Medical Mycology Lectures PDF

MEDICAL MYCOLOGY Lectures INTRODUCTION The term "mycology" is derived from Greek word "mykes" meaning mushroom. Therefore mycology is the study of fungi Fungi inhabit almost every niche in the environment and humans are exposed to these organisms in various fields of life. General prop...

MEDICAL MYCOLOGY Lectures INTRODUCTION The term "mycology" is derived from Greek word "mykes" meaning mushroom. Therefore mycology is the study of fungi Fungi inhabit almost every niche in the environment and humans are exposed to these organisms in various fields of life. General properties of fungi: They are eukaryotic. Have ergosterols in their membranes and possesses 80S ribosomes. Have a rigid cell wall and are therefore non-motile. possess cell wall made of chitin. They obtain nutrients as saprophytes (live off of decaying matter) or as parasites (live off of living matter). All fungi require water and oxygen. Typically reproduce asexually and/or sexually by producing spores. They grow either reproductively by budding or non-reproductively by hyphal tip elongation Food storage is generally in the form of lipids and glycogen. Beneficial Effects of Fungi: Decomposition - nutrient and carbon recycling. Biosynthetic factories. The fermentation property is used for the industrial production of alcohols, fats, citric, oxalic and gluconic acids. Important sources of antibiotics, such as Penicillin. Saccharomyces cerviciae is extensively used in recombinant DNA technology, which includes the Hepatitis B Vaccine. Some fungi are edible (mushrooms). Yeasts provide nutritional supplements such as vitamins and cofactors. Penicillium is used to flavour Roquefort and Camembert cheeses. Harmful Effects of Fungi: Destruction of food, lumber, paper, and cloth. 2. Animal and human diseases, including allergies. 3. Toxins produced by poisonous mushrooms and within food (Mycetism and Mycotoxicosis). 4. Plant diseases. 5. Spoilage of agriculture produce such as vegetables and cereals. 6. Damage the products such as magnetic tapes and disks, glass lenses, marble statues, bones and wax. Classification of Mycoses The clinical nomenclatures used for the mycoses are based on the (1)site of the infection, (2)route of acquisition of the pathogen, and (3)type of virulence exhibited by the fungus. Classification Based on Site  superficial,  cutaneous,  subcutaneous,  systemic (deep) infections depending on the type and degree of tissue involvement and the host response to the pathogen. Classification Based on Route of Acquisition Infecting fungi may be either  exogenous: Routes of entry for exogenous fungi include airborne, cutaneous or percutaneous  endogenous. Endogenous infection involves colonization by a member of the normal flora or reactivation of a previous infection. Classification Based on Virulence Primary pathogens can establish infections in normal hosts. Opportunistic pathogens cause disease in individuals with compromised host defense mechanisms. FUNGAL DISEASES Mycosis: Any fungal disease. Tend to be chronic because fungi grow slowly. Mycoses are classified into the following categories:. System c mycoses: Fungal infections deep within the body. Can affect a number if tissues and organs.. Usually caused by fungi that live in the soil and are inhaled..Examples:.Histoplasmosis (Histoplasma capsulatum): Initial infection in lungs. Later spreads through blood to most organs.. Coccidiomycosis (Coccidioides immites): Resembles tuberculosis Fungal Infections Superficial infections: involve outermost layers of skin and its appendages [ nails or hair] ( Dermatophytosis) Cutaneous infections: involve deeper layers of skin causing allergic or inflammatory response Subcutaneous infections: fungi with low virulence, localized infection, or spread by mycelial growth Systemic infections: caused by true pathogenic fungi or opportunistic saprobes Mycoses: diseases cause by fungi Superficial Cutaneous Subcutaneous Systemic Opportunistic Zarqa Private UniversityBiology 4223 – The Fungi Systemic Mycosis: Histoplasmosis Disseminated Histoplasma capsulatum, lung infection. Zarqa Private UniversityBiology 4223 – The Fungi Superficial mycoses Superficial mycoses are limited to the stratum corneum and essentially elicit no inflammation. -Pityriasis versicolor is a common superficial mycosis, which is characterized by hypopigmentation or hyperpigmentation of skin of the neck, shoulders, chest, and back. Pityriasis versicolor is due to Malassezia furfur which involves only the superficial keratin layer. Black piedra is a superficial mycosis due to Piedraia hortae which is manifested by a small firm black nodule involving the hair shaft. By comparison, White piedra due to T beigelii is characterized by a soft, friable, beige nodule of the distal ends of hair shafts. Tinea nigra most typically presents as a brown to black silver nitrate-like stain on the palm of the hand or sole of the foot  Black dot ringworm caused by Trichophyton tonsurans Treatment Topical Azol soaks macerated lesion with solutions such aluminum acetate, Anti-inflammatory effects of corticosteroids are markedly beneficial Topical antibiotic ointments, such as gentamicin, effective against gram-negative organisms Keratolytic agents, such as salicylic acid Cutaneous Mycoses may be classified as 1. dermatophytoses or 2. dermatomycoses. Dermatophytoses are caused by the agents of the genera  Epidermophyton,  Microsporum, and  Trichophyton  The dermatophytoses are characterized by an anatomic site- specificity according to genera. For example, Epidermophyton floccosum infects only skin and nails, but does not infect hair shafts and follicles. Microsporum spp. infect hair and skin, but do not involve nails. Trichophyton spp. may infect hair, skin, and nails.  Dermatomycoses are cutaneous infections due to other fungi, the most common of which are Candida spp Cutaneous mycoses Cutaneous mycoses: Fungal infections of the skin, hair, and nails.. 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).. Examples:. Ringworm (Tinea capitis and T. corporis). Athlete’s foot (Tinea pedis). Jock itch (Tinea cruris)  Tinea cruris in a woman  Tinea pedis showing interdigital scalping T. mentagrophytes  Dermatophyto sof the soles Trichophyton mantagrophyt es Trichophyton rubrum T. rubrum causes the majority of cases Produces a relatively non-inflammatory type of dermatophytosis characterized by a dull erythema and prnounced scaling involving the entire sole and sides of feet Producing a moccasin or sandel appearance  Kerion: inflammatory of tinea capitis caused by Microsporum canis or Trichophyton mentagrophytes  Permanent scarring alopecia post kerion Cutaneous Infections Microsporum canis Reservoir in cat May move to humans or dogs Dies out after one or two person-person transfers Cutaneous Infections Disease process Fungus stimulates epithelial cells of skin to divide more frequently Makes more keratin available to fungus Some species race specific in humans Some species body location specific  Tinea corporis: note sharp margin and central clearing Cutaneous Mycosis Ringworm skin infection: Tinea corporis Cutaneous Mycosis Candida albicans infection of the nails. Cutaneous Infections Trichophyton rubrum Chronic infections of the toe nails Topical Anticandidal Agents Azole derivative which include, clotrimazole ,econazole , ketaconazole (Nizoral), miconazole , oxiconazole ,sulconazole, nystatin, Topical amphotericin B lotion Terbinafine has been reported to be less active against Candida species by some authors Cutaneous Infections Candida albicans – candidiasis Normal component of gut mycota Excessive wetness  overgrowth on skin Vaginal candidiasis common in pregnant women  A thin-walled dimorphic fungus Morphogenesis Unicellular yeast (harmeless) Filamentous (pathogenic) Principal Cell Wall Polymers Gluccan Mannan Strict aerobe, favors moist surfaces Commensally found in gut, genitals, and lungs Body Temp 37º C, neutral pH  Oral Candidiasis (BabiesThrush) Mucous membrane of the mouth may be involved in healthy newborn & infant Newborn infection may be acquired from contact with vaginal tract of mother Grayish white membranous plaques are found on surface. Base of plaques are moist, reddish, and macerated Adult thrush Infection of the oral tissues with Candida albicans; often an opportunistic infection in immunodepleted patient. Papillae of tongue are atrophied, surface is smooth, glazed, and bright red Frequently infection extends onto angles of the mouth (seen in elderly, debilitated, and malnourished, and diabetics)  Oropharyngeal Thrush  Pseudomembranous Atrophic Figure 1. Angular chelitis Angular chelitis Symptoms Risk Factors HIV Treatment: topical Figure 3. Oral Thrush, pseudomembranous antifungals Figure 2. Oral Thrush, atrophic Genital Yeast Candidiasis Risk Factors - disruption of normal microbiota Treatment - direct genital administration - tablets, suppositories, creams  Host Recognition Adhesions Enzymes Hydrolases: Phosphoplipases, Lipases, Proteinases Morphogenesis Yeast form to Filamentous hyphae/pseudohyphae Phenotypic Switching Virulence assay of different C. albicans strains using the skin equivalent skin equivalent before infection. Infection with pathogenic clinical isolate of C. albicans. After 48 h the yeast penetrates the skin equivalent and destroys the tissue Infection with non-pathogenic C. albicans. This strain is not able to penetrate into the tissue and thus behaves as avirulent as shown in the mouse model of systemic infection Subcutaneous Infections Fungal Activity Fungi normally saprobic Introduced through wounds Adapt to the human animal by changes in morphology physiology Subcutaneous Mycoses There are three general types of subcutaneous mycoses: All appear to be caused by traumatic inoculation of the etiological fungi into the subcutaneous tissue:  chromoblastomycosis,  mycetoma, sporotrichosis  Chromoblastomycosis is a subcutaneous mycosis characterized by verrucoid lesions of the skin (usually of the lower extremities); histological examination reveals muriform cells (with perpendicular septations) or so-called "copper pennies" that are characteristic of this infection. Chromoblastomycosis is generally limited to the subcutaneous tissue with no involvement of bone, tendon, or muscle.  mycetoma is a suppurative and granulomatous subcutaneous mycosis, which is destructive of contiguous bone, tendon, and skeletal muscle. Mycetoma is characterized by the presence of draining sinus tracts from which small but grossly visible pigmented grains or granules are extruded. These grains are microcolonies of fungi causing the infection  Sporotrichosis is the third general class of subcutaneous mycoses. This infection is due to Sporothrix schenckii and involves the subcutaneous tissue at the point of traumatic inoculation. The infection usually spreads Subcutaneous Infections Mycotic Mycetoma Disease of barefoot tropical people Entry: wound on foot Attacks various tissues Stimulates formation of tumor Compact fungal colonies form within tumor Subcutaneous mycoses Tinea corporis Subcutaneous infections - over 35 species produce chronic inflammatory disease of subcutaneous tissues and lymphatics. e.g. sporotrichosis - ulcerated lesions at site of inoculation followed by multiple nodules - caused by a dimorphic fungus: Sporotrix schenckii Subcutaneous Infections Skin ruptures and some colonies extrude Deep Mycoses ( Systemic Mycoses) Deep mycoses are caused by primary pathogenic and opportunistic fungal pathogens  The primary deep pathogens usually gain access to the host via the respiratory tract.  Opportunistic fungi causing deep mycosis invade via the respiratory tract, alimentary tract, or intravascular devices. opportunistic pathogens require a compromised host in order to establish infection (e.g., cancer, organ transplantation, surgery, and AIDS) Systemic Mycoses Caused by... Specialized pathogens Dimorphic One form outside the host Another form inside the host Dimorphic Pathogen Mycoses Histoplasmosis Histoplasma capsulatum Grows on bird droppings, chicken manure, bat guano Conidia inhaled  primary lung infection  almost always fatal until recently Histoplasma capsulatum Systemic Mycoses Coddidioidomycosis Coccidioides immitis Dry, saline soils Endemic to deserts of North America Valley fever Until recently – almost always fatal Systemic Mycoses Infection, disease process, and clinical symptoms similar to histoplasmosis Can be effectively treated with fluconazole Opportunistic Pathogens/Disease Pathogens all grow well at 37C None cause disease in well individuals Require breakdown in resistance system Complication of diabetes, AIDS, advanced cancer, sequel to steroid or antibiotic treatments Opportunistic Pathogens/Disease Zygomycosis Species of Zygomycota Rhizopus, Mucor, Rhizomucor Rhinocerebral mycosis Spores enter through sinuses Grows rapidly outward to the eyes and inward towards the brain Cryptococcosis and Cryptococcus neoformans Cryptococcus neoformans causes cryptococcosis. A widespread encapsulated yeast that inhabits soil around pigeon roosts Common infection of AIDS, cancer or diabetes patients Infection of lungs leads to cough, fever, and lung nodules Dissemination to meninges and brain can cause severe neurological disturbance and death. 59 Pulmonary Cryptococcus Opportunistic Pathogens/Disease Surgical intervention often required Invasive aspergillosis Severely debilitated Immunosuppressed (AIDS) Almost always fatal until recently AIDS and Mycoses Aspergillosis Candidiases (Candidiasis seen in 2/3 of AIDS patients Cryptococcosis Zygomycosis Esophageal candidiasis and cryptococcosis are strong indicators of AIDS  Aspergillosis: Diseases of the Genus Aspergillus Very common airborne soil fungus 600 species, 8 involved in human disease; A. fumigatus most commonly Serious opportunistic threat to AIDS, leukemia, and transplant patients Infection usually occurs in lungs – spores germinate in lungs and form fungal balls; can colonize sinuses, ear canals, eyelids, and conjunctiva Invasive aspergillosis can produce necrotic pneumonia, and infection of brain, heart, and other organs. Amphotericin B and nystatin 63 Zygomycosis Zygomycota are extremely abundant saprophytic fungi found in soil, water, organic debris, and food. Genera most often involved are Rhizopus, Absidia, and Mucor. Usually harmless air contaminants invade the membranes of the nose, eyes, heart, and brain of people (Rhinocerebral mucormycosis) with diabetes and malnutrition, with severe consequences. main host defense is phagocytosis A typical sign & symptoms Malasezzia furfur Tinea versicolor (mild disease in normal person) can cause disseminated infection--Particularly in patients receiving hyperalimentation OPPORTUNISTIC FUNGAL INFECTIONS ARE: difficult to diagnose difficult to treat difficult to prevent more and more frequent PRIMARY ANTI-FUNGAL AGENTS 1. Polyene derivatives Amphotericin B Nystatin 2. Azoles Ketoconazole Fluconazole Itraconazole Voriconazole Zarqa Private UniversityBiology 4223 – The Fungi Azoles There are a few rare serious side effects from Itraconazole and Fluconazole 5-fluorocytosine(5-FC) Interferes With RNA Synthesis MECHANISMS OF ACTION Polyenes :- Ergosterol in cell membrane Azoles:- Interfere with ergosterol synthesis Griseofulvin:- Forms a barrier to fungal growth 5 – FC:- Inhibits RNA synthesis