tailored to the country diagnostic network needs. Methods: To establish Xpert® MTB/XDR accuracy, a secondary data analysis was performed using results from a cross sectional observational study previously conducted. A thematic literature review provided data on Pakistan TB diagnostic network. Findings: The accuracy analysis demonstrated that Xpert® MTB/XDR has the characteristics required by WHO for the detection of isoniazid resistance at the peripheral level. Regarding fluoroquinolones resistance, Xpert® MTB/XDR reaches only one of the WHO targets (i.e., sensitivity) in the RR-TB cohort (90,48%; 95%CI 80,7-95,8). Even if the standard for DST remains the phenotypic test, a faster and more reliable assay appears to be needed in this setting. Conclusion: The proposed DR-TB diagnostic algorithm, tailored to Pakistan diagnostic network needs, may reduce considerably TB diagnosis turnaround time. This strategy will contribute to ensure equitable and prompt access to DR-TB diagnosis, improving the diagnostic network effectiveness and efficacy in ensuring TB care and control.