Advanced Medical Mycology: Comprehensive Lecture Notes and Historical Overview

Introduction to Advanced Medical Mycology

• Definition of Mycology: Mycology is the branch of microbiology dedicated to the study of fungi (singular: fungus). This field focuses on fungi that cause diseases in humans, animals, and plants.
• Etymology: The word "fungi" is derived from the Latin word "fungus," which translates to "mushroom."
• Presentation Context: These lectures are designed for postgraduate students for the academic year $2023$ - $2024$. The material is presented by Mycologist Dr. Abbas M. Ammari.

Mini Glossary of Mycological Terms

• Aerial Mycelium: Hyphal elements that grow above the surface of the agar medium.
• Anamorph: This refers to the asexual state of a fungus.
• Arthroconidium: A thallic conidium formed and released through either the splitting of a double septum or by fragmentation.
• Ascomycetes: A specific group of fungi that reproduce sexually via the endogenous formation of ascospores within a specialized sac called an ascus.
• Ascospore: A haploid spore produced inside an ascus. These are formed following the biological processes of karyogamy and meiosis.
• Ascus (pl. asci): A sac-like cell containing ascospores, characteristic of the Ascomycetes group.
• Aseptate: The condition of lacking septa (cross-walls). This term often pertains to the hyphae observed in zygomycetes; it is also referred to as coenocytic.
• Basidiomycetes: A group of fungi reproducing sexually through the exogenous formation of basidiospores from a structure known as a basidium.
• Basidiospore: A haploid spore produced on a basidium following karyogamy and meiosis. Visually represented as approximately $100\,\mu m$ in size in certain morphological diagrams.
• Basidium (pl. basidia): A specialized cell that gives rise to basidiospores, characteristic of the Basidiosmycetes.
• Basipetal: Describing a chain of conidia where the oldest conidium is located at the apex (top) and the youngest is at the base.
• Blastoconidium (pl. blastoconidia): An asexual conidium formed through a budding process.
• Budding: A method of asexual multiplication resulting in the production of a small outgrowth or "bud" from a parent cell.
• Capsule: A hyaline mucopolysaccharide sheath that surrounds the cell wall of specific yeasts, notably Cryptococcus and Rhodotorula.
• Chlamydoconidium (pl. chlamydoconidia): A thick-walled, thallic conidium formed within the vegetative hyphae.
• Coenocytic: Multi-nucleate hyphae that are infrequently septate, typically seen in the Zygomycetes.
• Columella: A sterile, dome-like structure found at the tip of a sporangiophore or within a sporangium.
• Conidiogenous Cell: A specific cell type that forms conidia.
• Conidiophore: A specialized hypha upon which conidia develop.
• Conidium (pl. conidia): An asexual reproductive propagule formed without involving cytoplasmic cleavage. Conidia function as "organs of dissemination."
• Dematiaceous: Pertaining to fungi that exhibit a dark brown, greenish-gray, or black color.
• Dermatophyte: A fungus belonging to the genera Epidermophyton, Microsporum, or Trichophyton. These fungi possess the ability to utilize keratin to infect hair, nails, and skin.
• Deuteromycetes: An artificial subdivision used to categorize fungi where only the asexual state is currently known.
• Dimorphic: Reffering to fungi that possess two distinct morphological forms (typically yeast and mold forms).
• Downy: Descriptive of a mycelial texture that is short and dense, often associated with Aspergillus.
• Anthropophilic: A term for a fungus (specifically dermatophytes) that preferentially grows on humans rather than on other animals or in the soil.
• Zoophilic: Fungi that preferentially infect lower animals rather than humans.
• Heterothallic: Fungi that require mating between two compatible strains for sexual reproduction to take place.
• Hyalo-: A prefix meaning hyaline (transparent/clear) or lightly colored.
• Phaeo-: A prefix meaning darkly pigmented.
• Hypha (pl. hyphae): A single filament of a fungus.
• Mycelium: A mass of hyphae that constitutes the body (thallus) of a fungus.
• Macroconidium: The larger of two different types of conidia produced by a fungus in an identical manner.
• Microconidium (pl. microconidia): The smaller of two different types of conidia produced by a fungus in an identical manner.
• Penicillus (pl. penicilli): The brush-like conidiophore characteristic of the genus Penicillium.
• Phialide: A specialized conidiogenous cell that produces conidia in basipetal succession without increase in its own length.
• Phragmoconidium: A conidium possessed of two or more transverse septa.
• Pseudohyphae: A string of elongated blastoconidia, formed by some yeasts, that resembles a hypha-like filament.
• Rhizoids: Short, branching, root-like hyphae observed in certain Zygomycetes.
• Asteroid Body (Splendore-Hoeppli phenomenon): An eosinophilic substance that forms a thick covering around a basophilic yeast, specifically seen in cases of sporotrichosis.
• Sclerotium (pl. sclerotia): A mass of thick-walled cells formed by vegetative hyphae.
• Sporangiophore: A specialized hypha that bears a sporangium.
• Sporangiospore: An asexual spore produced endogenously within a sporangium.
• Sporangium (pl. sporangia): A sac-like structure that produces asexual spores endogenously through cytoplasmic cleavage.
• Spore: A reproductive propagule formed by either meiosis or mitosis. If formed asexually, cytoplasmic cleavage is usually involved.
• Teleomorph: The sexual state of a fungus.
• Biofilm: Microcolonies of organisms adhering to a surface (such as a catheter or blood vessel). They resist removal by fluid movement and exhibit decreased susceptibility to anti-microbials.
• Uniserate: Phialides that arise directly from a vesicle, as seen in Aspergillus.
• Zygospores: Thick-walled sexual spores formed by the fusion of two similar gametangia; characteristic of Zygomycetes.

Clinical Definitions and Classifications

• Mycosis: A disease caused by fungi.
• Aspergillosis: A group of diseases in animals and humans caused by various species of Aspergillus.
• Invasion Types in Hair:     * Ectothrix: Natural hair invasion characterized by arthroconidia on the outside of the hair shaft.     * Endothrix: Natural hair invasion characterized by the development of arthroconidia within the hair shaft only.
• Germ Tube: The initial hypha that develops from a conidium or spore.
• Tinea: Literally meaning "moth." It is a clinical term for "ringworm."

Specialized Dermatophytes (Named Species List)

• T. rubrum
• T. mentagrophytes
• T. tonsurans
• T. schoenleinii
• T. violaceum
• M. audouinii
• M. canis
• M. gypseum

Classification of Fungal Infections

• Superficial Mycosis: Fungal infections affecting the nails, skin, and mucous membranes (e.g., mouth, throat, or vagina).
• Cutaneous Mycosis: Infections extending deeper into the epidermis, including invasive hair and nail diseases. These are restricted to the keratinized layers of the skin, hair, and nails.
• Subcutaneous Mycosis: A fungal infection under the skin surface occurring when fungus enters through a cut or wound.
• Systemic Mycoses: Infections resulting from the inhalation of spores from dimorphic fungi which exist in mold form in the soil. Inside the lungs, these spores differentiate into yeasts or other specialized forms.
• Opportunistic Fungi: Fungi that typically do not induce disease in immunocompetent individuals but cause infection in those with impaired host defenses.

Veterinary Mycology

• Definition: A branch of mycology dealing with:     * Identification of veterinary fungi.     * Pathophysiology and diagnosis of fungal infections in animals.     * Pharmacodynamics of antifungals in animals.     * Epidemiology of animal mycoses.     * Vaccine development against invasive veterinary fungal infections.

Chronological History of Medical and Veterinary Mycology

Early Observations and Discoveries ($1580$ - $1850$)

• $1580$: Giambattista della Porta publishes the first observation of fungal spores.
• $1673$: Van Leeuwenhoek, in a letter to the Royal Society of London, describes S. cervease in fermented beer (the first observation of yeast cells).
• $1718$: Pier Antonio Micheli performs experiments on the culture of Agaricus mushrooms and molds from spores. His techniques remained standard for $125$ years.
• $1815$: Mayer and Emmert discover Aspergillosis.
• $1836$: The terms "mycology" and "mycologist" are first used by Berkeley.
• $1839$: Lagenbeck first demonstrates yeast-like fungus in thrush.
• $1843$: Robin names Oidium albicans.
• $1843$: Gruby names Microsporoum audouinii as the causative agent of ringworm in children.
• $1845$: Lebert describes favus caused by Trichophyton schoenleinii.

Late 19th Century and Animal Case Studies ($1881$ - $1899$)

• $1881$: Infections in chicken (T. gallinae).
• $1890$: Zopf names the fungus Monilia albicans.
• $1892$: Posadas reports the first case of Coccidioidomycosis in man.
• $1894$: Gilchrist first describes Blastomycosis in a human.
• $1894$ - $1895$: Busse and Buschke report the first human case of Cryptococcosis.
• $1894$: Infections in cattle recorded.
• $1896$ - $1897$: Infections recorded in horse and dog.
• $1896$: Georg Klebs advances fungal morphogenesis, working with Saprolegina.
• $1898$: Gilchrist and Stokes name B. dermatitidis.
• $1898$: Infection reported in horse.
• $1899$: Schenck provides the first report of sporotrichosis. The rat is the first animal species reported to be infected.

Modern Developments ($1900$ - $1953$)

• $1900$: Seeber describes the causative agent of Rhinosporidiosis.
• $1905$: Hansemann reports the first human meningitis case of Cryptococcosis.
• $1906$: S.T. Darling discovers the causative agent of Histoplasmosis in Panama.
• $1912$: Meyer reports Blastomycosis in dogs.
• $1913$: Zschokke reports the first animal case of Rhinosporidiosis in a horse.
• $1918$: Giltner reports the first naturally occurring case of Coccidioidomycosis in animals (cattle).
• $1923$: Berkhout renames Monilia albicans to Candida albicans.
• $1923$: Vogelsang and Ayyar & Rao report cases in cattle.
• $1928$: Mucor pusillus isolated from a nodule in a horse.
• $1929$: Sir Alexander Fleming discovers the antibiotic penicillin.
• $1941$: Van Pernis records skin testing in humans for histoplasmosis.
• $1952$: Holzworth first reports Cryptococcosis in a cat.
• $1953$: Seibold reports Cryptococcosis in a dog.

Key Individual Contributions

• Raimond Sabouraud: Established mycology as a field and published a medical mycology book.
• Nannizzi: Described the perfect stage (sexual state) of fungi.
• Emmons: Morphologically classified dermatophytes.
• Alma Whiffoin: Discovered cyclohexamides.
• Gold et al.: Discovered Amphotericin B.
• Hazen, Elizabeth, and Brown: Discovered Nystatin.
• Gentles: Discovered Griseofulvin.

Questions & Discussion

• Inquiry on Tinea capitis: Fig $1$ illustrates Tinea capitis. Tina conitio is mentioned as being predominant among children and adults; however, the transcript notes this is due to specific fungal pathogens.