Dynamic modelling of improved diagnostic testing for drug-resistant tuberculosis in high burden settings

BMC Infect Dis. 2024 Nov 5;24(1):1247. doi: 10.1186/s12879-024-10027-6.

Abstract

Background: Limited diagnostic testing for drug-resistant TB (DR-TB) may lead to high rates of misdiagnosis and undertreatment. Current diagnostic tests focus only on detection of rifampicin-resistant TB (RR-TB). This study aims to determine the impact of improved diagnostic testing for a wider range of drug resistance on DR-TB outcomes in high-burden TB settings, using the Philippines and Thailand as case studies.

Methods: A dynamic compartmental model was designed to simulate population level TB transmission, accounting for acquired drug resistance from treatment failure of drug susceptible TB. Three scenarios were analyzed: (1) Use of GeneXpert MTB/RIF on all presumptive TB cases (Status Quo); (2) GeneXpert MTB/RIF + GeneXpert XDR, (3) GeneXpert MTB/RIF + targeted Next Generation Sequencing (tNGS). Scenarios were modelled over a 10-year period, from 2025 to 2034.

Results: Compared to the status quo, Scenario 2 results in a fourfold increase in annual DR-TB cases diagnosed in the Philippines and a fivefold increase in Thailand. DR-TB treatment failure decreases by 20% in the Philippines and 23% in Thailand. Scenario 3 further increases DR-TB case detection, reducing DR-TB treatment failure by 26% in the Philippines and 29% in Thailand. Reductions in DR-TB incidence and mortality ranged from 3 to 6%.

Conclusion: The use of GeneXpert XDR or tNGS as an additional diagnostic test for DR-TB significantly improves DR-TB case detection and reduces treatment failure, supporting their consideration for use in high burden settings. These findings highlight the importance of detecting a wider range of TB resistance in addition to RR-TB, the potential impact these improved diagnostic tests can have on DR-TB outcomes, and the need for additional research on cost-effectiveness of these interventions.

Keywords: Acquired drug resistance; Diagnostic testing; Drug resistance; High-burden settings; Infectious disease modelling; Tuberculosis.

MeSH terms

  • Antitubercular Agents / pharmacology
  • Antitubercular Agents / therapeutic use
  • Diagnostic Tests, Routine / methods
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Mycobacterium tuberculosis* / drug effects
  • Mycobacterium tuberculosis* / genetics
  • Philippines / epidemiology
  • Rifampin / pharmacology
  • Rifampin / therapeutic use
  • Thailand / epidemiology
  • Tuberculosis, Multidrug-Resistant* / diagnosis

Substances

  • Antitubercular Agents
  • Rifampin