Medical Mycology Prof Khaled H AbuElteen Zarqa Private
Medical Mycology Prof. Khaled H. Abu-Elteen Zarqa Private University. Biology 4223 – The Fungi
Fungal Diseases n n n Mycosis- fungal infection n < 100 cause human disease n Not highly contagious n Humans acquire from nature Groups based on degree on tissue involvement and mode of entry Cutaneous mycoses-dermatophytes n Epidermis, hair & nails n Contagious-direct or indirect contact n Secrete keratinase that degrades keratin Zarqa Private University. Biology 4223 – The Fungi
Cutaneous Mycoses n n Tinea( worm) capitis –blisters with scaly ring Ringworm of the scalp n Spreads circularly forming bald spots n Spread by contact with fomites , cats and dogs Tinea cruris- ringworm of groin Tinea pedis - athlete's foot Zarqa Private University. Biology 4223 – The Fungi
Systemic Mycoses n n n Dimorphic fungi n Yeast form is invasive Can spread throughout body Usually caused by fungi in soil Inhalation of spores Begins in lungs and spread to rest of body Not contagious person to person Zarqa Private University. Biology 4223 – The Fungi
Introduction n Obligate Parasitic Fungi (dermatophytes): evolved to attack the outer surface of humans Facultative soil fungi: thermal dimorphic saprobes, adaptations to human body Opportunistic saprobes: attack people with compromised immune systems Zarqa Private University. Biology 4223 – The Fungi
Introduction Fungal Infections n Superficial infections: involve outermost layers of skin and its appendages [ nails or hair] ( Dermatophytosis) n Cutaneous infections: involve deeper layers of skin causing allergic or inflammatory response n Subcutaneous infections: fungi with low virulence, localized infection, or spread by mycelial growth Zarqa Private University. Biology 4223 – The Fungi
Introduction n Systemic infections: caused by true pathogenic fungi or opportunistic saprobes Zarqa Private University. Biology 4223 – The Fungi
Mycoses: diseases cause by fungi n n n Superficial Subcutaneous Opportunistic Cutaneous Systemic Zarqa Private University. Biology 4223 – The Fungi
The Situation Frequency - most common fungal pathogen worldwide - 4 th leading causes of nosocomial infections, 40% mortality - significant mortality and morbidity in low birth-weight infants - affects 75% women, 45% experience recurrence > 10 million visits/year - classified as a STD by CDC Immunocompromised - cancer and HIV-AIDs patients. C - most commonly manifested in patients with leukemia or HIV-AIDs infections. Oral candidiasis is often a clue to acute primary infection. C Public Concerns - increasing resistance to drug therapies due to antibiotics and antifungals Zarqa Private University. Biology 4223 – The Fungi
FUNGAL DISEASES Mycosis: Any fungal disease. Tend to be chronic because fungi grow slowly. Mycoses are classified into the following categories: I. Systemic mycoses: Fungal infections deep within the body. Can affect a number if tissues and organs. u Usually caused by fungi that live in the soil and are inhaled. Not contagious. u Examples: n Histoplasmosis (Histoplasma capsulatum): Initial infection in lungs. Later spreads through blood to most organs. n Coccidiomycosis (Coccidioides immites): Resembles tuberculosis. Zarqa Private University. Biology 4223 – The Fungi
Systemic Mycosis: Histoplasmosis Disseminated Histoplasma capsulatum, lung infection. Zarqa Private University. Biology 4223 – The Fungi
FUNGAL DISEASES (Continued) II. Cutaneous mycoses: Fungal infections of the skin, hair, and nails. u u u 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: n Ringworm (Tinea capitis and T. corporis) n Athlete’s foot (Tinea pedis) n Jock itch (Tinea cruris) Zarqa Private University. Biology 4223 – The Fungi
Opportunistic Infection by Candida albicans in an AIDS Patient Zarqa Private University. Biology 4223 – The Fungi
Severe nail infection with Trichophyton rubrum in a 37 -year-old male AIDS patient. Zarqa Private University. Biology 4223 – The Fungi
Disseminated Histoplasma capsulatum, skin infection. Zarqa Private University. Biology 4223 – The Fungi
Cutaneous Mycosis Ringworm skin infection: Tinea corporis Zarqa Private University. Biology 4223 – The Fungi
Cutaneous Mycosis Candida albicans infection of the nails. Zarqa Private University. Biology 4223 – The Fungi
FUNGAL DISEASES (Continued) III. Subcutaneous mycoses: Fungal infections beneath the skin. u u u 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. IV. Superficial mycoses: Infections of hair shafts and superficial epidermal cells. Prevalent in tropical climates. Zarqa Private University. Biology 4223 – The Fungi
FUNGAL DISEASES (Continued) Opportunistic mycoses: Caused by organisms that are generally harmless unless individual has weakened defenses: n n n u AIDS and cancer patients Individuals treated with broad spectrum antibiotics Very old or very young individuals (newborns). Examples: n n Aspergillosis: Inhalation of Aspergillus spores. Yeast Infections or Candidiasis: Caused mainly by Candida albicans. Part of normal mouth, esophagus, and vaginal flora. Zarqa Private University. Biology 4223 – The Fungi
Cutaneous Infections Dermatophytic hyphomycetes n 40 species n Epidermophyton (2 species) n Microsporum (17 species) n Trichophyton (24 species) n 50% of dermatophytes human specific Zarqa Private University. Biology 4223 – The Fungi
Cutaneous Infections n Cause common tinea (ringworm) n Grow only on humans n Reservoir not in soil or animals n Reservoir in carpets and upholstery for up to two years Zarqa Private University. Biology 4223 – The Fungi
Cutaneous Infections n n Trichophyton rubrum Chronic infections of the toe nails Zarqa Private University. Biology 4223 – The Fungi
Tinea corporis Subcutaneous mycoses 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. Zarqa Private University. Biology 4223 – The Fungi
Cutaneous Infections n Microsporum canis n Reservoir in cat n May move to humans or dogs n Dies out after one or two person transfers Zarqa Private University. Biology 4223 – The Fungi
Cutaneous Infections n Disease process n Fungus stimulates epithelial cells of skin to divide more frequently n Makes more keratin available to fungus n Some species race specific in humans n Some species body location specific Zarqa Private University. Biology 4223 – The Fungi
Cutaneous Infections n Candida albicans – candidiasis n Normal component of gut mycota n Excessive wetness overgrowth on skin n Vaginal candidiasis common in pregnant women Zarqa Private University. Biology 4223 – The Fungi
Zarqa Private University. Biology 4223 – The Fungi
Biology of Candida albicans Commensal Pathogen A thin-walled dimorphic fungus Morphogenesis Unicellular yeast (harmeless) Filamentous (pathogenic) Principal Cell Wall Polymers Gluccan Mannan Figure 1. Yeast in Oral Scraping A sample of an oral scraping contains yeast cells and pseudohyphae (www. doctorfungus. org) Strict aerobe, favors moist surfaces Commensally found in gut, genitals, and lungs Body Temp 37º C, neutral p. H Zarqa Private University. Biology 4223 – The Fungi Rapid Multiplication & Spread
Diseases by C. albicans Thrush Esophagitis Cutaneous Candidiasis Genital Yeast Infections Deep Candidiasis Zarqa Private University. Biology 4223 – The Fungi
Oropharyngeal Thrush * Pseudomembranous * Atrophic * Angular chelitis Figure 1. Angular chelitis Symptoms Risk Factors HIV Treatment: topical antifungals Figure 2. Oral Thrush, atrophic Zarqa Private University. Biology 4223 – The Fungi Figure 3. Oral Thrush, pseudomembranous
Genital Yeast Candidiasis Symptoms Risk Factors - disruption of normal microbiota Figure 1. Vaginal Yeast Culture Treatment - direct genital administration - tablets, suppositories, creams Figure 2. Plasma cell balanitis. A band-like infiltrate of plasma cells is in Zarqa Private University. Biology the dermis of the male penis. 4223 – The Fungi
Deep Candidiasis Figure 1. Four forms of invasive candidiasis (www. doctorfungus. org) Zarqa Private University. Biology 4223 – The Fungi
Pathogenesis Host Recognition Adhesins Enzymes Hydrolases: Phosphoplipases, Lipases, Proteinases Morphogenesis Yeast form to Filamentous hyphae/pseudohyphae Phenotypic Switching Zarqa Private University. Biology 4223 – The Fungi
Virulence assay of different C. albicans strains using the skin equivalent (AST 2000) Figure 1. skin equivalent before infection Figure 2. Infection with pathogenic clinical isolate of C. albicans. After 48 h the yeast penetrates the skin equivalent and destroys the tissue Figure 3. 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. Zarqa Private University. Biology 4223 – The Fungi (Fraunhofer, 2002)
MORPHOGENESIS Figure 1. Morphogenesis in C. albicans is a pivotal virulence factor that allows rapid multiplication and subsequent dissemination in host tissue. (www. kent. ac. uk) Figure 2. Morphogenic forms of Candida albicans http: //cbr-rbc. nrc-cnrc. gc. ca/thomaslab/candida/caindex. html Zarqa Private University. Biology 4223 – The Fungi
Subcutaneous Infections Fungal Activity n Fungi normally saprobic n Introduced through wounds n Adapt to the human animal by changes in n morphology n physiology Zarqa Private University. Biology 4223 – The Fungi
Subcutaneous Infections Chromoblastosis n Common among barefoot peoples of the tropics n Soil hyphomycete species n Enters human by thorns or wood slivers n Fungus grows host cells respond by rapid cell division wart-like growths on feet or legs Zarqa Private University. Biology 4223 – The Fungi
Subcutaneous Infections Mycotic Mycetoma n Disease of barefoot tropical people n Entry: wound on foot n Attacks various tissues n Stimulates formation of tumor n Compact fungal colonies form within tumor Zarqa Private University. Biology 4223 – The Fungi
Subcutaneous Infections n Skin ruptures and some colonies extrude Zarqa Private University. Biology 4223 – The Fungi
Systemic Mycoses Introduction n Caused by. . . n Specialized pathogens n Dimorphic n One form outside the host n Another form inside the host n Opportunistic saprobes Zarqa Private University. Biology 4223 – The Fungi
Systemic Mycoses Dimorphic Pathogen Mycoses n Histoplasmosis n Histoplasma capsulatum n Grows on bird droppings, chicken manure, bat guano n Conidia inhaled primary lung infection almost always fatal until recently Zarqa Private University. Biology 4223 – The Fungi
Systemic Mycoses n Histoplasma capsulatum Zarqa Private University. Biology 4223 – The Fungi
Systemic Mycoses Coddidioidomycosis n Coccidioides immitis n Dry, saline soils n Endemic to SW deserts of North America n Valley fever n Until recently – almost always fatal Zarqa Private University. Biology 4223 – The Fungi
Systemic Mycoses n n Infection, disease process, and clinical symptoms similar to histoplasmosis Can be effectively treated with fluconazole Zarqa Private University. Biology 4223 – The Fungi
Opportunistic Pathogens/Disease General n Pathogens all grow well at 37 C n None cause disease in well individuals n Require breakdown in resistance system n Complication of diabetes, AIDS, advanced cancer, sequel to steroid or antibiotic treatments Zarqa Private University. Biology 4223 – The Fungi
Opportunistic Pathogens/Disease Zygomycosis n Species of Zygomycota n Rhizopus, Mucor, Rhizomucor n Rhinocerebral mycosis n Spores enter through sinuses n Grows rapidly outward to the eyes and inward towards the brain Zarqa Private University. Biology 4223 – The Fungi
Opportunistic Pathogens/Disease Aspergillosis n Aspergillus sp. n Bronchiopulmonary aspergillosis n Mucus within the bronchi severe allergic reaction n Aspergilloma n Forms a mycelia ball in lung cavity formed from earlier TB Zarqa Private University. Biology 4223 – The Fungi
Opportunistic Pathogens/Disease n Surgical n n intervention often required Invasive aspergillosis n Severely debilitated n Immunosuppressed (AIDS) Almost always fatal until recently Zarqa Private University. Biology 4223 – The Fungi
AIDS and Mycoses n n n Aspergillosis Candidiases (Candidiasis seen in 2/3 of AIDS patients Cryptococcosis Zygomycosis Esophogeal candidiasis and cryptococcosis are strong indicators of AIDS Zarqa Private University. Biology 4223 – The Fungi
PRIMARY ANTI-FUNGAL AGENTS 1. 2. Polyene derivatives n Amphotericin B n Nystatin Azoles n Ketoconazole n Fluconazole n Itraconazole n Voriconazole Zarqa Private University. Biology 4223 – The Fungi
Zarqa Private University. Biology 4223 – The Fungi
Azoles There a few rare serious side effects from Itraconazole and Fluconazole Zarqa Private University. Biology 4223 – The Fungi
5 -fluorocytosine (5 -FC) Interferes With RNA Synthesis Zarqa Private University. Biology 4223 – The Fungi
MECHANISMS OF ACTION n Polyenes n n Azoles n n Griseofulvin n n 5 - FC n Ergosterol in cell membrane Interfere with ergosterol synthesis Forms a barrier to fungal growth Inhibits RNA synthesis Zarqa Private University. Biology 4223 – The Fungi
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