Medical Mycology Past Paper PDF 2025

Medical Mycology Cutaneous, subcutaneous, systemic, and opportunistic infections February 4, 2025...

Medical Mycology Cutaneous, subcutaneous, systemic, and opportunistic infections February 4, 2025 Shafik Habal, MD Assistant Dean for Curriculum Management and Reporting Professor, Medical Microbiology and Immunology Philadelphia College of Osteopathic Medicine Georgia Campus Certain materials are included under the fair use exemption of the U.S. Copyright Law and have been prepared according to the fair use guidelines and are restricted from further use.  Learning Objectives 1. Define terminology used in mycology 2. List basic structural components and properties of fungi 3. List the most common types of mycoses and sort them according to their clinical classifications 4. For the following fungal pathogens: – Candida spp., Dermatophytes, Malassezia furfur, Sporothrix schenckii, Histoplasma capsulatum, Coccidioides immitis, Blastomyces dermatitidis, Paracoccidioides brasiliensis, Aspergillus spp., Mucormycetes, Cryptococcus neoformans, Pneumocystis jiroveci 5. Describe their: 1. visual appearance 2. source and transmission, including the geographic distribution of the endemic mycoses 3. clinical manifestation(s) of infection 7. Know the common fungal stains used in the clinical laboratory and recognize structural components of fungi in clinical specimens Reading Assignment: Murray’s Medical Microbiology 9th edition Chapter 57, 62, 63, 64, 65  Microorganism Size Why study fungi? Cocci Bacilli 0.08μ 4-6μ Spirochetes 8-10μ Viruses 0.08μ More than 300,000 species, 200 are pathogenic Protozoa 15μ A major cause of nosocomial infections Nematodes 10mm Fungi 10-15μ Majority of fungal infections are cutaneous Invasive fungal infections are associated with increased mortality Infections are often misdiagnosed Annual cost in US: Mycoses Mortality Candida $3.0 billion Aspegillus $1.0 billion Candida 40% Aspergillus 60% Zygomycetes 80% Antifungal therapy Scedosporium 100% $4710 (10.5%)  Characteristics In general, all fungi are eukaryotic – Contain a nucleus – Contain membrane bound organelles (mitochondria, Golgi, etc.) Heterotrophic – They lack chlorophyll 🡪 No photosynthesis (not autotrophic) – They are saprophytes (feed on living and dead organic matter) or parasitic (utilize living tissue) Thermally dimorphic (mostly)  Fungal Structures Polysaccharide Capsule Present only in some fungi. Cryptococcus neoformans (encapsulated) Cell wall Antigenic, multilayered: Polysaccharides (90%) – Chitin, chitosan, cellulose, glucan and mannan Proteins and glycoproteins (10%) Provide shape, rigidity and protection against osmotic shock Cell membrane Bilayered, made up of phospholipids and sterols (ergosterol, zymosterol) Protects the cytoplasm and facilitates capsules and cell wall synthesis Cytoplasm Nucleus surrounded by a nuclear membrane Nucleolus, Endoplasmic reticulum, mitochondria and vacuoles Vacuole Membrane bound, used for storage and degradation  Thermal Dimorphism Cultured at 25-30˚C Cultured at 37˚C Filamentous (mold) Yeast Vegetative growth of filamentous (filaments packed Unicellular tightly) Reproduces asexually by budding 🡪 Blastoconida Aerobic filamentous fungi Also reproduces sexually 🡪 Basidiospore Reproduction by spores or conidia They may contain a capsule These filaments are also known as “Hyphae” – India ink can be used to identify the presence of a capsule A mass of hyphae collectively make up the “Mycelium” which is an intertwined filamentous All yeasts are aerobic and grows at wide range mass formed by hyphae and maybe visible to the of temperatures, the optimum being room naked eye. temperature  MOLD Yeast Multicellular Unicellular  Fungal Morphology Sporangium  Types of Hyphae Coenocytic Hyphae: Multinucleated, non-septate, functioning as a single unit. Pseudohyphae: Lack cytoplasmic connections between cells(maybe due to incomplete budding) 🡪 constrictions – Candida albicans  Germ Tubes Budding spore produced a few hours after incubation (at the start of hyphae formation) Diagnostic of certain Candida strains Considered a factor of pathogenicity and tissue invasion Fluorescence was observed, and photographs taken, using Candida albicans in human serum after 3-hour incubation at epi-illumination with ultra-violet excitation (330 to 380 nanometer 37⁰C (magnification x 450) wavelength range) with an oil-immersion ×50 Image 1_Torulopsis (Candida) glabrata. Weak fluorescence at the ends of the cells. objective.  Diagnosis Based on clinical manifestations Diagnosis of fungal infection depends on isolation and identification Laboratory Identification: – Sabouraud’s agar contains pentons, good for dermatophytes – Blood agar: usually with antibiotics to prevent cross contamination – Microscopy: Skin scrapings with 10% KOH 🡪 Light microscopy – Skin tests: Fungal antigens may cause cross-reactivity with other fungal infections (not diagnostic) – Serology and antibody detections currently available for certain fungal infections (Histoplasma, Blastomyces, etc) Pathogenesis Thermo tolerance Ability to withstand extreme conditions The ability to evade host immune defenses Pathogenicity is dependent on inoculums size and the resistance of the host In general, severity of infection depends on host’s immunity rather than virulence Transmission Most fungi are opportunistic Many switch to a hyphal form as they invade a human host (thermal dimorphism) Most are not communicable (person – person) except dermatophytes Spores enter the body via the respiratory rout, mucus membrane and the skin  Fungal Infections SUPERFICIAL INFECTIONS SYTEMIC FUNGAL INFECTIONS Piedras Histoplasma capsulatum Dermatophytes Blastomyces dermatitidis Coccidiodes immits Malassezia fufur Paracoccidiodes brasiliensis SUBCUTANEOUS INFECTIONS OPPURTUNISTIC MYCOSES Sporothrix schenckii Candida albicans Basidiobolus ranierum Cryptococcus neoformans Conidiobolus coronatus Rare Aspergillus fumigatus Lobomycosis Mucor rhizopus Tropics Mycetoma Pneumocystis jirovecii  Layers of the epidermis Superficial Mycoses Confined to the stratum corneum or distal portions of hair For the most part, they are cosmetic in nature In most cases, no cellular response from the host Essentially, no pathological changes are elicited Covered in this lecture: Dermatophytes and Malassezia https://www.earthslab.com/physiology/cells-layers-epidermis/  Dermatophytes Invade keratinized structures (nails, hair, stratum corneum) May cause secondary bacterial infections and mild inflammatory response in Tinea capitis caused by Microsporum canis, affected areas with blue-greenish fluorescence in scaly areas and parasitized follicles under WL One of the few fungi transmitted by contact (direct/indirect) Manifestations vary according to the affected area and the pathogen Diagnosis is usually done by: – Skin scraping reveal branched hyphae on KOH wet mount (10 – 25%) – Culture: Sabouraud agar (pH is 5.6 🡪 inhibits bacterial growth) – Wood’s light Trichophyton terrestre cultured on Sabouraud agar https://www.researchgate.net/publication/323228320_Wood%27s_lam p_in_dermatology_Applications_in_the_daily_practice/figures?lo=1  Dermatophytes Anthrophilic: – Associated with humans only – Person to person transmission – Contaminated objects (towels, clothing, etc) Geophilic: – Found in soil – Transmission via direct contact Zoophilic: – Associated with animals – Direct transmission through close contact  Types of Dermatophyte Infections All Dermatophyte infections are caused by members of :Microsporum (M)Epidermophyton (E), Trichophyton (T) Disease Etiology Signs Diagnosis Tinea corporis M, E, T Ringworm (trunk, arms, legs) Micro/macroconidia in scraping Tinea cruris M, T, E Jock itch (groin) Micro/macroconidia in scraping Tinea pedis M, T, E Athlete’s foot (feet) Micro/macroconidia in scraping Tinea capits M, T, E Ringworm of the scalp Micro/macroconidia in scraping Tinea unguium M, T, E Nail fungus Micro/macroconidia in scraping Tinea manus M, T, E Ringworm of the hand Micro/macroconidia in scraping Trichophyton Microsporum Epidermophyton Clinical manifestation associated with dermatophyte infections Tinea unguium Tinea pedis Tinea cruris Tinea corporis Tinea barbae Treatment: o Topical: Miconazole, Clotrimazole, o Oral: Griseofulvin, Ketoconazole Malassezia spp. Malassezia furfur Causes “Pityriasis versicolor” Normal skin flora especially in oily areas Presents as hypopigmented areas with flaky, white to yellowish scales Lipid dependent yeast 🡪 Infects young adults with oily skin (Lipophilic) It never penetrates the skin but in some cases it may infect lipid IV solutions Skin scraping on KOH mount reveal thick walled-yeast and branching hyphae resembling “spaghetti and meatballs” Managed by shampoo containing selenium sulfide Sporothrix schenckii Worldwide distribution, mainly in tropical areas Maybe the only subcutaneous fungal infection in the US Commonly found on soil and on decaying vegetation – It grows as mold (Hyphae) in soil – Switches to yeast in human host Transmission: Traumatic implantation At risk: Golfers, rose gardeners, landscapers  Sporothrix schenckii Clinically: It causes “Sporotrichosis” also known as “Rose – Gardner’s disease” Painless papule at site of inoculation Nodules often spread along draining lymphatics and may ulcerate Secondary spread to articular surfaces, bone and muscle is common Appears like ulcerating nodules along a hard cord It may become disseminated in immunocompromised patients 2 weeks with Itraconazole 8 weeks with Itraconazole 11 weeks with Itraconazole  Candida spp. Causes superficial and subcutaneous candidiasis Dimorphic fungi Common nosocomial pathogen It can spread by sexual contact Unlike most subcutaneous fungi, there’s person to person transmission  Systemic Mycoses Caused by dimorphic fungal pathogens which can overcome CMI Geographically restricted Usually cause pulmonary symptoms after inhalation of conidia – Humans inhale the spores – In the lungs, spores change into yeast (usually lower lobes) – Yeast is phagocytosed by macrophages 🡪 Hematogenous dissemination Non-communicable (no patient-to-patient transmission) Infections required a large inoculum (low virulence)  Histoplasma capsulatum Geographical distribution: Ohio – Mississippi river valley Loves nitrogen in soil 🡪 Found in bat, pigeon and chicken droppings At risk: Access to chicken coops and caves “spelunking” Unencapsulated yeast proliferating inside of macrophages (intracellular in tissue) Appears as a thin-walled, narrow-base budding yeast Diagnosis: Detection of urinary or blood antigens Narrow-base budding yeast in pus from intestinal mucosa Numerous yeast forms of Histoplasma capsulatum in alveolar macrophages www.cdc.gov Histoplasma capsulatum – Clinical manifestations “Summer Flu” in the Midwest is most probably due to Histoplasma capsulatum May affect the spleen, liver and bone marrow Often asymptomatic (95% of cases) Clinical symptoms may resemble TB pneumonia 🡪 Chronic progressive lung disease Some patients may present with symptoms of ocular histoplasmosis Disseminated in immunocompromised patients Managed with oral itraconazole, ketoconazole or amphotericin B in severe case  Blastomyces dermatitidis Geographical distribution: East of Mississippi river valley, Central America Loves organic debris. Found in soil, rotten wood and humid areas Grows as an extracellular yeast in tissue Appears as a thick-walled, broad-based budding yeast (much larger than Histoplasma) Antigens often detected in a skin test www.cdc.gov  Blastomyces dermatitidis – Clinical manifestations “Chicago Disease” Fever, night sweats, weight loss Pulmonary stage which maybe followed by a chronic granulomatous stage. Pulmonary symptoms often disappear after 2 – 12 days of the infection. However, the symptoms may return months later. Granuloma formation in the lungs and skin which may ulcerate. In 30% of patients, the infection may affect the spin, pelvis, cranial bones and ribs. Managed with oral itraconazole, ketoconazole or amphotericin B in severe cases  Coccidiodes immitis Geographical distribution: SW US, San Joaquin valley Considered to be the most virulent of systemic mycoses Unlike Histoplasma and Blastomyces, it produces “Spherules” Transmission: Inhalation of arthrospores 🡪 Spherules (tissue form) Prefers more dry and semi arid environments Detection: Enzyme immunoassay (EIA) for specific IgM and IgG San Joaquin Valley Https://webpath.med.utah.edu/INFEHTML/INFEC024.html  Coccidiodes immitis – Clinical manifestations 10% develop “San Joaquin Valley Fever” – usually children and visitors to the area. Fever, productive cough and chest pain and extreme fatigue. These symptoms are usually self-limiting Often associated with Anorexia Symptoms appear 7 – 28 days after exposure In some cases it becomes disseminated resulting in Erythema multiforme and granulomas often called “Desert bumps” (very similar to TB and Histoplasma)  Paracoccidiodes brasiliensis Geographical distribution: Rural Latin America Multiple, narrow base, budding yeast cells “ship’s wheel" The disease involves the lungs and the skin Infections are often self limiting Systemic disease is rare Endemic mycoses: geographical distribution is still a work in progress  Cryptococcus neoformans Encapsulated yeast (not dimorphic – no relevant mold phase) Opportunistic fungal infection (HIV, transplant, etc.) Worldwide distribution – soil, decaying wood, and bird (pigeon) droppings – Pigeon The pigeon is not infected, its core temperature is high 🡪 Spores path through GI – Droppings collect on air conditions, roof tops and cars 🡪 Aerosolized 🡪 Inhalation Detection: polysaccharide capsule (India ink), serology, culturing, and cryptococcal antigens in CSF  Cryptococcus neoformans – Clinical manifestations Pathogenesis: Inhalation 🡪 Colonizes the lung 🡪 Lung injury Cryptococcus loves brain tissue and the meninges “Cryptococomas” 🡪 Meningoencephalitis – Febrile, loss of vision, stiff neck, – Change in mental status – Maybe accompanied by hydrocephalus Treatment: Amphotericin B + flucytosine initially, Followed by fluconazole  Candida species Ubiquitous fungi found throughout the world as normal body flora. Candidiasis can range from mild (diapers rash) to fatal (systemic) Candida albicans is the most common species (90-100%). (others include: C. glabrata, C. parapsilosis, C. tropicalis) Candida auris is an emerging, multidrug-resistant type of Candida. It presents a serious global health threat, including in the US. Candida auris can cause severe infections and spreads easily in healthcare facilities. Appears as yeast, psuedohyphae and true hyphae Requires a slightly alkaline environment (pH 7.4) Psuedoyphae invades Most infections are endogenous Yeast disseminates Person-to-person transmission had been documented in healthcare workers (skin contact) They secrete Hydrolases, proteases and phospholipases 🡪 Destroy cells around them https://www.cdc.gov/fungal/diseases/candidiasis/index.html#:~:text=Candidiasis%20is%20a%20fungal%20infection,most%20common%20is%20Candida%20albicans.  Candida spp. – Clinical manifestations 1. Deficient cellular mediated immunity (CMI) 2. Patients receiving immunosuppressive treatment (transplant and cancer patients) 3. Patients with indwelling catheters, intravenous lines, or prosthetic devices Risk Factors 4. Patients receiving corticosteroid treatment (autoinflammatory) 5. Female patients receiving antibiotic treatment 6. Prolonged ICU stay is associated with increased risk of dissemination Vulvovaginitis Vaginosis with hick white “cottage cheese” vaginal discharge and itching Intertrigo Associated with warm and moist skin folds, groin, axilla, etc. Clinical manifestations Oral thrush White exudates in oral cavity. Mainly affects the immunocompromised Esophageal thrush Considered an AIDS defining illness. Dysphagia, substernal pain Disseminated Mainly affects the immunocompromised and IV drug users (IVDU) Cutaneous Microscopy of scrapings on a wet mount or KOH smears Mucocutaneous Microscopy of scrapings on a wet mount, KOH, or methylene blue dye Diagnosis Genitourinary Urinalysis (WBC, RBC, protein, yeast cells) or urine fungal cultures Gastrointestinal Endoscopy with or without biopsy  Candida albicans – Candidiasis Oral, esophageal and ocular Candidiasis Vulvovaginal and balantitis Intertriginous candidiasis Ocular candidiasis is spread via blood stream, In females, often associated with use of Most often seen in the axillae, groin, indwelling catheters, IVDU, ocular trauma, and broad spectrum antibiotics, pregnancy, intergluteal fold, interdigital. Moisture, surgery. Patients present with cloudy vision low vaginal pH, and diabetes. heat and friction are the principle In males, balanitis is often associated predisposing factors with poor hygiene, uncircumcised. Mimics dermatophytes  Aspergillus spp. Common organisms: Aspergillus fumigatus, and Aspergillus flavus Ubiquitous fungus with world wide distribution in soil and on plants. In the body an environment, it exists in hyphal form (no yeast) Appears as: Flowering sporangium with V-shaped (acute angle) branching septate hyphae Transmission: Inhalation of spores. Low infectious dose. Diagnosis: Serology, culture, biopsy, and galactomannan (GM) test  Aspergillosis – Clinical manifestations Aspergillus primary affects the lungs causing: Allergic Bronchopulmonary Aspergillosis (ABPA) due to presence of conidia (and transient growth) in nasal cavity, paranasal sinuses, and lower respiratory tract. Chronic necrotizing pulmonary aspergillosis (CNPA) manifests as a pneumonia characterized by a non-invasive growth (colonization without extensions) in preformed cavities and debilitated tissues Invasive, inflammatory, granulomatous disease of lungs, and other organs in immunocompromised patients Systemic and fatal disseminated disease.  Mucormycosis (Zygomycosis) Fungal infection caused by species in the class of Zygomycetes: – Rhizopus spp. (most common) – Mucor spp. – Others include: Rhizomucor, Cunninghamella bertholletiae, and Lichtheimia (aka Absidia) Worldwide distribution, mainly affecting immunocompromised, granulocytopenic, and diabetics patients Primitive and fast growing. Among the most common bread mold Transmission primarily by inhalation of spore or less frequently via ingestions and skin inoculation Appears as: Non-septate hyphae with wide (broad) angle branches Non septate hyphae characterized by broad irregular walls with “right angle” branches  Mucormycosis – Clinical manifestations One-sided facial pain, swelling and numbness Headache, congestion, and fever Rhinocerebral Black lesions on nasal bridge or inside of the mouth disease May involves cranial nerves (V and VII) May lead to retinal artery thrombosis 🡪 Loss of vision More frequent among the diabetes patients (w/ketoacidosis) Fever Pulmonary disease Cough Chest pain Presents as cellulitis which progresses to dermal necrosis (black eschar) Cutaneous Pain, excessive redness, and swelling More frequent in patients with trauma, IVDU, insulin injection site Abdominal pain GI mucomycosis GI bleeding Disseminated Involves kidneys, bones, heart Treatment Amphotericin B, posaconazole High mortality  Pneumocystis jirovecii Formerly known as: Pneumocystis carinii A unicellular fungus found in the respiratory tracts of many mammals and humans. Infections due to reactivation or new exposure (most exposed by age 4) Pneumocystis organisms are communicable; airborne transmission has been reported. Exists in 3 forms: Gomori methenamine silver stain of bronchoalveolar lavage fluid – Trophozoite – haploid form developing into a cyst – Sporozoite – a precystic form – Cyst – containing several precystic forms – often seen in clinical samples Opportunistic infection affecting immunocompromised and AIDS patients A fungus or a protozoan? It was initially mistaken for a trypanosome and then later for a protozoan. In the 1980s, biochemical analysis of the nucleic acid composition of Pneumocystis rRNA and mitochondrial DNA identified the organism as a unicellular fungus rather than a protozoan  Pneumocystis jirovecii – Clinical manifestations Risk Factors CD4 count < 200 cells/μL (Most cases in patients with CD4 count < 100 cells/μL) Prior PCP infection Oral thrush Recurrent bacterial pneumonia HIV Clinical presentation Pneumonia with bilateral infiltrate (alveoli fill with foamy exudate containing the organism) Non productive cough, breathing difficulty on exertion, respiratory failure, cyanosis Death by asphyxia Extrapulmonary disease seen rarely Management Treatment: Trimethoprim/Sulfamethoxazole PO 100%mortality if untreated