scholarly journals Cathelicidin-3 associated with serum extracellular vesicles enables early diagnosis of a transmissible cancer

2021 ◽  
Author(s):  
Camila Espejo ◽  
Richard Wilson ◽  
Ruth J. Pye ◽  
Julian C. Ratcliffe ◽  
Manuel Ruiz-Aravena ◽  
...  
Keyword(s):  
Early Diagnosis ◽  
Biomarker Discovery ◽  
Extracellular Vesicle ◽  
Conservation Strategies ◽  
Tasmanian Devil ◽  
Serum Samples ◽  
Visual Identification ◽  
Devil Facial Tumour Disease ◽  
Transmissible Cancer ◽  
One Year

AbstractThe identification of practical early diagnosis biomarkers is a cornerstone of improved prevention and treatment of cancers. Such a case is devil facial tumour disease (DFTD), a highly lethal transmissible cancer afflicting virtually an entire species, the Tasmanian devil (Sarcophilus harrisii). Despite a latent period that can exceed one year, to date DFTD diagnosis requires visual identification of tumour lesions. To enable earlier diagnosis, which is essential for the implementation of effective conservation strategies, we analysed the extracellular vesicle (EV) proteome of 87 Tasmanian devil serum samples. The antimicrobial peptide cathelicidin-3 (CATH3) was enriched in serum EVs of both devils with clinical DFTD (87.9% sensitivity and 94.1% specificity) and devils with latent infection (i.e., collected while overtly healthy, but 3-6 months before subsequent DFTD diagnosis; 93.8% sensitivity and 94.1% specificity). As antimicrobial peptides can play a variety of roles in the cancer process, our results suggest that the specific elevation of serum EV-associated CATH3 may be mechanistically involved in DFTD pathogenesis. This EV-based approach to biomarker discovery is directly applicable to improving understanding and diagnosis of a broad range of diseases in other species, and these findings directly enhance the capacity of conservation strategies to ensure the viability of the imperilled Tasmanian devil population.

scholarly journals Blood Parasites in Endangered Wildlife-Trypanosomes Discovered during a Survey of Haemoprotozoa from the Tasmanian Devil

Pathogens ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 873
Author(s):  
Siobhon L. Egan ◽  
Manuel Ruiz-Aravena ◽  
Jill M. Austen ◽  
Xavier Barton ◽  
Sebastien Comte ◽  
...  
Keyword(s):  
Emerging Infectious Diseases ◽  
Protozoan Parasite ◽  
Blood Parasites ◽  
Rapid Decline ◽  
Tasmanian Devil ◽  
Devil Facial Tumour Disease ◽  
Transmissible Cancer ◽  
Carnivorous Marsupial ◽  
The Impact ◽  
Single Blood Sample

The impact of emerging infectious diseases is increasingly recognised as a major threat to wildlife. Wild populations of the endangered Tasmanian devil, Sarcophilus harrisii, are experiencing devastating losses from a novel transmissible cancer, devil facial tumour disease (DFTD); however, despite the rapid decline of this species, there is currently no information on the presence of haemoprotozoan parasites. In the present study, 95 Tasmanian devil blood samples were collected from four populations in Tasmania, Australia, which underwent molecular screening to detect four major groups of haemoprotozoa: (i) trypanosomes, (ii) piroplasms, (iii) Hepatozoon, and (iv) haemosporidia. Sequence results revealed Trypanosoma infections in 32/95 individuals. Trypanosoma copemani was identified in 10 Tasmanian devils from three sites and a second Trypanosoma sp. was identified in 22 individuals that were grouped within the poorly described T. cyclops clade. A single blood sample was positive for Babesia sp., which most closely matched Babesia lohae. No other blood protozoan parasite DNA was detected. This study provides the first insight into haemoprotozoa from the Tasmanian devil and the first identification of Trypanosoma and Babesia in this carnivorous marsupial.

scholarly journals Sex bias in ability to cope with cancer: Tasmanian devils and facial tumour disease

2018 ◽  
Vol 285 (1891) ◽  
pp. 20182239 ◽  
Author(s):  
Manuel Ruiz-Aravena ◽  
Menna E. Jones ◽  
Scott Carver ◽  
Sergio Estay ◽  
Camila Espejo ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Body Condition ◽  
Interspecific Interactions ◽  
Reaction Norm ◽  
Life History Strategies ◽  
Tasmanian Devil ◽  
Devil Facial Tumour Disease ◽  
Transmissible Cancer ◽  
The Individual ◽  
Host Tolerance

Knowledge of the ecological dynamics between hosts and pathogens during the initial stages of disease emergence is crucial to understanding the potential for evolution of new interspecific interactions. Tasmanian devil ( Sarcophilus harrisii ) populations have declined precipitously owing to infection by a transmissible cancer (devil facial tumour disease, DFTD) that emerged approximately 20 years ago. Since the emergence of DFTD, and as the disease spreads across Tasmania, the number of devils has dropped up to 90% across 80% of the species's distributional range. As a result, the disease is expected to act as a strong selective force on hosts to develop mechanisms of tolerance and/or resistance to the infection. We assessed the ability of infected devils to cope with infection, which translates into host tolerance to the cancer, by using the reaction norm of the individual body condition by tumour burden. We found that body condition of infected hosts is negatively affected by cancer progression. Males and females presented significant differences in their tolerance levels to infection, with males suffering declines of up to 25% of their body condition, in contrast to less than 5% in females. Sex-related differences in tolerance to cancer progression may select for changes in life-history strategies of the host and could also alter the selective environment for the tumours.

scholarly journals A Tasmanian devil breeding program to support wild recovery

2019 ◽  
Vol 31 (7) ◽  
pp. 1296 ◽  
Author(s):  
C. E. Grueber ◽  
E. Peel ◽  
B. Wright ◽  
C. J. Hogg ◽  
K. Belov
Keyword(s):  
Genetic Diversity ◽  
Reproductive Success ◽  
Genetic Research ◽  
Breeding Program ◽  
Natural Environments ◽  
Tasmanian Devil ◽  
Strategic Approach ◽  
Devil Facial Tumour Disease ◽  
Transmissible Cancer ◽  
In The Wild

Tasmanian devils are threatened in the wild by devil facial tumour disease: a transmissible cancer with a high fatality rate. In response, the Save the Tasmanian Devil Program (STDP) established an ‘insurance population’ to enable the preservation of genetic diversity and natural behaviours of devils. This breeding program includes a range of institutions and facilities, from zoo-based intensive enclosures to larger, more natural environments, and a strategic approach has been required to capture and maintain genetic diversity, natural behaviours and to ensure reproductive success. Laboratory-based research, particularly genetics, in tandem with adaptive management has helped the STDP reach its goals, and has directly contributed to the conservation of the species in the wild. Here we review this work and show that the Tasmanian devil breeding program is a powerful example of how genetic research can be used to understand and improve reproductive success in a threatened species.

scholarly journals Ethyl-Iophenoxic acid as a serum marker for oral baiting of carnivorous marsupials

2021 ◽  
Author(s):  
Ruth Pye ◽  
David S Nichols ◽  
Amy T. Gilbert ◽  
Andrew S Flies
Keyword(s):  
Field Trials ◽  
Serum Marker ◽  
Negative Control ◽  
Vaccine Uptake ◽  
Tasmanian Devil ◽  
Serum Samples ◽  
Baseline Serum ◽  
Wildlife Species ◽  
Devil Facial Tumour Disease ◽  
In The Wild

Context: Ethyl-Iophenoxic acid (Et-IPA) has been widely used as a bait biomarker to determine oral bait consumption by vertebrate wildlife species. Oral bait vaccines have been delivered to numerous wildlife species to protect them from disease. The Tasmanian devil (Sarcophilis harrisii), the largest extant carnivorous marsupial species, is threatened by the transmissible cancers known as devil facial tumour disease (DFTD). Development of a protective DFTD vaccine is underway, and an oral bait has been proposed to deliver the vaccine in the wild. The bait delivery system requires a biomarker that can be detected for several months post-consumption in Tasmanian devils. Aim: To determine the suitability of Et-IPA as a bait biomarker in the Tasmanian devil. Method: Two Tasmanian devils were fed 50 mg Et-IPA (4.5 to 7.1 mg Et-IPA/kg bodyweight). Liquid chromatography with tandem mass spectrometry (LC-MS/-MS) was used to directly measure Et-IPA in baseline serum samples and samples collected on days 1, 14, 26 and 56 post-baiting. Key results: Both devils retained serum Et-IPA concentrations at two orders of magnitude above negative control sera when this study concluded. Conclusions: Et-IPA is a useful bait biomarker for Tasmanian devils and can be included in future DFTD bait vaccine field trials to determine bait vaccine uptake.

scholarly journals Transmissible cancer in Tasmanian devils: localized lineage replacement and host population response

2015 ◽  
Vol 282 (1814) ◽  
pp. 20151468 ◽  
Author(s):  
Rodrigo K. Hamede ◽  
Anne-Maree Pearse ◽  
Kate Swift ◽  
Leon A. Barmuta ◽  
Elizabeth P. Murchison ◽  
...  
Keyword(s):  
Population Decline ◽  
Emerging Infectious Diseases ◽  
Infectious Agent ◽  
Host Population ◽  
Future Research ◽  
Tasmanian Devil ◽  
Genetic Management ◽  
Genetic Lineages ◽  
Devil Facial Tumour Disease ◽  
Transmissible Cancer

Tasmanian devil facial tumour disease (DFTD) is a clonally transmissible cancer threatening the Tasmanian devil ( Sarcophilus harrisii ) with extinction. Live cancer cells are the infectious agent, transmitted to new hosts when individuals bite each other. Over the 18 years since DFTD was first observed, distinct genetic and karyotypic sublineages have evolved. In this longitudinal study, we investigate the associations between tumour karyotype, epidemic patterns and host demographic response to the disease. Reduced host population effects and low DFTD infection rates were associated with high prevalence of tetraploid tumours. Subsequent replacement by a diploid variant of DFTD coincided with a rapid increase in disease prevalence, population decline and reduced mean age of the population. Our results suggest a role for tumour genetics in DFTD transmission dynamics and epidemic outcome. Future research, for this and other highly pathogenic emerging infectious diseases, should focus on understanding the evolution of host and pathogen genotypes, their effects on susceptibility and tolerance to infection, and their implications for designing novel genetic management strategies. This study provides evidence for a rapid localized lineage replacement occurring within a transmissible cancer epidemic and highlights the possibility that distinct DFTD genetic lineages may harbour traits that influence pathogen fitness.

scholarly journals Historical and contemporary signatures of selection in response to transmissible cancer in the Tasmanian Devil (Sarcophilus harrisii)

2020 ◽  
Author(s):  
Amanda R. Stahlke ◽  
Brendan Epstein ◽  
Soraia Barbosa ◽  
Austin Patton ◽  
Sarah A. Hendricks ◽  
...  
Keyword(s):  
Recurrent Selection ◽  
Rapid Evolution ◽  
Tasmanian Devil ◽  
Management Actions ◽  
Devil Facial Tumour Disease ◽  
Evolutionary Response ◽  
Recent Emergence ◽  
Transmissible Cancer ◽  
Genomic Regions ◽  
Sarcophilus Harrisii

AbstractTasmanian devils (Sarcophilus harrisii) are evolving in response to a unique transmissible cancer, devil facial tumour disease (DFTD), first described in 1996. Persistence of wild populations and the recent emergence of a second independently evolved transmissible cancer suggest that transmissible cancers may be a recurrent feature in devils. We used a targeted sequencing approach, RAD-capture, to identify genomic regions subject to rapid evolution in approximately 2,500 devils as DFTD spread across the species range. We found evidence for genome-wide contemporary evolution, including 186 candidate genes related to cell cycling and immune response. We then searched for signatures of recurrent selection with a molecular evolution approach and found widespread evidence of historical positive selection in devils relative to other marsupials. We identified both contemporary and historical selection in 19 genes and enrichment for contemporary and historical selection independently in 22 gene sets. Nonetheless, the overlap between candidates for historical selection and for contemporary response to DFTD was lower than expected, supporting novelty in the evolutionary response of devils to DFTD. Our results can inform management actions to conserve adaptive capacity of devils by identifying high priority targets for genetic monitoring and maintenance of functional diversity in managed populations.

scholarly journals A metapopulation model of the spread of the Devil Facial Tumour Disease predicts the long term collapse of its host but not its extinction

2018 ◽  
Author(s):  
Veronika Siska ◽  
Anders Eriksson ◽  
Bernhard Mehlig ◽  
Andrea Manica
Keyword(s):  
Dynamic Equilibrium ◽  
Tasmanian Devil ◽  
Metapopulation Model ◽  
North East ◽  
The North ◽  
Devil Facial Tumour Disease ◽  
Transmissible Cancer ◽  
The Devil ◽  
Different Levels

AbstractThe Devil Facial Tumour Disease (DFTD), a unique case of a transmissible cancer, had a devastating effect on its host, the Tasmanian Devil. Current estimates of its density are at roughly 20% of the pre-disease state, and single-population epidemiological models have predicted the likely extinction of the host. Here we take advantage of extensive surveys across Tasmania providing data on the spatial and temporal spread of DFTD, and investigate the dynamics of this host-pathogen system using a spatial metapopulation model. We first confirm a most likely origin of DFTD in the north-east corner of the island, and then use the inferred dynamics to predict the fate of the species. We find that our medium-term predictions match additional data not used for fitting, and that on the longterm, Tasmanian Devils are predicted to coexist with the tumour. The key process allowing persistence is the repeated reinvasion of extinct patches from neighbouring areas where the disease has flared up and died out, resulting in a dynamic equilibrium with different levels of spatial heterogeneity. However, this dynamic equilibrium is predicted to keep this apex predator at about 9 % of its original density, with possible dramatic effects on the Tasmanian ecosystem.

scholarly journals Challenges of an Emerging Disease: The Evolving Approach to Diagnosing Devil Facial Tumour Disease

Pathogens ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 27
Author(s):  
Camila Espejo ◽  
Amanda L. Patchett ◽  
Richard Wilson ◽  
A. Bruce Lyons ◽  
Gregory M. Woods
Keyword(s):  
Schwann Cell ◽  
Diagnostic Techniques ◽  
Specific Protein ◽  
Serum Samples ◽  
Phenotypic Differences ◽  
Latent Stage ◽  
Devil Facial Tumour Disease ◽  
Transmissible Cancer ◽  
Fundamental Research ◽  
Cell Phenotypes

Devil Facial Tumour Disease (DFTD) is an emerging infectious disease that provides an excellent example of how diagnostic techniques improve as disease-specific knowledge is generated. DFTD manifests as tumour masses on the faces of Tasmanian devils, first noticed in 1996. As DFTD became more prevalent among devils, karyotyping of the lesions and their devil hosts demonstrated that DFTD was a transmissible cancer. The subsequent routine diagnosis relied on microscopy and histology to characterise the facial lesions as cancer cells. Combined with immunohistochemistry, these techniques characterised the devil facial tumours as sarcomas of neuroectodermal origin. More sophisticated molecular methods identified the origin of DFTD as a Schwann cell, leading to the Schwann cell-specific protein periaxin to discriminate DFTD from other facial lesions. After the discovery of a second facial cancer (DFT2), cytogenetics and the absence of periaxin expression confirmed the independence of the new cancer from DFT1 (the original DFTD). Molecular studies of the two DFTDs led to the development of a PCR assay to differentially diagnose the cancers. Proteomics and transcriptomic studies identified different cell phenotypes among the two DFTD cell lines. Phenotypic differences were also reflected in proteomics studies of extracellular vesicles (EVs), which yielded an early diagnostic marker that could detect DFTD in its latent stage from serum samples. A mesenchymal marker was also identified that could serve as a serum-based differential diagnostic. The emergence of two transmissible cancers in one species has provided an ideal opportunity to better understand transmissible cancers, demonstrating how fundamental research can be translated into applicable and routine diagnostic techniques.

Successful Treatment of Congenital Shoulder Luxation in a Dog by Closed Pinning

1994 ◽  
Vol 07 (04) ◽  
pp. 170-172 ◽  
Author(s):  
R. A. Read
Keyword(s):  
Early Diagnosis ◽  
Successful Treatment ◽  
Humeral Head ◽  
One Year

Congenital shoulder luxation in the dog is commonly associated with deformity of the humeral head and glenoid, making reduction and stabilization difficult. Early diagnosis of congenital luxation of the shoulder in a Papillon made it possible to successfully reduce and stabilize the luxation using a closed pinning technique. One year later the joint was functionally and radiographically normal.

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