Medical Mycology Lecture Notes PDF

MEDICAL MYCOLOGY Prof. Mohamed Shohayeb Dr Reham Magdy Dr Esraa Elsaeed Mycology Mycology is the study of fungi Fungi are eukaryotic organisms, containing a nucleus srounded by a membrane, endoplasmic reticulum, and mitochondria. Fungi - includes moulds and yeasts. Moulds - exhi...

MEDICAL MYCOLOGY Prof. Mohamed Shohayeb Dr Reham Magdy Dr Esraa Elsaeed Mycology Mycology is the study of fungi Fungi are eukaryotic organisms, containing a nucleus srounded by a membrane, endoplasmic reticulum, and mitochondria. Fungi - includes moulds and yeasts. Moulds - exhibit filamentous type of growth. Yeasts - exhibit pasty or mucoid form of fungal growth. There are about 50,000 species Fungi are heterotrophic; requiring organic nutrients as a source of energy. Mycology (Continued) They are saprophytes that live on dead and organic matter. They are essential in recycling of elements, especially carbon. Parasitic fungi live on living organisms. The cell wall consist of chitin and β-glucan, both are polysaccharide which are the site of action of some antifungal drugs. Cell membrane contains of ergosterol rather than cholesterol like bacterial cell membrane Ergosterol is the site of action of some antifungal drugs e.g, Amphotericin B & Azole group. Most fungi are obligatory aerobes , others are facultative anaerobes.  Morphology of Fungi 1. Filamentous fungi (molds) are long branching filaments. Mass of filaments called mycelium, which are septate or non-septate 2. Yeasts are round or oval bodies which reproduce by the formation of buds known as blastospores. 3. Yeast-like fungi that can grow as yeast by budding and can produce filaments (either true hyphae or pseudohyphae). it can reproduce by budding, spores or filaments while yeasts reproduce only by budding e.g. Candida. 4. Thermally Dimorphic Fungi: Exhibit a filamentous mycelial morphology (saprophytic phase) when grown at room temperature 27oC, but have a typical yeast morphology (parasitic phase) inside the body and when grown at 37oC in the laboratory (e.g. Histoplasmosis). 3 like Candida  Role of fungi in the economy Industrial uses of fungi Mushrooms (Class Basidiomycetes) Truffles (Class Ascomycetes) Yeast are used as food supplement, supplies vitamins. Penicillium is used in cheese to adds flavor (roquefort, etc.). Fungi used to alter texture, improve flavor of natural, processed foods and fermentation of fruit juices. Saccharomyces cerevisiae - brewer's and baker's yeast. Fermentation of industrial alcohol. Antibiotic production (penicillin by penicilium). Plant pathology: Most plant diseases are caused by fungi and lead to economic losses. Pathogenesis for humans Only 50-100 species are recognized human pathogens. Most prefer to be free-living as saprophytes; and only accidentally become pathogens. To be pathogenic, they must tolerate the temperature of the host site and possess an enzymatic system that allows them to utilize animal tissues. There has been increased incidence of fungal infections in recent times. Reported deaths have been increased probably due to: 1. The aging population. 2. The Immunosuppression of patients with AIDS 3. Immunosuppressant drugs used in organ-transplant patients, cancer and leukemia patients. Immune response to fungal infection Antibody mediated immunity (B-cell, humoral) Antibodies are often produced in response to a fungal infection, but do not confer immunity. Serological tests detect antibodies. Typically, white blood cells will attack pathogens through phagocytosis – where a pathogen is engulfed by the white blood cell. T-cell immunity confer Cellular mediated immunity (T-cell)  Basic terms Hypha (hyphae plural) - are tube-like structural units of fungi. Septate - divided by cross walls. Aseptate - lacking cross walls. Mycelium: A mass (mat) of hyphae forming the vegetative portion of the fungus. Aerial - growing or existing in the air. Vegetative - absorbs nutrients. Fertile - bears conidia (spores) for reproduction. Basic Terms (continued) Sporulation & Spores Asexual spores A spore produced through the process of sexual reproduction, involving the fusion of genetic material from two parent fungi For example, Conidia, Sporangiospore, Arthrospore, Blastospore, Chlamydospore, Thallospore Sexual spores (exhibit fusion of nuclei) A spore produced through the process of asexual reproduction, without the involvement of gamete fusion or genetic exchange. Ascospore, Basidiospore, Zygospore Saprophytes: Molds Produce a mass of mycelium and fruiting structures. They are associated with food spoilage. Examples are: Aspergillus, Penicillium, and Rhizopus. Rhizopus Aseptaaate ycelium Aspergillus spp. Mycelium: Septate and with unbranched condiophores. A. fumigatus is considered a potential pathogen. Penicillium spp. Rapid grower, colors vary. Brush-like conidiophores. Yeasts: Sacchromyces cerevisiae Saccharomyces cerevisiae, also known as brewer's or baker's yeast, has been a key ingredient in baking, winemaking, and brewing Candidia albicans Cutaneous infections, oral thrush or vaginitis, but can become systemic. It is generally referred to as a dimorphic fungus since it grows both as yeast and filamentous cells.  Mycosis (Fungal Infection) There are four such categories: 1. Systemic fungal diseases, wherein the organism is inhaled and the primary lesion(s) develops in the lung 2. Subcutaneous mycoses, characterized by the traumatic implantation of the fungus into the subcutaneous tissue 3. Cutaneous & Superficial mycoses which are superficial fungal infections of the skin, hair or nails. 13 Mycosis (Infection by a fungus) Cutaneous (Superficial): A group of superficial fungal infections affecting the skin, hair and nails. The disease is recognized purely on cosmetic basis. The disease is called a dermatophytosis or dermatomycosis. No host cellular or inflammatory response. Host response is patchy scaling or eczema Athlete’s foot eruptions. Examples: Ringworm (Tinea capitis and T. corporis) Athlete’s foot (Tinea pedis) Jock itch (Tinea cruris) Ringworm  Cutaneous (Cont.) Secrete keratinase, an enzyme that degrades keratin. Infection is transmitted by direct contact or contact with infected hair (hair salon) or cells (nail files, shower floors). Candida albicans Infection in an Nail infection with Trichophyton AIDS Patient rubrum in AIDS patient. 14 Subcutaneous: Involve the deeper layers of skin and often muscle tissue. Caused by saprophytic fungi that live in soil or on vegetation. Infection occurs by implantation of spores or mycelial fragments into a skin wound. Can spread to lymph vessels This type of infection is often identified by the presence of a characteristic tissue reaction or granule.. Systemic: Attack the deep tissues and organ systems Categories of systemic disease: Those caused by truly pathogenic fungi with the ability to cause disease in the normal human host when the inoculum is of sufficient size. E.g.( Histoplasma capsulatum ). Those caused by opportunistic fungi, low virulence organisms, which require the patient's defenses to be lowered before the infection is established ( e.g. Aspergillus spp. Candida albicans). Histoplasma capsulatum lung infection Candidiasis Frequency - Candida is the most common fungal pathogen worldwide - 4th leading causes of nosocomial infections. - Significant mortality and morbidity in low birth-weight infants - Affects 75% women, 45% experience recurrence Immunocompromised cancer and HIV-AIDs patients most commonly manifested in patients with leukemia or HIV- AIDs infections. Oral candidiasis is often a a clue to acute primary infection Public Concerns Increasing resistance to drug therapies due to antibiotics and antifungals 17  PRIMARY ANTI-FUNGAL AGENTS Polyene derivatives: Amphotericin B & Nystatin. Polyenes interact with ergosterol in cell membrane Azoles: Ketoconazole: Fluconazole, Itraconazole, Voriconazole Azoles Interfere with ergosterol synthesis Griseofulvin: The exact mechanism by which it inhibits the growth of dermatophytes is not clear. It probably inhibits fungal cell mitosis and nuclear acid synthesis. Benzoic acid: It is combined with keratolytic agents. 20 Mushroom poisonings Mushroom poisonings may happen after the consumption of toxic mushroom. It ranges from benign symptoms of generalized gastrointestinal upset to potentially devastating manifestations. These manifestations include liver failure, kidney failure, and neurologic sequelae.  Mycotoxicoses Mycotoxicoses are diseases caused by mycotoxins. Poisoning can result from feed contaminated with toxins like Ergot alkaloids & Aflatoxin Ergot poisoning The fungus Claviceps purpurea grows on grains and cause ergotism. Ergot alkaloids which causes constriction of blood vessel, gangrene, delusion, convulsion and abortion.  Aflatoxins Aflatoxins are mycotoxins produced by Apergillus species. There are more than 20 known aflatoxins. The four main ones are aflatoxin: B1, B2, G1 and G2 aflatoxins. Apergillus Exist in Cereals like maize, rice and wheat and Nuts Aflatoxins cannot be destroyed by normal cooking processes. Aflatoxin at high amounts: Mental impairment convulsions, and death. Abdominal pain, vomiting, liver damage and cancer, Pulmonary Edema and haemorrhage Aflatoxins (cont.) Aflatoxin at low amounts : Small amounts over a long period may cause growth and development impairment in children and liver cancer. If animals feed is contaminated with aflatoxin it can end up in milk, eggs and meat.