Serology
The immune response to M. bovis infections is complex, and it varies substantially between species. A strong humoral response partially replaces the predominantly delayed cell-mediated immune response found during the early and mid-stages of the disease.
Early detection of an antibody response is characteristically present only in a few species. In some of them, the response may be detectable as early as 10 days but usually from 3 to 4 weeks after infection allowing the use of ELISA as a reliable test in them. The low Sp of serology is probably the consequence of the characteristics of the humoral response in animals with tuberculosis. The initial characteristically strong cell-mediated immune response of BTB that is replaced by a humoral response influences the accuracy of tests based on both the cell-mediated and the humoral responses. The timeframe leading to this shift depends on many factors, including the species, its immunological status, and infection dose, and may be as long as 20 weeks in experimentally infected cattle. The antibody response in deer seems to develop earlier compared to cattle (Ritacco et al. 1991).The use of multi-antigen combinations and cocktails of selected antigens led to the development of more refined serological tests such as multi-antigen print immunoassay (MAPIA), lateral flow rapid tests, the fluorescence polarization assay (FPA), multiplex plate systems, dual platform assays, chemiluminescent platforms, and improved ELISAs. Numerous issues such as the questions about Sp and its variability depending on the stage of the disease, remain. Other factors including immune compromised animals and coinfections with non-tuberculous mycobacteria must be addressed before these techniques will have the same Se and Sp as the cell-mediated immunity (CMI)-based tests and before they can be used with confidence as a replacement of the CMI-based diagnostic tests (reviewed by Schiller et al.
2010a).The ELISAs generally have a lower Se and Sp than the TSTs and the IFN-γ assays, and there is a considerable variation in their efficacy, which is likely to improve during the later stages of the disease when the humoral response is the predominant immunological response (Nunez-Garcia et al. 2018). Different animal species and mycobacterial strains respond to different antigens as they have distinct antigen reactivity profiles that affect the sensitivity of the tests (Bezos et al. 2014;
Lyashchenko et al. 2018). In goats, for instance, the Se was higher with the CCT and IFN-γ assay (83.7%, each) and the anamnestic ELISA (88.6%) compared to the Se of the standard ELISA (54.9%; Gutierrez et al. 1998). The current application of the serological tests lies in using them in parallel with the TSTs and IFN-γ (Casal et al. 2014; Waters et al. 2017).
Using antibody detection as a diagnostic procedure would have the advantage of being cheap, allowing the testing of large numbers of specimens in a short time and standardization of the technique in different laboratories. Its use for the diagnosis of BTB has been investigated for a long time, but because of numerous unresolved issues and the general lack of Sp, very few serological tests are suitable for field use, and a substantial amount of work will still have to be done to allow their use for general diagnostic purposes.
9.5.1 Serology in Wildlife
Serology as a test for BTB has also been assessed in wildlife. The results, with few exceptions, have been similar to those in cattle. Serological tests though have been approved for diagnostic purposes in the USA for elephants and deer, and in the UK for badgers, but in general the results are too limited to determine the Se and Sp of the individual assays. The use of a test combination consisting of STAT-PAK, Enferplex, and Mycobacterium culture from tracheal lavage and swabs for BTB monitoring appears to have potential for general use for surveillance purposes (Bruns et al. 2017), but they require further refinement. There seems to be a strong relationship between serological responses and the presence of tuberculosis in African lions too, but the data are yet insufficient to determine the Se and Sp of the ElephantTB STAT-PAK® and VetTB® assays used (Miller et al. 2015).
9.6