RESEARCH REVIEW extinction mechanism owing to such intrinsic theoretical biotic limita- were shown to occur worldwide(Fig.Ib).Web of Science literature tions".Inspection of species conservation databases would seem to searches and compilation of previous meta-analyses of infection-related confirm this idea.The International Union for Conservation of species extinction and regional extirpation events show that fungi com- Nature (IUCN)red list database details threats to species worldwide, prise the highest threat for both animal-host(72%)and plant-host and analysis of the database has shown that of the 833 recorded species (64%)species(Fig.Ic and Supplementary Tables 3 and 4).This effect extinctions,less than 4%(31 species)were ascribed to infectious is more pronounced for animal hosts(39 animal species affected versus disease.Ecological studies on host-pathogen relationships support this 4 plant species);moreover,there is a notable increase in host loss during finding by showing that lower parasite richness occurs in threatened the second half of the twentieth century,driven mainly by the emergence host species,suggesting that parasite decline and'fade out'occurs when of B.dendrobatidis(Fig.Id).This effect is moderated after correcting for hosts become rare3.Therefore,given that macroevolutionary and eco- mass-species loss in regions of high epizootic loss (such as the mass logical processes should promote diversity and prevent infectious dis- extirpations of amphibians in Central America).However,fungi remain eases from driving their host species to extinction,we posed the question the major cause(65%)of pathogen-driven host loss after this correction. of whether we are witnessing increasing disease and extinction events Our estimates are probably conservative owing to the cryptic nature of driven by fungi on an increasingly large scale,or,alternatively,if there is most disease-driven species impacts.For example,the lack of disease- evidence that a reporting bias has skewed our opinion of the current related IUCN red list records is due to a lack of baseline data on the level of threat. incidence of pathogens in natural systems compounded by inadequate EIDs are those pathogens that are increasing in their incidence,geo- disease diagnostics,reporting protocols and a lack of centralized record- graphic or host range,and virulence.Current attempts to detect EID ing mechanisms.Hence,the true numbers of extinctions and extirpa- events centre on capturing changes in the patterns of disease alerts tions caused by fungi and oomycetes are likely to be greater as we have recorded by disease monitoring programmes.ProMED(the Program not been able to categorize the probably high levels of species loss in for Monitoring Emerging Diseases;http://www.promedmail.org)and major plant(such as the Phytophthora dieback in Australia caused by HealthMap (http://healthmap.org)have two approaches for detecting Phytophthora cinnamomi;Supplementary Table 3)or animal outbreaks and monitoring outbreaks worldwide in plant and animal hosts:first,by (for example,the effects of B.dendrobatidis emergence in the American active reporting of disease outbreaks,and second,by capturing diverse wet tropics).We cannot discount the idea that sampling bias owing to online data sources.To ascertain whether there are changing patterns of increasing awareness of pathogenic fungi as EIDs may contribute to the fungal disease,we reviewed all disease alerts in ProMED (1994-2010) patterns that we document.However,because of our observation that and HealthMap(2006-10)for combinations of search terms to cata- increases in the amount of disease caused by fungi are seen across many logue fungal alerts.We then classified these according to their relative sources of data,including disease alerts,the peer-reviewed literature and proportion against the total number of disease alerts,and discriminated previously noted patterns in human fungal EIDs*,we believe that these between plant-or animal-associated fungal pathogens (Supplementary trends are real.Therefore,the answer to our question seems to be that Table 2).We also searched the primary research literature for reports in the data do indeed support the idea that fungi pose a greater threat to which EIDs have caused host extinction events,either at the regional plant and animal biodiversity relative to other taxonomic classes of scale(extirpations)or globally(Supplementary Table 3).These analyses pathogen and hosts,and that this threat is increasing. show a number of positive trends associated with infectious fungi. Overall,fungal alerts comprise 3.5%of the ~38,000 ProMED records Fungal-disease dynamics leading to host extinction screened.However,over the period from 1995 to 2010,the relative Here we illustrate several key biological features of fungi that contribute proportion of fungal alerts increased in the ProMED database from to the epidemiological dynamics underlying contemporary increases in 1%to 7%of the database total(Fig.la and Supplementary Table 2). disease emergence and host extinction(Box 1). This trend is observed for both plant-infecting (0.4%to 5.4%)and animal-infecting (0.5%to 1.4%)fungi.HealthMap shows a recent High virulence (2007-11)positive trend in the proportion of records of fungi infecting Fungi,like some bacterial and viral infections,can be highly lethal to animals (0.1%to 0.3%)and plants (0.1 to 0.2%),and fungal disease alerts naive hosts with rates of mortality approaching 100%(for example, a Figure 1 Worldwide reporting trends in fungal EIDs.a,b,Disease alerts in the ProMED database for pathogenic fungi of animals and plants(a),and 6 .Plant-infecting fungi the spatial location of the associated reports Animal- (b).c,d,Relative proportions of species extinction infecting fung and/or extirpation events for major classes of infectious disease agents(c)and their temporal 3 trends for fungal pathogens (d).Primary data 2 sources are given in the Supplementary Information. 995 Fungi ■Protist 905 ■Viruses / ■Bacteria Helmint 10- ■OhE 5 01 900 2 194 980-200 9 00 188 NATURE VOL APRIL 2012 2012 Macmillan Publishers Limited.All rights reservedextinction mechanism owing to such intrinsic theoretical biotic limita￾tions32. Inspection of species conservation databases would seem to confirm this idea. The International Union for Conservation of Nature (IUCN) red list database details threats to species worldwide, and analysis of the database has shown that of the 833 recorded species extinctions, less than 4% (31 species) were ascribed to infectious disease7 . Ecological studies on host–pathogen relationships support this finding by showing that lower parasite richness occurs in threatened host species, suggesting that parasite decline and ‘fade out’ occurs when hosts become rare33. Therefore, given that macroevolutionary and eco￾logical processes should promote diversity and prevent infectious dis￾eases from driving their host species to extinction, we posed the question of whether we are witnessing increasing disease and extinction events driven by fungi on an increasingly large scale, or, alternatively, if there is evidence that a reporting bias has skewed our opinion of the current level of threat. EIDs are those pathogens that are increasing in their incidence, geo￾graphic or host range, and virulence34,35. Current attempts to detect EID events centre on capturing changes in the patterns of disease alerts recorded by disease monitoring programmes. ProMED (the Program for Monitoring Emerging Diseases; http://www.promedmail.org) and HealthMap (http://healthmap.org) have two approaches for detecting and monitoring outbreaks worldwide in plant and animal hosts: first, by active reporting of disease outbreaks, and second, by capturing diverse online data sources. To ascertain whether there are changing patterns of fungal disease, we reviewed all disease alerts in ProMED (1994–2010) and HealthMap (2006–10) for combinations of search terms to cata￾logue fungal alerts. We then classified these according to their relative proportion against the total number of disease alerts, and discriminated between plant- or animal-associated fungal pathogens (Supplementary Table 2). We also searched the primary research literature for reports in which EIDs have caused host extinction events, either at the regional scale (extirpations) or globally (Supplementary Table 3). These analyses show a number of positive trends associated with infectious fungi. Overall, fungal alerts comprise 3.5% of the ,38,000 ProMED records screened. However, over the period from 1995 to 2010, the relative proportion of fungal alerts increased in the ProMED database from 1% to 7% of the database total (Fig. 1a and Supplementary Table 2). This trend is observed for both plant-infecting (0.4% to 5.4%) and animal-infecting (0.5% to 1.4%) fungi. HealthMap shows a recent (2007–11) positive trend in the proportion of records of fungi infecting animals (0.1% to 0.3%) and plants (0.1 to 0.2%), and fungal disease alerts were shown to occur worldwide (Fig. 1b). Web of Science literature searches and compilation of previous meta-analyses of infection-related species extinction and regional extirpation events show that fungi com￾prise the highest threat for both animal-host (72%) and plant-host (64%) species (Fig. 1c and Supplementary Tables 3 and 4). This effect is more pronounced for animal hosts (39 animal species affected versus 4 plant species); moreover, there is a notable increase in host loss during the second half of the twentieth century, driven mainly by the emergence of B. dendrobatidis (Fig. 1d). This effect is moderated after correcting for mass-species loss in regions of high epizootic loss (such as the mass extirpations of amphibians in Central America). However, fungi remain the major cause (65%) of pathogen-driven host loss after this correction. Our estimates are probably conservative owing to the cryptic nature of most disease-driven species impacts. For example, the lack of disease￾related IUCN red list records is due to a lack of baseline data on the incidence of pathogens in natural systems compounded by inadequate disease diagnostics, reporting protocols and a lack of centralized record￾ing mechanisms. Hence, the true numbers of extinctions and extirpa￾tions caused by fungi and oomycetes are likely to be greater as we have not been able to categorize the probably high levels of species loss in major plant (such as the Phytophthora dieback in Australia caused by Phytophthora cinnamomi; Supplementary Table 3) or animal outbreaks (for example, the effects of B. dendrobatidis emergence in the American wet tropics). We cannot discount the idea that sampling bias owing to increasing awareness of pathogenic fungi as EIDs may contribute to the patterns that we document. However, because of our observation that increases in the amount of disease caused by fungi are seen across many sources of data, including disease alerts, the peer-reviewed literature and previously noted patterns in human fungal EIDs35, we believe that these trends are real. Therefore, the answer to our question seems to be that the data do indeed support the idea that fungi pose a greater threat to plant and animal biodiversity relative to other taxonomic classes of pathogen and hosts, and that this threat is increasing. Fungal-disease dynamics leading to host extinction Here we illustrate several key biological features of fungi that contribute to the epidemiological dynamics underlying contemporary increases in disease emergence and host extinction (Box 1). High virulence Fungi, like some bacterial and viral infections, can be highly lethal to naive hosts with rates of mortality approaching 100% (for example, 0 1 2 3 4 5 6 7 Percentage of total alerts Year Plant-infecting fungi Animal￾infecting fungi Fungi Protist Viruses Bacteria Helminth Other 0 5 10 15 20 25 30 35 Number of extinction or extirpation events a b c d 1995 2000 2005 2010 1900–20 1920–40 1940–60 1960–80 1980–2000 2000– Year i st es eria minth r Figure 1 | Worldwide reporting trends in fungal EIDs. a, b, Disease alerts in the ProMED database for pathogenic fungi of animals and plants (a), and the spatial location of the associated reports (b). c, d, Relative proportions of species extinction and/or extirpation events for major classes of infectious disease agents (c) and their temporal trends for fungal pathogens (d). Primary data sources are given in the Supplementary Information. RESEARCH REVIEW 188 | NATURE | VOL 484 | 12 APR IL 2012 ©2012 Macmillan Publishers Limited. All rights reserved