To Lose Both Would Look Like Carelessness Tasmanian Devil Facial Tumour Disease

To Lose Both Would Look Like Carelessness Tasmanian Devil Facial Tumour Disease To Lose Both Would Look Like Carelessness: Tasmanian Devil Facial Tumour Disease * Hamish McCallum , Menna Jones Introduction t the time of European settlement, Tasmania was the last remaining refuge of the two largest marsupial carnivores: the thylacine (or Tasmanian tiger), A Thylacinus cynocephalus, and the Tasmanian devil, Sarcophilus harrisii. The extinction of the thylacine is perhaps the most notorious of the many Australian mammal extinctions since European colonisation. It has been partially blamed on disease [1], although there is little hard evidence to support this idea [2]. In 1996, Tasmanian devils were photographed in northeast Tasmania with what were apparently large tumours on their faces [3] (Figure 1). Sporadic reports continued during the next ,ve years. By 2005, the tumours were occurring on more than half of the range of the species, and associated with substantial population declines. Following DOI: 10.1371/journal.pbio.0040342.g001 concerns that the disease might cause the extinction of the Figure 1. Tasmanian Devil Facial Tumour Disease devil, the species has recently been listed as vulnerable to (Photo: Menna Jones) extinction at state and national levels. In the words Oscar Wilde put into Lady Bracknell’s mouth, to lose one large marsupial carnivore may be regarded as a misfortune; to lose rearrangements in all tumours karyotyped, and the discovery both would look like carelessness. of a devil that was heterozygous for a chromosome inversion that is homozygous in all tumours suggest that tumours This paper uses the Tasmanian devil facial tumour disease (DFTD) as a case study of the wider issue of how to manage may be transmitted directly between individuals as a rogue cell line (an allograft) [8]. Such a mode of transmission is an emerging disease threat that poses a serious conservation known in one other infectious cancer: transmissible venereal threat: how should you proceed when you know very little? This is a question common to many ecological problems; sarcoma in dogs [9,10]. If this theory is correct, transmission all environmental management operates in the face of probably occurs though biting. Transmission via tumour cells shed into carcasses or via vectors seems unlikely but cannot be uncertainty [4]. If actions are postponed until higher-quality unequivocally ruled out. The degree of infectivity of DFTD is information is available, then it is likely that substantial costs poorly understood. Early indications are that it is not highly will be incurred. Further, with emerging diseases or invasive infectious. Despite individual devils being capable of moving species in general, it is likely that control will become more dif,cult or indeed impossible once the agent becomes up to 50 kilometres in one night, the disease appears to have established [5]. Rapid action is therefore essential but will taken three years to travel the 30 kilometres of the Freycinet Peninsula in eastern Tasmania [3]. In addition, DFTD does inevitably be based on incomplete knowledge. not appear to have spread into any captive populations, What Is and Is Not Known? even in situations where there are adjacent affected wild individuals (H. Hesterman, personal communication), DFTD appears to be a new disease that is restricted to devils. which suggests that transmission requires direct or very close No affected animals were detected amongst the 2,000-plus devils trapped by six biologists between 1964 and 1995 [3]. Whilst neoplasms are quite common in dasyurids [6,7], there Citation: McCallum H, Jones M (2006) To lose both would look like carelessness: Tasmanian devil facial tumour disease. PLoS Biol 4(10): e342. DOI: 10.1371/journal. is no evidence of a similar cancer in any other Tasmanian pbio.0040342 mammal. Further, the tumour is suf,ciently obvious (Figure 1) that it is inconceivable that it would not have been DOI: 10.1371/journal.pbio.0040342 reported. Copyright: ? 2006 McCallum and Jones. This is an open-access article distributed The apparent spatial and temporal progression of the under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the disease [3] strongly suggests that it is infectious and that it is original author and source are credited. spreading. Transmission trials that are now under way should determine unequivocally whether it is infectious and provide Abbreviations: DFTD, devil facial tumour disease an estimate of the incubation period. The identi,cation Hamish McCallum is a reader in Zoology at the School of Integrative Biology, of identical characteristic and complex chromosomal The University of Queensland, Brisbane, Queensland, Australia. Menna Jones is a research fellow at the School of Zoology, University of Tasmania, Tasmania, Australia. Unsolved Mysteries discuss a topic of biological importance that is poorly understood and in need of research attention. * To whom correspondence should be addressed. E-mail: h.mccallum@uq.edu.au 1671 PLoS Biology | www.plosbiology.org October 2006 | Volume 4 | Issue 10 | e342 contact. Con,dence in this conclusion requires transmission serious threat, may lead to extinction. For devils, these sources include road mortality [19], persecution, and habitat trials and estimation of R (the number of secondary cases 0 loss [20]. The prognosis for extinction risk may not be good. per primary case, when disease is rare). It is unclear whether resistance is developing and although the disease appears to Possible Control Options have a genetic basis [8], the role of genetics and immunology in susceptibility or resistance is unknown. In principle, the elimination of an infectious disease from a Once the cancer becomes visible, it appears to be invariably population requires driving the basic reproductive rate R 0 fatal within a few months. The disease is rare in juveniles [3]. below one [21]. R can be reduced either by decreasing the 0 Nearly all devils appear to succumb between two (modal age rate of disease transmission per unit time or by reducing the of ,rst breeding in females) and three years of age, resulting time during which infected individuals are able to transmit in very young age-structured populations in which most infection. females are reduced to a single breeding event (from a mode Options therefore include: (1) reduction of rates of contact of three) (M. Jones, A. Cockburn, C. Hawkins, H. Hesterman, between infected and susceptible individuals, including S. Lachish et al., unpublished data). Populations where the quarantine and movement controls; (2) culling infected disease has been present for several years appear to have individuals; (3) culling all individuals in a given area; (4) declined by up to 80 percent, with as yet no evidence of either vaccination or similar prophylactic treatment of uninfected a cessation of decline or a diminution in the prevalence of individuals; (5) treating infected individuals; and (6) disease [3] (S. Lachish, personal communication). There are decontamination of the environment. signs of compensatory changes in the reproductive pattern An Agenda for Action and Research of the animals following the appearance of the disease: there has been a three-fold increase in female devils breeding early, Figure 2 presents a decision tree for managing an emerging in their ,rst year (M. Jones, A. Cockburn, C. Hawkins, H. disease in wildlife. Given the uncertainties associated with Hesterman, S. Lachish et al., unpublished data) an emerging disease, it is better to aim for a robust decision- making pathway that aims to maximize the chance of an Anecdotal evidence is that devil numbers have been acceptable outcome whilst maintaining ,exibility to modify quite variable in the past century and that numbers about ten years ago were at historic highs [11]. Whilst a pattern actions as more data become available [22,23], rather than of increases followed by collapses in the population size is seeking an optimal decision. consistent with the impact of density-dependent disease The ,rst step is to determine whether the threat is severe [12], it is also consistent with the action of a range of other enough to warrant action: “no action” is a valid management density-dependent factors. Cessation of broad-scale strychnine decision, but should be associated with ongoing monitoring poisoning for rabbits in the early 1950s [13] may also have of the situation. The obvious next step, especially if the led to a recent increase in population size. It is inconceivable conservation threat appears severe, is to attempt to establish that DFTD, which is so distinctive, had been responsible for disease-free captive and/or free-living populations in places previous reductions in population size. that can be isolated from the disease. This approach may fail if vectors are involved, if the pathogen is highly infectious, What Does Conventional Epidemiology Predict? or if the individuals transferred into such “insurance” populations are already infected but asymptomatic. For Disease has been responsible for the extinction of a DFTD, the ,rst two seem unlikely and the risk of the third number of species worldwide [14], but we know of no cases where a host-speci,c pathogen has driven its host entirely can be managed. to extinction: there is usually at least one reservoir host The potential for the effects of disease to interact with the upon which the pathogen has a limited effect and which remainder of the ecological community must be assessed can, therefore, provide a high force of infection onto the early; in some cases, this interaction may be more important endangered species, even as the host declines towards than the direct effects of the disease on the focal species extinction [2,15]. Given that any reservoir for DFTD appears itself. Red foxes, Vulpes vulpes, have recently been introduced unlikely, there is some cause to be optimistic about the to Tasmania [24], and there is concern that reduced devil likelihood of the disease itself not leading to extinction if populations may permit foxes to become established, with transmission is density dependent. The pathogen should the potential to cause the extinction of many mammals disappear once the host population drops below the (including devils). The increased urgency of fox eradication threshold necessary for disease transmission, before host does not rely on further knowledge about DFTD. extinction [16]. However, empirical evidence for a wide range Whether or not the disease is infectious also requires an of pathogens suggests that transmission is rarely linearly early decision, because it makes a fundamental difference dependent on density [17]. If the frequency of infected hosts to management, particularly whether removal of diseased in the population determines transmission rather than their animals is warranted. Recent examples of noninfectious density, there is no threshold population size. A pathogen diseases in the conservation literature include the decline in may therefore be able to drive its single host species to vultures on the Indian subcontinent attributable to residues extinction. The extent to which DFTD transmission might of a veterinary drug [25], and widespread sea otter mortalities depend on host density is unknown. Biting is particularly caused by domoic acid in algal blooms [26]. In these cases, associated with sexual behaviour in devils, and therefore the the appropriate management action is to identify the factor dynamics of the disease may resemble those of a sexually (probably an environmental toxin) that induces disease and transmitted disease, in which case frequency-dependent then to remove or neutralise it. transmission is to be expected [18]. Sources of mortality, Crucially, the next decision point is to determine the which in the absence of the disease would not present a degree of infectivity because of the extreme consequences of PLoS Biology | www.plosbiology.org 1672 October 2006 | Volume 4 | Issue 10 | e342 allowing a highly infectious disease to become established. disruption of social organisation with increased movement and consequent increase in disease transmission [29]. If R is extremely high, which does not appear to be the 0 For a moderately infective pathogen, culling only infected case with DFTD, then the strategy of culling all individuals in the affected area (termed “stamping out” in the hosts (particularly in relatively closed populations) is likely to be a more acceptable and feasible management option. veterinary literature) may be an appropriate action. This is a standard approach used to control highly infectious It may be less effective if there is a lengthy incubation diseases in livestock, such as foot-and-mouth disease period, because most infection may occur before the disease [27]. For livestock, re-establishing the population may be becomes apparent. However, if DFTD is indeed caused by expensive, but it is biologically straightforward. However, interindividual transfer of tumour cells, it is unlikely that stamping out is a high-risk strategy for wild species. It will transmission will occur until the tumour grows to a size certainly increase the probability of extinction, at least on a that is visible. The potential negative consequences of this local scale, and re-establishment is often dif,cult [28], with strategy are much less than those of unselective culling; but, substantial issues relating to loss of genetic diversity. Further, if infected individuals have some reproductive value, this attempting to eliminate the species over a substantial part value will need to be weighed against the bene,t of removing of its current range would almost certainly be politically them as potential sources of infection. “Learning by doing”, and ethically unacceptable as well as logistically extremely or adaptive management [30], with adequate replication and dif,cult. Whether broad-scale culling at an intensity less control sites is likely to be the only appropriate management than total elimination of the local population would be strategy for implementing selective culling. Epidemiological successful is unknown without detailed knowledge of models are central to evaluation of strategies throughout the transmission dynamics. Such culling has been shown to be decision process. However, delaying management decisions counterproductive in some cases, because it can lead to until suf,cient data are collected to parameterise detailed population viability analysis–type models [31] is unwise. The next decision point requires determining whether there are multiple hosts or a single host involved, whether there are vectors, and whether there are environmental reservoirs. Because there is a high level of con,dence that DFTD is a single-host infection (Figure 2), we do not follow this branch in detail. In other, multiple-host systems, it is critical to manage infection in the reservoirs and transmission from the reservoirs to the species of conservation concern [32]. For example, the chytrid fungus Batrachochytrium dendrobatidis is associated with declines and extinctions in a wide variety of amphibian communities, and understanding the relative susceptibility to infection of different species and populations is essential [33]. In this decision tree, we have placed identi,cation of the aetiological agent at a relatively late stage. Obviously, it is desirable to identify the causative agent of infectious disease, because it may open up a range of prophylactic or treatment options. There may be the possibility of treating infected individuals in captive situations. The canine transmissible sarcoma appears to be quite sensitive to standard cytotoxic drugs [34]. However, because these drugs require multiple intravenous treatments, they are not likely to be feasible for treating animals in the wild. If disease susceptibility (or resistance) is shown to be associated with particular genotypes, genetic management (arti,cial selection) could be incorporated into all aspects of management. Identi,cation of the agent is neither suf,cient nor necessary, however, for adequately managing a disease threat. For example, despite the frog chytrid fungus being identi,ed as the causative agent of widespread amphibian mortality [35] almost ten years ago, we are little closer to managing (as distinct from studying) its impact on amphibian communities. None of the previous DOI: 10.1371/journal.pbio.0040342.g002 steps in the decision tree, any of which might be helpful in Figure 2. A Decision Tree for the Management of Emerging Wildlife managing disease, absolutely requires the identi,cation of the Disease, with Particular Reference to Tasmanian Devil Facial Tumour causative agent. Disease Evaluating the remaining potential control strategies, The relative thickness of arrows indicates the current likelihood of the which focus on reducing contact and/or transmission given path representing the true situation. Probabilities determined by consensus of expert opinion at a recent technical workshop on rates within free-living populations, relies on estimating DFTD [40] are shown in italics on the arrows. Colours represent the cost R and understanding something of its dependence on 0 associated with the speci,ed action, if it proves to be as a result of an population density, social organisation and behaviour, and incorrect decision. Red, high; yellow/orange, medium; green, low. PLoS Biology | www.plosbiology.org 1673 October 2006 | Volume 4 | Issue 10 | e342 13. 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Department of Primary Industries, Water, and Environment. PLoS Biology | www.plosbiology.org 1674 October 2006 | Volume 4 | Issue 10 | e342