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Lec-3- خلود حمدان.د Mycology Pathogenesis of fungal diseases (Mycoses): Most fungi are saprophytic or parasitic to plants and animals are adapted to their natural environment. Infection in humans is a chance event, occurring only when conditions are favorable. Except for few fungi such as the dimorphic fungi that cause systemic mycoses and dermatophytes, which are primary pathogens, the rest are only opportunistic pathogens. The complex interplay between fungal virulence factors and host defense factors will determine if a fungal infection will cause a disease. Infection depends on inoculums size and the general immunity of the host. The two major physiologic barriers to fungal growth within the human body are temperature and redox potential. Most fungi are mesophilic and cannot grow at 37oC. In general, the development of human mycoses is related primarily to the immunological status of the host and environmental exposure, rather than to the infecting organism. A small number of fungi have the ability to cause infections in normal healthy humans. Fungal Pathogenicity (virulence factors) Candida albicans elastase, collagenase sm -mediated immune defines of the host. Host defiance factors: turnover (monocytes and macrophages) . Factors predisposing to fungal infections: CLINICAL GROUPINGS FOR FUNGAL INFECTIONS 1- SKIN MYCOLOGY Superficial Mycoses Cutaneous Mycoses Subcutaneous Mycoses 2- INFECTIOUS DISEASE MYCOLOGY Dimorphic Systemic Mycoses Opportunistic Systemic Mycoses SKIN MYCOLOGY The Superficial Mycoses These are superficial fungal infections of the skin or hair. No living tissue is invaded and there is no cellular response from the host. Essentially no pathological changes. These infections are often so innocuous that patients are often unaware of their condition. Pityriasis (tinea) versicolor A chronic, superficial fungal disease of the skin characterized by white, pink, or brownish lesions, , and covered with thin scales. The color varies according to the normal pigmentation of the patient, exposure of the area to sunlight,. Lesions occur on the trunk, shoulders and arms, rarely on the neck and face, and fluoresce a pale greenish color under Wood's ultra-violet light. Young adults are affected most often, but the disease may occur in children and old age. The Cutaneous Mycoses These are superficial fungal infections of the skin, hair or nails. No living tissue is invaded, however a pathological changes occur in the host because of the presence of the infectious agent and its metabolic products. Dermatophytosis - Ringworm or Tinea Ringworm of scalp, glabrous skin, and nails caused by a closely related group of fungi known as dermatophytes which have the ability to utilize keratin as a nutrient source. they have a unique enzymatic capacity keratinase. (e.g. Microsporum Canis and Trichophyton rubrum). The Subcutaneous Mycoses These are chronic, localized infections of the skin and subcutaneous tissue. The causative fungi are all soil saprophytes of regional epidemiology whose ability to adapt to the tissue environment and elicit disease is extremely variable. Sporotrichosis and Chromoblastomycosis Primarily a chronic mycotic infection of the cutaneous or subcutaneous tissues and lymphatics characterized by nodular lesions which may suppurate and ulcerate. Infections are caused by the traumatic implantation of the fungus into the skin, or very rarely, by inhalation into the lungs. And the infection may also involve the central nervous system, lungs or genitourinary tract. INFECTIOUS DISEASE MYCOLOGY Dimorphic Systemic Mycoses These are fungal infections of the body caused by dimorphic fungal pathogens which can overcome the physiological and cellular defences of the normal human host by changing their morphological form. They are geographically restricted and the primary site of infection is usually pulmonary, following the inhalation of conidia. Histoplasmosis An intracellular mycotic infection of the reticuloendothelial system caused by the inhalation of the fungus. Approximately 95% of cases of histoplasmosis are subclinical . 5% of the cases have chronic progressive lung disease, chronic cutaneous or systemic disease . All stages of this disease may mimic tuberculosis. Coccidioidomycosis Initially, a respiratory infection, resulting from the inhalation of conidia, that typically resolves rapidly leaving the patient with a strong specific immunity to re-infection. However, in some individuals the disease may progress to a chronic pulmonary condition or as a systemic disease involving the meninges, bones, joints and subcutaneous and cutaneous tissues. Opportunistic Systemic Mycoses Opportunistic fungal infections of the body occur almost exclusively in debilitated patients whose normal defence mechanisms are impaired. The organisms involved are cosmopolitan fungi which have a very low inherent virulence. The increased incidence of these infections and the diversity of fungi causing them, has paralleled the emergence of AIDS and the use of antibiotics, cytotoxins, immunosuppressives, steroids and other macro disruptive procedures that result in lowered resistance of the host. Candidiasis A primary or secondary mycosis infection caused by members of the genus Candida. The clinical manifestations may be acute, sub acute or chronic to episodic. Involvement may be localized to the mouth, throat, skin, scalp, vagina, fingers, nails, bronchi, lungs, or the gastrointestinal tract, or become systemic as in septicemia, endocarditis and meningitis. In healthy individuals, Candida infections are usually due to impaired epithelial barrier functions and occur in all age groups, but are most common in the newborn and the old ages. They usually remain superficial and respond readily to treatment. Systemic candidiasis is usually seen in patients with cell-mediated immune deficiency, and those receiving aggressive cancer, immunosuppression, or transplantation therapy. Several species of Candida may be a etiological agents, most commonly, Candida albicans and rarely C. tropicalis, C. krusei. And C. pseudotropicalis.. All are ubiquitous and occur naturally on humans. Aspergillosis Aspergillosis is a spectrum of diseases of humans and animals caused by members of the genus Aspergillus. These include (1) mycotoxicosis due to ingestion of contaminated foods; (2) allergy (3) colonization (4) necrotizing disease of lungs, and other organs; and rarely (5) systemic disease. The type of disease and severity depends upon the physiologic state of the host and the species of Aspergillus involved. The a etiological agents are include Aspergillus fumigatus, A. flavus, A. niger, and A. terreus Laboratory diagnosis of mycoses: Specimen collection: specimen collection depends on the site affected. Different specimens include hair, skin scrapings, nail clippings, sputum, blood, CSF, urine, corneal scraping, discharge or pus from lesions and biopsy. to prevent bacterial overgrowth. In case of delay specimens except skin specimen, blood and CSF may be refrigerated for a short period. under Wood’s lamp may be selectively plucked. Hairs may be collected in sterilized paper envelopes. lesion is scraped by forceps and collected in sterilized paper envelopes. Discolored or hyperkeratotic areas of nail may be scraped or diseased nail clipping may be collected in sterilized paper envelopes. scraping and transported to laboratory in sterile tube containing saline. positive microscopic results. -mouthed container. In certain cases, pus or exudates must be looked for presence of granules. Microscopy: Microscopy is used to observe clinical specimens for the presence of fungal elements or to identify the fungus following culture. In the latter case, lacto phenol cotton blue is stain of choice, which stains the fungal elements blue. Direct examination of clinical specimens could be stained or unstained. -20% KOH mount: Several specimens are subjected to KOH mount for direct examination . Addition of Dimethyl sulphoxide (DMSO) . t dye, which binds selectively to chitin of the fungal cell wall. The specimen then can be observed under fluorescent microscope. Cryptococcus neoformans. useful