背景:牛结核病(bTB)是一种慢性疾病,由结核分枝杆菌复合体的任何成员感染引起。根据目前使用的世界动物健康组织,通常用基于结核菌素的皮内皮肤试验诊断感染的动物。然而,由于假阳性反应率高,结核菌素不适合在BCG疫苗接种的动物中使用。已使用BCG中不存在的抗原(ESAT-6,CFP-10和Rv3615c)鉴定了基于肽的定义皮肤试验(DST)抗原,但他们在水牛中的表现仍然未知。为了评估DST与基于结核菌素的单个皮内试验(SIT)和单个皮内宫颈比较试验(SICCT)的比较性能,我们筛选了来自印度哈里亚纳邦两个地区49个有组织的奶牛场的543只雌性水牛。
结果:我们发现37(7%),4只(1%)和18只(3%)水牛是使用SIT的反应堆,SICCT和DST测试,分别。在37个SIT反应堆中,4例SICCT阳性,12例DST阳性.结果表明,所有动物的三项测试均未呈阳性,6只DST阳性动物为SIT阴性。一起,共有43只动物是SIT反应器,DST,或者两者兼而有之,和两个测定显示中等一致性(科恩的Kappa0.41;95%置信区间(CI):0.23,0.59)。相比之下,在SIT和SICCT之间仅观察到轻微的一致性(Cohen'sKappa0.18;95%CI:0.02,0.34)。使用贝叶斯潜在类模型,我们估计测试特异性为96.5%(95%CI,92-99%),SIT的99.7%(95%CI:98-100%)和99.0%(95%CI:97-100%),SICCT和DST,分别,但敏感度明显较低,为58%(95%CI:35-87%),9%(95%CI:3-21%),34%(95%CI:18-55%),尽管有广泛和重叠的可信区间。
结论:综合来看,我们的调查表明,DST具有与SICCT相当的测试特异性,SIT和SICCT之间的敏感性介于对疑似结核病的水牛的鉴定之间。我们的研究强调了对未来进行详细尸检的有力试验的迫切需要,通过对反应器和非反应器动物的免疫学和微生物学分析,更好地定义了检测性能中观察到的巨大差异的潜在因素,特别是在SIT和SICCT之间。
BACKGROUND: Bovine tuberculosis (bTB) is a chronic disease that results from infection with any member of the Mycobacterium tuberculosis complex. Infected animals are typically diagnosed with
tuberculin-based intradermal skin tests according to World Organization of Animal Health which are presently in use. However,
tuberculin is not suitable for use in BCG-vaccinated animals due to a high rate of false-positive reactions. Peptide-based defined skin test (DST) antigens have been identified using antigens (ESAT-6, CFP-10 and Rv3615c) which are absent from BCG, but their performance in buffaloes remains unknown. To assess the comparative performance of DST with the
tuberculin-based single intradermal test (SIT) and the single intradermal comparative cervical test (SICCT), we screened 543 female buffaloes from 49 organized dairy farms in two districts of Haryana state in India.
RESULTS: We found that 37 (7%), 4 (1%) and 18 (3%) buffaloes were reactors with the SIT, SICCT and DST tests, respectively. Of the 37 SIT reactors, four were positive with SICCT and 12 were positive with the DST. The results show that none of the animals tested positive with all three tests, and 6 DST positive animals were SIT negative. Together, a total of 43 animals were reactors with SIT, DST, or both, and the two assays showed moderate agreement (Cohen\'s Kappa 0.41; 95% Confidence Interval (CI): 0.23, 0.59). In contrast, only slight agreement (Cohen\'s Kappa 0.18; 95% CI: 0.02, 0.34) was observed between SIT and SICCT. Using a Bayesian latent class model, we estimated test specificities of 96.5% (95% CI, 92-99%), 99.7% (95% CI: 98-100%) and 99.0% (95% CI: 97-100%) for SIT, SICCT and DST, respectively, but considerably lower sensitivities of 58% (95% CI: 35-87%), 9% (95% CI: 3-21%), and 34% (95% CI: 18-55%) albeit with broad and overlapping credible intervals.
CONCLUSIONS: Taken together, our investigation suggests that DST has a test specificity comparable with SICCT, and sensitivity intermediate between SIT and SICCT for the identification of buffaloes suspected of tuberculosis. Our study highlights an urgent need for future well-powered trials with detailed necropsy, with immunological and microbiological profiling of reactor and non-reactor animals to better define the underlying factors for the large observed discrepancies in assay performance, particularly between SIT and SICCT.