Medical Microbiology: Mycology 2023 PDF

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2023

Karen Clatt, M. Ed., MLS(ASCP)

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medical microbiology mycology fungal infections pathogens

Summary

Medical microbiology lecture notes on Medical Mycology. Predisposing factors, examination methods, and detailed information on various fungal species are discussed, including Candida spp. Cryptococcus spp., Pneumocystis, Coccidioides, and Histoplasma.

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MEDICAL MICROBIOLOGY MYCOLOGY HS 4310 Karen Clatt, M. Ed., MLS(ASCP) GENERAL ▪ Predisposing factors: ▪ Immunosuppressive therapy ▪ Broad-spectrum antibiotics ▪ Long-term catheterization ▪ Radiation ▪ Disease ▪ Diabetes mellitus ▪ Neoplasm GENERAL ▪ Methods of examination ▪ Gra...

MEDICAL MICROBIOLOGY MYCOLOGY HS 4310 Karen Clatt, M. Ed., MLS(ASCP) GENERAL ▪ Predisposing factors: ▪ Immunosuppressive therapy ▪ Broad-spectrum antibiotics ▪ Long-term catheterization ▪ Radiation ▪ Disease ▪ Diabetes mellitus ▪ Neoplasm GENERAL ▪ Methods of examination ▪ Gram stain ▪ KOH ▪ Lactophenol cotton blue stain ▪ India ink stain EXAMINATION Gram Stain EXAMINATION ▪ KOH ▪ 10% to 20% KOH ▪ Allows visualization of yeast & hyphae ▪ Acts as a clearing agent EXAMINATION ▪ Lactophenol cotton blue ▪ Phenol: kills organisms ▪ Cotton blue: stains chitin & cellulose EXAMINATIONS ▪ India ink ▪ “Negative” stain ▪ Stain everything except capsule ▪ Used to diagnose cryptococcal meningitis YEAST YEAST ▪ Unicellular ▪ Reproduce by asexual fission ▪ Known as budding ▪ Colonies: ▪ Round, pasty, waxy looking YEAST ▪ 2 main genera/species: ▪ Candida spp ▪ Cryptococcus neoformans CANDIDA SPP. ▪ Most common opportunistic fungal pathogen ▪ 100+ species: ▪ C. albicans ▪ C. glabrata ▪ C. parapsilosis ▪ C. tropicalis ▪ C. krusei ▪ C. auris ▪ Resistance to fluconazole (90%), voriconazole (3-73%), amphotericin B (13-35%) CANDIDA SPP. ▪ Colonizer of: ▪ GI tract ▪ Skin ▪ Nails ▪ Vagina ▪ Urethra ▪ Oral cavity CANDIDA SPP. ▪ Pathogenesis ▪ Adherence to a variety of tissues and inanimate surfaces ▪ Yeast-to-hypha transformation ▪ Regulated by pH and/or temperature ▪ Germ tube ▪ Secreted enzymes ▪ Aspartyl proteinases hydrolyze host proteins ▪ Phospholipases damage host cells for invasion CANDIDA SPP. ▪ Thrush ▪ Yeast infection of oral cavity ▪ Thick, white patches on tongue, palate, or elsewhere ▪ May be red without white patches ▪ Painful ▪ May bleed, if wiped CANDIDA SPP. ▪ Genital ▪ Vaginal ▪ Thick, white discharge ▪ Cottage cheese appearance ▪ Itching and irritation in vagina and surrounding tissue ▪ Pain during sex or urination ▪ Penial ▪ May occur after sex ▪ Not considered STI ▪ Itching and burning of penis ▪ Skin rash CANDIDA SPP. ▪ Sepsis ▪ Occurs from gastrointestinal translocation ▪ Contaminated catheters ▪ Intravascular spread ▪ Invade deep tissues of liver, spleen, kidneys, heart, and brain CANDIDA SPP. ▪ Cutaneous rash ▪ Babies = diaper rash ▪ Adults = skin rash ▪ Armpits ▪ Skin folds ▪ Under breasts ▪ Nipple (breast feeding) CRYPTOCOCCUS SPP. ▪ 2 main species: ▪ C. neoformans ▪ C. gatti ▪ Encapsulated yeast ▪ Mainly occurs in immunocompromised hosts ▪ Host defense mainly: ▪ Alveolar macrophages ▪ Inflammatory phagocytic cells ▪ T- & B-cells CRYPTOCOCCUS SPP. ▪ Transmission ▪ Inhalation from ▪ Bird feces ▪ Soil ▪ Birds harbor Cryptococcus spp. ▪ Pigeons ▪ Canaries ▪ Parrots ▪ Cockatoos ▪ Parakeets ▪ Chickens ▪ Sparrows CRYPTOCOCCUS SPP. ▪ Host defense ▪ Alveolar macrophages ingest yeast cells ▪ Limited ability to kill ▪ Recruit neutrophils, monocytes, NK cells ▪ Complement system enhances immune response ▪ Impaired response allows disseminated infection ▪ Macrophages contain viable yeast cells ▪ Transports yeast from lung to lymphatics and blood ▪ Eventually lead to brain CRYPTOCOCCUS SPP. ▪ Pathogenesis ▪ Thick polysaccharide capsule ▪ Protects from phagocytosis and responding cytokines ▪ Suppresses cellular and humoral immunity ▪ Blocks opsonization from complement and antibodies ▪ Produces a negative charge, allowing repulsive effects from immune cells ▪ Melanin ▪ Produced via phenoloxidase enzyme ▪ Deposited on cell wall ▪ Enhances cell wall integrity ▪ Protects yeast from oxidative stress, temperature extremes, iron reduction, and microbicidal peptides CRYPTOCOCCUS SPP. ▪ Meningitis ▪ Mostly in immunocompromised patients ▪ 7-10% of AIDS patients ▪ 50% of all cases are in AIDS patients ▪ Mortality ranges: ▪ 9% to 15% in US ▪ 22% to 96% in other areas ”YEAST-LIKE” PNEUMOCYSTIS ▪ Originally classified as a protozoa ▪ DNA evidence classified it as fungus ▪ Pneumocystis carinii divided into 2 species ▪ P. carinii (rat variant, formerly human) ▪ P. jirovecii (human variant) PNEUMOCYSTIS ▪ Most seropositive between 2 to 4 years age ▪ Immunocompetent = asymptomatic infection ▪ Immunocompromised = symptomatic pneumonia ▪ AIDS ▪ Organ transplant or malignancies PNEUMOCYSTIS ▪ Symptoms ▪ Low-grade fever ▪ Non-productive cough ▪ Difficult breathing ▪ Normal chest radiographs or diffuse interstitial infiltrate PNEUMOCYSTIS ▪ Transmission ▪ Life cycle terminology = protozoan names ▪ Respiratory route ▪ Cyst = infective stage ▪ Asexual & Sexual reproduction DIMORPHIC MOLD-TO-YEAST COCCIDIOIDES C. immitis San Joaquin Valley fever C. posadasii Endemic to the Desert Southwest U.S. Northern Mexico South America COCCIDIOIDES ▪ Symptoms: ▪ Fatigue ▪ Cough ▪ Fever ▪ SOB ▪ Headache ▪ Night sweats ▪ Muscle aches ▪ Rash on upper body or legs COCCIDIOIDES ▪ Two cycles ▪ Saprophytic phase (mold) = soil ▪ Parasitic phase (yeast) = host ▪ Inhalation from soil ▪ Breaches respiratory barrier, enters blood and lymphatics, disseminates to other organs COCCIDIOIDES ▪ Pathogenesis ▪ Outer wall ▪ Prevents phagocytosis ▪ Molecular mimicry ▪ Produces protein similar structurally, antigenically, and function to host molecules ▪ Urease production ▪ Endospores phagocytosed by alveolar macrophages ▪ Viable endospores surrounded by ammonia ▪ Counteracts acidic environment in macrophages ▪ Extracellular proteinases ▪ Secreted enzymes allow invasive growth ▪ Permit ingress of skin and mucosal barriers, neutralization of host defense, transmigration of endothelial layers, and many more COCCIDIOIDES ▪ Diagnosis: ▪ EIA – Enzyme Immunoassay ▪ Culture ▪ Microscopy ▪ PCR HISTOPLASMA CAPSULATUM ▪ Disease known as: ▪ Histoplasmosis ▪ Reticuloendothelial cytomycosis ▪ Cave disease ▪ Spelunker’s disease ▪ Darling disease HISTOPLASMA CAPSULATUM ▪ Worldwide range ▪ U.S. endemicity: ▪ Ohio ▪ Missouri-Mississippi river delta ▪ Requires soil with high nitrogen content ▪ Bat and bird guano (poop) HISTOPLASMA CAPSULATUM ▪ Symptoms ▪ Fever ▪ Cough ▪ Fatigue ▪ Chills ▪ Headache ▪ Chest pain ▪ Body aches HISTOPLASMA CAPSULATUM ▪ Inhalation of microconidia ▪ Phagocytized by pulmonary macrophages ▪ Usually asymptomatic ▪ Heavy exposure = acute pulmonary disease ▪ Viable organism remain quiescent for years ▪ Immunocompromised = progressive disseminated disease HISTOPLASMA CAPSULATUM ▪ Pathogenesis ▪ pH modulation ▪ Yeast cause increase of pH in macrophages from 6.0 to 6.5 ▪ Above optimal range for lysosmal enzymes ▪ Prevents antigen processing ▪ Iron uptake ▪ Uses a siderophore to trap iron ▪ pH modulation is important for iron uptake ▪ pH >6.5 prevents iron uptake ▪ Calcium uptake ▪ Release calcium-binding protein (CBP1) into environment ▪ Prevents phagolysosome activity in macrophage HISTOPLASMA CAPSULATUM ▪ Pathogenesis ▪ Converts to yeast within hours of infection ▪ Phagocytes effective against conidia but not against yeast form ▪ Resistant towards neutrophils ▪ Macrophages can ingest but not kill HISTOPLASMA CAPSULATUM ▪ Host defense ▪ T cell-mediated immunity allows full recovery ▪ Faulty T cell immunity leads to progressive dissemination ▪ AIDS ▪ Immunosuppressive medication ▪ Malignancy HISTOPLASMA CAPSULATUM ▪ Diagnosis ▪ Antigen detection ▪ Antibody test ▪ Culture ▪ Microscopy ▪ PCR DERMATOPHYTES ▪ Trichophyton, Epidermophyton and Microsporum ▪ Keratinophilic – adapted to grow on hair, nails and skin ▪ Produce macroconidium and/or microconidium ▪ Helps with identification ▪ Cause our “tinea” infections ▪ Tinea corporis ▪ Tinea unguium ▪ Tinea capitis DERMATOPHYTES Copyright © 2023 by Elsevier Inc. All rights reserved ASPERGILLUS ▪ Ubiquitous in the environment ▪ In culture, must determine if a pathogen or contaminant ▪ Second most commonly isolated fungus after Candida species ▪ Aspergillus fumigatus is the most commonly seen species ▪ Transmission: Inhalation ▪ Conidia are constantly inhaled ▪ Immunocompetent clear conidia ▪ Immunocompromised – mortality is high Copyright © 2023 by Elsevier Inc. All rights reserved ASPERGILLUS ▪ Diseases ▪ Allergic reactions ▪ Sensitivities to molds ▪ Fungus balls in lungs of those with constant exposure with conidia ▪ Chronic pulmonary aspergillosis seen in patients with structural damage to the lungs Copyright © 2023 by Elsevier Inc. All rights reserved ASPERGILLUS ▪ Diseases ▪ Cause disease in bone marrow transplant recipients, other transplant recipients and those with cancer ▪ Disseminated infection ▪ Starts with inhalation of conidia -> become hyphae that invade tissue and blood vessels ▪ Infections spreads hematogenously → multiorgan system involvement (brain, liver, heart and bone) Copyright © 2023 by Elsevier Inc. All rights reserved THE END

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