Economic evaluation of microbiological and host biomarker-based tests for the diagnosis of pleural tuberculosis in a high burden setting

Abstract

Background: Pleural tuberculosis (TB) remains difficult to diagnose. Tests measuring host biomarkers, such as adenosine deaminase (ADA) and unstimulated interferon-gamma, perform better than conventional microbiological tests for TB diagnosis using pleural fluid. However, there is no data on the cost-effectiveness of these diagnostic approaches.

Methods: A cost-consequence analysis was performed from the South African healthcare provider perspective to determine the cost-effectiveness of the following strategies for the diagnosis of pleural TB: (I) Smear microscopy (SM); (II) Mycobacterial-Growth-In-Tube liquid culture (MGIT); (III) adenosine deaminase (ADA); (IV) Xpert ULTRA (Xpert); (V) unstimulated interferon-gamma using IRISA-TB™ (IRISA-TB). Costs (2019 USD) were derived from national sources and outcomes from published literature. Cost-effectiveness was expressed as the cost per pleural TB case diagnosed and initiated on treatment (per 1,000 patients screened). Sensitivity analyses were performed.

Results: Total strategy costs ranged from $354,632 (SM) to $390,363 (ADA). Strategies incorporating highly specific tests, including IRISA-TB and Xpert, had the lowest costs associated with unnecessary treatment. In terms of outcomes (per 1,000 screened), IRISA-TB and ADA correctly identified the most pleural TB cases (8.4 and 8.0 cases, respectively), almost double that of MGIT (4.2 cases) and Xpert ULTRA (3.7 cases). IRISA-TB was the most cost-effective strategy, as the cost per pleural TB patient diagnosed and initiated on treatment was $44,084, ~$5,000 less than ADA (the second most cost-effective strategy; $49,065). These values were most sensitive to changes in pleural TB prevalence, treatment costs, and empirical treatment rates. The cost difference, compared to ADA, equated to a potential saving of ~US$45 million per year in South Africa.

Conclusions: IRISA-TB offers good value for money and is a potentially more cost-effective alternative to ADA for pleural TB diagnosis.

Keywords: Cost-effectiveness; adenosine deaminase; diagnosis; interferon-gamma; pleural tuberculosis.

Figure 1

Univariate analysis of each pleural TB diagnostic strategy. A univariate sensitivity analysis, represented as a tornado diagram, to demonstrate the effect of varying specific parameters on the cost per pleural TB patient diagnosed and initiated on TB treatment for the following diagnostic strategies (A) MGIT; (B) Xpert ULTRA; (C) ADA; (D) IRISA-TB. TB, tuberculosis; MGIT, Mycobacterial-Growth-In-Tube liquid culture; Xpert ULTRA, Xpert MTB/RIF ULTRA; ADA, Adenosine deaminase; IRISA-TB, Interferon-gamma Release Immuno-Suspension Assay.

Figure 2

The effect of pleural TB prevalence and empirical treatment rate on cost-effectiveness of each diagnostic strategy. The effect of varying (A) pleural TB prevalence (0.2–20%) and (B) empirical treatment rate (0–80%) on the cost per pleural TB patient diagnosed and initiated on TB treatment for each of the diagnostic strategies: MGIT (blue); Xpert ULTRA (grey); ADA (green); IRISA-TB (red). Costs on the y-axis of Figure 2A is expressed in a log₁₀ scale to better represent the relationship between prevalence and the cost effectiveness of each strategy. TB, tuberculosis; MGIT, Mycobacterial-Growth-In-Tube liquid culture; Xpert ULTRA, Xpert MTB/RIF ULTRA; ADA, adenosine deaminase; IRISA-TB, Interferon-gamma Release Immuno-Suspension Assay.

Figure 3

The effect of IRISA-TB test performance on cost-effectiveness of the IRISA-TB diagnostic strategy. The effect of varying IRISA-TB (A) sensitivity and (B) specificity on the cost per pleural TB patient diagnosed and initiated on TB treatment. The red dot represents the baseline cost-effectiveness of IRISA-TB ($44,084). Each dotted line represents the cost-effectiveness (y-axis) of each of the other diagnostic strategies: MGIT; Xpert ULTRA; ADA. Once the red line is below the dotted line of a particular strategy then IRISA-TB is more cost-effective strategy. IRISA-TB, Interferon-gamma Release Immuno-Suspension Assay; MGIT, Mycobacterial-Growth-In-Tube liquid culture; Xpert ULTRA, Xpert MTB/RIF ULTRA; ADA, adenosine deaminase; TB, tuberculosis.