Introduction to Medical Mycology Foundation1.Sep 2024.pdf

Introduction to: Medical Mycology Foundation 1 (2024-2025) INTRODUCTION  Medical Mycology is the study of fungi that impact human health. (fungi = moulds, yeasts, and mushrooms)  The importance of fungi increased over the years due to; - increase in the use of immunosuppressive drugs...

Introduction to: Medical Mycology Foundation 1 (2024-2025) INTRODUCTION  Medical Mycology is the study of fungi that impact human health. (fungi = moulds, yeasts, and mushrooms)  The importance of fungi increased over the years due to; - increase in the use of immunosuppressive drugs - increase in the incidence of opportunistic fungal infection  All fungi have the following characteristics: Eukaryotic (e.g., true nucleus, 80S ribosomes, mitochondria) Complex carbohydrate cell walls: chitin, glucan, and mannan Ergosterol is a major membrane sterol – Imidazole antifungals inhibit the synthesis of ergosterol – Polyene antifungals bind more tightly to ergosterol than to cholesterol  Characteristics of Fungi:  Eukaryotic  Some fungi can cause superficial, cutaneous subcutaneous, and systemic diseases.  Reproduce using spores (conidia), usually wind- disseminated  Both sexual (meiotic) and asexual (mitotic) spores may be produced.  Typically, not motile, although a few (e.g. Chytrids) have a motile phase.  Vegetative bodies may be unicellular (yeasts) or multicellular molds composed of microscopic threads called hyphae. Characteristics of Fungi  Fungi are heterotrophic ( “other feeding,” must feed on preformed organic material), not autotrophic ( “self-feeding,”)  Fungi digest then ingest. It produces exoenzymes to accomplish this.  Many are ecologically important saprophytes (consume dead and decaying matter) – Others are parasites.  Most are multicellular, but yeasts are unicellular.  Most are aerobes or facultative anaerobes.  Over 100,000 fungal species were identified. Only about 100 are human or animal pathogens. – Most human fungal infections are nosocomial and occur in immunocompromised individuals (opportunistic infections). Classification of fungi depending on Cell Morphology 1. Yeasts 2. Yeast-like Fungi 3. Molds 4. Dimorphic Fungi Yeasts  Yeasts are unicellular (single- celled) (round to oval) fungi.  3–15 μm.  Reproduce by budding. Budding  On culture it produces smooth, creamy colonies E.g Candida. Yeast Like Fungi  Grow partly as yeast and partly as elongated cells resembling hyphae which are called pseudo hyphae e.g. Candida albicans  Pseudo hyphae (Candida albicans) are hyphae with constrictions at each septum. Mold  Mold is a fungus that has a Hyphal or mycelial form of growth.  Hyphae are filamentous cellular units of molds and mushrooms. hyphae (s., hypha)  Septate hyphae have cross walls and fairly regular width (tube-like).  Non-septate hyphae have no cross walls, are broad hyphae with irregular width, and have a broad angle of branching.  The mycelium is the mat of hyphae. Dimorphic Fungi  Fungi able to convert from hyphal to yeast (or yeast-like) forms are called dimorphic fungi. They are thermally dimorphic: - Molds (Filaments) – 25-30 C (soil) - Yeasts – 37 C (in host tissue)  Most fungi causing systemic infections are dimorphic: include Histoplasma, Blastomyces, Coccidioides, and Sporothrix. Reproduction of Fungi Most fungi reproduce by forming spores that can survive extreme conditions such as cold and lack of water. Both sexual meiotic and asexual mitotic spores may be produced, depending on the species and conditions. Spores may be dispersed by moving water, wind, or other organisms Spores are the Reproductive structures and include: Conidia: asexual spores; formed off of hyphae; Blastoconidia: “buds” (asexual budding daughter yeast cells) Arthroconidia: asexual spores formed by the fragmentation of hyphal cells into compact conidia Spherules and endospores (Coccidioides): spores inside spherules in tissue. Mycoses Mycoses is the fungal infections 1- Superficial mycoses: These are fungal infections that are confined to the stratum corneum without tissue invasion e.g. tinea versicolor. 2- Cutaneous mycoses: Are fungal infections that involve the skin, nail or hair with tissue destruction and immunological reaction e.g. dermatophytes and cutaneous candidiasis. 3- Subcutaneous mycoses: Are infections of subcutaneous tissue without dissemination to distant sites as mycetoma. 4- Systemic (endemic) mycoses: Are primary pulmonary lesions that may disseminate to any organ mainly in immunocompromised patients. 5-Opportunistic mycoses e.g. systemic candidiasis, cryptococcosis, aspergillosis infections. 1. Superficial Infections  It is a superficial chronic skin infection caused by Malassezia furfur  Malassezia furfur is lipid-dependent, commensal yeasts lives as normal skin flora. It secrete lipases and phospholipases that likely release host fatty acids  Disease = Pityriasis or tinea versicolor – Superficial infection of keratinized cells – common in moist, warm climates. – Hypopigmented spots on chest/back (blotchy suntan) – Potassium Hydroxide (KOH) skin scale preparations show short thick septate hyphae and clusters of budding yeast cells. – Treatment is topical selenium sulfide or topical azole antifungal. – Lesions tend to recur and permanent cure is difficult to achieve. 2. Cutaneous Fungal Infections Cutaneous fungal infections are either Dermatophytosis or Cutaneous candidiasis Candidiasis of skin, mucosa, or nails Yeast skin infections Commonly cutaneous or mucocutaneous candidiasis May disseminate in compromised patients Opportunistic fungi Dermatophytes (group of fungi) Filamentous fungi (monomorphic) Infect only skin and hair and/or nails (do not disseminate) The dermatophytes include 3 genera Epidermophyton, Microsporum and Trichophyton. These organisms affect the keratinized tissues; skin, hair and nails. They spread peripherally from foci to produce ring-like lesions. Hence the name ringworm or tinea. Infection does not spread to deeper tissues. Cutaneous Dermatophytosis  Dermatophytes invade and feed on keratinized tissue like skin, hair and nails, causing an infection  The source of infection is man to man by direct contact or from the animals e.g. cats and dogs or from the soil.  Intact skin is an important barrier against infection.  Hot climate and humidity enhance the infection.  The clinical forms of the disease are named according to the site affected e.g. tinea capitis in the head, tinea cruris in the groin area, tinea unguium in the nail.  Diagnosis of Dermatophytosis is made with; - KOH mount of nail or skin scrapings (shows arthroconidia and hyphae).  Treatment is topical imidazole or tolnaftate (use oral imidazole or griseofulvin where hairs are infected or skin contact hurts).  Keep infected areas dry 3. SUBCUTANEOUS MYCOSES These are caused by fungi that grow in soil and through trauma are introduced into subcutaneous tissue. Mycetoma (Madura foot)  Mycetoma is a chronic granulomatous infection that usually involves the lower limbs. Fungal mycetoma is caused by Madurella mycetomatis and others.  The condition is characterized by swelling, purplish discoloration, and multiple sinuses that drain pus containing yellow, white, red, or black granules. It is common in tropical areas in bare-footed persons.  Mycetoma may be bacterial or fungal. So, it is important to identify the aetiologic agent of mycetoma since the bacterial mycetoma is curable by antibiotics while fungal mycetoma is resistant to antibiotics and needs surgical interference or amputation. Diagnosis:  Macroscopic examination of granules. Black-colored granules are common with fungi, other colors are common with actinomycetes (bacteria).  Microscopic examination of crushed granules will reveal hyphae in fungal infection and fragmented filaments in bacterial infection.  Cultivation on special media. 4. Systemic (endemic) mycoses  These infections result from inhalation of the spores of fungi that have their saprophytic filamentous forms in the soil. Within the lungs, the spores differentiate into yeasts forms.  There are 4 important classical pathogens. All of them cause acute pulmonary (asymptomatic or self-resolving in 95% of cases), chronic pulmonary, or disseminated infection.  Histoplasma  Coccidioides  Blastomyces  Paracoccidioides  In immuno-compromised patients, infection may disseminate to other organs and may be fatal.  No person-to-person transmission of the disease. Diagnosis of Systemic Fungal Infections  Diagnosis is made with sputum cytology, sputum culture on blood agar, and special fungal media (Sabouraud’s agar ).  Peripheral blood culture is useful for Histoplasma since it circulates in reticuloendothelial system (RES) cells.  Serologic tests show a rise in antibody titers when dissemination occurs.  Skin tests using fungal antigens e.g. coccidiosis or histoplasmin.  Detection of fungal antigens in specimens by RIA and fungal nucleic acids by DNA probes or PCR. 5. Opportunistic Mycoses Opportunistic fungi fail to induce disease in most normal persons but can do so in those with impaired host defenses. Candida Candida albicans is the most important species of candida. C. albicans are gram-positive oval budding yeast that produces pseudohyphae. It is part of the normal flora of mucous membranes of the upper respiratory, gastro- intestinal, and female genital tract. In these sites, it may predominate and cause superinfection that include: I. In the mouth, overgrowth of C. albicans produces white patches i.e. oral thrush II. Vulvovaginitis with itching and discharge. Is favored by high pH, diabetes, or prolonged use of antibiotics. III. Skin invasion occurs in warm, moist areas, such as the axilla most common in obese & diabetics. IV. Nails become involved when repeatedly immersed in water; Painful redness and swelling of nail folds, thickening and loss of nail. V. Candida may disseminate to many organs, especially in debilitated children, diabetics, immunosuppressed patients, or drug addicts. Opportunistic Fungi Aspergillus fumigatus Aspergillus fumigatus is a saprophytic fungus; its primary habitat is the soil and decaying organic matter. It is a monomorphic filamentous fungus; its transmission occurs through inhalation of airborne conidia. Diseases caused by Aspergillus include the following: Allergic bronchopulmonary aspergillosis asthma Fungus ball: free in preformed lung cavities (surgical removal to reduce coughing, which may induce pulmonary haemorrhage) Invasive aspergillosis/severe neutropenia, – Nasal colonization, leading to pneumonia or meningitis – Cellulitis: in burn patients; may also disseminate Other Types of fungal diseases: a- Allergies to fungal spores: As Aspergillus. Mainly type I hypersensitivity reactions or atopy manifesting as bronchial asthma, hay fever....etc. b- Mycotoxicosis: These are diseases due to the consumption of food containing fungal toxins: e: - Mycotoxicosis that occurs after eating mushrooms which produce potent hepatotoxins. - Other toxins ingested with spoiled grains and peanuts are aflatoxins which are metabolized in the liver to epoxide, a potent carcinogen. Fungi Useful Benefits  They are a major source of citric acid (vitamin C).  They produce antibiotics such as penicillin (produced by Penicillium moulds), which has saved countless lives.  They can be genetically engineered to produce insulin and other human hormones.  They are model research organisms.