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Abstract

Anthropogenic climate change, primarily driven by greenhouse gas emissions, is reshaping ecosystems and creating conditions that affect 58% of all known human infectious diseases, including fungal infections. Specifically, increasing temperatures, changing precipitation patterns, and extreme weather events are influencing fungal growth, distribution, and virulence. These factors may expand the geographic range of pathogenic fungi, exposing populations to novel, potentially more virulent, or drug-resistant strains. Simultaneously, human factors such as declining immunity, aging populations, and increased use of immunosuppressive therapies are enhancing host susceptibility. This review explores the intricate relationship between climate change and fungal infections, highlighting pathogens that may demonstrate increased virulence and antifungal resistance, along with emerging novel pathogens. The clinical implications are profound, with increased morbidity, mortality, and the spread of fungal infections into new regions. Immediate action is required to develop policies, educational initiatives, and novel antifungal therapies, enhance early diagnostic capabilities, and address healthcare disparities to mitigate the growing burden of fungal infections.

Keywords

antifungal agents climate change extreme weather fungi healthcare disparities mycoses temperature

Introduction

The anthropogenic climate crisis is altering global temperatures and precipitation patterns, disrupting ecosystems, and creating conditions that favor the emergence and spread of infectious diseases, including fungal infections (Figure 1).^1–5 Environmental shifts are impacting 58% of all known human infectious diseases.⁶ Rising temperatures and altered precipitation patterns are influencing fungal growth, distribution, and virulence.^3–5 These changes may facilitate the geographic spread of pathogenic fungi, increasing human exposure to novel, potentially more virulent or antifungal-resistant strains.

Figure 1.

Impact of climate change on the epidemiology and evolution of fungal infections.

While the human core body temperature provides some defense against fungal infections, thermotolerant fungi like Aspergillus fumigatus can adapt to warmer environments.^5,7 A gradual decline in average human body temperature—potentially associated with lower metabolic rates and reduced chronic inflammation—may weaken this thermal barrier.⁸ Climate-induced changes in temperature and humidity, combined with heightened susceptibility due to the rising prevalence of age-related, disease-related, and medication-induced immunosuppression, could synergistically increase both the risk and severity of fungal infections.^9–11

The clinical consequences of climate change-driven fungal infections are significant. Emerging pathogens may lead to a broader range of diseases with increased morbidity and mortality.^3–5 Moreover, shifts in the geographic distribution of endemic fungi will place new populations at risk. Disparities in healthcare access and socioeconomic conditions will likely amplify these effects, disproportionately affecting vulnerable populations.¹²

This review examines the intricate connections between climate change and fungal infections, exploring the underlying mechanisms, clinical implications, and the urgent need for research and public health interventions.

Expanded geographical range

Climate change is a major driver for the emergence and expansion of fungal infections.^13–17 Rising global temperatures and shifting precipitation patterns create favorable conditions for the proliferation and migration of fungal pathogens, enabling their colonization in regions previously uninhabitable. In addition, extreme weather events further exacerbate the dispersal of fungal propagules, increasing the risk of both endemic and emerging fungal infections.^18–20

Dimorphic fungi, once confined to specific geographic regions, are particularly susceptible to climate-induced environmental shifts.^13–17 Disruptions caused by climate change are allowing these fungi to establish themselves in new ecological niches, thereby increasing human exposure. Species such as Blastomyces dermatitidis, Histoplasma capsulatum, Coccidioides species, Paracoccidioides species, Talaromyces marneffei, and Emergomyces species have demonstrated notable expansions in their geographic range (Table 1).^{13,14,17–66} However, even within traditionally endemic regions, the distribution of these fungi can be highly variable, ranging from areas with low incidence to those with hyperendemic outbreaks. These spatial and temporal fluctuations in fungal prevalence hinder effective disease surveillance and prevention. Climate change further complicates this challenge by altering environmental conditions and potentially generating new endemic zones.

Table 1.

Emerging geographic distribution of endemic mycoses in response to climate change.*

Fungal species	Historical distribution	Recent geographic expansion	Climate change impacts
Blastomyces dermatitidis complex^{13,14,21–28}	Endemic to North America (Mississippi and Ohio River valleys, and Great Lakes regions); incidence rates range from 0.5 to 100/100,000 persons	Increasing cases reported in Ontario, Quebec, Manitoba, and Saskatchewan (Canada), Tunisia, South Africa, Zimbabwe (Africa), and parts of India	Seasonal patterns, drought-associated, and influenced by climate extremes
Histoplasma capsulatum ^{13,14,18–20,29–35,65,66}	Globally distributed, with high prevalence in the St. Lawrence, Mississippi, and Ohio river basins and parts of Central and South America; incidence rates range from 0.1 to 100/100,000 persons	Northward expansion in North America (Canada) and new cases in temperate regions such as northern Italy, Neuquén (Argentina), and Turkey	Rising temperatures contributing to emergence of more virulent, thermally tolerant strains and vector suitability
Coccidioides species^13,36–45	Endemic to arid regions of the southwestern US (Southern Arizona and the San Joaquin Valley account for 95% of US cases), Mexico, and parts of Central and South America (e.g., Honduras, Bolivia, Colombia, Venezuela, and Brazil)	New cases reported in Missouri, Washington State (US), and Portugal	Warmer temperatures, shifting precipitation, dust storms, and wildfire smoke aiding spread
Paracoccidioides species^{13,46–56,67}	Endemic to South and Central America, with highest prevalence in southeastern, southern, and central-west Brazil; Venezuela, Colombia, northern Argentina, eastern Paraguay, and Cuenca River valley (Ecuador); incidence rates range from 0.5 to 40/100,000 persons	Increasingly reported in non-endemic areas including North America, Europe, Africa, and Asia, often linked to human migration	Deforestation, soil disruption, and rising temperatures; El Niño events contributing to expansion
Talaromyces marneffei (formerly Penicillium marneffei)^17,57–60	Endemic to tropical and subtropical regions of Southeast Asia, including Thailand, Vietnam, and Southern China	Evidence suggests possible geographic expansion into northern China	Likely influenced by rising humidity, stronger monsoons, and warmer oceans; more research needed to establish a definitive link between climate factors and range expansion
Emergomyces species^13,61–63	Recently recognized with global distribution, including South Africa (Es. africanus), Italy, Spain, the Netherlands, France, India, China, South Africa, and Uganda (Es. pasteurianus), Canada and the US (Es. canadensis), China (Es. orientalis), and Germany (Es. europaeus)	Limited data on specific range expansions, though increasing prevalence observed	Limited data on epidemiological and climate change impacts

Current understanding of climate-driven expansion of endemic mycoses is limited by diagnostic test reliability and lack of population-based prevalence data.

For a visual representation of the geographic distribution of these endemic mycoses, please see the following references: Ashraf et al. Mycopathologia 2020; Gorris et al. Geohealth 2019; Thompson et al. Lancet Infect Dis 2021; Mazi et al. Clin Infect Dis 2023; and the resource available at mycoses.org.

Thermotolerant strains

Rising global temperatures and more frequent heat extremes are likely to drive fungal adaptation to human body temperature, potentially facilitating the emergence of novel fungal pathogens.⁶⁸ Thermotolerant fungi, which can exploit this environmental niche, may represent significant emerging threats.

C. auris is a globally disseminated pathogen known for its exceptional adaptability.^69–71 It demonstrates superior thermal and halotolerance compared to other Candida species, enabling survival in extreme environments characterized by high temperatures and salinity.^72–75 Its detection in aquatic environments and animal hosts raises concerns regarding zoonotic transmission and ongoing thermal adaptation.^76–80 Since its initial identification in 2009, C. auris has been reported in over 50 countries across six continents, where it has been associated with frequent healthcare-associated outbreaks.⁸¹ In the United States, the prevalence of C. auris has significantly increased in recent years, with clinical cases increasing by over 200% and positive screening cultures rising by 275% between 2019 and 2021.⁸²

Similarly, C. orthopsilosis, a species within the C. parapsilosis complex originating from warm marine habitats, highlights the role of rising ocean temperatures in reshaping fungal ecology.⁸³ Global warming may have exerted selective pressure favoring thermotolerant C. orthopsilosis strains and promoting their proliferation in marine ecosystems. Consequently, C. orthopsilosis isolation rates and nosocomial outbreaks have increased globally, with notable reports from Brazil and Italy.^84,85

Fusarium species pose significant threats to both human and agricultural health.^86–89 These fungi exhibit remarkable ecological adaptability, including efficient dispersal, mycotoxin production, and correlations between environmental and clinical isolates.^87–93 Climate change is projected to exacerbate these risks by altering species distribution, increasing disease prevalence, and enhancing mycotoxin contamination in both crops and the food supply. Invasive fusariosis, though relatively rare, remains a serious infection, particularly affecting individuals who are immunocompromised.⁹⁴ Recent outbreaks of multidrug-resistant central nervous system fusariosis linked to medical tourism in Mexico demonstrate the evolving threat of these fungi.⁹⁴

The C. gattii species complex has expanded its geographic range, in part due to climate change-induced shifts, with increased thermotolerance and melanin production potentially enhancing pathogenicity.^95–102 This species complex has been reported in the U.S. (including Oregon, Washington, California, and other states), Canada (British Columbia), Australia, Brazil, Colombia, and sub-Saharan Africa, though reporting varies by species.^96,103 While C. gattii species complex infections are more common in immunocompetent individuals, and cases in patients who are immunocompromised are increasingly observed.⁹⁶

Additionally, heat stress may induce genetic alterations in C. deneoformans (formerly C. neoformans var. neoformans, serotype D), impacting virulence and resistance to antifungal agents.^104–106 While globally distributed, C. deneoformans is more frequently reported in Europe.¹⁰⁷ However, recent studies indicate the increasing prevalence of C. neoformans × C. deneoformans hybrids (serotype AD) worldwide.

Dermatophytes, including species from the genera Epidermophyton, Microsporum, and Trichophyton, are the most prevalent pathogenic fungi in the U.S. and among the leading causes of skin diseases worldwide.^108–110 These fungi thrive in warm, humid environments and infect keratinized tissues. Predisposing factors, such as immunosuppression, skin trauma, and exposure to high environmental temperatures and humidity, are often necessary for infection. Rising temperatures and more frequent heat waves contribute to increased transmission rates and a wider geographic distribution of dermatophyte infections.

Social determinants of health

Vulnerable populations are disproportionately affected by natural disasters due to underlying socioeconomic factors, including limited education, poor healthcare access, and inadequate housing quality.¹¹¹ These individuals are more likely to reside in geographically vulnerable areas and experience a higher burden of comorbidities, increasing their susceptibility to fungal infections.^12,111 Natural disasters further exacerbate this risk through trauma, physical and psychological stress, and immunosuppression, creating a complex interplay of factors that increase vulnerability.^112–118 Additionally the prevalence of chronic diseases, medication use, malnutrition, and emerging infectious diseases such as SARS-CoV-2 or influenza, further amplifies the risk.^{7,10,12,112–122} These challenges are particularly severe in regions with limited healthcare infrastructure and resources, where delayed diagnoses and suboptimal treatment remain common due to healthcare disparities, including restricted access to care and the affordability of antifungal therapies.^12,123–126

A 2021 survey conducted by the European Confederation of Medical Mycology assessed diagnostic capacities for invasive fungal infections across 45 European countries.¹²⁷ The survey reported nearly universal access to culture-based methodologies (99%), microscopy (97%), and antigen-detection assays (94%), with molecular diagnostics and antibody tests available in 85% and 84% of institutions, respectively. However, significant disparities emerged based on gross domestic product (GDP) per capita. For example, antigen-detection tests were available in 95%–96% of institutions in high-income countries (GDP per capita ⩾$30,000) compared to 83% in low-income countries (GDP per capita <$30,000). While Europe has generally robust diagnostic and therapeutic capacities for fungal infections, institutions in lower-income regions continue to face challenges accessing essential diagnostics.

Many countries in the Asia-Pacific, African, Latin American, and Caribbean regions have limited or no access to diagnostic tools included in the World Health Organization (WHO) Model List of In Vitro Diagnostics, such as microscopy, fungal culture, blood culture, histopathology, and various antigen and polymerase chain reaction assays.^128–131 The scarcity of mycology laboratories and expertise in many Low- and Middle-Income Countries (LMICs) further contributes to low awareness of fungal infections among healthcare professionals.

Access to antifungal therapies is similarly inconsistent worldwide. While most countries in Europe, Asia-Pacific, Latin America and the Caribbean report access to at least one triazole (commonly fluconazole and voriconazole) and one formulation of amphotericin B, access to other antifungals, including liposomal amphotericin B, echinocandins, itraconazole, posaconazole, isavuconazole, and flucytosine varies considerably.^{127,129–131} European countries have the highest reported access rates, whereas access remains severely limited across Africa.

Addressing disparities driven by social determinants of health is critical to mitigate the growing burden of fungal infections, particularly in the context of climate change. Strengthening healthcare infrastructure, improving access to diagnostics and antifungal treatments, and investing in mycology expertise in resource-limited settings are essential to mitigate the impact of these infections and improve global health outcomes.

Displaced populations

Climate change is a major driver of forced displacement, significantly increasing the vulnerability of affected populations to natural disasters and subsequent fungal infections.¹³² According to the United Nations High Commissioner for Refugees (UNHCR), an average of 24 million people are displaced annually due to disasters, with weather-related events constituting the majority.¹³² Displaced populations often inhabit climate-vulnerable regions, where insufficient resources and infrastructure amplify their susceptibility to health risks, including fungal infections.

Extreme weather events, exacerbated by climate change, disrupt ecosystems and infrastructure, creating conditions conducive to fungal growth and dissemination.^{3–5,133–135} These events compromise human health directly through injury and exposure to contaminated environments, and indirectly, by overwhelming healthcare systems.^136–138 Aerosolized fungal spores and contaminated water are significant vectors, especially for individuals with immune deficiencies or disrupted skin barriers.

The synergistic effects of physical trauma, psychological stress, immunosuppression, and weakened healthcare infrastructure substantially increase the risk of fungal infections in disaster survivors.^112–118 A variety of natural disasters—including dust storms, tornadoes, wildfires, earthquakes, hurricanes, tsunamis, and volcanic eruptions—have been associated with increased incidences of fungal infections (Table 2).^{45,137,139–142} For instance, dust storms can aerosolize spores, leading to outbreaks of coccidioidomycosis.¹⁴¹ Wildfires also contribute to the risk of fungal infections by altering soil conditions and dispersing spores.^45,138,143

Table 2.

Fungal infections associated with dust-related disasters.

Fungal pathogen	Disaster and geographic location (year)	Impact
Apophysomyces trapeziformis	Tornado in Joplin, Missouri, US (2011)¹³⁷	Thirteen individuals with severe injuries developed mucormycosis, likely acquired from environmental exposure to organic matter and waterRisk factors included penetrating trauma and multiple wounds
Coccidioides immitis	Dust storm in Arvin, Kern County, California, US (1977)¹³⁹	Pulmonary and disseminated infections were reported up to 500 km away from the epicenter
Coccidioides immitis	Northridge earthquake, Simi Valley, Ventura County, California, US (1994)¹⁴¹	A surge in acute coccidioidomycosis cases occurred within two weeks of the earthquake, associated with strong winds dispersing fungal spores
Coccidioides immitis	Wildfires in California, US (2017)⁴⁵	Increased risk of coccidioidomycosis observed months after wildfire smoke exposure, likely exacerbated by soil disturbance during firefighting efforts
Rhizopus arrhizus (syn. Rhizopus oryzae)	Volcanic eruption in Armero, Colombia (1985)¹⁴²	Eight cases of mucormycosis were reported among patients with necrotizing skin lesions, following the volcanic eruption

Flooding is particularly conducive to fungal proliferation and dispersal (Table 3).^144–159 Water-damaged infrastructure fosters mold growth, while contaminated water and debris increase exposure to fungal pathogens.^144–148 These risks are especially problematic in regions prone to hurricanes and tsunamis, where large populations may be affected simultaneously.^149–154

Table 3.

Fungal infections associated with flooding.

Fungal pathogen (s)	Disaster and geographic location (year)	Impact
Aspergillus fumigatus	Great East Earthquake and Tsunami, Japan (2011)¹⁵⁶	Fatal disseminated aspergillosis in a previously healthy individual
Aspergillus fumigatus	Tsunami, Colombo, Sri Lanka (2005)¹⁵⁹	Five cases of cerebral aspergillosis linked to spinal anesthesia, likely due to medical supplies stored in humid, improper conditions
Aspergillus species, Fusarium species, Rhizopus species, Syncephalastrum species, Conidiobolus species	Hurricane Harvey, Houston, Texas, US (2017)^149,150,152	Increased incidence of invasive mold infections within one-year post-hurricane, although some studies reported no significant change
Chromoblastomycosis	Hurricane Ike, Galveston, Texas, US (2008)¹⁵⁷	At least three cases linked to injuries sustained during tree removal
Rhizopus arrhizus (syn. Rhizopus oryzae)	Flooding, Denver-Boulder Metropolitan Area, Colorado, US (2013)¹⁵⁸	Four cases of rhino-orbital-cerebral mucormycosis reported

Refugees and displaced persons residing in climate-vulnerable regions are disproportionately affected by these factors.¹³² Inadequate shelter, limited access to healthcare, and scarce resources exacerbate their vulnerability to fungal infections. Furthermore, population shifts toward densely populated, hot, and humid environments increase the transmission risk of dermatophytes, such as antifungal-resistant T. indotineae, compounding the public health burden.^108,109,160

The complex relationship between climate change, displacement, and fungal infections necessitates a multidisciplinary approach. Research is urgently needed to elucidate the mechanisms of fungal dispersal in disaster settings, develop robust prevention and treatment strategies, and fortify healthcare infrastructure in vulnerable regions.

Healthcare systems

Natural disasters significantly increase the risk of fungal infections by disrupting healthcare systems and compromising medical care. Damage to infrastructure—such as power outages, structural collapse, and water intrusion—impairs the delivery of essential health services. Floods pose a particularly severe threat by damaging healthcare facilities, contaminating medical supplies, and creating conditions conducive to fungal proliferation.^159,161

One notable example occurred in the aftermath of Hurricane Sandy (2012), which devastated the Atlantic coast of the U.S., leading to a polymicrobial fungal outbreak in a burn intensive care unit.¹⁶¹ This nosocomial outbreak was attributed to severe water infiltration and high winds preceding landfall. Similarly, a case series from Sri Lanka reported A. fumigatus infections following a flood-related disaster, with infections linked to medical supplies stored under humid, suboptimal conditions.¹⁵⁹

These cases emphasize the critical need to strengthen the climate resilience of healthcare infrastructure, ensuring that facilities and medical supplies are protected from the adverse effects of increasingly frequent and severe extreme weather events.¹⁶²

Agricultural impact

Climate change is exacerbating the threat of fungal diseases to both crop production and human health.¹⁶³ Increasingly frequent and severe weather events, driven by climate change, are increasing crop vulnerability to fungal pathogens. Altered precipitation patterns, combined with rising temperatures, are expanding the geographic range and abundance of these pathogens, leading to elevated incidences of fungal infections and increased mycotoxin contamination in food crops.^86,92 For instance, extreme precipitation and warmer temperatures have been directly linked to higher concentrations of mycotoxin contamination in maize, driven by the proliferation of F. graminearum.⁹²

In response to these threats, the intensive application of agricultural azoles has become a widespread strategy for managing fungal pathogens. However, this approach is creating significant selective pressure, driving the emergence of azole-resistant strains.^164,165 A. fumigatus, in particular, has developed resistance to azoles, raising concerns about the effectiveness of fungicidal strategies in both agriculture and human health.^166,167 As climate change continues to intensify crop losses, reliance on fungicides is expected to increase, further promoting resistance development in both crop-specific and environmental fungi with the potential for human infection.

The persistent and widespread use of agricultural azoles, such as difenoconazole, epoxiconazole, propiconazole, and tebuconazole, is especially concerning due to their structural similarity to medically important antifungal agents, including isavuconazole, itraconazole, posaconazole, and voriconazole.^168,169 With global azole consumption exceeding 30,000 metric tons annually, and environmental half-lives ranging from 47 to 120 days, these fungicides create a selective environment that fosters resistance to both agricultural and clinical fungal pathogens.

The widespread use of azole fungicides in agriculture since the 1980s has contributed to the emergence of azole-resistant fungal pathogens in clinical settings.¹⁶³ Climate change, by increasing the frequency and severity of fungal diseases in crops, is likely to further accelerate the development and dissemination of antifungal resistance, as farmers rely more heavily on fungicide applications to protect their yields.^164,165

Antifungal resistance

Climate change is increasingly recognized as playing a critical role in the emergence of antifungal resistance, particularly in A. fumigatus, where azole resistance has become a global concern, reported on all continents except Antarctica.^166,167 The global prevalence of azole-resistant A. fumigatus varies significantly, ranging from 0.6% to 30%, with some regions, such as Yunnan Province in China, reporting rates as high as 80%.^{166,167,170–184} The widespread use of agricultural azoles is believed to be a major driver of this resistance.^185,186 Notably, azole-resistant A. fumigatus is more prevalent in warmer environments, such as agricultural, healthcare, and public settings.^{169,170,187–190} Heat stress can induce ascospore germination, and when combined with azole exposure, may accelerate the development of resistance, suggesting a synergistic relationship between environmental temperature and antifungal resistance.^187,189,191

Resistance to azoles in A. fumigatus is primarily mediated by mutations in the CYP51A gene, which encodes the 14α-demethylase enzyme targeted by azoles (Table 4).^{171,189,190,192,193} These mutations have been detected globally in both clinical and environmental isolates. Although novel antifungal agents with alternative mechanisms of action have shown efficacy against azole-resistant A. fumigatus, concerns about potential cross-resistance with agricultural fungicides remain, as many of these agents share similar targets.^194–197

Table 4.

Mechanism of agricultural-related resistance to Aspergillus fumigatus.

Antifungal class (clinical antifungals)	Agricultural antifungals	Mechanism of resistance	Clinical impact
Triazoles^{171,189,190,192,193} (fluconazole, itraconazole, posaconazole, voriconazole, and isavuconazole)	Prothioconazole, bromuconazole, tebuconazole, epoxiconazole, and difenoconazole	Structural similarities between agricultural and medical triazoles result in selective pressure. Resistance is primarily driven by mutations in the cyp51A gene, which encodes the 14α-demethylase enzyme, commonly involving point mutations such as TR34/L98H or TR46/Y121F/T289	Molecular epidemiology studies have identified genetically identical resistant isolates from environmental and clinical sources, suggesting environmental reservoirs as a significant source of resistant isolates
Orotomide^194–196 (olorofim)	Ipflufenoquin	Both olorofim and ipflufenoquin inhibit dihydroorotate dehydrogenase (DHODH). Resistance can emerge from mutations at the G119 residue, altering enzyme binding affinity	Cross-resistance is a potential concern due to the shared target
Gwt1 enzyme inhibitor^194,197 (fosmanogepix (active moiety manogepix))	Aminopyrifen	While the specific risk of cross-resistance between manogepix and aminopyrifen is not yet established, both target fungal cell wall synthesis	The potential for cross-resistance is unknown but warrants further investigation

In addition to A. fumigatus, the overuse of agricultural azoles has been linked to resistance in Candida species.¹⁹⁸ For example, Candida species isolated from non-organic fruit had higher fluconazole minimum inhibitory concentrations (MICs) than those from organic fruit, suggesting a link between agricultural practices and antifungal resistance.¹⁹⁹ Genetic analyses have revealed similarities between clinical and environmental azole-resistant C. tropicalis isolates, further supporting the possibility of cross-resistance.¹⁹⁸ In addition, C. albicans isolated from the oropharynx of individuals with human immunodeficiency virus have demonstrated resistance to both clinical and agricultural azoles.²⁰⁰ In vitro studies have confirmed the development of azole resistance in C. glabrata and the C. parapsilosis complex following exposure to agricultural fungicides.^201–203

The environmental niche of C. auris remains poorly defined, but its geographic overlap with regions of high agricultural azole use raises concerns about agrochemical exposure contributing to resistance.^68,74,204 A case of azole-resistant C. albicans in a wild porcupine further illustrates the potential impact that environmental azoles pose to clinical antifungal efficacy.205 Beyond fostering resistance, agricultural fungicides can influence the morphology and virulence of Candida species.^202,206 For example, tebuconazole alters the metabolism of C. parapsilosis complex during adhesion, while azole-treated soils have produced azole-tolerant, biofilm-forming C. albicans variants.

While C. neoformans and the C. gattii species complex are less commonly found in agricultural settings, exposure to environmental fungicides can still impact their antifungal susceptibility and virulence.²⁰⁷ Studies have demonstrated that fungicide exposure can induce cross-resistance to fluconazole in both Cryptococcus species, with some strains retaining resistance even after fungicide removal.^208,209 Moreover, heat stress has been shown to promote the emergence of fungicide-resistant colonies in Cryptococcus species, and recent evidence suggests a link between heat stress and increased mutation rates in C. deneoformans.^104,105 These findings align with studies demonstrating temperature-dependent selection for antifungal resistance in C. neoformans when exposed to fluconazole and amphotericin B.^208–210 Collectively, these data suggest that both environmental fungicides and elevated temperatures can influence the acquisition and expression of antifungal resistance in Cryptococcus species, with potential implications for virulence and clinical management.

Agricultural workers, especially in South India, are at an increased risk of keratomycosis due to Fusarium species following plant- or soil-related corneal injuries.²¹¹ The extensive use of agricultural azoles, known for their persistence in soil, and the elevated MICs observed in both clinical and environmental Fusarium isolates, raise concerns regarding the potential for resistance emergence in these populations.²¹²

In addition, a novel fungal pathogen, Rhodosporidiobolus fluvialis, was recently identified as capable of temperature-induced mutagenesis, providing further evidence that rising global temperatures may accelerate the evolution of resistance and hypervirulence in fungi.²¹³ It is crucial to address the effects of climate change on fungal evolution and antifungal resistance, as these changes present substantial challenges to clinical management in an increasingly warming climate.

Mitigating the impact of climate change on fungal infections

Climate change presents a multifaceted and escalating challenge in the management of fungal infections.^3–5 The emergence of novel, thermotolerant fungal species, coupled with increasing resource demands, has further constrained available treatment options. The growing prevalence of fungal infections demands the urgent need for strategies to mitigate climate change, alongside enhanced surveillance, revised healthcare protocols, and strengthened educational initiatives.^214–218 A comprehensive, multidisciplinary approach to combat antifungal resistance is critical to addressing these emerging challenges effectively. The rising incidence of climate-related fungal infections highlights the necessity for proactive strategies aimed at mitigating their impact and fortifying healthcare system resilience.

Strategies to mitigate climate change

The healthcare sector contributes significantly to global greenhouse gas emissions, including carbon dioxide, methane, and nitrous oxide.^218,219 This contribution is projected to increase as healthcare demand grows worldwide. To mitigate this impact, a comprehensive approach encompassing both operational and systemic changes is required.

To initiate the decarbonization process, healthcare organizations should establish a sustainability team led by executive leadership and comprising diverse representatives from operational and clinical departments.^218,220 Engaging key stakeholders, including staff, clinicians, board members, and patients, is crucial for achieving sustainability objectives. A fundamental initial step involves conducting a greenhouse gas inventory to assess both direct emissions and indirect emissions, such as those arising from business travel, employee commuting, and waste disposal. By setting specific, measurable decarbonization targets, including annual greenhouse gas reduction goals and long-term net-zero emission targets, clear direction and accountability are established. Developing a comprehensive implementation plan with defined milestones facilitates progress tracking and ensures successful execution.

To achieve decarbonization goals, healthcare systems must prioritize high-impact interventions.^218,220 These include reducing building emissions through improved energy efficiency and increased use of renewable energy sources, addressing emissions from anesthetic gases and inhalers, minimizing waste, and reducing reliance on single-use plastics. Other essential strategies include promoting sustainable food services, reducing the carbon footprint of meals, and encouraging sustainable transportation options such as electric vehicles and active commuting. By systematically integrating these interventions, healthcare systems can reduce their carbon footprint, improve operational efficiency, and contribute to global climate change mitigation efforts.

In addition to operational changes, a systemic shift toward preventive care and value-based healthcare can reduce unnecessary treatments and procedures, thereby lowering both costs and emissions.^218,220 However, a comprehensive understanding of the economic and environmental implications of such strategies is essential to inform decision-making.

While evidence suggests that sustainable healthcare practices offer both environmental and economic benefits, challenges remain.^218,220 Implementing these changes often requires substantial investment, changes in work routines, and strong leadership. Overcoming these barriers requires raising awareness about the environmental and health consequences of unsustainable practices and fostering a culture of sustainability among healthcare professionals and the public.

Management strategies

Rapid and accurate diagnostic strategies are essential to address the rising incidence of fungal infections driven by climate change.²²¹ As global temperatures shift and weather patterns become more erratic, the geographic distribution and virulence of pathogenic fungi are evolving, leading to higher infection rates and the emergence of novel, antifungal-resistant organisms. Early identification is critical for reducing disease severity, enabling timely and effective treatment, and ultimately lowering morbidity and mortality.^222,223 Moreover, rapid diagnosis is key for infection control and public health responses during outbreaks. Given the dynamic epidemiological landscape, advanced diagnostic methodologies are indispensable for optimizing clinical management and protecting public health from the growing threat of climate change-related fungal infections.

A thorough assessment of individual risk factors is equally important, including travel history, environmental exposures, living conditions, and preexisting medical conditions. Such detailed evaluations guide both diagnostic decisions and subsequent therapeutic interventions.

Diagnosing fungal infections remains challenging due to nonspecific clinical presentations, limited availability of essential diagnostic tests, and the inherent limitations of conventional culture techniques.^{127–130,221} Non-culture–based diagnostic tests offer significant advantages in speed, sensitivity, and specificity, providing promising alternatives for detecting fungal pathogens that are often difficult or slow to culture.^224,225 This is particularly important as climate change accelerates shifts in environmental conditions favorable for fungal proliferation and transmission.^3–5 These non-culture-based tests also have a high negative predictive value, making them valuable for ruling out fungal etiologies, but they should be used alongside conventional and serological methods to confirm diagnoses in patients with diverse clinical symptoms.^224,225

Despite their benefits, non-culture-based diagnostic tests have limitations.^224–227 Performance variability between platforms can affect accuracy, and false positives may arise from nonpathogenic colonization misinterpreted as infection, particularly when sampling from nonsterile sites. In addition, the specialized expertise required for implementation and interpretation, coupled with higher costs, may limit accessibility in resource-constrained settings.^127–130

Antifungal susceptibility testing

Current methods for detecting antifungal resistance and tolerance have significant limitations.²²⁸ Phenotypic susceptibility testing, which relies on isolating fungi from clinical specimens, is inherently less sensitive.^228,229 This approach is further constrained by the limited availability of antifungal susceptibility testing in LMICs and the potential discordance between in vitro susceptibility results and actual clinical outcomes.^128,228,230 Low-level clinical resistance may be masked by antifungal drug tolerance, leading to discrepancies between treatment efficacy and susceptibility testing.²²⁸ Although molecular methods provide an alternative, their accuracy is influenced by prior antifungal exposure, the diversity of resistance mechanisms, and limited accessibility in resource-constrained environments.²³⁰

A multifaceted approach is essential to combat the rise of antifungal resistance. This includes optimizing antifungal use, enhancing access to antifungal therapeutic monitoring, improving existing antifungals, and developing novel agents with broad-spectrum activity and unique mechanisms of action.^{128,231–234} Key strategies include robust surveillance programs to monitor resistance trends, stewardship initiatives to promote appropriate antifungal therapy, and advanced diagnostics for detecting fungal infections and resistance. Maintaining the efficacy of current antifungals also requires exploring combination therapies and host-directed strategies, such as immunotherapy, fungal vaccines, and antibodies that target fungal virulence factors.^234–238

Disparities in healthcare infrastructure, coupled with financial strain on hospitals and health systems, limit access to essential antifungals.^125,126 Disrupted supply chains and affordability challenges further exacerbate these issues, contributing to delayed diagnoses, suboptimal treatments, and a heightened burden of fungal infections. Effective antifungal management remains difficult, particularly in the face of emerging resistant pathogens.²³⁹ A comprehensive understanding of cross-resistance mechanisms is critical for optimizing treatment, preserving therapeutic efficacy, and identifying evolving resistance patterns.²³⁴ The association between the widespread use of agricultural antifungals and the development of clinical resistance underscores the need for stringent monitoring of agricultural practices to mitigate their impact on medical antifungal therapy (Table 4). Furthermore, the significant financial burden on hospitals and health systems, coupled with formulary constraints and an already strained healthcare system, underscores the critical need for effective antifungal stewardship. Surveillance programs provide invaluable insights into the regional and global prevalence of resistant strains, guiding empirical treatment decisions and supporting public health efforts. As climate change drives an increase in fungal infections, improving antifungal susceptibility testing methods becomes essential for personalized therapy.

Development of new antifungal agents

The increasing prevalence of antifungal resistance among pathogenic fungi highlights the urgent need for novel therapeutic strategies.^{231–234,236–238} Current research efforts are focused on developing antifungal agents that target novel pathways to overcome existing resistance mechanisms and enhance treatment efficacy against resistant strains. The US Food and Drug Administration (FDA) Limited Population Pathway for Antibacterial and Antifungal Drugs (LPAD) has been instrumental in accelerating the development and approval of antifungal therapies for serious or life-threatening infections caused by resistant pathogens.²⁴⁰ By streamlining clinical trials and regulatory reviews, the LPAD pathway promotes innovation and broadens the range of treatment options available to patients with limited alternatives.

Given the growing influence of climate change on antifungal resistance patterns, proactive measures are critical to mitigate the associated risks. Advancing susceptibility testing, developing novel antifungal agents, and utilizing regulatory frameworks such as the LPAD are essential for optimizing the management of fungal infections and curbing the spread of antimicrobial resistance.

Policy, education, and future directions

The growing impact of climate change on the emergence and reemergence of fungal infections requires an integrated approach that combines policy, education, and research.^5,128,241 International collaboration and stringent regulatory frameworks are essential to mitigate climate change and its environmental consequences. Simultaneously, substantial investments in research are needed to advance our understanding of fungal pathogens, enhance diagnostic tools, elucidate antifungal resistance mechanisms, and develop innovative therapeutic strategies.

Public health initiatives must prioritize raising awareness of fungal infections and their associated risk factors. Advocacy efforts should emphasize the critical connection between climate change mitigation and a reduced burden of fungal diseases. Policy changes promoting clean energy transitions and sustainable environmental practices are vital for building resilience against the rising threat of fungal infections.

To combat the expanding geographic distribution of fungal pathogens driven by climate change, key research areas need to be prioritized. Developing robust predictive models for fungal pathogens requires improved environmental monitoring and comprehensive characterization of fungal isolates.^39,242 In addition, compiling data on antifungal usage and disease burden is essential to inform public health strategies, policy development, and timely interventions.^243–245 Research should focus on developing novel diagnostic tools with enhanced sensitivity, specificity, and rapid turnaround times.^224,225

Understanding the mechanisms underlying antifungal resistance is essential for guiding future antifungal development.^{4,171,200,246} This includes studying the effects of agricultural fungicide use and environmental exposures on the selection of resistant fungal strains. Investigating novel resistance mechanisms in fungi will be critical for developing new antifungal agents, especially due to the widespread use of azoles.^{163,247–249} Integrated management strategies, such as disease-resistant crops and sustainable fungicide practices, are essential in agriculture, and minimizing overlap between agricultural and clinical antifungal use is crucial to slowing resistance development.

Developing new therapeutic strategies remains a high priority.^{232,234,236–238} Given the limited antifungal options available, research should focus on creating broad-spectrum antifungals with enhanced fungicidal activity and a lower risk of resistance development. In addition, immunotherapies, fungal vaccines, and antibody-based therapies targeting fungal virulence factors are promising areas for investigation.

A One Health approach, integrating human, animal, and environmental health, is crucial to effectively address the global threat of fungal infections.^247,248 This approach emphasizes equitable access to diagnostics, antifungals, and healthcare, with a focus on early detection and intervention.

To address the growing threat of fungal infections exacerbated by climate change, it is imperative to implement robust strategies to mitigate greenhouse gas emissions and reduce the frequency and intensity of extreme weather events. In addition, a deeper understanding of the complex ecological factors that influence fungal growth, dissemination, and virulence is essential to develop effective prevention and control measures.

Conclusion

Climate change is altering fungal ecology, increasing the risk of both emerging and reemerging fungal infections, necessitating a paradigm shift in clinical practice. Clinicians must remain vigilant for novel fungal pathogens, which may be more virulent or drug-resistant. Early and accurate diagnosis is essential for optimizing patient outcomes, as misdiagnosis can delay the initiation of appropriate antifungal therapy, worsening prognosis. The increasing threat of antifungal resistance highlights the urgent need for new antifungal agents with distinct mechanisms of action. Exploring combination therapies and host-directed strategies, such as immunotherapies and vaccines, may help preserve the efficacy of existing antifungals. However, healthcare disparities and limited access to antifungal treatments continue to impede optimal care, exacerbating the global burden of fungal infections.

Footnotes

Acknowledgements

None.

Declarations

ORCID iDs

David B. Cluck

Andrés F. Henao-Martínez

Daniel B. Chastain

References

Intergovernmental Panel on Climate Change. Climate change 2007: synthesis report. World Meteorol Organ 2007; 52: 1–43.

Clarke

Otto

Stuart-Smith

, et al. Extreme weather impacts of climate change: an attribution perspective. Environ Res Clim 2022; 1: 012001.

Buckley

Roughgarden

Effects of changes in climate and land use. Nature 2004; 430: 34–34.

Fisher

Gurr

Cuomo

, et al. Threats posed by the fungal kingdom to humans, wildlife, and agriculture. mBio 2020; 11: e00449-20.

Casadevall

Climate change brings the specter of new infectious diseases. J Clin Invest 2020; 130: 553–555.

Mora

McKenzie

Gaw

, et al. Over half of known human pathogenic diseases can be aggravated by climate change. Nat Clim Chang 2022; 12: 869–875.

Bhabhra

Askew

DS.

Thermotolerance and virulence of Aspergillus fumigatus: role of the fungal nucleolus. Med Mycol 2005; 43: S87–S93.

Protsiv

Ley

Lankester

, et al. Decreasing human body temperature in the United States since the industrial revolution. Elife 2020; 9: e49555.

Martinson

Lapham

Prevalence of immunosuppression among US adults. JAMA 2024; 331: 880–882.

10.

Clark

Drummond

RA.

The hidden cost of modern medical interventions: how medical advances have shaped the prevalence of human fungal disease. Pathogens 2019; 8: 45.

11.

Chastain

Stover

KR.

Urgent need to address infectious diseases due to immunosuppressive therapies. Ther Adv Infect Dis 2023; 10: 20499361231168512.

12.

Jenks

Prattes

Wurster

, et al. Social determinants of health as drivers of fungal disease. eClinicalMedicine 2023; 66: 102325.

13.

Ashraf

Kubat

Poplin

, et al. Re-drawing the maps for endemic mycoses. Mycopathologia 2020; 185: 843–865.

14.

Brown

McTaggart

Dunn

, et al. Epidemiology and geographic distribution of blastomycosis, histoplasmosis, and coccidioidomycosis, Ontario, Canada, 1990–2015. Emerg Infect Dis 2018; 24: 1257–1266.

15.

Benedict

Thompson

3rd Deresinski

, et al. Mycotic infections acquired outside areas of known endemicity, United States. Emerg Infect Dis 2015; 21: 1935–1941.

16.

Mazi

Sahrmann

Olsen

, et al. The geographic distribution of dimorphic mycoses in the United States for the Modern Era. Clin Infect Dis 2023; 76: 1295–1301.

17.

Wang

Han

Chen

An overlooked and underrated endemic mycosis-talaromycosis and the pathogenic fungus talaromyces marneffei. Clin Microbiol Rev 2023; 36: e0005122.

18.

Anderson

Honish

Taylor

, et al. Histoplasmosis cluster, golf course, Canada. Emerg Infect Dis 2006; 12: 163–165.

19.

Calanni

Pérez

Brasili

, et al. [Outbreak of histoplasmosis in province of Neuquén, Patagonia Argentina]. Rev Iberoam Micol 2013; 30: 193–199.

20.

Taylor

Reyes-Montes

MDR

Estrada-Bárcenas

, et al. Considerations about the geographic distribution of histoplasma species. Appl Environ Microbiol 2022; 88: e0201021.

21.

Restrepo

Baumgardner

Bagagli

, et al. Clues to the presence of pathogenic fungi in certain environments. Med Mycol 2000; 38(Suppl. 1): 67–77.

22.

Litvinov

St-Germain

Pelletier

, et al. Endemic human blastomycosis in Quebec, Canada, 1988–2011. Epidemiol Infect 2013; 141: 1143–1147.

23.

Baumgardner

Paretsky

Baeseman

, et al. Effects of season and weather on blastomycosis in dogs: Northern Wisconsin, USA. Med Mycol 2011; 49: 49–55.

24.

Proctor

Klein

Jones

, et al. Cluster of pulmonary blastomycosis in a rural community: evidence for multiple high-risk environmental foci following a sustained period of diminished precipitation. Mycopathologia 2002; 153: 113–120.

25.

Pfister

Archer

Hersil

, et al. Non-rural point source blastomycosis outbreak near a yard waste collection site. Clin Med Res 2011; 9: 57–65.

26.

Williams

Cook

Smerdon

, et al. Large contribution from anthropogenic warming to an emerging North American megadrought. Science 2020; 368: 314–318.

27.

Marvel

Cook

Bonfils

, et al. Twentieth-century hydroclimate changes consistent with human influence. Nature 2019; 569: 59–65.

28.

Saccente

Woods

GL.

Clinical and laboratory update on blastomycosis. Clin Microbiol Rev 2010; 23: 367–381.

29.

Menges

Furcolow

Larsh

, et al. Laboratory studies on histoplasmosis. I. The effect of humidity and temperature on the growth of Histoplasma capsulatum. J Infect Dis 1952; 90: 67–70.

30.

Maiga

Deppen

Scaffidi

, et al. Mapping Histoplasma capsulatum exposure, United States. Emerg Infect Dis 2018; 24: 1835–1839.

31.

Nett

Skillman

Riek

, et al. Histoplasmosis in Idaho and Montana, USA, 2012–2013. Emerg Infect Dis 2015; 21: 1071–1072.

32.

Skillman

Riek

Davis

, et al. Histoplasmosis in a state where it is not known to be endemic–Montana, 2012–2013. MMWR Morb Mortal Wkly Rep 2013; 62: 834–837.

33.

Armstrong

Jackson

Haselow

, et al. Multistate epidemiology of histoplasmosis, United States, 2011–2014. Emerg Infect Dis 2018; 24: 425–431.

34.

Farina

Rizzi

Ricci

, et al. Imported and autochthonous histoplasmosis in Italy: new cases and old problems. Rev Iberoam Micol 2005; 22: 169–171.

35.

Antinori

Magni

Nebuloni

, et al. Histoplasmosis among human immunodeficiency virus-infected people in Europe: report of 4 cases and review of the literature. Medicine (Baltimore) 2006; 85: 22–36.

36.

Head

Sondermeyer-Cooksey

Heaney

, et al. Effects of precipitation, heat, and drought on incidence and expansion of coccidioidomycosis in western USA: a longitudinal surveillance study. Lancet Planet Health 2022; 6: e793–e803.

37.

Oltean

Etienne

Roe

, et al. Utility of whole-genome sequencing to ascertain locally acquired cases of Coccidioidomycosis, Washington, USA. Emerg Infect Dis 2019; 25: 501–506.

38.

Turabelidze

Aggu-Sher

Jahanpour

, et al. Coccidioidomycosis in a state where it is not known to be endemic - Missouri, 2004–2013. MMWR Morb Mortal Wkly Rep 2015; 64: 636–639.

39.

Gorris

Treseder

Zender

, et al. Expansion of coccidioidomycosis endemic regions in the United States in response to climate change. Geohealth 2019; 3: 308–327.

40.

Carvalho

Ferreira

Gaião

, et al. Cerebral coccidioidomycosis after renal transplantation in a non-endemic area. Transpl Infect Dis 2010; 12: 151–154.

41.

Porter

Gade

Montfort

, et al. Understanding the exposure risk of aerosolized Coccidioides in a Valley fever endemic metropolis. Sci Rep 2024; 14: 1311.

42.

Gade

McCotter

Bowers

, et al. The detection of Coccidioides from ambient air in Phoenix, Arizona: evidence of uneven distribution and seasonality. Med Mycol 2020; 58: 552–559.

43.

Laws

Jain

Cooksey

, et al. Coccidioidomycosis outbreak among inmate wildland firefighters: California, 2017. Am J Ind Med 2021; 64: 266–273.

44.

Marlon

Bartlein

Gavin

, et al. Long-term perspective on wildfires in the western USA. Proc Natl Acad Sci 2012; 109: E535–E543.

45.

Mulliken

Hampshire

Rappold

, et al. Risk of systemic fungal infections after exposure to wildfires: a population-based, retrospective study in California. Lancet Planet Health 2023; 7: e381–e386.

46.

Teixeira Mde

Theodoro

Oliveira

, et al. Paracoccidioides lutzii sp. nov.: biological and clinical implications. Med Mycol 2014; 52: 19–28.

47.

Rodrigues

Hagen

Puccia

, et al. Paracoccidioides and Paracoccidioidomycosis in the 21st Century. Mycopathologia 2023; 188: 129–133.

48.

Martinez

New trends in paracoccidioidomycosis epidemiology. J Fungi (Basel) 2017; 3: 1.

49.

Vieira Gde

Alves Tda

Lima

, et al. Paracoccidioidomycosis in a western Brazilian Amazon State: clinical-epidemiologic profile and spatial distribution of the disease. Rev Soc Bras Med Trop 2014; 47: 63–68.

50.

Coutinho

Wanke

Travassos

, et al. Hospital morbidity due to paracoccidioidomycosis in Brazil (1998–2006). Trop Med Int Health 2015; 20: 673–680.

51.

Peçanha

Peçanha-Pietrobom

Grão-Velloso

, et al. Paracoccidioidomycosis: what we know and what is new in epidemiology, diagnosis, and treatment. J Fungi (Basel) 2022; 8: 1098.

52.

Cermeño

Godoy

, et al. Epidemiological study of paracoccidioidomycosis and histoplasmosis in a suburb of San Félix city, Bolívar state, Venezuela. Invest Clin 2009; 50: 213–220.

53.

Barrozo

Mendes

Marques

, et al. Climate and acute/subacute paracoccidioidomycosis in a hyper-endemic area in Brazil. Int J Epidemiol 2009; 38: 1642–1649.

54.

Conti-Diaz

Mackinnon

Furcolow

ML.

Effect of drying on Paracoccidioides brasiliensis. Sabouraudia 1971; 9: 69–78.

55.

Simões

Marques

Bagagli

Distribution of paracoccidioidomycosis: determination of ecologic correlates through spatial analyses. Med Mycol 2004; 42: 517–523.

56.

Barrozo

Benard

Silva

, et al. First description of a cluster of acute/subacute paracoccidioidomycosis cases and its association with a climatic anomaly. PLoS Negl Trop Dis 2010; 4: e643.

57.

Bulterys

Quang

, et al. Environmental predictors and incubation period of AIDS-associated penicillium marneffei infection in Ho Chi Minh City, Vietnam. Clin Infect Dis 2013; 56: 1273–1279.

58.

Wolbers

Chi

, et al. Epidemiology, seasonality, and predictors of outcome of AIDS-associated Penicillium marneffei infection in Ho Chi Minh City, Viet Nam. Clin Infect Dis 2011; 52: 945–952.

59.

Ying

Cai

, et al. Clinical epidemiology and outcome of HIV-associated talaromycosis in Guangdong, China, during 2011–2017. HIV Med 2020; 21: 729–738.

60.

Yang

Liu

, et al. Disseminated Talaromyces marneffei infection associated with haemophagocytic syndrome in an HIV-negative patient in northern China: a case report. BMC Infect Dis 2024; 24: 63.

61.

Vinayagamoorthy

Gangavaram

Skiada

, et al. Emergomycosis, an emerging thermally dimorphic fungal infection: a systematic review. J Fungi (Basel) 2023; 9: 1039.

62.

Jiang

Dukik

Muñoz

, et al. Phylogeny, ecology and taxonomy of systemic pathogens and their relatives in Ajellomycetaceae (Onygenales): Blastomyces, Emergomyces, Emmonsia, Emmonsiellopsis. Fungal Div 2018; 90: 245–291.

63.

Schwartz

Kenyon

Lehloenya

, et al. AIDS-related endemic mycoses in Western Cape, South Africa, and clinical mimics: a cross-sectional study of adults with advanced HIV and recent-onset, widespread skin lesions. Open Forum Infect Dis 2017; 4: ofx186.

64.

Williamson

Zepp

Lucas

, et al. Solar ultraviolet radiation in a changing climate. Nat Clim Change 2014; 4: 434–441.

65.

Campbell

Berliner

MD.

Virulence differences in mice of type A and B Histoplasma capsulatum yeasts grown in continuous light and total darkness. Infect Immun 1973; 8: 677–678.

66.

Medoff

Maresca

Lambowitz

, et al. Correlation between pathogenicity and temperature sensitivity in different strains of Histoplasma capsulatum. J Clin Invest 1986; 78: 1638–1647.

67.

Restrepo

McEwen

Castañeda

The habitat of Paracoccidioides brasiliensis: how far from solving the riddle?

Med Mycol 2001; 39: 233–241.

68.

Smith

DFQ

Casadevall

. Disaster mycology. Biomedica 2023; 43: 267–277.

69.

Casadevall

Kontoyiannis

Robert

On the emergence of Candida auris: climate change, azoles, swamps, and birds. mBio 2019; 10: e01397-19.

70.

Satoh

Makimura

Hasumi

, et al. Candida auris sp. nov., a novel ascomycetous yeast isolated from the external ear canal of an inpatient in a Japanese hospital. Microbiol Immunol 2009; 53: 41–44.

71.

Chow

Muñoz

Gade

, et al. Tracing the evolutionary history and global expansion of Candida auris using population genomic analyses. mBio 2020; 11: e03364-19.

72.

Welsh

Bentz

Shams

, et al. Survival, persistence, and isolation of the emerging multidrug-resistant pathogenic yeast Candida auris on a plastic health care surface. J Clin Microbiol 2017; 55: 2996–3005.

73.

Arora

Singh

Wang

, et al. Environmental isolation of Candida auris from the Coastal Wetlands of Andaman Islands, India. mBio 2021; 12: e03181-20.

74.

Escandón

Novel environmental niches for Candida auris: isolation from a Coastal Habitat in Colombia. J Fungi (Basel) 2022; 8: 748.

75.

Casadevall

Kontoyiannis

Robert

Environmental Candida auris and the global warming emergence hypothesis. mBio 2021; 12: e00360-21.

76.

Ekowati

Ferrero

Kennedy

, et al. Potential transmission pathways of clinically relevant fungi in indoor swimming pool facilities. Int J Hyg Environ Health 2018; 221: 1107–1115.

77.

Rossi

Chavez

Iverson

, et al. Candida auris discovery through community wastewater surveillance during healthcare outbreak, Nevada, USA, 2022. Emerg Infect Dis 2023; 29: 422–425.

78.

Babler

Sharkey

Arenas

, et al. Detection of the clinically persistent, pathogenic yeast spp. Candida auris from hospital and municipal wastewater in Miami-Dade County, Florida. Sci Total Environ 2023; 898: 165459.

79.

Yadav

Wang

Jain

, et al. Candida auris in Dog Ears. J Fungi (Basel) 2023; 9: 720.

80.

White

Esquivel

Rouse Salcido

, et al. Candida auris detected in the oral cavity of a dog in Kansas. mBio 2024; 15: e0308023.

81.

Kim

HYP

Nguyen

TAM

Kidd

, et al. Candida auris-a systematic review to inform the world health organization fungal priority pathogens list. Med Mycol 2024; 62: myae042.

82.

Lyman

Forsberg

Sexton

, et al. Worsening spread of Candida auris in the United States, 2019 to 2021. Ann Intern Med 2023; 176: 489–495.

83.

Del Olmo

Mixão

Fotedar

, et al. Origin of fungal hybrids with pathogenic potential from warm seawater environments. Nat Commun 2023; 14: 6919.

84.

Luo

Ning

, et al. The first established microsatellite markers to distinguish Candida orthopsilosis isolates and detection of a nosocomial outbreak in China. J Clin Microbiology 2023; 61: e00806–00823.

85.

Tavanti

Hensgens

Ghelardi

, et al. Genotyping of Candida orthopsilosis clinical isolates by amplification fragment length polymorphism reveals genetic diversity among independent isolates and strain maintenance within patients. J Clin Microbiol 2007; 45: 1455–1462.

86.

Martínez

Biganzoli

Arata

, et al. Warm nights increase Fusarium Head Blight negative impact on barley and wheat grains. Agric Forest Meteorol 2022; 318: 108909.

87.

Nucci

Anaissie

Fusarium infections in immunocompromised patients. Clin Microbiol Rev 2007; 20: 695–704.

88.

Batista

Chaves

Reginatto

, et al. Human fusariosis: an emerging infection that is difficult to treat. Rev Soc Bras Med Trop 2020; 53: e20200013.

89.

Ejaz

Jaoua

Ahmadi

, et al. An examination of how climate change could affect the future spread of Fusarium spp. around the world, using correlative models to model the changes. Environ Technol Innovation 2023; 31: 103177.

90.

Al-Hatmi

Hagen

Menken

, et al. Global molecular epidemiology and genetic diversity of Fusarium, a significant emerging group of human opportunists from 1958 to 2015. Emerg Microbes Infect 2016; 5: e124.

91.

Zingales

Taroncher

Martino

, et al. Climate change and effects on molds and mycotoxins. Toxins (Basel) 2022; 14: 445.

92.

Janić Hajnal

Kos

Radić

, et al. Impact of climate changes on the natural prevalence of fusarium mycotoxins in Maize Harvested in Serbia and Croatia. Foods 2023; 12: 1002.

93.

Sáenz

Alvarez-Moreno

Pape

, et al. A one health perspective to recognize fusarium as important in clinical practice. J Fungi (Basel) 2020; 6: 235.

94.

Beltran-Reyes

Ostrosky-Zeichner

Gonzalez-Lara

MF.

Update on diagnosis and treatment of fungal meningitis: lessons from recent outbreaks. Curr Opin Infect Dis 2024; 37: 437–442.

95.

Cogliati

Global warming impact on the expansion of fundamental niche of Cryptococcus gattii VGI in Europe. Environ Microbiol Rep 2021; 13: 375–383.

96.

Bruner

Franco-Paredes

Henao-Martínez

, et al. Cryptococcus gattii complex infections in HIV-infected patients, Southeastern United States. Emerg Infect Dis 2018; 24: 1998–2002.

97.

Granados

Castañeda

Influence of climatic conditions on the isolation of members of the Cryptococcus neoformans species complex from trees in Colombia from 1992–2004. FEMS Yeast Res 2006; 6: 636–644.

98.

Kidd

Bach

Hingston

, et al. Cryptococcus gattii dispersal mechanisms, British Columbia, Canada. Emerg Infect Dis 2007; 13: 51–57.

99.

Fernandes

Dwyer

Campbell

, et al. Species in the Cryptococcus gattii complex differ in capsule and cell size following growth under capsule-inducing conditions. Msphere 2016; 1: e00350-16.

100.

Rosas

ÁL

Casadevall

. Melanization affects susceptibility of Cryptococcus neoformans to heat and cold. FEMS Microbiol Lett 1997; 153: 265–272.

101.

de Sousa

de Oliveira

GP Frazão

SdO

, et al. Faster Cryptococcus melanization increases virulence in experimental and human cryptococcosis. J Fungi 2022; 8: 393.

102.

Singaravelan

Grishkan

Beharav

, et al. Adaptive melanin response of the soil fungus Aspergillus niger to UV radiation stress at “Evolution Canyon”, Mount Carmel, Israel. PloS one 2008; 3: e2993.

103.

Poplin

Smith

Caceres

, et al. Geographical distribution of the Cryptococcus gattii species complex: a systematic review. Lancet Microbe 2024; 5: 100921.

104.

Gusa

Yadav

Roth

, et al. Genome-wide analysis of heat stress-stimulated transposon mobility in the human fungal pathogen Cryptococcus deneoformans. Proc Natl Acad Sci USA 2023; 120: e2209831120.

105.

Gusa

Williams

Cho

, et al. Transposon mobilization in the human fungal pathogen Cryptococcus is mutagenic during infection and promotes drug resistance in vitro. Proc Natl Acad Sci USA 2020; 117: 9973–9980.

106.

Hagen

Khayhan

Theelen

, et al. Recognition of seven species in the Cryptococcus gattii/Cryptococcus neoformans species complex. Fungal Genet Biol 2015; 78: 16–48.

107.

Gago

Serrano

Alastruey-Izquierdo

, et al. Molecular identification, antifungal resistance and virulence of Cryptococcus neoformans and Cryptococcus deneoformans isolated in Seville, Spain. Mycoses 2017; 60: 40–50.

108.

Zhan

Liu

The changing face of dermatophytic infections Worldwide. Mycopathologia 2017; 182: 77–86.

109.

Nenoff

Verma

Vasani

, et al. The current Indian epidemic of superficial dermatophytosis due to Trichophyton mentagrophytes—a molecular study. Mycoses 2019; 62: 336–356.

110.

Moskaluk

VandeWoude

Current topics in dermatophyte classification and clinical diagnosis. Pathogens 2022; 11: 957.

111.

EPA. Climate change and the health of socially vulnerable people, https://www.epa.gov/climateimpacts/climate-change-and-health-socially-vulnerable-people (2024, accessed 11 June 2024).

112.

Skevaki

Nadeau

Rothenberg

, et al. Impact of climate change on immune responses and barrier defense. J Allergy Clin Immunol 2024; 153: 1194–1205.

113.

Passos

Vasconcelos-Moreno

Costa

, et al. Inflammatory markers in post-traumatic stress disorder: a systematic review, meta-analysis, and meta-regression. Lancet Psychiatry 2015; 2: 1002–1012.

114.

von Känel

Hepp

Kraemer

, et al. Evidence for low-grade systemic proinflammatory activity in patients with posttraumatic stress disorder. J Psychiatr Res 2007; 41: 744–752.

115.

Kario

McEwen

Pickering

TG.

Disasters and the heart: a review of the effects of earthquake-induced stress on cardiovascular disease. Hypertens Res 2003; 26: 355–367.

116.

Aiello

Dowd

Jayabalasingham

, et al. PTSD is associated with an increase in aged T cell phenotypes in adults living in Detroit. Psychoneuroendocrinology 2016; 67: 133–141.

117.

Cheng

Chai

, et al. Dynamic changes in trauma-induced myeloid-derived suppressor cells after polytrauma are associated with an increased susceptibility to infection. Int J Clin Exp Pathol 2017; 10: 11063–11068.

118.

Zhang

, et al. Effect of elevated temperatures on inflammatory cytokine release: an in vitro and population-based study. Environ Health 2024; 2: 721–728.

119.

Salazar

Bignell

Brown

, et al. Pathogenesis of respiratory viral and fungal coinfections. Clin Microbiol Rev 2022; 35: e0009421.

120.

Rohr

Barrett

Civitello

, et al. Emerging human infectious diseases and the links to global food production. Nat Sustain 2019; 2: 445–456.

121.

Pacheco

Guidos-Fogelbach

Annesi-Maesano

, et al. Climate change and global issues in allergy and immunology. J Allergy Clin Immunol 2021; 148: 1366–1377.

122.

Hughes

Price

Sisko

, et al. Protein-calorie malnutrition: a host determinant for Pneumocystis carinii infection. Am J Dis Children 1974; 128: 44–52.

123.

Alirol

Getaz

Stoll

, et al. Urbanisation and infectious diseases in a globalised world. Lancet Infect Dis 2011; 11: 131–141.

124.

Jafarlou

Unveiling the menace: a thorough review of potential pandemic fungal disease. Front Fungal Biol 2024; 5: 1338726.

125.

Kneale

Bartholomew

Davies

, et al. Global access to antifungal therapy and its variable cost. J Antimicrob Chemother 2016; 71: 3599–3606.

126.

Bongomin

Gago

Oladele

, et al. Global and multi-national prevalence of fungal diseases—estimate precision. J Fungi 2017; 3: 57.

127.

Salmanton-García

Hoenigl

Gangneux

, et al. The current state of laboratory mycology and access to antifungal treatment in Europe: a European Confederation of Medical Mycology survey. Lancet Microbe 2023; 4: e47–e56.

128.

Arendrup

Armstrong-James

Borman

, et al. The impact of the fungal priority pathogens list on medical mycology: a Northern European perspective. Open Forum Infect Dis 2024; 11: ofae372.

129.

Salmanton-García

Hoenigl

, et al. The current state of laboratory mycology in Asia/Pacific: A survey from the European Confederation of Medical Mycology (ECMM) and International Society for Human and Animal Mycology (ISHAM). Int J Antimicrob Agents 2023; 61: 106718.

130.

Driemeyer

Falci

Oladele

, et al. The current state of clinical mycology in Africa: a European Confederation of Medical Mycology and International Society for Human and Animal Mycology survey. Lancet Microbe 2022; 3: e464–e470.

131.

Falci

Pasqualotto

AC.

Clinical mycology in Latin America and the Caribbean: a snapshot of diagnostic and therapeutic capabilities. Mycoses 2019; 62: 368–373.

132.

UNHCR. Climate crisis fuels flooding and deepens displacement, https://www.unhcr.org/news/stories/climate-crisis-fuels-flooding-and-deepens-displacement (2024, accessed 4 August 2024).

133.

Bonfils

Santer

Fyfe

, et al. Human influence on joint changes in temperature, rainfall and continental aridity. Nat Clim Change 2020; 10: 726–731.

134.

Zeng

Ziegler

Searchinger

, et al. A reversal in global terrestrial stilling and its implications for wind energy production. Nat Clim Change 2019; 9: 979–985.

135.

McKenzie

Aucamp

Bais

, et al. Ozone depletion and climate change: impacts on UV radiation. Photochem Photobiol Sci 2011; 10: 182–198.

136.

Benedict

Park

BJ.

Invasive fungal infections after natural disasters. Emerg Infect Dis 2014; 20: 349–355.

137.

Neblett Fanfair

Benedict

Bos

, et al. Necrotizing cutaneous mucormycosis after a tornado in Joplin, Missouri, in 2011. N Engl J Med 2012; 367: 2214–2225.

138.

Kobziar

Thompson

3rd . Wildfire smoke, a potential infectious agent. Science 2020; 370: 1408–1410.

139.

Flynn

Hoeprich

Kawachi

, et al. An unusual outbreak of windborne coccidioidomycosis. N Engl J Med 1979; 301: 358–361.

140.

Williams

Sable

Mendez

, et al. Symptomatic coccidioidomycosis following a severe natural dust storm. An outbreak at the Naval Air Station, Lemoore, Calif. Chest 1979; 76: 566–570.

141.

Schneider

Hajjeh

Spiegel

, et al. A coccidioidomycosis outbreak following the Northridge, Calif, earthquake. JAMA 1997; 277: 904–908.

142.

Patiño

Castro

Valencia

, et al. Necrotizing soft tissue lesions after a volcanic cataclysm. World J Surg 1991; 15: 240–247.

143.

Nelson

Narrowe

Rhoades

, et al. Wildfire-dependent changes in soil microbiome diversity and function. Nat Microbiol 2022; 7: 1419–1430.

144.

Crook

Burton

NC.

Indoor moulds, sick building syndrome and building related illness. Fungal Biol Rev 2010; 24: 106–113.

145.

Cummings

Cox-Ganser

Riggs

, et al. Health effects of exposure to water-damaged New Orleans homes six months after Hurricanes Katrina and Rita. Am J Public Health 2008; 98: 869–875.

146.

Barbeau

Grimsley

White

, et al. Mold exposure and health effects following hurricanes Katrina and Rita. Annu Rev Public Health 2010; 31: 165–178.

147.

Omebeyinje

Adeluyi

Mitra

, et al. Increased prevalence of indoor Aspergillus and Penicillium species is associated with indoor flooding and coastal proximity: a case study of 28 moldy buildings. Environ Sci Process Impacts 2021; 23: 1681–1687.

148.

CDC. Health concerns associated with mold in water-damaged homes after Hurricanes Katrina and Rita–New Orleans area, Louisiana, October 2005. MMWR Morb Mortal Wkly Rep 2006; 55: 41–44.

149.

Toda

Williams

Jackson

, et al. Invasive mold infections following hurricane Harvey-Houston, Texas. Open Forum Infect Dis 2023; 10: ofad093.

150.

Kontoyiannis

Shah

Wurster

, et al. Culture-documented invasive mold infections at MD anderson cancer center in Houston, Texas, Pre- and Post-Hurricane Harvey. Open Forum Infect Dis 2019; 6: ofz138.

151.

Wurster

Paraskevopoulos

Toda

, et al. Invasive mould infections in patients from floodwater-damaged areas after hurricane Harvey - a closer look at an immunocompromised cancer patient population. J Infect 2022; 84: 701–709.

152.

Benedict

Jackson

Toda

Diagnosis codes for mold infections and mold exposure before and after hurricane harvey among a commercially insured population-Houston, Texas, 2016–2018. Disaster Med Public Health Prep 2023; 17: e504.

153.

Chow

Toda

Pennington

, et al. Hurricane-associated mold exposures among patients at risk for invasive mold infections after Hurricane Harvey - Houston, Texas, 2017. MMWR Morb Mortal Wkly Rep 2019; 68: 469–473.

154.

Etzel

Montaña

Sorenson

, et al. Acute pulmonary hemorrhage in infants associated with exposure to Stachybotrys atra and other fungi. Arch Pediatr Adolesc Med 1998; 152: 757–762.

155.

Engelthaler

Casadevall

On the emergence of Cryptococcus gattii in the Pacific Northwest: Ballast Tanks, Tsunamis, and Black Swans. mBio 2019; 10: e02193-19.

156.

Kawakami

Tagami

Kusakabe

, et al. Disseminated aspergillosis associated with tsunami lung. Respir Care 2012; 57: 1674–1678.

157.

Riddel

Surovik

Chon

, et al. Fungal foes: presentations of chromoblastomycosis post-hurricane Ike. Cutis 2011; 87: 269–272.

158.

Davies

Smith

Hink

, et al. Increased incidence of rhino-orbital-cerebral mucormycosis after colorado flooding. Ophthalmic Plast Reconstr Surg 2017; 33: S148–S151.

159.

Gunaratne

Wijeyaratne

Chandrasiri

, et al. An outbreak of Aspergillus meningitis following spinal anaesthesia for caesarean section in Sri Lanka: a post-tsunami effect? Ceylon Med J 2006; 51: 137–142.

160.

Uhrlaß

Verma

Gräser

, et al. Trichophyton indotineae-an emerging pathogen causing recalcitrant dermatophytoses in india and worldwide-a multidimensional perspective. J Fungi (Basel) 2022; 8: 757.

161.

Sood

Vaidya

Dam

, et al. A polymicrobial fungal outbreak in a regional burn center after Hurricane Sandy. Am J Infect Control 2018; 46: 1047–1050.

162.

Ebi

Vanos

Baldwin

, et al. Extreme weather and climate change: population health and health system implications. Annu Rev Public Health 2021; 42: 293–315.

163.

Fisher

Hawkins

Sanglard

, et al. Worldwide emergence of resistance to antifungal drugs challenges human health and food security. Science 2018; 360: 739–742.

164.

Rhodes

McCarl

BA.

An analysis of climate impacts on herbicide, insecticide, and fungicide expenditures. Agronomy 2020; 10: 745.

165.

Velásquez

Castroverde

CDM

SY.

Plant-pathogen warfare under changing climate conditions. Curr Biol 2018; 28: R619–R634.

166.

Resendiz Sharpe

Lagrou

Meis

, et al. Triazole resistance surveillance in Aspergillus fumigatus. Med Mycol 2018; 56: 83–92.

167.

van der Linden

Arendrup

Warris

, et al. Prospective multicenter international surveillance of azole resistance in Aspergillus fumigatus. Emerg Infect Dis 2015; 21: 1041–1044.

168.

Toda

Beer

Kuivila

, et al. Trends in agricultural triazole fungicide use in the United States, 1992–2016 and possible implications for antifungal-resistant fungi in human disease. Environ Health Perspect 2021; 129: 055001.

169.

Chen

Dong

Zhao

, et al. High azole resistance in aspergillus fumigatus isolates from strawberry fields, China, 2018. Emerg Infect Dis 2020; 26: 81–89.

170.

Duong

Tran

, et al. Azole-resistant Aspergillus fumigatus is highly prevalent in the environment of Vietnam, with marked variability by land use type. Environ Microbiol 2021; 23: 7632–7642.

171.

Rhodes

Abdolrasouli

Dunne

, et al. Population genomics confirms acquisition of drug-resistant Aspergillus fumigatus infection by humans from the environment. Nat Microbiol 2022; 7: 663–674.

172.

Zhou

Korfanty

, et al. Extensive genetic diversity and widespread azole resistance in greenhouse populations of aspergillus fumigatus in Yunnan, China. mSphere 2021; 6: e00066-21.

173.

Wiederhold

Gil

Gutierrez

, et al. First detection of TR34 L98H and TR46 Y121F T289A Cyp51 Mutations in Aspergillus fumigatus Isolates in the United States. J Clin Microbiol 2016; 54: 168–171.

174.

Chowdhary

Kathuria

, et al. Clonal expansion and emergence of environmental multiple-triazole-resistant Aspergillus fumigatus strains carrying the TR₃₄/L98H mutations in the cyp51A gene in India. PLoS One 2012; 7: e52871.

175.

Nabili

Shokohi

Moazeni

, et al. High prevalence of clinical and environmental triazole-resistant Aspergillus fumigatus in Iran: is it a challenging issue? J Med Microbiol 2016; 65: 468–475.

176.

Tsuchido

Tanaka

Nakano

, et al. Prospective multicenter surveillance of clinically isolated Aspergillus species revealed azole-resistant Aspergillus fumigatus isolates with TR34/L98H mutation in the Kyoto and Shiga regions of Japan. Med Mycol 2019; 57: 997–1003.

177.

Wang

Lee

, et al. Azole-resistant Aspergillus fumigatus isolates carrying TR₃₄/L98H mutations in Taiwan. Mycoses 2015; 58: 544–549.

178.

Kidd

Goeman

Meis

, et al. Multi-triazole-resistant Aspergillus fumigatus infections in Australia. Mycoses 2015; 58: 350–355.

179.

Alvarez-Moreno

Lavergne

Hagen

, et al. Azole-resistant Aspergillus fumigatus harboring TR(34)/L98H, TR(46)/Y121F/T289A and TR(53) mutations related to flower fields in Colombia. Sci Rep 2017; 7: 45631.

180.

Alvarez-Moreno

Lavergne

Hagen

, et al. Fungicide-driven alterations in azole-resistant Aspergillus fumigatus are related to vegetable crops in Colombia, South America. Mycologia 2019; 111: 217–224.

181.

Gonçalves

SS.

Global aspects of triazole resistance in Aspergillus fumigatus with Focus on Latin American countries. J Fungi (Basel) 2017; 3: 5.

182.

Isla

Leonardelli

Tiraboschi

, et al. First clinical isolation of an azole-resistant aspergillus fumigatus isolate harboring a TR46 Y121F T289A mutation in South America. Antimicrob Agents Chemother 2018; 62: e00872-18.

183.

Macedo

Leonardelli

Gamarra

, et al. Emergence of triazole resistance in Aspergillus spp. in Latin America. Curr Fungal Infect Rep 2021; 15: 93–103.

184.

Pontes

Beraquet

CAG

Arai

, et al. Aspergillus fumigatus clinical isolates carrying CYP51A with TR34/L98H/S297T/F495I substitutions detected after four-year retrospective azole resistance screening in Brazil. Antimicrob Agents Chemother 2020; 64: e02059-19.

185.

Abdolrasouli

Rhodes

Beale

, et al. Genomic context of azole resistance mutations in Aspergillus fumigatus determined using whole-genome sequencing. mBio 2015; 6: e00536.

186.

Berger

El Chazli

Babu

, et al. Azole resistance in Aspergillus fumigatus: a consequence of antifungal use in agriculture? Front Microbiol 2017; 8: 1024.

187.

Zhang

Snelders

Zwaan

, et al. A novel environmental azole resistance mutation in Aspergillus fumigatus and a possible role of sexual reproduction in its emergence. mBio 2017; 8: e00791-17.

188.

Schoustra

Debets

AJM

Rijs

, et al. Environmental hotspots for azole resistance selection of Aspergillus fumigatus, the Netherlands. Emerg Infect Dis 2019; 25: 1347–1353.

189.

Verweij

Snelders

Kema

GHJ

, et al. Azole resistance in Aspergillus fumigatus: a side-effect of environmental fungicide use? Lancet Infect Dis 2009; 9: 789–795.

190.

Burks

Darby

Gómez Londoño

, et al. Azole-resistant Aspergillus fumigatus in the environment: Identifying key reservoirs and hotspots of antifungal resistance. PLoS Pathog 2021; 17: e1009711.

191.

Fisher

Alastruey-Izquierdo

Berman

, et al. Tackling the emerging threat of antifungal resistance to human health. Nat Rev Microbiol 2022; 20: 557–571.

192.

Chowdhary

Sharma

Meis

JF.

Azole-resistant aspergillosis: epidemiology, molecular mechanisms, and treatment. J Infect Dis 2017; 216: S436–S444.

193.

Snelders

Camps

Karawajczyk

, et al. Triazole fungicides can induce cross-resistance to medical triazoles in Aspergillus fumigatus. PLoS One 2012; 7: e31801.

194.

Umetsu

Shirai

Development of novel pesticides in the 21st century. J Pestic Sci 2020; 45: 54–74.

195.

van Rhijn

Storer

ISR

Birch

, et al. Aspergillus fumigatus strains that evolve resistance to the agrochemical fungicide ipflufenoquin in vitro are also resistant to olorofim. Nat Microbiol 2024; 9: 29–34.

196.

Buil

Oliver

Law

, et al. Resistance profiling of Aspergillus fumigatus to olorofim indicates absence of intrinsic resistance and unveils the molecular mechanisms of acquired olorofim resistance. Emerg Microbes Infect 2022; 11: 703–714.

197.

Hatamoto

Aizawa

Kobayashi

, et al. A novel fungicide aminopyrifen inhibits GWT-1 protein in glycosylphosphatidylinositol-anchor biosynthesis in Neurospora crassa. Pestic Biochem Physiol 2019; 156: 1–8.

198.

Yang

Lin

Chang

, et al. Comparison of human and soil Candida tropicalis isolates with reduced susceptibility to fluconazole. PLoS One 2012; 7: e34609.

199.

Arendrup

MC.

Update on antifungal resistance in Aspergillus and Candida. Clin Microbiol Infect 2014; 20(suppl 6): 42–48.

200.

Müller

Staudigel

Salvenmoser

, et al. Cross-resistance to medical and agricultural azole drugs in yeasts from the oropharynx of human immunodeficiency virus patients and from environmental Bavarian vine grapes. Antimicrob Agents Chemother 2007; 51: 3014–3016.

201.

Faria-Ramos

Tavares

Farinha

, et al. Environmental azole fungicide, prochloraz, can induce cross-resistance to medical triazoles in Candida glabrata. FEMS Yeast Res 2014; 14: 1119–1123.

202.

Brilhante

RSN

Alencar

Bandeira

, et al. Exposure of Candida parapsilosis complex to agricultural azoles: an overview of the role of environmental determinants for the development of resistance. Sci Total Environ 2019; 650: 1231–1238.

203.

Rocha

Alencar

Paiva

, et al. Cross-resistance to fluconazole induced by exposure to the agricultural azole tetraconazole: an environmental resistance school? Mycoses 2016; 59: 281–290.

204.

Richtel

Jacobs

A mysterious infection, spanning the globe in a climate of secrecy. The New York Times 2019, p. 6.

205.

Castelo-Branco

Brilhante

Paiva

, et al. Azole-resistant Candida albicans from a wild Brazilian porcupine (Coendou prehensilis): a sign of an environmental imbalance? Med Mycol 2013; 51: 555–560.

206.

Sidrim

JJC

de Maria

Paiva

MAN

, et al. Azole-resilient biofilms and non-wild Type C. albicans among Candida Species isolated from agricultural soils cultivated with azole fungicides: an environmental issue? Microb Ecol 2021; 82: 1080–1083.

207.

Del Poeta

Casadevall

. Ten challenges on Cryptococcus and cryptococcosis. Mycopathologia 2012; 173: 303–310.

208.

Bastos

Carneiro

HCS

Oliveira

LVN

, et al. Environmental triazole induces cross-resistance to clinical drugs and affects morphophysiology and virulence of Cryptococcus gattii and C. neoformans. Antimicrob Agents Chemother 2018; 62 20171221.

209.

Bastos

Freitas

GJC

Carneiro

HCS

, et al. From the environment to the host: How non-azole agrochemical exposure affects the antifungal susceptibility and virulence of Cryptococcus gattii. Sci Total Environ 2019; 681: 516–523.

210.

Carlson

Lupinacci

Moseley

, et al. Effects of environmental factors on sensitivity of Cryptococcus neoformans to fluconazole and amphotericin B. FEMS Microbiol Lett 2021; 368: fnab040.

211.

Homa

Shobana

Singh

, et al. Fusarium keratitis in South India: causative agents, their antifungal susceptibilities and a rapid identification method for the Fusarium solani species complex. Mycoses 2013; 56: 501–511.

212.

Homa

Galgóczy

Manikandan

, et al. South Indian isolates of the Fusarium solani species complex from clinical and environmental samples: identification, antifungal susceptibilities, and virulence. Front Microbiol 2018; 9: 362396.

213.

Huang

, et al. Pan-drug resistance and hypervirulence in a human fungal pathogen are enabled by mutagenesis induced by mammalian body temperature. Nat Microbiol 2024; 9: 1686–1699.

214.

WHO. WHO fungal priority pathogens list to guide research, development and public health action, https://www.who.int/publications/i/item/9789240060241 (2022, accessed 11 June 2024).

215.

CDC. Advancing health equity: fungal diseases, https://www.cdc.gov/fungal/health-equity/index.html (2024, accessed 11 June 2024).

216.

CDC. Fungal disease awareness week, https://www.cdc.gov/fungal/fungal-disease-awareness-week/index.html (2024, accessed 11 June 2024).

217.

de Perio

Benedict

Williams

, et al. Occupational histoplasmosis: epidemiology and prevention measures. J Fungi 2021; 7: 510.

218.

Seppänen

A-V.

The role of the health sector in tackling climate change: a narrative review. Health Policy 2024; 143: 105053.

219.

Pichler

P-P

Jaccard

Weisz

, et al. International comparison of health care carbon footprints. Environ Res Lett 2019; 14: 064004.

220.

NAM. National Academy of Medicine Climate Collaborative Health Care Delivery Working Group. Key actions to reduce greenhouse gas emissions by U.S. Hospitals and health systems, https://nam.edu/programs/climate-change-and-human-health/action-collaborative-on-decarbonizing-the-u-s-health-sector/key-actions-to-reduce-greenhouse-gas-emissions-by-u-s-hospitals-and-health-systems/ (2024, accessed 17 December 2024).

221.

Zhang

Babady

Hanson

, et al. Recognition of diagnostic gaps for laboratory diagnosis of fungal diseases: expert opinion from the fungal diagnostics laboratories consortium (FDLC). J Clin Microbiol 2021; 59: e0178420.

222.

Danion

Rouzaud

Duréault

, et al. Why are so many cases of invasive aspergillosis missed? Med Mycol 2019; 57: S94–S103.

223.

Mendonça

Santos

Franco-Duarte

, et al. Fungal infections diagnosis – past, present and future. Res Microbiol 2022; 173: 103915.

224.

Patterson

Donnelly

JP.

New concepts in diagnostics for invasive mycoses: non-culture-based methodologies. J Fungi 2019; 5: 9.

225.

Wickes

Wiederhold

NP.

Molecular diagnostics in medical mycology. Nat Commun 2018; 9: 5135.

226.

Chindamporn

Chakrabarti

, et al. Survey of laboratory practices for diagnosis of fungal infection in seven Asian countries: an Asia Fungal Working Group (AFWG) initiative. Med Mycol 2018; 56: 416–425.

227.

Lakoh

Kamudumuli

Penney

ROS

, et al. Diagnostic capacity for invasive fungal infections in advanced HIV disease in Africa: a continent-wide survey. Lancet Infect Dis 2023; 23: 598–608.

228.

Berkow

Lockhart

Ostrosky-Zeichner

Antifungal susceptibility testing: current approaches. Clin Microbiol Rev 2020; 33: e00069-19.

229.

Clancy

Nguyen

MH.

Finding the “missing 50%” of invasive candidiasis: how nonculture diagnostics will improve understanding of disease spectrum and transform patient care. Clin Infect Dis 2013; 56: 1284–1292.

230.

Perlin

Wiederhold

NP.

Culture-independent molecular methods for detection of antifungal resistance mechanisms and fungal identification. J Infect Dis 2017; 216: S458–S465.

231.

Johnson

Lewis

Dodds Ashley

, et al. Core recommendations for antifungal stewardship: a statement of the mycoses study group education and research consortium. J Infect Dis 2020; 222: S175–S198.

232.

Hoenigl

Sprute

Egger

, et al. The antifungal pipeline: fosmanogepix, ibrexafungerp, olorofim, opelconazole, and rezafungin. Drugs 2021; 81: 1703–1729.

233.

Alegria

Patel

PK.

The current state of antifungal stewardship in immunocompromised populations. J Fungi 2021; 7: 352.

234.

Perfect

JR.

The antifungal pipeline: a reality check. Nat Rev Drug Discov 2017; 16: 603–616.

235.

Belanger

Yang

Forrest

GN.

Combination antifungal therapy: when, where, and why. Curr Clin Microbiol Rep 2015; 2: 67–75.

236.

Ulrich

Ebel

Monoclonal antibodies as tools to combat fungal infections. J Fungi (Basel) 2020; 6: 22.

237.

Oliveira

LVN

Wang

Specht

, et al. Vaccines for human fungal diseases: close but still a long way to go. NPJ Vacc 2021; 6: 33.

238.

Armstrong-James

Brown

Netea

, et al. Immunotherapeutic approaches to treatment of fungal diseases. Lancet Infect Dis 2017; 17: e393–e402.

239.

Brown

Denning

Levitz

SM.

Tackling human fungal infections. Science 2012; 336: 647.

240.

FDA. Limited population pathway for antibacterial and antifungal drugs – the LPAD pathway, https://www.fda.gov/drugs/development-resources/limited-population-pathway-antibacterial-and-antifungal-drugs-lpad-pathway (2024, accessed 4 August 2024).

241.

Cavicchioli

Ripple

Timmis

, et al. Scientists’ warning to humanity: microorganisms and climate change. Nat Rev Microbiol 2019; 17: 569–586.

242.

Alkhalifah

DHM

Damra

Melhem

, et al. Fungus under a changing climate: modeling the current and future global distribution of Fusarium oxysporum using geographical information system data. Microorganisms 2023; 11: 468.

243.

Garvey

Meade

Rowan

NJ.

Effectiveness of front line and emerging fungal disease prevention and control interventions and opportunities to address appropriate eco-sustainable solutions. Sci Total Environ 2022; 851: 158284.

244.

Cole

Govender

Chakrabarti

, et al. Improvement of fungal disease identification and management: combined health systems and public health approaches. Lancet Infect Dis 2017; 17: e412–e419.

245.

Barber

Crank

Papp

, et al. Community-scale wastewater surveillance of Candida auris during an ongoing outbreak in Southern Nevada. Environ Sci Technol 2023; 57: 1755–1763.

246.

Lee

Robbins

Cowen

LE.

Molecular mechanisms governing antifungal drug resistance. npj Antimicrob Resist 2023; 1: 5.

247.

WHO. One health, https://www.who.int/health-topics/one-health#tab=tab_1 (2024, accessed 11 June 2024).

248.

CDC. One health and fungal diseases, https://www.cdc.gov/fungal/about/one-health.html (2024, accessed June 11 2024).

249.

Mann

CWG

Sawyer

Gardiner

, et al. RNA-based control of fungal pathogens in plants. Int J Mol Sci 2023; 24: 12391.

The impact of climate change on the epidemiology of fungal infections: implications for diagnosis,treatment,and public health strategies

Abstract

Keywords

Introduction

Expanded geographical range

Thermotolerant strains

Social determinants of health

Displaced populations

Healthcare systems

Agricultural impact

Antifungal resistance

Mitigating the impact of climate change on fungal infections

Strategies to mitigate climate change

Management strategies

Antifungal susceptibility testing

Development of new antifungal agents

Policy, education, and future directions

Conclusion

Footnotes

Acknowledgements

Declarations

ORCID iDs

References