First time whole genome sequencing of Mycobacterium bovis from the environment supports transmission at the animal-environment interface.

Spreading of Mycobacterium bovis causing animal tuberculosis (TB) at livestock-wildlife-environment interfaces remains a significant problem. Recently, we provided evidence of widespread environmental contamination of an endemic animal TB setting with viable and dormant M. bovis cells able to recover metabolic activity, making indirect transmission via environmental contamination plausible. We now report the first whole genome sequences of M. bovis recovered from the environment. We establish epidemiological links at the environment-animal interface by phylogenomic comparison of these M. bovis genomes with those isolated from livestock and wild ungulates from the same area. Environmental and animal genomes are highly intertwined and distribute similarly into the same M. bovis lineages, supporting several instances of environmental contamination. This study provides compelling evidence of M. bovis excretion into the environment and viability maintenance, supporting the environment as a potential source of new infection. These insights have clear implications for policy formulation, advocating environmental surveillance and an ecosystem perspective in TB control programs. ENVIRONMENTAL IMPLICATION: We report the first whole genome sequences of M. bovis from the environment and establish epidemiological links at the environment-animal interface, demonstrating close phylogenomic relatedness of animal and environmental M. bovis. Definitive evidence of M. bovis excretion into the environment with viability maintenance is provided, supporting the environment as a potential source of new infection. Implications of this work include methodological innovations offering a tool to resolve indirect transmission chains and support customized biosecurity measures. Policy formulation aiming at the control of animal tuberculosis and cost mitigation should consider these findings, encouraging environmental surveillance in official eradication programmes.

Population structure and history of Mycobacterium bovis European 3 clonal complex reveal transmission across ecological corridors of unrecognized importance in Portugal.

Mycobacterium bovis causes animal tuberculosis in livestock and wildlife, with an impact on animal health and production, wildlife management, and public health. In this work, we sampled a multi-host tuberculosis community from the official hotspot risk area of Portugal over 16 years, generating the largest available data set in the country. Using phylogenetic and ecological modeling, we aimed to reconstruct the history of circulating lineages across the livestock-wildlife interface to inform intervention and the implementation of genomic surveillance within the official eradication plan. We find evidence for the co-circulation of M. bovis European 1 (Eu1), Eu2, and Eu3 clonal complexes, with Eu3 providing sufficient temporal signal for further phylogenetic investigation. The Eu3 most recent common ancestor (bovine) was dated in the 1990s, subsequently transitioning to wildlife (red deer and wild boar). Isolate clustering based on sample metadata was used to inform phylogenetic inference, unravelng frequent transmission between two clusters that represent an ecological corridor of previously unrecognized importance in Portugal. The latter was associated with transmission at the livestock-wildlife interface toward locations with higher temperature and precipitation, lower agriculture and road density, and lower host densities. This is the first analysis of M. bovis Eu3 complex in Iberia, shedding light on background ecological factors underlying long-term transmission and informing where efforts could be focused within the larger hotspot risk area of Portugal. IMPORTANCE: Efforts to strengthen surveillance and control of animal tuberculosis (TB) are ongoing worlwide. Here, we developed an eco-phylodynamic framework based on discrete phylogenetic approaches informed by M. bovis whole-genome sequence data representing a multi-host transmission system at the livestock-wildlife interface, within a rich ecological landscape in Portugal, to understand transmission processes and translate this knowledge into disease management benefits. We find evidence for the co-circulation of several M. bovis clades, with frequent transmission of the Eu3 lineage among cattle and wildlife populations. Most transition events between different ecological settings took place toward host, climate and land use gradients, underscoring animal TB expansion and a potential corridor of unrecognized importance for M. bovis maintenance. Results stress that animal TB is an established wildlife disease without ecological barriers, showing that control measures in place are insufficient to prevent long-distance transmission and spillover across multi-host communities, demanding new interventions targeting livestock-wildlife interactions.

Rescue of Mycobacterium bovis DNA Obtained from Cultured Samples during Official Surveillance of Animal TB: Key Steps for Robust Whole Genome Sequence Data Generation.

Epidemiological surveillance of animal tuberculosis (TB) based on whole genome sequencing (WGS) of Mycobacterium bovis has recently gained track due to its high resolution to identify infection sources, characterize the pathogen population structure, and facilitate contact tracing. However, the workflow from bacterial isolation to sequence data analysis has several technical challenges that may severely impact the power to understand the epidemiological scenario and inform outbreak response. While trying to use archived DNA from cultured samples obtained during routine official surveillance of animal TB in Portugal, we struggled against three major challenges: the low amount of M. bovis DNA obtained from routinely processed animal samples; the lack of purity of M. bovis DNA, i.e., high levels of contamination with DNA from other organisms; and the co-occurrence of more than one M. bovis strain per sample (within-host mixed infection). The loss of isolated genomes generates missed links in transmission chain reconstruction, hampering the biological and epidemiological interpretation of data as a whole. Upon identification of these challenges, we implemented an integrated solution framework based on whole genome amplification and a dedicated computational pipeline to minimize their effects and recover as many genomes as possible. With the approaches described herein, we were able to recover 62 out of 100 samples that would have otherwise been lost. Based on these results, we discuss adjustments that should be made in official and research laboratories to facilitate the sequential implementation of bacteriological culture, PCR, downstream genomics, and computational-based methods. All of this in a time frame supporting data-driven intervention.

Detection of Mycobacterium bovis in nasal swabs from communal goats (Capra hircus) in rural KwaZulu-Natal, South Africa.

Animal tuberculosis, caused by Mycobacterium bovis, presents a significant threat to both livestock industries and public health. Mycobacterium bovis tests rely on detecting antigen specific immune responses, which can be influenced by exposure to non-tuberculous mycobacteria, test technique, and duration and severity of infection. Despite advancements in direct M. bovis detection, mycobacterial culture remains the primary diagnostic standard. Recent efforts have explored culture-independent PCR-based methods for identifying mycobacterial DNA in respiratory samples. This study aimed to detect M. bovis in nasal swabs from goats (Capra hircus) cohabiting with M. bovis-infected cattle in KwaZulu-Natal, South Africa. Nasal swabs were collected from 137 communal goats exposed to M. bovis-positive cattle and 20 goats from a commercial dairy herd without M. bovis history. Swabs were divided into three aliquots for analysis. The first underwent GeneXpert® MTB/RIF Ultra assay (Ultra) screening. DNA from the second underwent mycobacterial genus-specific PCR and Sanger sequencing, while the third underwent mycobacterial culture followed by PCR and sequencing. Deep sequencing identified M. bovis DNA in selected Ultra-positive swabs, confirmed by region-of-difference (RD) PCR. Despite no other evidence of M. bovis infection, viable M. bovis was cultured from three communal goat swabs, confirmed by PCR and sequencing. Deep sequencing of DNA directly from swabs identified M. bovis in the same culture-positive swabs and eight additional communal goats. No M. bovis was found in commercial dairy goats, but various NTM species were detected. This highlights the risk of M. bovis exposure or infection in goats sharing pastures with infected cattle. Rapid Ultra screening shows promise for selecting goats for further M. bovis testing. These techniques may enhance M. bovis detection in paucibacillary samples and serve as valuable research tools.

Genomic epidemiology sheds light on the emergence and spread of Mycobacterium bovis Eu2 Clonal Complex in Portugal.

ABSTRACTAnimal tuberculosis (TB) remains a serious concern for animal and human health. Mycobacterium bovis circulates in multi-host systems, dominated by the European 2 clonal complex (Eu2) in Iberia. In this work, we use genomic epidemiology to infer the emergence, spread, and spatiotemporal patterns of Eu2 in the official epidemiological risk area of animal TB in Portugal. Phylogenetic analysis of 144 M. bovis whole-genome sequences from cattle, wild boar, and red deer, representing the 2002-2021 period, distinguished three Eu2 clades that evolved independently. The major Eu2 clade underwent phylodynamic inferences to estimate the time and location of outbreaks, host transitions, and spatial diffusion as well. The origin of this Eu2 clade was attributed to the red deer population in the Castelo Branco district, near the border with Spain. Most host transitions were intraspecific (80%), while interspecific transmissions between wildlife species (wild boar-red deer), and between wild boar and cattle, were highly supported. Phylogeographic reconstruction evidenced that most transitions (82%) occur within municipalities, highlighting local transmission corridors.Our study indicates that M. bovis continues to spread at the cattle-wildlife interface within the animal TB hotspot area, possibly driven by the foraging behaviour of wild boar near agricultural lands. Red deer seems to be an important driver of TB within wildlife hosts, while the wild boar links the multi-host wildlife community and livestock. This work highlights the value of combining genomic epidemiology with phylodynamic inference to resolve host jumps and spatial patterns of M. bovis, providing real-time clues about points of intervention.

Systematic review and meta-analysis of tuberculosis in animals in Nigeria.

Animal tuberculosis (TB) is a contagious and chronic disease caused by mycobacteria belonging to theMycobacterium tuberculosis complex (MTBC) in domestic and wild animals. MTBC strains infection has been confirmed in many animal species in Nigeria, including captive wildlife, cattle, dromedary camels, goats, and pigs. Despite widespread infection and the potential impact of the disease on public health, active surveillance and control strategies are absent in Nigeria. This study aimed to conduct the first comprehensive meta-analysis to assess the distribution of tuberculosis and analyze the potential moderators of infection in animals in Nigeria. Eligible studies (sixty-one (Cadmus et al., 2014) [61] prevalence and seven (Menzies and Neill, 2000) [7] case reports) were retrieved and included in the analysis. The analyses showed an overall pooled TB prevalence of 7.0% (95% CI: 6.0-8.0) comprising of infection distributed in cattle (8.0%, 95% CI: 7.0-8.0), goats (0.47%, 95% CI: 0-1.2), sheep (0.27%, 95% CI: 0.14-0.46), camels (13.0%, 95% CI: 0-47), and wildlife (13.0%, 95% CI: 9-16) respectively. The occurrence of infection was significantly moderated by the publication periods, geographical location, sample size, and detection methods. TB prevalence was heterogeneous across several predictors, with the year of publication exhibiting a higher rate (46%) of the detected heterogeneity. These findings should provide policy-relevant information to guide the design and establishment of prevention and control measures amenable to the local situations in Nigeria.

Unlocking environmental contamination of animal tuberculosis hotspots with viable mycobacteria at the intersection of flow cytometry, PCR, and ecological modelling.

Mycobacterium bovis, a member of the Mycobacterium tuberculosis complex (MTBC), circulates in multi-host mammal communities. While interactions between different host species are mainly indirect, current knowledge postulates interspecific transmission is favored by animal contact with natural substrates contaminated with droplets and fluids from infected animals. However, methodological constraints have severely hampered monitoring of MTBC outside its hosts and the subsequent validation of this hypothesis. In this work, we aimed to evaluate the extent to which environmental contamination with M. bovis occurs in an endemic animal TB setting, taking advantage of a new real-time monitoring tool we recently developed to quantify the proportion of viable and dormant MTBC cell fractions in environmental matrices. Sixty-five natural substrates were collected nearby the International Tagus Natural Park region, in the epidemiological TB risk area in Portugal. These included sediments, sludge, water, and food deployed at unfenced feeding stations. The tripartite workflow included detection, quantification, and sorting of different M. bovis cell populations: total, viable, and dormant. Real-time PCR targeting IS6110 to detect MTBC DNA was performed in parallel. The majority of samples (54 %) contained metabolically active or dormant MTBC cells. Sludge samples had a higher burden of total MTBC cells and a high concentration of viable cells (2.3 × 104 cells/g). Ecological modelling informed by climate, land use, livestock and human disturbance data suggested eucalyptus forest and pasture cover as potential major factors affecting the occurrence of viable MTBC cells in natural matrices. Our study demonstrates, for the first time, the widespread environmental contamination of animal TB hotspots with viable MTBC bacteria and with dormant MTBC cells that are able to recover metabolic activity. Further, we show that viable MTBC cell load in natural substrates is superior to the estimated minimum infective dose, providing real-time insights into the potential magnitude of environmental contamination for indirect TB transmission.

Seroepidemiology of tuberculosis in sheep in southern Spain.

Tuberculosis (TB) is a multi-host infectious disease caused by members of the Mycobacterium tuberculosis complex (MTC). In Mediterranean ecosystems, where multiple animal hosts of TB are present, identifying the role of the different species involved in the epidemiology of TB is a key point to be able to implement proper control measures. Sheep are susceptible to MTC infection but have traditionally been considered a spillover host. However, the occurrence of outbreaks involving sheep in recent years evidences the need to better understand the role of this small ruminant species in the epidemiology of the disease. Here, we aimed to determine the seroprevalence and risk factors associated with MTC seropositivity in sheep in Andalusia (southern Spain), a region with one of the highest prevalence of MTC infection in both cattle and wild ungulates. A total of 2266 sheep from 83 flocks were tested for antibodies against MTC using an in-house indirect ELISA. Anti-MTC antibodies were detected in 16 (0.7%) of the 2266 sheep (adjusted true prevalence 0.29%, 95% posterior probability interval 0.01-1.05). Seropositivity was found in 14.5% (12/83; 95%CI: 6.9-22.0) of the sheep farms analyzed. A semi-extensive management system was identified as a risk factor associated with MTC seropositivity in sheep farms (OR = 3.7; p < 0.038; 95%CI: 1.1-12.4) in the study area. To the best of the authors' knowledge, this is the first active TB surveillance study carried out to assess MTC exposure in sheep. Our results indicate MTC circulation in sheep farms in southern Spain. However, the low individual seroprevalence obtained suggests that sheep may play a limited role in the epidemiology of TB in this region. Serosurveillance programs could be a valuable tool to detect MTC circulation in sheep in risk scenarios or target farms, in order to optimize control measures on TB animal in multi-host Mediterranean ecosystems.

Low impact of tuberculosis severity on wild boar body condition.

Body condition (BC), is a measure to assess the health status of domestic and wild animals. When food resources are abundant, a decrease in BC may indicate an increase in the energetic expenditure due to the effects of growth, reproduction, or disease. BC impoverishment is one of the most common clinical effects of diseases progressing chronically, such as animal tuberculosis (TB) caused by bacteria belonging to the Mycobacterium tuberculosis complex. The Eurasian wild boar (Sus scrofa) is the main wild TB reservoir in the Mediterranean basin. The specific aims of this work were to assess the relationship between sex, age and TB severity altogether on the BC of wild boar. For this purpose, we used the kidney fat index (KFI), to assess the impact of TB progression on the BC of 1372 hunter-harvested free-ranging wild boar in seven populations in southern Spain. Surprisingly, TB had only slight effects on wild boar BC and individuals exhibiting severe TB showed greater BC than TB-free individuals. The age (adults had greater BC than juveniles) and sex (females had greater BC than males) were the main BC determinants in wild boar. Sampling population and season explained more BC variability than individual factors, suggesting that other external factors might play an important role in the BC, and probably on the impact of the disease on this wild reservoir. The low impact of TB on wild boar BC suggests that individuals with severe TB and good BC represent potential long-term super-shedders of this pathogen.

Evidence, Challenges, and Knowledge Gaps Regarding Latent Tuberculosis in Animals.

Mycobacterium bovis and other Mycobacterium tuberculosis complex (MTBC) pathogens that cause domestic animal and wildlife tuberculosis have received considerably less attention than M. tuberculosis, the primary cause of human tuberculosis (TB). Human TB studies have shown that different stages of infection can exist, driven by host-pathogen interactions. This results in the emergence of heterogeneous subpopulations of mycobacteria in different phenotypic states, which range from actively replicating (AR) cells to viable but slowly or non-replicating (VBNR), viable but non-culturable (VBNC), and dormant mycobacteria. The VBNR, VBNC, and dormant subpopulations are believed to underlie latent tuberculosis (LTB) in humans; however, it is unclear if a similar phenomenon could be happening in animals. This review discusses the evidence, challenges, and knowledge gaps regarding LTB in animals, and possible host-pathogen differences in the MTBC strains M. tuberculosis and M. bovis during infection. We further consider models that might be adapted from human TB research to investigate how the different phenotypic states of bacteria could influence TB stages in animals. In addition, we explore potential host biomarkers and mycobacterial changes in the DosR regulon, transcriptional sigma factors, and resuscitation-promoting factors that may influence the development of LTB.

COVID-19 and zoonoses in Brazil: Environmental scan of one health preparedness and response.

The emergence of the COVID-19 pandemic reinforced the central role of the One Health (OH) approach, as a multisectoral and multidisciplinary perspective, to tackle health threats at the human-animal-environment interface. This study assessed Brazilian preparedness and response to COVID-19 and zoonoses with a focus on the OH approach and equity dimensions. We conducted an environmental scan using a protocol developed as part of a multi-country study. The article selection process resulted in 45 documents: 79 files and 112 references on OH; 41 files and 81 references on equity. The OH and equity aspects are poorly represented in the official documents regarding the COVID-19 response, either at the federal and state levels. Brazil has a governance infrastructure that allows for the response to infectious diseases, including zoonoses, as well as the fight against antimicrobial resistance through the OH approach. However, the response to the pandemic did not fully utilize the resources of the Brazilian state, due to the lack of central coordination and articulation among the sectors involved. Brazil is considered an area of high risk for emergence of zoonoses mainly due to climate change, large-scale deforestation and urbanization, high wildlife biodiversity, wide dry frontier, and poor control of wild animals' traffic. Therefore, encouraging existing mechanisms for collaboration across sectors and disciplines, with the inclusion of vulnerable populations, is required for making a multisectoral OH approach successful in the country.

Mycobacterium microti Infection in Wild Boar (Sus scrofa): Histopathology Analysis Suggests Containment of the Infection.

The European wild boar (WB) (Sus scrofa) population has rapidly expanded over the years, raising public health concerns over the species reservoir of several pathogens, including Mycobacterium microti (Mm), a Mycobacterium tuberculosis complex member. In this study, we aimed to investigate the Mm natural infection in WB in Lombardy and Emilia Romagna Italian regions by statistically evaluating the granulomatous lesions' histological features and Mm microbiological isolation. We analyzed 103 WB retropharyngeal and submandibular lymph nodes (LNs) for Mm identified by gyrB PCR-restriction fragment length polymorphism, and were retrospectively selected and histologically assessed. For each sample, Hematoxylin-eosin and Ziehl-Neelsen stained slides were evaluated. Considered histological variables were: the number of granulomas, size and maturational stage of granulomas, granulomas completeness within the section, number of multinucleated giant macrophages (MGMs), and acid-fast (AF) bacilli per granuloma. Furthermore, Mm microbiological results were also considered. Mm microbiological isolation was negatively influenced by granulomas maturation and positively affected by AF bacilli's presence within the section. Granuloma maturation was positively influenced by granuloma size and granuloma incompleteness and negatively affected by the number of granulomas in the section and the number of MGMs within the granuloma. The results indicate that granuloma maturation should ensures an efficient containment of Mm infection in the WB, suggesting that the intra-species transmission of the disease might be an unlikely event.

Whole Genome Sequencing Refines Knowledge on the Population Structure of Mycobacterium bovis from a Multi-Host Tuberculosis System.

Classical molecular analyses of Mycobacterium bovis based on spoligotyping and Variable Number Tandem Repeat (MIRU-VNTR) brought the first insights into the epidemiology of animal tuberculosis (TB) in Portugal, showing high genotypic diversity of circulating strains that mostly cluster within the European 2 clonal complex. Previous surveillance provided valuable information on the prevalence and spatial occurrence of TB and highlighted prevalent genotypes in areas where livestock and wild ungulates are sympatric. However, links at the wildlife-livestock interfaces were established mainly via classical genotype associations. Here, we apply whole genome sequencing (WGS) to cattle, red deer and wild boar isolates to reconstruct the M. bovis population structure in a multi-host, multi-region disease system and to explore links at a fine genomic scale between M. bovis from wildlife hosts and cattle. Whole genome sequences of 44 representative M. bovis isolates, obtained between 2003 and 2015 from three TB hotspots, were compared through single nucleotide polymorphism (SNP) variant calling analyses. Consistent with previous results combining classical genotyping with Bayesian population admixture modelling, SNP-based phylogenies support the branching of this M. bovis population into five genetic clades, three with apparent geographic specificities, as well as the establishment of an SNP catalogue specific to each clade, which may be explored in the future as phylogenetic markers. The core genome alignment of SNPs was integrated within a spatiotemporal metadata framework to further structure this M. bovis population by host species and TB hotspots, providing a baseline for network analyses in different epidemiological and disease control contexts. WGS of M. bovis isolates from Portugal is reported for the first time in this pilot study, refining the spatiotemporal context of TB at the wildlife-livestock interface and providing further support to the key role of red deer and wild boar on disease maintenance. The SNP diversity observed within this dataset supports the natural circulation of M. bovis for a long time period, as well as multiple introduction events of the pathogen in this Iberian multi-host system.

Spoligotype-specific risk of finding lesions in tissues from cattle infected by Mycobacterium bovis.

BACKGROUND: Although the pathogenic effect of members of the Mycobacterium tuberculosis complex in susceptible hosts is well known, differences in clinical signs and pathological findings observed in infected animals have been reported, likely due to a combination of host and pathogen-related factors. Here, we investigated whether Mycobacterium bovis strains belonging to different spoligotypes were associated with a higher risk of occurrence of visible/more severe lesions in target organs (lungs and/or lymph nodes) from infected animals. A large collection of 8889 samples belonging to cattle were classified depending on the presence/absence of tuberculosis-like lesions and its degree of severity. All samples were subjected to culture irrespective of the presence of lesions, and isolates retrieved were identified and subjected to spoligotyping. The association between the presence/severity of the lesions and the isolation of strains from a given spoligotype was assessed using non-parametric tests and Bayesian mixed multivariable logistic regression models that accounted for origin (region and herd) effects. RESULTS: Results suggested a difference in severity in lesioned samples depending on the strain's spoligotype. An association between specific spoligotypes and presence of lesions was observed, with a higher risk of finding lesions in animals infected with strains with spoligotypes SB0120, SB0295 and SB1142 compared with SB0121, and in those coming from certain regions in Spain. CONCLUSIONS: Our results suggest that strains belonging to certain spoligotypes may be associated with a higher probability in the occurrence of gross/macroscopic lesions in infected cattle, although these observational findings should be confirmed in further studies that allow accounting for the effect of other possible confounders not considered here, and ultimately through experimental studies.

Diagnosis of tuberculosis in wildlife: a systematic review.

Animal tuberculosis (TB) is a multi-host disease caused by members of the Mycobacterium tuberculosis complex (MTC). Due to its impact on economy, sanitary standards of milk and meat industry, public health and conservation, TB control is an actively ongoing research subject. Several wildlife species are involved in the maintenance and transmission of TB, so that new approaches to wildlife TB diagnosis have gained relevance in recent years. Diagnosis is a paramount step for screening, epidemiological investigation, as well as for ensuring the success of control strategies such as vaccination trials. This is the first review that systematically addresses data available for the diagnosis of TB in wildlife following the Preferred Reporting Items of Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The article also gives an overview of the factors related to host, environment, sampling, and diagnostic techniques which can affect test performance. After three screenings, 124 articles were considered for systematic review. Literature indicates that post-mortem examination and culture are useful methods for disease surveillance, but immunological diagnostic tests based on cellular and humoral immune response detection are gaining importance in wildlife TB diagnosis. Among them, serological tests are especially useful in wildlife because they are relatively inexpensive and easy to perform, facilitate large-scale surveillance and can be used both ante- and post-mortem. Currently available studies assessed test performance mostly in cervids, European badgers, wild suids and wild bovids. Research to improve diagnostic tests for wildlife TB diagnosis is still needed in order to reach accurate, rapid and cost-effective diagnostic techniques adequate to a broad range of target species and consistent over space and time to allow proper disease monitoring.

The hard numbers of tuberculosis epidemiology in wildlife: A meta-regression and systematic review.

Tuberculosis (TB) is a widespread disease that crosses the human and animal health boundaries, with infection being reported in wildlife, from temperate and subtropical to arctic regions. Often, TB in wild species is closely associated with disease occurrence in livestock but the TB burden in wildlife remains poorly quantified on a global level. Through meta-regression and systematic review, this study aimed to summarize global information on TB prevalence in commonly infected wildlife species and to draw a global picture of the scientific knowledge accumulated in wildlife TB. For these purposes, a literature search was conducted through the Web of Science and Google Scholar. The 223 articles retrieved, concerning a 39-year period, were submitted to bibliometric analysis and 54 publications regarding three wildlife hosts fulfilled the criteria for meta-regression. Using a random-effects model, the worldwide pooled TB prevalence in wild boar is higher than for any other species and estimated as 21.98%, peaking in Spain (31.68%), Italy (23.84%) and Hungary (18.12%). The pooled prevalence of TB in red deer is estimated at 13.71%, with Austria (31.58%), Portugal (27.75%), New Zealand (19.26%) and Spain (12.08%) positioning on the top, while for European badger it was computed 11.75%, peaking in the UK (16.43%) and Ireland (22.87%). Despite these hard numbers, a declining trend in wildlife TB prevalence is apparent over the last decades. The overall heterogeneity calculated by multivariable regression ranged from 28.61% (wild boar) to 60.92% (red deer), indicating that other unexplored moderators could explain disease burden. The systematic review shows that the most prolific countries contributing to knowledge related with wildlife TB are settled in Europe and Mycobacterium bovis is the most reported pathogen (89.5%). This study provides insight into the global epidemiology of wildlife TB, ascertaining research gaps that need to be explored and informing how should surveillance be refined.

Global trends of epidemiological research in livestock tuberculosis for the last four decades.

Animal tuberculosis (TB) caused by Mycobacterium tuberculosis complex (MTC) bacteria remains as one of the most significant infectious diseases of livestock, despite decades of eradication programmes and research efforts, in an era where the livestock sector is among the most important and rapidly expanding commercial agricultural segments worldwide. This work provides a global overview of the spatial and temporal trends of reported scientific knowledge of TB in livestock, aiming to gain insights into research subtopics within the animal TB epidemiology domain and to highlight territorial inequalities regarding data reporting and research outputs over the years. To deliver such information, peer-reviewed reports of TB studies in livestock were retrieved from the Web of Science and Google Scholar, systematized and dissected. The validated data set contained 443 occurrence observations, covering the 1981-2020 period (39 years). We highlight a clear move towards transdisciplinary areas and the One Health approach, with a global temporal increase in publications combining livestock with wildlife and/or human components, which reflect the importance of non-prototypical hosts as key to understanding animal TB. It becomes evident that cattle is the main host across works from all continents; however, many regions remain poorly surveyed. TB research in livestock in low-/middle-income countries is markedly growing, reflecting changes in animal husbandry, but also mirroring the globalization era, with a marked increase in international collaboration and capacitation programmes for scientific and technological development. This review gives an overview of the most prolific continents, countries and research fields in animal TB epidemiology, clearly outlining knowledge gaps and key priority topics. The estimated growth trend of livestock production until 2050, particularly in Asia and Africa, in response to human population growth and animal-protein demand, will require further investment in early surveillance and adaptive research to accommodate the higher diversity of livestock species and MTC members and raising the possibility to fine-tune funding schemes.

Quantifying the Economic Impact of Bovine Tuberculosis on Livestock Farms in South-Western Spain.

Pasture-based livestock farming generates income in regions with limited resources and is key to biodiversity conservation. However, costs derived from fighting disease can make the difference between profit and loss, eventually compromising farm survival. Animal TB (TB), a chronic infection of cattle and other domestic and wild hosts, is one of the primary limitations of beef cattle farming in some parts of Europe. When an animal tests positive for TB, a loss of profit is caused in the farm, which is due mainly to the animal's slaughter, replacement of the slaughtered animal and the need to immobilize the rest of the herd. We estimated the economic impact in terms of loss of profit as a result of incremental costs and forgone incomes. We show that farms with a larger number of heads are more capable of dealing with the loss of profit caused by the disease. The quantification of the loss of profit contributes to the ongoing debate on the co-sharing of TB costs between government and farmers. The compensation farmers receive from the public administration to mitigate the economic effects of the disease control interventions is only intended to balance the loss due to slaughter of the infected cattle, being the loss of profit a more global concept.

Estimates of the global and continental burden of animal tuberculosis in key livestock species worldwide: A meta-analysis study.

Zoonotic animal tuberculosis (TB) is a One Health paradigm infectious disease, caused by Mycobacterium tuberculosis complex bacteria, that affects different host species with varying levels of management. In most developed countries, official surveillance and control strategies support the longitudinal reporting of herd and/or animal prevalence. However, for under resourced countries without surveillance plans, this information may be obtained from cross-sectional studies only. The objective of this meta-analysis was to perform a worldwide estimate of the overall prevalence of animal TB in different livestock species whose importance in production systems varies according to the region of the world. The ISI's Web of Science and Google Scholar were searched combining keywords and related database-specific subject terms to identify relevant cohort or cross-sectional work published in this topic. A total of 443 articles were retrieved, screened, and a final set of 182 references included. Potential sources of variation were investigated using subgroup analyses and meta-regression. Prevalence estimates in five mammalian host groups were stratified according to host species, host characteristics, anatomical localization of lesions, sample size, geographical location, and diagnostic tests. The multivariable meta-regression analysis accounted for a range between 0% (farmed wild boar) and 68.71% (camelids) of the overall observed heterogeneity, indicating that the pondered predictors partially explain the observed variability. Differences in the overall prevalence of TB across hosts were small, with most groups showing values around 10%, except farmed wild boar (41%). The sample size emerged as an important moderator, with small size studies leading to the overestimation of prevalence. TB prevalence rates were very heterogeneous across continents and depended on the host, with lower values (below 10%) in Africa and Asia, while North America (33.6%, cattle), Europe (51%, goats), and South America (85.7%, pigs) exhibited higher rates, possibly related to greater densities of specific host groups managed on more intensive production systems. Stratification by diagnostic tests evidenced heterogeneous prevalence rates depending on the host group, possibly reflecting differences in test performance across different hosts. Results from this study highlight different TB burden scenarios, pinpointing host groups and diagnostics that should be prioritized in surveillance systems in different regions, thus providing policy-relevant information to catalyse TB control in settings with lower installed capacity and better resource allocation at the human-animal-environment interface.

Tuberculosis caused by Mycobacterium caprae in a camel (Camelus dromedarius).

BACKGROUND: Animal tuberculosis (TB) is distributed worldwide and has a wide range of wild and domestic reservoirs. Few studies concerning TB in camelids have been published in the last decade, particularly as regards Old World Camelids (OWC), but the increase in reports of TB outbreaks in these species in recent years suggests a high susceptibility to the infection. CASE PRESENTATION: We studied a dromedary camel (Camelus dromedarius) herd (n = 24) in which a Mycobacterium caprae infection was detected. The TB infection was confirmed in one animal at necropsy through the detection of TB lesions, mainly in the abdominal organs, and the subsequent isolation of M. caprae (SB0157 spoligotype). The whole herd was additionally tested using cellular and humoral based diagnostic techniques. The intradermal tuberculin test results were compared with those obtained using P22 ELISA for the detection of specific antibodies against the M. tuberculosis complex. The TB infected animal was a positive reactor to both the intradermal tuberculin tests and P22 ELISA, while the others were negative to all the diagnostic tests. CONCLUSION: The present study found M. caprae infection in OWC. This is the first report of M. caprae infection in an OWC not living in a zoo. Since the animal was born in the herd and fed with goat's milk, this practice was suspected to be the potential source of TB infection, which was not confirmed in the other animals present in the herd. Moreover, our results highlight that the intradermal tuberculin test and the P22 ELISA could be valuable tools for the diagnosis of TB in OWC.