Evaluation of the Performance of the IDvet IFN-Gamma Test for Diagnosis of Bovine Tuberculosis in Spain

Abstract

In Spain, the national bovine tuberculosis (bTB) eradication program is based on yearly skin testing of every ≥6 weeks old animal using the single or comparative tuberculin test and parallel use of the interferon-gamma (IFN-γ) assay as an ancillary diagnostic test in infected herds. There are several versions of the latter. Recently, a new commercial IDvet IFN-γ assay has been authorized for use in the program, but there is limited scientific evidence about its performance in different epidemiological settings. Therefore, two studies to evaluate the performance of the IDvet assay were conducted. In study 1, a concordance analysis between the new IDvet and the Bovigam IFN-γ assay in use in Spain for over 10 years was conducted. In study 2, results from the IDvet assay when applied in tandem with a single intradermal tuberculin (SIT) test were used to evaluate the concordance between both tests and to estimate their sensitivity (Se) and specificity (Sp) using a Bayesian latent-class model. Field data from cattle herds located in Madrid and Castilla y Leon (Spain) were collected. For study 1, herd selection was based on a high expected prevalence of reactors to the IFN-γ assay, while herds were selected at random to estimate Se and Sp of the new IDvet assay in study 2. Agreement between the results obtained with both kits for IFN-γ assay was poor (Kappa = 0.20), and a receiver operating characteristic (ROC) analysis indicated a low Se of the new IDvet relative to the Bovigam in a heavily bTB infected population. The Bayesian latent-class analysis estimated the Se of the IDvet assay to be 36.7% [95% probability posterior interval (PPI) 14.7–78.8%] with estimated Sp close to 100% when the cut-off recommended by the manufacturer (35) was applied. At the alternative cut-off values of 16 and 4, the estimated Se of the IDvet assay increased to 49.0% (PPI: 24.8–94.1%) and 56.0% (PPI: 30.8–96.3%), respectively, while maintaining a high specificity. The results suggest that the new IDvet assay may have lower sensitivity than the Bovigam for diagnosis of bTB in cattle herds in Spain, and that adjusting its cut-off might be considered.

Tuberculin PPD Potency Assays in Naturally Infected Tuberculous Cattle as a Quality Control Measure in the Irish Bovine Tuberculosis Eradication Programme

“…Casal et al (69) compared the performance of the SIT, ID-Vet IFN γ, and the Bovigam ® noting that “Over the 113 cattle with confirmed bTB (group 2), 32 (28.3%) were classified as positive reactors by Bovigam ® but negative to the SIT test;” and in the same group “36 cattle (31.9%) were positive with Bovigam ® (0.05 cut-off point) but negative to IDvet IFN-γ assay (35% s/p cut-off point).” However, similar results were achieved between the IFN-γ assays applying the 0.1 cut-off point in the Bovigam and the S/P ratio of 16 in the IDvet test. These results were comparable to the results obtained by de la Cruz et al (70) who also found the IDvet IFN-γ assay less sensitive than the Bovigam ® but that the Se of the IDvet IFN-γ assay might be improved by adjusting the cut off points. The Bovigam TB kit flier states that BOVIGAM Tuberculin PPD produced by Prionics Lelystad B.V. uses bovine Tuberculin PPD at a potency of 30,000 IU/mL and avian Tuberculin PPD at a potency of 25,000 IU/mL (https://assets.thermofisher.com/TFS-Assets/LSG/Flyers/animalhealth_flier_bovigam_tb_CO121138.pdf).…”

Modeling the Accuracy of Two in-vitro Bovine Tuberculosis Tests Using a Bayesian Approach

“…Based on DIC models with three (Se, Sp, Prev) parameters were preferred above those with seven (Se 1 , Se 2 , rhoD, Sp 1 , Sp 2 , rhoDc, Prev). Correlation between test results were very low in all models/test pairs, what had been already described for the IGRA and single skin test (5, 6) such result is expected because the diagnostic tests evaluated here have high Sp (1). However, the comparatively higher correlation between the ELISA and CFT or CFT-CCT estimates in bTB-infected animals (rohD) was surprising, given that the ELISA and the skin tests target different immune responses and therefore a larger degree of independence is often assumed (32, 56).…”

“…In order to estimate the performance of the in-vitro assays evaluated here we used LCA, a suitable analytical approach when no reliable gold standard is available (1, 53, 54), as it is the case for bTB (5, 6, 55). We fitted two different latent-class models using prevalence priors based on expert opinion or diagnostic test results in order to evaluate the potential impact of a given methodological approach.…”

Evaluation of Three Commercial Interferon-γ Assays in a Bovine Tuberculosis Free Population

“…Recently, a new IFN-γ assay has become commercially available (ID Screen Bovine Tuberculosis IFN-γ, IDvet, Grabels, France), and it has already been extensively used in different countries including Switzerland. However, independent evaluations on the test accuracy under field conditions are either not publicly available or scarce, showing low Se (36.7%) when applying the cutoff recommended by the manufacturer or slightly better values (49.0–56.0%) using more stringent cutoff thresholds ( 25 ).…”