RESEARCH REVIEW release of270 megatonnesofCO2 over the period from 2000 to 2020,with policy makers.If this occurs,then there will be more sympathy for a clearly ascribed economic cost both for the wood itself and the carbon attempts to improve the regulatory frameworks that are associated with released.These,and other diseases such as 'sudden oak death'in biosecurity in international trade,as this is the most important tool to California and foliar and twig blight'and 'dieback'on ornamental trees, tackle both plant and animal fungal EIDs now and in the future.The woody shrubs and forestry plants in the European Union,affect eco- monitoring of fungal inocula in wild populations should be the utmost logical diversity,are costly to manage and account for huge losses of fixed priority and tighter control of international trade in biological material CO2.Indeed,we calculate regional losses of absorbed COz to total 230- must be imposed,and with considerable haste.Inadequate biosecurity 580 megatonnes for just a handful of diseases(Supplementary Table 5) will mean that new fungal EIDs and virulent races will emerge at an with the higher figure equating to 0.069%of the global atmospheric COz. increasingly destructive rate.In addition to better global monitoring and We have included both emerging (Jarrah dieback,sudden oak death and control,attention must also be turned to increasing our understanding pine beetle-blue-stain fungus)and emergent diseases(Dutch elm blight of the interactions between hosts,pathogens and the environment, and chestnut blight),as these represent the few examples for which across regional and global scales.Integrated approaches encompassing informed estimates are possible.We are unable to quantify any of the theoretical and practical epidemiology,climate forecasting,genomic many other recent emerging diseases,such as red band needle blight of surveillance and monitoring molecular evolution are needed.These pines,Phytophthora alni on alders or pitch pine canker on Monterey should be facilitated by scientists from currently disparate research fields pines,owing to a lack of data and economic interest,both of which are entering into regular global discussions to develop clear and urgent trends that must be reversed.Assessing the economic burden of fungal strategies for working towards the elusive magic bullet for emerging mycoses in animals is a challenging task Although the impact of fungal fungal diseases:effective prevention and timely control EIDs is manifested in domestic animal settings,particularly the amphibian trades and in regions where virulent lineages have establisheds,reporting 1. The Institute of Medicine.Fungal Diseases:an Emerging Threatto Human Animal and mechanisms for outbreaks do not widely exist.In natural settings,valua- Wildlife Health (National Academy of Sciences,2011). The output of a key workshop assessing the risk of novel fungal diseases. tions have recently estimated the losses to US agriculture that are the result Pennisi,E.Armed and dangerous.Science 327,804-805(2010). of declines in bat populations at more than US$3.7 billion per year(ref.12). 3. Grunwald,N.J.,Goss,E.M.Press,C.M.Phytophthora ramorum:a pathogen with a However,although broad ecosystem-level impacts of other fungal EIDs of remarkably wide host range causing sudden oak death on oaks and ramorum blight on woody ornamentals.Mol.Plant Pathol.9.729-740(2008) wildlife are suspected,economic valuations of the ecosystem services that 4. Anderson,P.K.etal.Emerging infectious diseases of plants:pathogen pollution. these species support are wholly lacking. climate change and agrotechnology drivers.Trends Ecol Evol.19,535-544 (2004) Mitigating fungal EIDs in animals and plants The first meta-analysis of emerging plant diseases.Reasons for this emergence are proposed and the cost to hu welfare and biodiversity is estimated. The high socioeconomic value of crops means that detection and control 5. Brown,J.K.M.Hovmoller,M.S.Aerial dispersal of pathogens on the global and of fungal diseases in agriculture far outpaces that in natural habitats. continental scales and its impact on plant disease.Science 297,537-541(2002). Daszak,P.,Cunningham,A.A.Hyatt,A.D.Emerging infectious diseases of Epidemiological models have been developed to predict the risk of wildlife-threats to biodiversity and human health.Science 287,443-449(2000) seasonally specific crop pathogens,allowing targeted control,and spe- 7. Smith,K.F.Sax,D.F.Lafferty,K.D.Evidence for the role of infectious disease in cific threats are assessed through consortia of research,governmental species extinction and endangerment Conserv.Biol.20.1349-1357(2006). 8. Blehert,D.S.et al.Bat white-nose syndrome:an emerging fungal pathogen? and global non-governmental organizations,led by the United Nations Science323,227(2009). Food and Agricultural Organization(FAO),and related organizations. 9. Gargas,A,Trest,M.T,Christensen,M.Volk,T.J.Blehert,D.S.Geomyces Scientifically led development of disease-resistant crop varieties has been destructans sp.nov.associated with bat white-nose syndrome.Mycotaxon 108, 147-154(2009). mainly successful,although monocultures have in some instances vastly 10.Lorch,J.M.et al.Experimental infection of bats with Geomyces destructans causes increased the susceptibility of harvests to highly virulent pathogens,a white-nose syndrome.Nature 480,376-378(2011). pertinent example being P.graminis Ug99.Conversely,although there 11. Frick,W.F.et al.An emerging disease causes regional population collapse of a common North American bat species.Science 329,679-682(2010). have been some attempts to mitigate the fungal disease burden in wildlife Population viability analysis showing the high risk of extinction of little brown in situ-most notably efforts to eliminate B.dendrobatidis in infected bats caused by the emergence of a pathogenic fungus. populations with the antifungal itraconazole"and the use of probiotic 12. Boyles,J.G.Cryan,P.M.McCracken,G.F.Kunz,T.H.Economic importance of bats in agriculture.Science 332,41-42(2011). bacteria-communicable wildlife EIDs are essentially unstoppable 13. Berger,L.et al Chytridiomycosis causes amphibian mortality associated with once they have emerged.International biosecurity against the spread population declines in the rain forests of Australia and Central America.Proc.Natl of plant fungal pathogens,although not perfect,is more advanced than Acad.Sci.US495.9031-9036(1998). protocols to protect against the introduction of animal-associated fungi The first study describing the discovery of amphibian chytridiomycosis in the tropics. Fundamentally,this is the result of a financial dynamic:wildlife is not 14.Longcore,J.E.,Pessier,A.P.&Nichols,D.K.Batrachochytrium dendrobatidis gen.et correctly valued economically,whereas crops are. sp.Nov.,a chytrid pathogenic to amphibians.Mycologia 91,219-227 (1999). The World Organisation for Animal Health(also known as the OIE) 15.Fisher,M.C.Garner,T.W.J.Walker,S.F.Global emergence of Batrachochytrium dendrobatidis and amphibian chytridiomycosis in space,time,and host.Annu.Rev. and the FAO may be the best-placed authorities to coordinate tighter Microbiol.63,291-310(2009) biosecurity controls for trade-associated fungal pathogens of animals. 16. Bd-Maps.(http://www.bd-maps.net/)(accessed,February 2012). The OIE has listed B.dendrobatidis and the crayfish pathogen A.astaci 17.Cheng,T.L.,Rovito,S.M.,Wake,D.B.Vredenburg,V.T.Coincident mass extirpation of neotropical amphibians with the emergence of the infectious fungal in the Aquatic Animal Health Code as internationally notifiable pathogen Batrachochytrium dendrobatidis.Proc.Natl Acad.Sci.USA 108, infections,and the FAO compiles outbreak data on transboundary 6502-9507(2011) animal diseases using the emergency prevention information system 18. Crawford,A J.,Lips,K.R.Bermingham,E Epidemic disease decimates (EMPRES-i).Similarly,the IUCN Wildlife Health Specialist Group amphibian abundance,species diversity,and e wolutionary history in the highlands of central Panama.Proc.Nat/Acad.Sci.USA 107,13777-13782(2010). determines policy that is specific to combating emerging wildlife disease 19. Colon-Gaud,C.etal.Assessing ecological responses to catastrophic amphibian internationally.On national scales there are a number of initiatives declines:patterns of macroinvertebrate production and food web structure in being deployed and in the United States the National Wildlife Health upland Panamanian streams Limnol.Oceanogr.54,331-343(2009). 20.Stuart,S.N.et al Status and trends of amphibian declines and extinctions Centre has developed the national federal plan to mitigate WNS in worldwide.Science 306,1783-1786(2004). bats.Intensive monitoring and surveillance will be increasingly import- Analysis describing the high levels of amphibian extinctions caused by many environmental factors and disease. ant in the coming years because predictive modelling and small-scale 21. Kim,K.Harvell,C.D.The rise and fall of a six-year coral-fungal epizootic.Am.Nat experiments can never fully predict future disease spread and severity. 164.S52-S63(2004). An increased political and public profile for the effects of fungal diseases Cameron,S.A et al.Patterns of wides ead decline in North American bumble bees.Proc.Natl Acad.Sci.USA 108,662-667 (2011). in natural habitats is needed to highlight the importance of fungal 23.Bymes,E J.Ill etal Emergence and pathogenicity of highly virulent Cryptococcus disease control outside of the managed agricultural environment to gatti genotypes in the northwest United States.PLoS Pathog.6,e1000850(2010) 192 NATURE VOL 484 12 APRIL 2012 2012 Macmillan Publishers Limited.All rights reservedrelease of 270 megatonnes of CO2 over the periodfrom 2000 to 2020, with a clearly ascribed economic cost both for the wood itself and the carbon released94. These, and other diseases such as ‘sudden oak death’ in California and ‘foliar and twig blight’ and ‘dieback’ on ornamental trees, woody shrubs and forestry plants in the European Union, affect eco￾logical diversity, are costly to manage and account for huge losses of fixed CO2. Indeed, we calculate regional losses of absorbed CO2 to total 230– 580 megatonnes for just a handful of diseases (Supplementary Table 5) with the higher figure equating to 0.069% of the global atmospheric CO2. We have included both emerging (Jarrah dieback, sudden oak death and pine beetle–blue-stain fungus) and emergent diseases (Dutch elm blight and chestnut blight), as these represent the few examples for which informed estimates are possible. We are unable to quantify any of the many other recent emerging diseases, such as red band needle blight of pines, Phytophthora alni on alders or pitch pine canker on Monterey pines, owing to a lack of data and economic interest, both of which are trends that must be reversed. Assessing the economic burden of fungal mycoses in animals is a challenging task. Although the impact of fungal EIDs is manifested in domestic animal settings, particularly the amphibian trade95 and in regions where virulent lineages have established96, reporting mechanisms for outbreaks do not widely exist. In natural settings, valua￾tions have recently estimated the losses to US agriculture that are the result of declines in bat populations at more than US$3.7 billion per year (ref. 12). However, although broad ecosystem-level impacts of other fungal EIDs of wildlife are suspected, economic valuations of the ecosystem services that these species support are wholly lacking. Mitigating fungal EIDs in animals and plants The high socioeconomic value of crops means that detection and control of fungal diseases in agriculture far outpaces that in natural habitats. Epidemiological models have been developed to predict the risk of seasonally specific crop pathogens, allowing targeted control, and spe￾cific threats are assessed through consortia of research, governmental and global non-governmental organizations, led by the United Nations Food and Agricultural Organization (FAO), and related organizations. Scientifically led development of disease-resistant crop varieties has been mainly successful, although monocultures have in some instances vastly increased the susceptibility of harvests to highly virulent pathogens, a pertinent example being P. graminis Ug99. Conversely, although there have been some attempts to mitigate the fungal disease burden in wildlife in situ—most notably efforts to eliminate B. dendrobatidis in infected populations with the antifungal itraconazole97 and the use of probiotic bacteria98—communicable wildlife EIDs are essentially unstoppable once they have emerged. International biosecurity against the spread of plant fungal pathogens, although not perfect, is more advanced than protocols to protect against the introduction of animal-associated fungi. Fundamentally, this is the result of a financial dynamic: wildlife is not correctly valued economically, whereas crops are. The World Organisation for Animal Health (also known as the OIE) and the FAO may be the best-placed authorities to coordinate tighter biosecurity controls for trade-associated fungal pathogens of animals. The OIE has listed B. dendrobatidis and the crayfish pathogen A. astaci in the Aquatic Animal Health Code as internationally notifiable infections, and the FAO compiles outbreak data on transboundary animal diseases using the emergency prevention information system (EMPRES-i). Similarly, the IUCN Wildlife Health Specialist Group determines policy that is specific to combating emerging wildlife disease internationally. On national scales there are a number of initiatives being deployed and in the United States the National Wildlife Health Centre has developed the national federal plan99 to mitigate WNS in bats. Intensive monitoring and surveillance will be increasingly import￾ant in the coming years because predictive modelling and small-scale experiments can never fully predict future disease spread and severity. An increased political and public profile for the effects of fungal diseases in natural habitats is needed to highlight the importance of fungal disease control outside of the managed agricultural environment to policy makers. If this occurs, then there will be more sympathy for attempts to improve the regulatory frameworks that are associated with biosecurity in international trade, as this is the most important tool to tackle both plant and animal fungal EIDs now and in the future. The monitoring of fungal inocula in wild populations should be the utmost priority and tighter control of international trade in biological material must be imposed, and with considerable haste. Inadequate biosecurity will mean that new fungal EIDs and virulent races will emerge at an increasingly destructive rate. In addition to better global monitoring and control, attention must also be turned to increasing our understanding of the interactions between hosts, pathogens and the environment, across regional and global scales. Integrated approaches encompassing theoretical and practical epidemiology, climate forecasting, genomic surveillance and monitoring molecular evolution are needed. These should be facilitated by scientists from currently disparate research fields entering into regular global discussions to develop clear and urgent strategies for working towards the elusive magic bullet for emerging fungal diseases: effective prevention and timely control. 1. The Institute ofMedicine. Fungal Diseases: an Emerging Threat to Human Animal and Wildlife Health (National Academy of Sciences, 2011). The output of a key workshop assessing the risk of novel fungal diseases. 2. Pennisi, E. Armed and dangerous. Science 327, 804–805 (2010). 3. Gru¨nwald, N. J., Goss, E. M. & Press, C. M. Phytophthora ramorum: a pathogen with a remarkably wide host range causing sudden oak death on oaks and ramorum blight on woody ornamentals. Mol. Plant Pathol. 9, 729–740 (2008). 4. Anderson, P. K. et al. Emerging infectious diseases of plants: pathogen pollution, climate change and agrotechnology drivers. Trends Ecol. Evol. 19, 535–544 (2004). The first meta-analysis of emerging plant diseases. Reasons for this emergence are proposed and the cost to human welfare and biodiversity is estimated. 5. Brown, J. K. M. & Hovmoller, M. S. Aerial dispersal of pathogens on the global and continental scales and its impact on plant disease. Science 297, 537–541 (2002). 6. Daszak, P., Cunningham, A. A. & Hyatt, A. D. Emerging infectious diseases of wildlife—threats to biodiversity and human health. Science 287, 443–449 (2000). 7. Smith, K. F., Sax, D. F. & Lafferty, K. D. Evidence for the role of infectious disease in species extinction and endangerment. Conserv. Biol. 20, 1349–1357 (2006). 8. Blehert, D. S. et al. Bat white-nose syndrome: an emerging fungal pathogen? Science 323, 227 (2009). 9. Gargas, A., Trest, M. T., Christensen, M., Volk, T. J. & Blehert, D. S. Geomyces destructans sp. nov. associated with bat white-nose syndrome. Mycotaxon 108, 147–154 (2009). 10. Lorch, J. M. et al. Experimental infection of bats with Geomyces destructans causes white-nose syndrome. Nature 480, 376–378 (2011). 11. Frick, W. F. et al. An emerging disease causes regional population collapse of a common North American bat species. Science 329, 679–682 (2010). Population viability analysis showing the high risk of extinction of little brown bats caused by the emergence of a pathogenic fungus. 12. Boyles, J. G., Cryan, P. M., McCracken, G. F. & Kunz, T. H. Economic importance of bats in agriculture. Science 332, 41–42 (2011). 13. Berger, L. et al. Chytridiomycosis causes amphibian mortality associated with population declines in the rain forests of Australia and Central America. Proc. Natl Acad. Sci. USA 95, 9031–9036 (1998). The first study describing the discovery of amphibian chytridiomycosis in the tropics. 14. Longcore, J. E., Pessier, A. P. & Nichols, D. K. Batrachochytrium dendrobatidis gen. et sp. Nov., a chytrid pathogenic to amphibians. Mycologia 91, 219–227 (1999). 15. Fisher, M. C., Garner, T. W. J. & Walker, S. F. Global emergence of Batrachochytrium dendrobatidis and amphibian chytridiomycosis in space, time, and host.Annu. Rev. Microbiol. 63, 291–310 (2009). 16. Bd-Maps. Æhttp://www.bd-maps.net/æ (accessed, February 2012). 17. Cheng, T. L., Rovito, S. M., Wake, D. B. & Vredenburg, V. T. Coincident mass extirpation of neotropical amphibians with the emergence of the infectious fungal pathogen Batrachochytrium dendrobatidis. Proc. Natl Acad. Sci. USA 108, 9502–9507 (2011). 18. Crawford, A. J., Lips, K. R. & Bermingham, E. Epidemic disease decimates amphibian abundance, species diversity, and evolutionary history in the highlands of central Panama. Proc. Natl Acad. Sci. USA 107, 13777–13782 (2010). 19. Colo´n-Gaud, C. et al. Assessing ecological responses to catastrophic amphibian declines: patterns of macroinvertebrate production and food web structure in upland Panamanian streams. Limnol. Oceanogr. 54, 331–343 (2009). 20. Stuart, S. N. et al. Status and trends of amphibian declines and extinctions worldwide. Science 306, 1783–1786 (2004). Analysis describing the high levels of amphibian extinctions caused by many environmental factors and disease. 21. Kim, K. & Harvell, C. D. The rise and fall of a six-year coral-fungal epizootic. Am. Nat. 164, S52–S63 (2004). 22. Cameron, S. A. et al. Patterns of widespread decline in North American bumble bees. Proc. Natl Acad. Sci. USA 108, 662–667 (2011). 23. Byrnes, E. J. III et al. Emergence and pathogenicity of highly virulent Cryptococcus gattii genotypes in the northwest United States.PLoS Pathog.6, e1000850 (2010). RESEARCH REVIEW 192 | NATURE | VOL 484 | 12 APR IL 2012 ©2012 Macmillan Publishers Limited. All rights reserved