Application of Bayesian modeling for diagnostic assays of Mycobacterium avium subsp. paratuberculosis in sheep and goats flocks

Abstract

Background This study aimed to screen the sera of goats and sheep from flocks suspected of Mycobacterium avium subsp. paratuberculosis (MAP) infection by a newly standardized Mce-truncated ELISA (Mt-ELISA) kit for the detection of antibodies against MAP. Four diagnostic applied tests were evaluated including Indigenous plate-ELISA (IP-ELISA), Mt-ELISA, fecal Polymerase Chain Reaction (f-PCR) and fecal culture (FC). Materials and methods Assuming the absence of a gold standard, latent-class models in a Bayesian framework were used to estimate the diagnostic accuracy of the four tests for MAP. Results Mt-ELISA had higher Sensitivity (Se) in sheep (posterior median: 0.68 (95% Probability Interval (PI): 0.43–0.95), while IP-ELISA recorded the highest Se in goats as 0.83 (95% PI, 0.61–0.97). The f-PCR Se estimate slightly differed between species [sheep 0.36 (0.19–0.58), goats 0.19 (0.08–0.35)], while the Se of FC was similar between species [sheep 0.29 (0.15–0.51), goats 0.27 (0.13–0.45)]. The specificity estimates for all tests were high, close to unity, and similar between species. Conclusion Overall, the results showed that the Mt-ELISA method can be used for MAP detection in small ruminants’ flocks.

Immuno-reactivity evaluation of Mce-truncated subunit candidate vaccine against Mycobacterium avium subspecies paratuberculosis challenge in the goat models

“…Developing the appropriate vaccine for JD is a successful strategy for the treatment of this incurable disease [ 44 ]. Current trends in JD monitoring are looking for MAP-specific immunogenic antigens, to develop improved diagnostic and vaccine reagents for animal and human protection [ 16 , 33 , 45 , 46 ]. Biological functions of Mce proteins are unknown, but there is growing evidence that mce gene expression is important for mycobacterial virulence [ 47 – 49 ].…”

“…Biological functions of Mce proteins are unknown, but there is growing evidence that mce gene expression is important for mycobacterial virulence [ 47 – 49 ]. MAP Mce operon is surface exposed, which corresponds to their proposed roles in pathogenicity of MAP, invasiveness of host cells and interactions between bacteria and hosts, making them suitable candidates for the JD vaccine production [ 16 , 33 , 49 ]. In this study, the immune-reactivity and protective efficacy of the novel Mce-truncated protein to be used as an immunogenic candidate to develop a subunit vaccine against paratuberculosis infection was assessed in the goat models.…”

“…Mammalian cell entry (Mce) protein of MAP play an important role in mycobacterial invasion and survival within macrophages [ 32 – 36 ]. These Mce-families of protein are present on the outer membrane of MAP, and are among the virulence-related proteins which can elicit an immune response against mycobacterial infection [ 22 , 33 , 36 – 39 ]. MAP2191 gene encodes a protein which is a unique membrane protein of MAP with unknown function [ 33 , 40 ].…”

“…These Mce-families of protein are present on the outer membrane of MAP, and are among the virulence-related proteins which can elicit an immune response against mycobacterial infection [ 22 , 33 , 36 – 39 ]. MAP2191 gene encodes a protein which is a unique membrane protein of MAP with unknown function [ 33 , 40 ]. In earlier studies, we have expressed Mce-truncated protein (encoded by a partial part of MAP2191 gene), used as a potential candidate for the development of Mce-ELISA kit for the diagnosis of JD in domestic livestock [ 16 ].…”

Role of Mce proteins inMycobacterium avium paratuberculosisinfection

“…Proteins in the Mce family in pathogen Mycobacteria have been observed to aid the attachment and invasion of the bacteria to host epithelial cells. More recently, the mce5 cluster has been identified as important for MAP virulence (Hemati et al, 2018), and mutation of mce1D resulted in a reduced capacity of MAP to infect MDBK cells (Alonso-Hearn et al, 2008).…”