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Tuberculosis is a major global concern. Tuberculosis in wildlife is a risk for zoonotic transmission and becoming one of the challenges for conservation globally. In elephants, the number of cases is likely rising. The aim of this study was to identify proteins related to tuberculosis infection in elephants, which could then be used for the development of diagnostic tools and/or vaccines. A serum proteomics approach was used to characterize differentially represented proteins in response to Mycobacterium tuberculosis in Asian elephants (Elaphas maximus). Blood samples were collected from eight elephants, four of which were antibody positive for tuberculosis and four were antibody negative. Proteomics analysis identified 26 significantly dysregulated proteins in response to tuberculosis. Of these, 10 (38%) were identified as immunoglobulin and 16 (62%) as non-immunoglobulin proteins. The results provided new information on the antibody response to mycobacterial infection and biomarkers associated with tuberculosis and protective response to mycobacteria in Asian elephants. Protective mechanisms included defense against infection (Alpha-1-B glycoprotein A1BG, Serpin family A member 1 SERPINA1, Transthyretin TTR), neuroprotection (TTR), and reduced risks of inflammation, infections, and cancer (SERPINA1, Keratin 10 KRT10). Using a translational biotechnology approach, the results provided information for the identification of candidate diagnostic, prognostic, and protective antigens for monitoring and control of tuberculosis in Asian elephants.

Animal tuberculosis (TB) is endemic in wild boar (Sus scrofa), red deer (Cervus elaphus), fallow deer (Dama dama) and cattle in south and central Spain. In order to clarify the processes that operate in the medium and long-term, we studied TB at the wildlife–livestock interface in Doñana National Park for 14 years (2006–2018) in relation to host density, stochastic factors (rainfall) and environmental features (e.g., aggregation points such as waterholes). Wild boar showed the highest prevalence of TB (76.7%), followed by red deer (42.5%), fallow deer (14.4%) and cattle (10.7%). We found evidence of relevant epidemiological processes which operate over the long-term and interact with host and community ecology. Interestingly, the effect of high wild boar population density on increased TB rates was mediated by sows, which could determine high incidence in young individuals already in maternal groups. Rainfall significantly determined a higher risk of TB in male red deer, probably mediated by sex-related differences in life history traits that determined more susceptibility and/or exposure in comparison to females. The positive association between the prevalence of TB in fallow deer and cattle may indicate significant interspecies transmission (in either direction) and/or similar exposure to risk factors mediated by ecological overlapping of grazing species. The identification of long-term drivers of TB provided evidence that its control in extensive pastoral systems can only be achieved by targeting all relevant hosts and integrating measures related to all the factors involved, such as: population abundance and the aggregation of wild and domestic ungulates, environmental exposure to mycobacteria, cattle testing and culling campaigns and adjustments of appropriate densities.

Vaccination with Bacillus Calmette–Guérin (BCG) constituted a major advance in the prevention of human tuberculosis (TB) in the beginning of the past century. BCG has also a clear potential for use in animals and, in particular, in the main domestic species subjected to TB control programs, cattle. Nowadays, the use of BCG vaccination against TB in cattle is not permitted by European Union legislation because BCG can induce a cellular immune response producing diagnostic interference in the eradication programs based on tuberculin single and comparative intradermal tests imposed worldwide. In this review, we recall the history of TB vaccination as well as different vaccine trials and the response to vaccination in both domestic and wild animals. Promising potential inactivated vaccines are also reviewed. Research studies are mainly focused to improve vaccine efficacy, and at the same time to ensure its easy administration, safety and stability in the environment. Great challenges remain, particularly in terms of vaccine candidates and also in the acceptance of vaccination. Vaccination should be included in a strategic plan for integrated control of TB under a “one health” perspective, which also includes other measures such as improved biosafety on farms to avoid or decrease contact between domestic and wild animals or control of wildlife reservoirs to avoid overabundance that may favor infection maintenance.

Animal tuberculosis (TB) is a multi-host zoonotic disease whose prevalence in cattle herds in Europe has been increasing, despite a huge investment in eradication. The composition of the host community is a fundamental driver of pathogen transmission, and yet this has not been formally quantified for animal TB in Europe. We quantified multi-host communities of animal TB, using stochastic models to estimate the number of infected domestic and wild hosts in three regions: officially TB-free Central–Western Europe, and two largely TB-endemic regions, the Iberian Peninsula and Britain and Ireland. We show that the estimated number of infected animals in the three regions was 290,059–1,605,612 and the numbers of infected non-bovine domestic and wild hosts always exceeded those of infected cattle, with ratios ranging from 3.3 (1.3–19.6):1 in Britain and Ireland to 84.3 (20.5–864):1 in the Iberian Peninsula. Our results illustrate for the first time the extent to which animal TB systems in some regions of Europe are dominated by non-bovine domestic and wild species. These findings highlight the need to adapt current strategies for effective future control of the disease.

The wild pig population on Molokai, Hawaii, USA is a possible reservoir for bovine tuberculosis, caused by Mycobacterium bovis, and has been implicated in decades past as the source of disease for the island’s domestic cattle. Heat-inactivated vaccines have been effective for reducing disease prevalence in wild boar in Spain and could prove useful for managing M. bovis in Molokai wild pigs. We designed an experiment to test this vaccine in wild pigs of Molokai genetics. Fifteen 3−4-month-old pigs were orally administered 106−107 colony forming units (cfu) of heat-inactivated M. bovis (Vaccinates; n = 8; 0.2 mL) or phosphate buffered saline (Controls; n = 7; 0.2 mL). Each dose was administered in a 0.5 mL tube embedded in a fruit candy/cracked corn mix. Boosters were given seven weeks post-prime in the same manner and dose. Nineteen weeks post-prime, pigs were orally challenged with 1 × 106 cfu of virulent M. bovis. Twelve weeks post-challenge, pigs were euthanized and necropsied, at which time 23 different tissues from the head, thorax, and abdomen were collected and examined. Each tissue was assigned a lesion score. Ordinal lesion score data were analyzed using non-parametric Wilcoxon Signed Rank test. Effect size was calculated using Cohen’s d. Four of eight Vaccinates and four of seven Controls had gross and microscopic lesions, as well as culture-positive tissues. Vaccinates had statistically lower lesion scores than Controls in the following areas: gross thoracic lesion scores (p = 0.013 Cohen’s d = 0.33) and microscopic thoracic lesion scores (p = 0.002, Cohen’s d = 0.39). There were no differences in head lesion scores alone, both gross and microscopic, nor were there differences when comparing combined gross and microscopic head and thoracic lesion scores. These results are indicative that this vaccination protocol affords a modest degree of infection containment with this vaccine in Molokai wild pigs.

The presence of Mycobacterium bovis and other members of the Mycobacterium tuberculosis complex (MTC) is a main concern in wildlife populations such as the Eurasian wild boar (Sus scrofa). Tests detecting antibodies against the MTC are valuable for tuberculosis (TB) monitoring and control and particularly useful in suids. The development of accurate, efficient, and non-invasive new tools to detect exposure to MTC would be highly beneficial for improving disease surveillance. This study aimed to determine if antibodies against MTC could be detected in oral fluid (OF) samples by a new ELISA test (IgG detection) from naturally TB-infected wild boar. For this, individual, paired serum and OF samples were collected from 148 live wild boar in two TB-status areas from Spain and quantitatively used to validate the new ELISA test. Antibodies against MTC were widely detected in OF samples, for which a significant positive correlation (r = 0.83) was found with the validated serology test. OF ELISA sensitivity and specificity were 67.3% and 100%, respectively. The results of this work suggest that OF samples have the potential to be used for MTC diagnosis as a further step in TB surveillance and control in suid populations. Based on our results, further research is warranted and could be performed using non-invasive new tools directly in field conditions to detect exposure to MTC.