Climate change brings the specter of new infectious diseases

Arturo Casadevall

J Clin Invest. 2020;130(2):553-555. https://doi.org/10.1172/JCI135003.

Viewpoint

Climate change will bring major changes to the epidemiology of infectious diseases through changes in microbial and vector geographic range. Human defenses against microbial diseases rely on advanced immunity that includes innate and adaptive arms and endothermy, which creates a thermal restriction zone for many microbes. Given that microbes can adapt to higher temperatures, there is concern that global warming will select for microbes with higher heat tolerance that can defeat our endothermy defenses and bring new infectious disease. New microbial threats in a changing climate Almost three decades ago, experts began to sound the alarm that climate change could be associated with changes to the epidemiology of infectious diseases (1, 2). Since then a large body of literature has accumulated on this subject focused primarily on how climate will affect locations of pathogenic microbes and vectors of infectious diseases. In this Viewpoint, I focus on another threat: the strong possibility that new, previously unknown infectious diseases will emerge from warmer climates as microbes adapt to higher global temperatures that can defeat our endothermy thermal barrier. The field of infectious diseases has the unenviable distinction of being the only subdiscipline of that routinely has to deal with new diseases and where therapies lose their potency and value from drug resistance. New infectious diseases caused by pathogenic microbes not previously […]

Find the latest version: https://jci.me/135003/pdf The Journal of Clinical Investigation VIEWPOINT Climate change brings the specter of new infectious diseases

Arturo Casadevall Department of Molecular and , Johns Hopkins School of Public Health, Baltimore, Maryland, USA.

Climate change will bring major chang- often the source of so-called opportunis- The synergistic efficacy of the twin pil- es to the epidemiology of infectious dis- tic . The latter are rare and are lars of advanced immunity and endothermy eases through changes in microbial and usually the topic of case reports, although in protection against fungi is evident from vector geographic range. Human defens- epidemics can occur, as exemplified by the two situations (Figure 1). Events that damage es against microbial diseases rely on outbreak of Exserohilum rostratum menin- the immune pillar, such as HIV and advanced immunity that includes innate gitis following the use of contaminated ste- immunosuppressive therapies, are associat- and adaptive arms and endothermy, roids in 2012 (3). Even though new infec- ed with a high prevalence of infectious dis- which creates a thermal restriction zone tious diseases are relatively frequent, with eases that are very rare in immunologically for many microbes. Given that microbes several reported each year, they involve a intact hosts. As to the endothermy pillar, can adapt to higher temperatures, there miniscule proportion of the microbial flora there are no good examples of fungal dis- is concern that global warming will select in the biosphere, which is a testament to eases associated with hypothermia because for microbes with higher heat tolerance remarkably powerful defense mechanisms humans are not capable of surviving pro- that can defeat our endothermy defenses in humans and mammals. longed periods of colder body temperatures. and bring new infectious disease. However, evidence for the importance of the Two major lines of defense endothermy pillar comes from hibernating New microbial threats in a The human organism is protected from animals such as bats, which are susceptible changing climate infectious diseases by an advanced to the fungal disease white-nose syndrome Almost three decades ago, experts began immune system that includes innate and during the winter (5). Hence, interference to sound the alarm that climate change adaptive arms and physical defenses. with either pillar makes mammalian hosts could be associated with changes to the Although physical defenses such as skin susceptible to infectious diseases. epidemiology of infectious diseases (1, are well known to physicians, the role 2). Since then a large body of literature of temperature is often unappreciated. Adaptation in the fungal has accumulated on this subject focused Mammals are remarkable among animals kingdom and beyond primarily on how climate will affect loca- in their endothermy and homeothermy, Regarding climate change, there is a spe- tions of pathogenic microbes and vectors which maintains an elevated body tem- cific concern about new diseases from of infectious diseases. In this Viewpoint, I perature through life. Infectious diseases the fungal kingdom (6). The endothermy focus on another threat: the strong possi- are acquired from other hosts (e.g., influ- pillar is robust in humans, but it can be bility that new, previously unknown infec- enza virus) or directly from the environ- defeated if the fungi adapt to higher tem- tious diseases will emerge from warmer ment, usually by inhalation (e.g., crypto- peratures. Although most fungal species climates as microbes adapt to higher global coccosis and histoplasmosis). Microbes cannot tolerate mammalian temperatures temperatures that can defeat our endo- acquired from other humans are already (4), some species can be trained to survive thermy thermal barrier. adapted to mammalian temperatures, higher temperatures by gradual exposure The field of infectious diseases has the and these are not inhibited by endother- to warmer temperatures. Hence, we have unenviable distinction of being the only my. However, for many microbes, espe- proposed that global warming will lead subdiscipline of medicine that routinely cially those in the environment that are many fungal species to adapt to higher has to deal with new diseases and where adapted to cooler ambient temperatures, temperatures, and some with pathogenic therapies lose their potency and value from mammalian endothermy creates a ther- potential for humans will break through drug resistance. New infectious diseases mal inhibitory zone. For example, about the thermal defensive barrier provided by caused by pathogenic microbes not pre- 95% of fungal species are inhibited by endothermy (6). The nearly simultane- viously known to medicine emerge from human core temperatures (4), which ous emergence of Candida auris on three acquisition from another species (e.g., probably accounts for the paucity of fun- continents (7), an event proposed to result species jump), as occurred with HIV, and gal diseases in mammals relative to their from global warming (8), has raised the from increased susceptibility in humans high frequency in ectothermic species specter that increased warmth by itself will who become immunosuppressed, who are such as plants and insects. trigger adaptations on certain microbes to make them pathogenic for humans. Fungi that are pathogenic for insects can be Conflict of interest: The author has declared that no conflict of interest exists. Copyright: © 2020, American Society for Clinical Investigation. experimentally adapted to replicate at Reference information: J Clin Invest. 2020;130(2):553–555. https://doi.org/10.1172/JCI135003. mammalian temperatures through cycles

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microbial life in the biosphere, and there is no guarantee that currently available antimicrobial therapies would be effective against new pathogenic microbes. This is illustrated with C. auris, which is resistant to several of our most effective antifun- gal agents. Perhaps the greatest insurance against new organisms would be to devel- op host-targeted therapies that nonspecif- ically enhance the ability of hosts to resist infectious diseases. Figure 1. The remarkable resistance of humans (and mammals) to fungal diseases rests on the two Develop threat matrices to identify new pillars of advanced immunity and endothermy (i.e., the state of being warm-blooded). Immune likely potential threats. Threat matrices are suppression or climate change with microbial adaptation to survive at higher temperatures can already used to identify the most worrisome undermine these pillars and make the host vulnerable to fungal disease. pathogenic microbes for biological warfare and bioterrorism (10), which guide research priorities and expenditures on preparedness of progressive warming, demonstrating Enhance surveillance for new diseases. measures, such as vaccines. Currently, there that fungi are able to adapt rapidly to high- Designing enhanced surveillance systems is probably not enough information available er temperatures (9). for human and animal diseases would pro- to construct such threat matrices, but any The concern is that there are a large vide early information about new patho- such exercise would inform on the research number of fungal species that are patho- genic microbes. Early warning provides needed to obtain the required information. genic to plants and ectothermic animals, potentially actionable information that can With enhanced information into the types which means that they have the virulence be used to design containment measures of microbial diseases that affect plants and tools to defeat immunity in these hosts, and diagnostic tests and to develop new animals and the temperature tolerance of and if they adapt to higher temperatures, therapies and vaccines. environmental microbes, it should be pos- that could pose a new threat to humans. Promote research into nonhuman sible to develop threat matrices that stratify The same concern raised with the fungi host-microbe interactions. New pathogenic risk of new infectious diseases. applies to other microbes. Viruses are microbes may use virulence strategies that completely dependent on their hosts for are fundamentally different from those Outlook replication and survival. As hosts adapt of known infectious diseases. For exam- Whereas climate change will almost cer- to higher temperatures, their associated ple, when HIV burst onto the scene in the tainly bring new infectious diseases and viruses must follow suit to survive. Viruses 1980s, medical science had no experience change the epidemiology of many existing associated with ectothermic animals with a virus whose pathogenic strategy crip- diseases, it is worthwhile to note with opti- that currently pose no threat to humans pled the immune system and left the host mism that humanity has confronted new could jump to mammals if they acquire vulnerable to a variety of other lethal infec- deadly diseases in recent years, such as the capacity for replication at higher tious diseases. Microbes that are currently SARS coronaviruses and Ebola. Previous temperatures. Similar arguments apply pathogenic in plants and invertebrates may successes should not be a cause for compla- to bacteria and parasites. Hence, the con- pose fundamentally different virulence cency, and these reflect advances in science ceptual threat originally identified with strategies if they adapt to the human host. and clinical medicine that provide our spe- fungi, and exemplified by C. auris as the Today, needs to be justi- cies with tools to cope with new microbial canary in the coal mine, applies across fied concerning its value for human health, threats. Clearly, prior success is no guaran- the microbial world. and there is often little enthusiasm in tee for future success, especially given that If these threats materialize, medi- diverting scarce research funds into nonhu- each new infectious disease brings in its cine will need to confront new infectious man diseases. However, it is worth remem- own set of challenges. The best insurance diseases for which it has no experience. bering that pioneering work into nonhu- against future threats is continued invest- Although the experience with Lyme dis- man retroviruses in the decades before the ment in surveillance, epidemiology, antimi- ease, HIV, SARS coronaviruses, Zika virus, HIV epidemic created the knowledge base crobial therapeutics, and basic research into and C. auris shows that medicine and sci- that allowed rapid progress in developing mechanisms of microbial pathogenesis. ence can eventually respond successfully antiretroviral therapies once HIV was iden- to previously unknown microbes with new tified as a retrovirus. Address correspondence to: Arturo Casa- diagnostics, control measures, and thera- Promote continued development of anti- devall, Department of Molecular Micro- peutics, effective responses take time, and microbial therapeutics. The majority of biology and Immunology, Johns Hopkins countless lives are lost in the meantime. existing antimicrobial therapeutics target School of Public Health, 615 N. Wolfe However, various measures could be taken microorganisms associated with humans Street, Room E5132, Baltimore, Maryland today to increase preparedness for con- and livestock. However, these represent 21205, USA. Phone: 410.955.3457; Email: fronting new infectious diseases. an infinitesimally small proportion of the [email protected].

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1. Centers for Disease Control and Prevention. my restricts most fungi as potential pathogens. 2017;64(2):134–140. Emerging : Microbial Threats to the J Infect Dis. 2009;200(10):1623–1626. 8. Casadevall A, Kontoyiannis DP, Robert V. . Washington, DC, USA: Institute 5. Blehert DS, et al. Bat white-nose syndrome: On the emergence of Candida auris: climate of Medicine; 1992. an emerging fungal ? Science. change, azoles, swamps, and birds. MBio. 2. Patz JA, Epstein PR, Burke TA, Balbus JM. Global 2009;323(5911):227. 2019;10(4):e01397-19. climate change and emerging infectious diseas- 6. Garcia-Solache MA, Casadevall A. Global warm- 9. de Crecy E, Jaronski S, Lyons B, Lyons TJ, Keyhani es. JAMA. 1996;275(3):217–223. ing will bring new fungal diseases for mammals. NO. Directed evolution of a filamentous 3. Andes D, Casadevall A. Insights into fungal MBio. 2010;1(1):e00061-10. for thermotolerance. BMC Biotechnol. 2009;9:74. pathogenesis from the iatrogenic epidemic of 7. Lockhart SR, et al. Simultaneous emergence of 10. Rotz LD, Khan AS, Lillibridge SR, Ostroff SM, Exserohilum rostratum fungal meningitis. multidrug-resistant Candida auris on 3 conti- Hughes JM. Public health assessment of poten- Fungal Genet Biol. 2013;61:143–145. nents confirmed by whole-genome sequencing tial biological terrorism agents. Emerging Infect 4. Robert VA, Casadevall A. Vertebrate endother- and epidemiological analyses. Clin Infect Dis. Dis. 2002;8(2):225–230.

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