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

Abstract

Accuracy of new or alternative diagnostic tests is typically estimated in relation to a well-standardized reference test referred to as a gold standard. However, for bovine tuberculosis (bTB), a chronic disease of cattle, affecting animal and public health, no reliable gold standard is available. In this context, latent-class models implemented using a Bayesian approach can help to assess the accuracy of diagnostic tests incorporating previous knowledge on test performance and disease prevalence. In Uruguay, bTB-prevalence has increased in the past decades partially because of the limited accuracy of the diagnostic strategy in place, based on intradermal testing (caudal fold test, CFT, for screening and comparative cervical test, CCT, for confirmation) and slaughter of reactors. Here, we evaluated the performance of two alternative bTB-diagnostic tools, the interferon-gamma assay, IGRA, and the enzyme-linked immunosorbent assay (ELISA), which had never been used in Uruguay in the absence of a gold standard. In order to do so animals from two heavily infected dairy herds and tested with CFT-CCT were also analyzed with the IGRA using two antigens (study 1) and the ELISA (study 2). The accuracy of the IGRA and ELISA was assessed fitting two latent-class models: a two test-one population model (LCA-a) based on the analysis of CFT/CFT-CCT test results and one in-vitro test (IGRA/ELISA), and a one test-one population model (LCA-b) using the IGRA or ELISA information in which the prevalence was modeled using information from the skin tests. Posterior estimates for model LCA-a suggested that IGRA was as sensitive (75–78%) as the CFT and more sensitive than the serial use of CFT-CCT. Its specificity (90–96%) was superior to the one for the CFT and equivalent to the use of CFT-CCT. Estimates from LCA-b models consistently yielded lower posterior Se estimates for the IGRA but similar results for its Sp. Estimates for the Se (52% 95%PPI:44.41-71.28) and the Sp (92% 95%PPI:78.63–98.76) of the ELISA were however similar regardless of the model used. These results suggest that the incorporation of IGRA for detection of bTB in highly infected herds could be a useful tool to improve the sensitivity of the bTB-control in Uruguay.

Risk factors and true prevalence of bovine tuberculosis in Bangladesh

“…Within this area, we are also confident that 90% of all herds have a prevalence less or equal to 0.35 and we are 95% certain that it does not exceed 0.45 [17][18][19]21]. The mean values of the reported sensitivity and specificity of caudal fold test (CFT) were 80% and 90% and we can be 95% sure that they are higher than 51% and 80%, respectively [34][35][36][37][38][39]. Whereas the mean values of the reported sensitivity and specificity of CFT-comparative cervical tuberculin tests (CFT-CCT) were 53% and 97% and we can be 95% certain that they are higher than 46% and 94%, respectively [34][35][36][37][38][39].…”

Intra-vitam Diagnosis of Tuberculosis in Pigs: Concordance Between Interferon-Gamma Release Assay and Comparative Tuberculin Skin Test

“…Unfortunately, no PCR on tissues was performed in our study, so the supposed lack of sensitivity of microbiological examination cannot be ruled out. However, although culture and PCR are widely accepted as a gold-standard diagnostic method for bTB, Bayesian latent class statistical analysis has been recently used to assess sensitivity and specificity of the different diagnostic tools for bTB (29)(30)(31)(32)(33)(34) in the absence of a "perfect" gold-standard method. Since these studies were conducted on Tuberculosis affecting cattle, similar studies are envisaged also in the pig population.…”

Modelling the effect of test‐and‐slaughter strategies to control bovine tuberculosis in endemic high prevalence herds

“…The six alternatives were the use of CFT only, the use of IGRA (assessing two different antigens commercially available for the region), and the parallel combination of CFT + IGRA, CFT + ELISA or IGRA + ELISA (Table 1). For the parallel combination, the IGRA selected used peptide‐cocktail antigens given it demonstrated to have an improved specificity with similar sensitivity under Uruguayan field conditions (Picasso‐Risso, Gil, et al, 2019; Picasso‐Risso, Perez, et al, 2019).…”

“…Within the past two decades, however, the number of bTB‐infected dairy herds, the within‐herd bTB prevalence and the time required from detection to regaining the officially tuberculosis‐free status (OTF) increased (Picasso‐Risso, Gil, et al, 2019; Picasso‐Risso, Perez, et al, 2019) leading to unprecedented challenges in the control of bTB in Uruguay. The difficulty in controlling bTB has been associated with changes in dairy demographic structure and management (Picasso et al., 2017; Picasso‐Risso, Gil, et al, 2019; Picasso‐Risso, Perez, et al, 2019), including larger herds (>360 animals), higher animal density (DIEA, 2018), increased animal movements and more intensive animal rearing than traditional dairy farming prior to the 1990s (Picasso et al., 2017). In this context, the question is whether the current Uruguayan bTB programme is sufficient to control bTB in herds once the infection is confirmed and some level of within‐herd transmission is suspected.…”

“…An integrated within‐ and between‐herd model has been parameterized and validated to evaluate the performance of risk‐targeted bTB surveillance using the current test‐and‐slaughter bTB strategies in Uruguay (VanderWaal et al., 2017). However, previous studies have suggested that the sensitivity of the test‐and‐slaughter programme is impaired in high prevalence dairy herds in Uruguay (Picasso‐Risso, Gil, et al, 2019; Picasso‐Risso, Perez, et al, 2019), and given that depopulation of these large herds is not economically, logistically or socially feasible, the use of alternative diagnostic in vitro assays is a reasonable alternative strategy to evaluate for control in these herds. In this study, we aimed to assess the effectiveness of different alternative bTB‐control strategies, to ultimately elucidate the optimal option for control in bTB‐high prevalence dairy herds in Uruguay when depopulation is not an alternative.…”