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Research Project
Incorporating the genomic signature of environmental Mycobacterium bovis into transmission models of animal TB under a phylodynamics conceptual framework
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The hard numbers of tuberculosis epidemiology in wildlife: A meta‐regression and systematic review
Publication . Reis, Ana C.; Ramos, Beatriz; Pereira, André C.; Cunha, Mónica V.
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.
Estimates of the global and continental burden of animal tuberculosis in key livestock species worldwide: A meta-analysis study
Publication . Ramos, Beatriz; Pereira, André C.; Reis, Ana C.; Cunha, Mónica V.
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.
Animal tuberculosis: impact of disease heterogeneity in transmission, diagnosis, and control
Publication . Pereira, André C.; Reis, Ana C.; Ramos, Beatriz; Cunha, Mónica V.
Animal tuberculosis (TB) in terrestrial mammals is mainly caused by Mycobacterium bovis. This pathogen is adapted to a wide range of host species, representing a threat to livestock, wildlife and human health. Disease heterogeneity is a hallmark of multi-host TB and a challenge for control. Drivers of animal TB heterogeneity are very diverse and may act at the level of the causative agent, the host species, the interface between mycobacteria and the host, community of hosts, the environment and even policy behind control programmes. In this paper, we examine the drivers that seem to contribute to this phenomenon. We begin by reviewing evidence accumulated to date supporting the consensus that a complex range of genetic, biological and socio-environmental factors contribute to the establishment and maintenance of animal TB, setting the grounds for heterogeneity. We then highlight the complex interplay between individual, species-specific and community protective factors with risk/maintenance variables that include animal movements and densities, co-infection and super-shedders. We finally consider how current interventions should seek to consider and explore heterogeneity in order to tackle potential limitations for diagnosis and control programmes, simultaneously increasing their efficacy.
An effective culturomics approach to study the gut microbiota of mammals
Publication . Pereira, André C.; Cunha, Mónica V.
The microbial characterization of the mammal's gut is an emerging research area, wherein culturomics methodologies applied to human samples are transposed to the animal context without improvement. In this work, using Egyptian mongoose as a model, we explore wet bench conditions to define an effective experimental design based on culturomics and DNA barcoding with potential application to different mammal species. After testing a battery of solid media and enrichments, we show that YCFA-based media, in aerobic and anaerobic conditions, together with PDA supplemented with chloramphenicol, are sufficient to maximize bacterial and fungal microbiota diversity. The pasteurization of the sample enrichment before cultivation is central to gain insight into sporogenic communities. We suggest the application of this optimized culturomics strategy to accurately expand knowledge on the microbial richness of mammals' gut, maximizing the application of common laboratory resources, without dramatic time and consumables expenditure but with high resolution of microbial landscapes. The analysis of ten fecal samples proved adequate to assess the core gastrointestinal microbiota of the mesocarnivore under analysis. This approach may empower most microbiology laboratories, particularly the veterinary, to perform studies on mammal's microbiota, and, in contrast with metagenomics, enabling the recovery of live bacteria for further studies.
Non-Tuberculous Mycobacteria: Molecular and Physiological Bases of Virulence and Adaptation to Ecological Niches
Publication . Pereira, André C.; Ramos, Beatriz; Reis, Ana C.; Cunha, Mónica V.
Non-tuberculous mycobacteria (NTM) are paradigmatic colonizers of the total environment, circulating at the interfaces of the atmosphere, lithosphere, hydrosphere, biosphere, and anthroposphere. Their striking adaptive ecology on the interconnection of multiple spheres results from the combination of several biological features related to their exclusive hydrophobic and lipid-rich impermeable cell wall, transcriptional regulation signatures, biofilm phenotype, and symbiosis with protozoa. This unique blend of traits is reviewed in this work, with highlights to the prodigious plasticity and persistence hallmarks of NTM in a wide diversity of environments, from extreme natural milieus to microniches in the human body. Knowledge on the taxonomy, evolution, and functional diversity of NTM is updated, as well as the molecular and physiological bases for environmental adaptation, tolerance to xenobiotics, and infection biology in the human and non-human host. The complex interplay between individual, species-specific and ecological niche traits contributing to NTM resilience across ecosystems are also explored. This work hinges current understandings of NTM, approaching their biology and heterogeneity from several angles and reinforcing the complexity of these microorganisms often associated with a multiplicity of diseases, including pulmonary, soft-tissue, or milliary. In addition to emphasizing the cornerstones of knowledge involving these bacteria, we identify research gaps that need to be addressed, stressing out the need for decision-makers to recognize NTM infection as a public health issue that has to be tackled, especially when considering an increasingly susceptible elderly and immunocompromised population in developed countries, as well as in low- or middle-income countries, where NTM infections are still highly misdiagnosed and neglected.
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Fundação para a Ciência e a Tecnologia
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Funding Award Number
SFRH/BD/136557/2018