Srinivasan Sreenidhi, Subramanian Saraswathi, Shankar Balakrishnan Sai, Ramaiyan Selvaraju Kathiravan, Manomohan Vandana, Selladurai Suganya, Jothivelu Monika, Kandasamy Srinivasan, Gopal Dhinakar Raj, Kathaperumal Kumanan, Conlan Andrew J K, Veerasami Maroudam, Bakker Douwe, Vordermeier Martin, Kapur Vivek
Department of Animal Science, The Pennsylvania State University, University Park, PA, United States.
The Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, PA, United States.
Front Vet Sci. 2020 Jul 24;7:391. doi: 10.3389/fvets.2020.00391. eCollection 2020.
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 ( ssp. . ssp. ) calves were compared with the performance of traditional PPD-tuberculin in both the skin test and 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.
在大多数低收入和中等收入国家（LMICs），由于缺乏控制计划，牛结核病（bTB）仍然流行。这是因为成功的牛结核病控制和根除计划依赖于检测和扑杀策略，而这些策略在低收入和中等收入国家在社会经济方面是不可行的。虽然卡介苗（BCG）疫苗对牛的诱导保护作用在实验和田间试验中早已得到证明，但其在控制计划中的使用却因无法使用国际兽疫局规定的基于纯化蛋白衍生物（PPD）的结核菌素皮肤试验区分接种卡介苗的动物和自然感染动物而受到阻碍。在本研究中，将一种新型的定义抗原皮肤试验（DST）在接种卡介苗的（.亚种.亚种.）犊牛中的诊断特异性和区分感染动物与接种动物（DIVA）的能力与传统PPD结核菌素在皮肤试验和干扰素-γ释放测定（IGRA）中的性能进行了比较。用两种PPD刺激全血细胞产生的IFN-γ从第0周的基线水平显著增加，而DST在接种卡介苗的犊牛中未诱导出可测量的IFN-γ产生。15头接种卡介苗的犊牛中没有一头对DST皮肤试验有反应（特异性为100%；单尾下限95%CI：82）。相比之下，15头接种卡介苗的犊牛中有10头被归类为基于PPD的单皮内试验（SIT）的反应者（接种动物中的特异性=33%；95%CI：12，62）。综上所述，这些结果提供了强有力的证据，表明DST具有高度特异性，并在皮肤试验和IGRA检测形式中都具有DIVA能力，从而能够实施基于卡介苗的牛结核病控制，特别是在检测和扑杀仍然不可行的情况下。
