Considerable effort has been directed toward controlling Johne’s disease (JD), a chronic granulomatous intestinal inflammatory disease caused by Mycobacterium avium subsp. paratuberculosis (MAP) in cattle and other ruminants. However, progress in controlling the spread of MAP infection has been impeded by the lack of reliable diagnostic tests that can identify animals early in the infection process and help break the transmission chain. To identify reliable antigens for early diagnosis of MAP infection, we constructed a MAP protein array with 868 purified recombinant MAP proteins, and screened a total of 180 well-characterized serum samples from cows assigned to 4 groups based on previous serological and fecal test results: negative low exposure (NL, n = 30); negative high exposure (NH, n = 30); fecal-positive, ELISA-negative (F + E−, n = 60); and both fecal- and ELISA-positive (F + E+, n = 60). The analyses identified a total of 49 candidate antigens in the NH, F + E−, and F + E+ with reactivity compared with the NL group (p < 0.01), a majority of which have not been previously identified. While some of the antigens were identified as reactive in only one of the groups, others showed reactivity in multiple groups, including NH ( n = 28), F + E− ( n = 26), a n d F + E+ ( n = 17) groups. Using combinations of top reactive antigens in each group, the results reveal sensitivities of 60.0%, 73.3%, and 81.7% in the NH, F + E−, and F + E+, respectively at 90% specificity, suggesting that early detection of infection in animals may be possible and enable better opportunities to reduce within herd transmission that may be otherwise missed by traditional serological assays that are biased towards more heavily infected animals. Together, the results suggest that several of the novel candidate antigens identified in this study, particularly those that were reactive in the NH and F + E− groups, have potential utility for the early sero-diagnosis of MAP infection.
A defined antigen skin test has been developed for the reliable diagnosis and vaccine-based control of bovine tuberculosis.
Bovine tuberculosis (bTB) is a chronic disease of cattle that impacts productivity and represents a major public health threat. Despite the considerable economic costs and zoonotic risk consequences associated with the disease, accurate estimates of bTB prevalence are lacking in many countries, including India, where national control programmes are not yet implemented and the disease is considered endemic. To address this critical knowledge gap, we performed a systematic review of the literature and a meta-analysis to estimate bTB prevalence in cattle in India and provide a foundation for the future formulation of rational disease control strategies and the accurate assessment of economic and health impact risks. The literature search was performed in accordance with PRISMA guidelines and identified 285 cross-sectional studies on bTB in cattle in India across four electronic databases and handpicked publications. Of these, 44 articles were included, contributing a total of 82,419 cows and buffaloes across 18 states and one union territory in India. Based on a random-effects (RE) meta-regression model, the analysis revealed a pooled prevalence estimate of 7.3% (95% CI: 5.6, 9.5), indicating that there may be an estimated 21.8 million (95% CI: 16.6, 28.4) infected cattle in India-a population greater than the total number of dairy cows in the United States. The analyses further suggest that production system, species, breed, study location, diagnostic technique, sample size and study period are likely moderators of bTB prevalence in India and need to be considered when developing future disease surveillance and control programmes. Taken together with the projected increase in intensification of dairy production and the subsequent increase in the likelihood of zoonotic transmission, the results of our study suggest that attempts to eliminate tuberculosis from humans will require simultaneous consideration of bTB control in cattle population in countries such as India.