Abstract
In most low- and middle-income countries (LMICs), bovine tuberculosis (bTB) remains endemic due to the absence of control programs. This is because successful bTB control and eradication programs have relied on test-and-slaughter strategies that are socioeconomically unfeasible in LMICs. While Bacillus Calmette–Guérin (BCG) vaccine-induced protection for cattle has long been documented in experimental and field trials, its use in control programs has been precluded by the inability to differentiate BCG-vaccinated from naturally infected animals using the OIE-prescribed purified protein derivative (PPD)-based tuberculin skin tests. In the current study, the diagnostic specificity and capability for differentiating infected from vaccinated animals (DIVA) of a novel defined antigen skin test (DST) in BCG-vaccinated (Bos taurus ssp. taurus x B. t. ssp. indicus) calves were compared with the performance of traditional PPD-tuberculin in both the skin test and in vitro interferon-gamma release assay (IGRA). The IFN-γ production from whole blood cells stimulated with both PPDs increased significantly from the 0 week baseline levels, while DST induced no measurable IFN-γ production in BCG-vaccinated calves. None of the 15 BCG-vaccinated calves were reactive with the DST skin test (100% specificity; one-tailed lower 95% CI: 82). In contrast, 10 of 15 BCG-vaccinated calves were classified as reactors with the PPD-based single intradermal test (SIT) (specificity in vaccinated animals = 33%; 95% CI: 12, 62). Taken together, the results provide strong evidence that the DST is highly specific and enables DIVA capability in both skin and IGRA assay format, thereby enabling the implementation of BCG vaccine-based bTB control, particularly in settings where test and slaughter remain unfeasible.
Highlights
Bovine tuberculosis is a chronic, granulomatous, inflammatory disease that is predominantly caused by members of the Mycobacterium tuberculosis complex (MTBC) in cattle
Given that the specificity of using tuberculin as stimulating antigen in interferon-gamma release assay (IGRA) is expected to be around 95%, this is not an unexpected test outcome, given the fact that most animals at this time point were younger than 6 months, the minimum age cut-off for IGRA to avoid increased false-positive rates due to natural killer (NK) cell activity [22]
The results showed no differences in the IFN-γ responses of whole blood from BCGvaccinated animals stimulated with either of the purified protein derivative (PPD), suggesting that Bacillus Calmette–Guérin (BCG) stimulates immune responses that are crossreactive to antigens contained in PPD-B and PPD-A (Table 1)
Summary
Bovine tuberculosis (bTB) is a chronic, granulomatous, inflammatory disease that is predominantly caused by members of the Mycobacterium tuberculosis complex (MTBC) in cattle. Bacillus Calmette–Guérin (BCG) is a live attenuated strain of M. bovis that was initially isolated from the udder of a tuberculous cow [8, 9] This M. bovis strain was serially passaged for a period of 13 years (1908–1921) at the Pasteur Institute and since has been used as a vaccine against TB in humans. Numerous reports have demonstrated BCG-induced protection in field trials conducted in many different countries and settings [10] Despite this promise, BCG has previously not been considered for widespread use as a livestock vaccine against bTB, primarily due to its cross-reactivity with the OIE-recommended purified protein derivatives (PPDs)-tuberculin based skin tests, resulting in an inability to differentiate naturally M. tuberculosis complex infected from BCG-vaccinated animals
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
