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Clonally transmissible cancers are somatic cell lineages that are spread between individuals via the transfer of living cancer cells. There are only three known naturally occurring transmissible cancers, and these affect dogs, soft-shell clams, and Tasmanian devils, respectively. The Tasmanian devil transmissible facial cancer was first observed in 1996, and is threatening its host species with extinction. Until now, this disease has been consistently associated with a single aneuploid cancer cell lineage that we refer to as DFT1. Here we describe a second transmissible cancer, DFT2, in five devils located in southern Tasmania in 2014 and 2015. DFT2 causes facial tumors that are grossly indistinguishable but histologically distinct from those caused by DFT1. DFT2 bears no detectable cytogenetic similarity to DFT1 and carries a Y chromosome, which contrasts with the female origin of DFT1. DFT2 shows different alleles to both its hosts and DFT1 at microsatellite, structural variant, and major histocompatibility complex (MHC) loci, confirming that it is a second cancer that can be transmitted between devils as an allogeneic, MHC-discordant graft. These findings indicate that Tasmanian devils have spawned at least two distinct transmissible cancer lineages and suggest that transmissible cancers may arise more frequently in nature than previously considered. The discovery of DFT2 presents important challenges for the conservation of Tasmanian devils and raises the possibility that this species is particularly prone to the emergence of transmissible cancers. More generally, our findings highlight the potential for cancer cells to depart from their hosts and become dangerous transmissible pathogens.

Most pathogens threatening to cause extinction of a host species are maintained on one or more reservoir hosts, in addition to the species that is threatened by disease. Further, most conventional host—pathogen theory assumes that transmission is related to host density, and therefore a pathogen should become extinct before its sole host. Tasmanian devil facial tumor disease is a recently emerged infectious cancer that has led to massive population declines and grave concerns for the future persistence of this largest surviving marsupial carnivore. Here we report the results of mark—recapture studies at six sites and use these data to estimate epidemiological parameters critical to both accurately assessing the risk of extinction from this disease and effectively managing this disease threat. Three sites were monitored from before or close to the time of disease arrival, and at three others disease was well established when trapping began, in one site for at least 10 years. We found no evidence for sex-specific differences in disease prevalence and little evidence of consistent seasonal variation in the force of infection. At all sites, the disease was maintained at high levels of prevalence (>50% in 2–3-year-old animals), despite causing major population declines. We also provide the first estimates of the basic reproductive rate R₀ for this disease. Using a simple age-structured deterministic model, we show that our results are not consistent with transmission being proportional to the density of infected hosts but are consistent with frequency-dependent transmission. This conclusion is further supported by the observation that local disease prevalence in 2–3-year-olds still exceeds 50% at a site where population density has been reduced by up to 90% in the past 12 years. These findings lend considerable weight to concerns that this host-specific pathogen will cause the extinction of the Tasmanian devil. Our study highlights the importance of rapidly implementing monitoring programs to determine how transmission depends on host density and emphasizes the need for ongoing management strategies involving a disease-free \"insurance population,\" along with ongoing field monitoring programs to confirm whether local population extinction occurs.

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.

Infectious diseases are a major threat for biodiversity conservation and can exert strong influence on wildlife population dynamics. Understanding the mechanisms driving infection rates and epidemic outcomes requires empirical data on the evolutionary trajectory of pathogens and host selective processes. Phylodynamics is a robust framework to understand the interaction of pathogen evolutionary processes with epidemiological dynamics, providing a powerful tool to evaluate disease control strategies. Tasmanian devils have been threatened by a fatal transmissible cancer, devil facial tumour disease (DFTD), for more than two decades. Here we employ a phylodynamic approach using tumour mitochondrial genomes to assess the role of tumour genetic diversity in epidemiological and population dynamics in a devil population subject to 12 years of intensive monitoring, since the beginning of the epidemic outbreak. DFTD molecular clock estimates of disease introduction mirrored observed estimates in the field, and DFTD genetic diversity was positively correlated with estimates of devil population size. However, prevalence and force of infection were the lowest when devil population size and tumour genetic diversity was the highest. This could be due to either differential virulence or transmissibility in tumour lineages or the development of host defence strategies against infection. Our results support the view that evolutionary processes and epidemiological trade‐offs can drive host‐pathogen coexistence, even when disease‐induced mortality is extremely high. We highlight the importance of integrating pathogen and population evolutionary interactions to better understand long‐term epidemic dynamics and evaluating disease control strategies.

Emerging infectious diseases are rising globally and understanding host‐pathogen interactions during the initial stages of disease emergence is essential for assessing potential evolutionary dynamics and designing novel management strategies. Tasmanian devils (Sarcophilus harrisii) are endangered due to a transmissible cancer—devil facial tumour disease (DFTD)—that since its emergence in the 1990s, has affected most populations throughout Tasmania. Recent studies suggest that devils are adapting to the DFTD epidemic and that disease‐induced extinction is unlikely. However, in 2014, a second and independently evolved transmissible cancer—devil facial tumour 2 (DFT2)—was discovered at the d’Entrecasteaux peninsula, in south‐east Tasmania, suggesting that the species is prone to transmissible cancers. To date, there is little information about the distribution, epidemiology and effects of DFT2 and its interaction with DFTD. Here, we use data from monitoring surveys and roadkills found within and adjacent to the d’Entrecasteaux peninsula to determine the distribution of both cancers and to compare their epidemiological patterns. Since 2012, a total of 51 DFTD tumours have been confirmed among 26 individuals inside the peninsula and its surroundings, while 40 DFT2 tumours have been confirmed among 23 individuals, and two individuals co‐infected with both tumours. All devils with DFT2 were found within the d’Entrecasteaux peninsula, suggesting that this new transmissible cancer is geographically confined to this area. We found significant differences in tumour bodily location in DFTD and DFT2, with non‐facial tumours more commonly found in DFT2. There was a significant sex bias in DFT2, with most cases reported in males, suggesting that since DFT2 originated from a male host, females might be less susceptible to this cancer. We discuss the implications of our results for understanding the epidemiological and evolutionary interactions of these two contemporary transmissible cancers and evaluating the effectiveness of potential management strategies.

Adaptive management has a long history in the natural resource management literature, but despite this, few practitioners have developed adaptive strategies to conserve threatened species. Active adaptive management provides a framework for valuing learning by measuring the degree to which it improves long-run management outcomes. The challenge of an active adaptive approach is to find the correct balance between gaining knowledge to improve management in the future and achieving the best short-term outcome based on current knowledge. We develop and analyze a framework for active adaptive management of a threatened species. Our case study concerns a novel facial tumor disease affecting the Australian threatened species Sarcophilus harrisii : the Tasmanian devil. We use stochastic dynamic programming with Bayesian updating to identify the management strategy that maximizes the Tasmanian devil population growth rate, taking into account improvements to management through learning to better understand disease latency and the relative effectiveness of three competing management options. Exactly which management action we choose each year is driven by the credibility of competing hypotheses about disease latency and by the population growth rate predicted by each hypothesis under the competing management actions. We discover that the optimal combination of management actions depends on the number of sites available and the time remaining to implement management. Our approach to active adaptive management provides a framework to identify the optimal amount of effort to invest in learning to achieve long-run conservation objectives.

Devil facial tumor disease (DFTD) is renowned for its successful evasion of the host immune system. Down regulation of the major histocompatabilty complex class I molecule (MHC-I) on the DFTD cells is a primary mechanism of immune escape. Immunization trials on captive Tasmanian devils have previously demonstrated that an immune response against DFTD can be induced, and that immune-mediated tumor regression can occur. However, these trials were limited by their small sample sizes. Here, we describe the results of two DFTD immunization trials on cohorts of devils prior to their wild release as part of the Tasmanian Government's Wild Devil Recovery project. 95% of the devils developed anti-DFTD antibody responses. Given the relatively large sample sizes of the trials (  = 19 and  = 33), these responses are likely to reflect those of the general devil population. DFTD cells manipulated to express MHC-I were used as the antigenic basis of the immunizations in both trials. Although the adjuvant composition and number of immunizations differed between trials, similar anti-DFTD antibody levels were obtained. The first trial comprised DFTD cells and the adjuvant combination of ISCOMATRIX™, polyIC, and CpG with up to four immunizations given at monthly intervals. This compared to the second trial whereby two immunizations comprising DFTD cells and the adjuvant combination ISCOMATRIX™, polyICLC (Hiltonol ) and imiquimod were given a month apart, providing a shorter and, therefore, more practical protocol. Both trials incorporated a booster immunization given up to 5 months after the primary course. A key finding was that devils in the second trial responded more quickly and maintained their antibody levels for longer compared to devils in the first trial. The different adjuvant combination incorporating the RNAase resistant polyICLC and imiquimod used in the second trial is likely to be responsible. The seroconversion in the majority of devils in these anti-DFTD immunization trials was remarkable, especially as DFTD is hallmarked by its immune evasion mechanisms. Microsatellite analyzes of MHC revealed that some MHC-I microsatellites correlated to stronger immune responses. These trials signify the first step in the long-term objective of releasing devils with immunity to DFTD into the wild.

Sustainable strategies to manage infectious diseases in threatened wildlife are still lacking despite considerable concern over the global increase in emerging infectious diseases of wildlife and their potential to drive populations to extinction. Selective culling of infected individuals will often be the most feasible option to control infectious disease in a threatened wildlife host, but has seldom been implemented or evaluated as a management tool for the conservation of threatened species. The Tasmanian devil ( Sarcophilus harrisii) is threatened with extinction by an infectious cancer, devil facial tumor disease (DFTD). We assess the success of an adaptive management trial involving selective culling of infected Tasmanian devils to control DFTD. Demographic and epidemiological parameters indicative of disease progression and impact were compared between the management site and a comparable unmanaged control site. Selective culling of infected individuals neither slowed rate of disease progression nor reduced population-level impacts of this debilitating disease. Culling mortality simply compensated for disease mortality in this system. Failure of selective culling to impede DFTD progress and reduce its impacts in the managed population was attributed to DFTD's frequency-dependent nature, its long latent period and high degree of infectivity, and the presence of a cryptic hidden disease reservoir or continual immigration of diseased individuals. We suggest that increasing the current removal rate and focusing removal efforts prior to the breeding season are options worth pursuing for future management of DFTD in this population. On the basis of our experience, we suggest that disease-management programs for threatened wildlife populations be developed on the principles of adaptive management and utilize a wide variety of strategies with regular reviews and adaptation of strategies undertaken as new information is obtained.

1. Understanding the nature and characteristics of contact heterogeneities is crucial for predicting the epidemic behaviour of infectious diseases. Nonetheless, few studies include contact heterogeneities when modelling disease outbreaks in wildlife, which differ in their population impact from human diseases. 2. We use empirical estimates of contact heterogeneities and network metrics to simulate outbreaks of devil facial tumour disease (DFTD), an extinction-threatening infectious cancer. We incorporate tuneable algorithms, with a range of transmission rates and latent periods of DFTD, to grow devil population networks capable of reproducing observed aspects of devil ecology, demographic and seasonal-based mixing preferences. The outputs of the network model are compared with a stochastic mean-field model, in which every individual is equally likely to pass or acquire infection through time. 3. Our network model predicts a lower epidemic threshold for DFTD compared with the stochastic mean-field model. While host extinction probabilities are similar in both models, the network model predicts faster devil extinction and higher DFTD extinction probabilities, particularly for intermediate levels of transmissibility. 4. While the time taken to devil extinction increases with the longer estimate of latent period, probabilities of both, disease and devil extinction, are greater with the shorter latent period. Host-pathogen coexistence is strictly subject to the longest plausible estimate of latent period and low transmissibility. 5. Synthesis and applications. In the particular case of DFTD, incorporating observed host network structure has only a modest effect on the outcome of the host pathogen interaction. In general, however, non-random network structure may have major implications for the management of wildlife diseases. Our results suggest that this is particularly likely for pathogens in which the probability of transmission given a contact is intermediate. Our approach provides a template for using empirically obtained data on contact networks to develop models to explore the extent to which network structure influences R o , the probability of extinction and the mean time until extinction.

Barriers are used to achieve diverse objectives in conservation and biosecurity. In conservation management, fences are often erected to exclude introduced predators and to contain diseased animals or invasive species. Planning an efficient conservation fence involves a number of decisions, including the size and design of the enclosure. We formulated the first general framework for building a fence that minimizes long-term management costs by balancing the expense of constructing a more secure barrier against the costs of coping with more frequent failures. The approach systematically considers the range of potential solutions to a well-defined fencing problem and results in a solution that maximizes conservation return on investment. We illustrated this method by designing efficient fences to address two different conservation goals: exclusion of invasive predators from populations of threatened eastern barred bandicoots (Perameles gunnii) and maintenance of isolated populations of healthy Tasmanian devils (Sarcophilus harrisii). A systematic approach to conservation fencing allows the best fence design to be chosen quantitatively and defensibly. It also facilitates conservation decisions at a strategic level by allowing fencing to be compared transparently with alternative conservation management actions.