**1. Introduction**

Fungi represent the second largest estimated species numbers after insects. Their kingdom comprises a huge variety of microorganisms, the newer estimates, based on data acquired from molecular methods, have predicted from 1.5 million fungal species, in some conservative estimates [1–4], to a spectacular 13.2 million, in others [5, 6], less than 150.000 species being merely cataloged to date [5–8]. For many years, it was believed that fungi were clinically insignificant, but the increased incidence of invasive fungal infections during the past 20 years has contradicted this hypothesis [9].

Compared to the enormous biomass of fungal species, the number of human pathogenic fungi is minuscule, but they exert a profound, global impact on human health. Billions of people are infected, [10] fungi causing more than a billion skin infections, more than 100 million mucosal infections, 10 million serious allergies [11], and more than 1.5 million deaths every year [4, 12]. Worldwide, mortality due to fungal infections exceeds that from breast cancer and malaria and is comparable

to that owing to tuberculosis and HIV, exerting a major threat to human health and, consequently, a huge burden to global healthcare budgets [11, 12].

In the past 15 years, in the world landscape, new species of fungi were yearly discovered at a rate varying from 2100 to 2600 species, most of them in Asia (41%) and Europe (23%), and a small part even in Antarctica (0.5%) (**Figure 1**) [8].

Also, the number of clinically relevant fungal species continued to grow, this fact being clearly demonstrated by their increasing number in the Atlas of Clinical Fungi, of which the first edition, in 1995, contained 320 species, while the fourth edition of the same book, published in 2020, counts more than 660 fungal species [13, 14].

Climate change will have an impact on the way we interact with our environment and, because fungi can easily adapt to these changes, the overall epidemiological picture of pathogens will also modify. This will likely expose us to varieties of fungi that humans and animals have never interacted with. Due to climate change, the diversity and number of soil microorganisms will undoubtedly change, as already seen with endemic fungi (**Figure 2**) and with the emergence of new fungal pathogens [4].

Furthermore, modern life-saving medical procedures and aggressive medical treatments may affect normal immune functions and, paradoxically, have given rise to large groups of people at risk for fungal infections. Patients at high risk include those with AIDS, those receiving immunosuppressive therapy, transplant recipients, and certain surgeries and those in intensive care settings [15, 16].

There is a growing body of evidence supporting the concern that climate change will affect the morbidity and mortality rates of infectious diseases, and that fungi will play an increasing role as primary or secondary pathogens [4].

#### **Figure 1.**

*Graphic map of the world's continents showing the uneven distribution of newly described species of fungi. The size of each continent is proportional to the global percentage of new species published from there and mainly reflects both the quantity of taxonomic expertise and the presence of undescribed species in those areas. Also, the map reflects the location of most research activity and taxonomic expertise. Artwork Creative Services/ RBG Kew. [8]. https://nph.onlinelibrary.wiley.com/doi/10.1002/ppp3.10148.*

#### **Figure 2.**

*Schematic overview of changes in the epidemiological landscape of fungal pathogens and associated changes in environmental parameters [4]. https://www.mdpi.com/2309-608X/7/5/367.*

To infect and cause disease in healthy humans, true pathogenic fungi should meet four basic criteria: (i) growth at elevated human body temperatures, (ii) bypassing around or penetrating through surface host barriers, (iii) secretion of lytic enzymes for acquiring nutrients from the host tissues, and (iv) evasion or resistance to the host's immune defense systems. The fungi that infect previous healthy humans represent a small group, many more invasive fungal infections now occurring in patients with underlying serious illnesses [15, 17].

The severity and outcome of infection is determined by both the extent of the exposure to the organism and by the immune status of the patient [18].

Therefore, with the expansion of the susceptible population and the increase in the frequency of mycotic infections, the mortality due to invasive mycoses was estimated at one and a half million deaths annually [12, 18].

Histoplasmosis is the most prevalent cause of fungal respiratory infections and has a vast spectrum of clinical manifestations, ranging from a self-limited, acute, influenza-like illness to a progressive disseminated life-threatening infection [19, 20].
