Microbiology, virusology, immunology department Medical Mycology as. O.B. Kuchmak

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Transcript of Microbiology, virusology, immunology department Medical Mycology as. O.B. Kuchmak

  • Microbiology, virusology, immunology departmentMedical Mycologyas. O.B. Kuchmak

  • Medical MycologyTheseLectureStudentsThe Sea of Knowledge

  • Medical Mycology Outline

    Introduction, ActinomycetesYeasts, DermatophytesFilamentous Fungi, Dimorphic FungiDimorphic FungiOpportunistic Fungi

  • OBJECTIVESTo impart sufficient basic science of the medically important fungi to assist you in diagnosing mycotic diseases.To impart sufficient clinical knowledge to raise your index of suspicion for mycotic diseases.

  • What is a Fungus ?

    Eukaryotic a true nucleus Do not contain chlorophyll Have cell wallsProduce filamentous structuresProduce spores

  • ALL EUKARYOTIC CELLS CONTAIN STEROLSMammalian cells cholesterolFungal cells - ergosterol

  • SIZE COMPARISON OF PATHOGENS

    Cocci0.8 uBacilli4-6 uSpirochetes8 - 10 uViruses0.08 uProtozoa15 uNematodes10 mmFungi10 15 u

  • Species of Fungi

    100,000 200,000 species

    About 300 pathogenic for man

  • The taxonomy of the Kingdom Fungi is evolving and is controversial. Formerly based on gross and light microscopic morphology, studies of ultra structure, biochemistry and molecular biology provide new evidence on which to base taxonomic positions.

    Medically important fungi are in four phyla:

    Ascomycota - Sexual reproduction in a sack called an ascus with the production of ascopsporesBasidiomycota -Sexual reproduction in a sack called a basidium with the production of basidiospores Zygomycota - sexual reproduction by gametes and asexual reproduction with the formation of zygosporesMitosporic Fungi (Fungi Imperfecti) - no recognizable form of sexual reproduction. Includes most pathogenic fungi.

  • ClassificationASCOMYCOTA TrichophytonMicrosporumBlastomycesBASIDIOMYCOTA Cryptococcus neoformansDEUTEROMYCOTAEpidermophytonSporothrixCandida species ZYGOMYCOTA Rhizopus nigrans

  • Actinomyces(True Bacteria)TraditionClinical infection resembles mycosesActinomyces grow on mycotic mediaActinomyces grow slowly (24-48 h)Gross colonies resemble fungi(rough,heaped, short aerial filaments)Resemble mycelia microscopically, with branched mycelia in tissue and smears.

  • What is Medical Mycology ?

  • PATHOGENIC FUNGINORMAL HOSTSystemic pathogens - 25 speciesCutaneous pathogens- 33 speciesSubcutaneous pathogens - 10 species

    IMMUNOCOMPROMISED HOSTOpportunistic fungi - 300 species

  • MYCOTIC DISEASES(Four Types)HypersensitivityAllergyMycotoxicosisProduction of toxinMycetismus (mushroom poisoning)Pre-formed toxinInfection

  • Hypersensitivity Farmers lung Moldy hay

    Malt workers disease Moldy barley Cheese washers lung Moldy cheese

    Wood trimmers disease Moldy wood

  • PARASITIC STATEIncreased metabolic stateModified metabolic pathwaysModified cell wall structureCarbohydrate contentLipid structureRNA aggregates

  • PATHOGENICITY OF FUNGI

    Thermotolerance

    Ability to survive in tissue environment

    Ability to withstand host defenses

  • REVIVED INTEREST IN MYCOLOGY

    Increased frequency of mycotic diseasesIncreased awareness by physiciansBetter trained laboratory personnelMore invasive procedures used on patientsIncreased use of immunosuppressive drugsIncrease in immunosuppressive diseaseBetter laboratory diagnostic tools

  • EYESKINUROGENITAL TRACTANUSMOUTHRESPIRATORY TRACTPORTAL OF ENTRYSKINHAIR NAILSRESPIRATORY TRACTGASTROINTES-TINAL TRACTURINARY TRACT

  • EYESKINUROGENITAL TRACTANUSMOUTHRESPIRATORY TRACTCOLONIZATIONMultiplication of an organism at a given site without harm to the host

  • EYESKINUROGENITAL TRACTANUSMOUTHRESPIRATORY TRACTINFECTIONInvasion and multiplication of organisms in body tissue resulting in local cellular injury.

  • GEOGRAPHIC DISTRIBUTION The present ease and frequency of world-wide travel make it more likely that physicians in the United States will be confronted with a variety of unfamiliar mycoses acquired in distant parts of the country or of the world.

  • MORPHOLOGY

    Fungi exist in three morphologic form:

    1. Yeasts 2. Molds. 3. Dimorphs.

  • Pathogenic fungi can exist as yeasts or as hyphae (figure 4). A mass of hyphae is called mycelia. Yeasts are unicellular organisms and mycelia are multicellular filamentous structures, constituted by tubular cells with cell walls. The yeasts reproduce by budding. The mycelial forms branch and the pattern of branching is an aid to the morphological identification. If the mycelia do not have SEPTA, they are called coenocytic (nonseptate). The terms "hypha" and "mycelium" are frequently used interchangeably. Some fungi occur in both the yeast and mycelial forms. These are called dimorphic fungi.

  • Clinical Classification of MycosesCutaneousSubcutaneousSystemicOpportunistic

  • Cutaneous Mycoses

    Skin, hair and nailsRarely invade deeper tissue

    Dermatophytes

  • Subcutaneous MycosesConfined to subcutaneous tissue and rarely spread systemically. The causative agents are soil organisms introduced into the extremities by trauma

  • Systemic MycosesInvolve skin and deep viscera

    May become widely disseminated

    Predilection for specific organs

  • OPPORTUNISTIC FUNGI

    Ubiquitous saprophytes and occasional pathogens that invade the tissues of those patients who have:

    Predisposing diseases: Diabetes, cancer, leukemia, etc.Predisposing conditions: Agammaglobulinemia, steroid or antibiotic therapy.

  • MOST MYCOTIC AGENTS

    ARE SOIL SAPRPHYTESEPIDEMIOLOGY

  • Mycotic Diseases Are NOTContagious

  • 1. Wet Mount2. Skin test3. Serology4. Fluorescent antibody5. Biopsy and histopathology6. Culture7. DNA probesDIAGNOSIS

  • Diagnosis

    1. Wet Mount2. Skin test3. Serology4. Fluorescent antibody5. Biopsy and histopathology6. Culture7. DNA probes

  • DIRECT MICROSCOPIC OBSERVATION

    10 % KOH

    Gentle Heat

  • KOH Wet Mount

  • Diagnosis

    1. Wet Mount2. Skin test3. Serology4. Fluorescent antibody5. Biopsy and histopathology6. Culture7. DNA probes

  • SKIN TESTING(DERMAL HYPERSENSTIVITY)

    Use is limited to :

    Determine cellular defense mechanismsEpidemiologic studies

  • Diagnosis

    1. Wet Mount2. Skin test3. Serology4. Fluorescent antibody5. Biopsy and histopathology6. Culture7. DNA probes

  • FUNGI ARE POOR ANTIGENS

  • FUNGAL SEROLOGYANTIBODIESLatex AgglutinationIgM

    ImmunodiffusionIgG

    Complement FixationIgG

  • Most serological tests for fungi measure antibody. Newer tests to measure antigen are now being developedANTIGEN DETECTION PRESENTLY AVAILABLECryptococcosisAspergillosisHistoplasmosis

  • Diagnosis

    1. Wet Mount2. Skin test3. Serology4. Fluorescent antibody5. Biopsy and histopathology6. Culture7. DNA probes

  • DIRECT FLUORESCENT ANTIBODYCAN BE APPLIED TOHISTOLOGIC SECTIONSCULTURE

    Viable organismsNon-viable organisms

  • Diagnosis

    1. Wet Mount2. Skin test3. Serology4. Fluorescent antibody5. Biopsy and histopathology6. Culture7. DNA probe

  • INFLAMMATORY REACTIONNormal hostPyogenicGranulomatousImmunodeficient hostNecrosis

  • Polymorphic Nuclear Leukocytes

  • GMS

  • Diagnosis

    1. Wet Mount2. Skin test3. Serology4. Fluorescent antibody5. Biopsy and histopathology6. Culture7. DNA probes

  • ISOLATION MEDIASABOURAUD DEXTROSE AGAR(pH ~ 5.6)PlainWith antibioticsWith cycloheximide

  • INCUBATION TEMPERATURE

    37 C - Body temperature

    25 C - Room temperature

  • Diagnosis

    1. Wet Mount2. Skin test3. Serology4. Fluorescent antibody5. Biopsy and histopathology6. Culture7. DNA probes

  • DNA Probes

    Rapid (1 Hour)Species specificExpensive

  • TREATMENT

  • THERAPY

    Because they are eukaryotic, fungi are biochemically similar to the human host. Therefore it is difficult to develop chemotherapeutic agents that will destroy the invading fungus without harming the patient.

  • A BASIC TENET OF PATHOLGY IS:

    A CAUSE OF IRREVERSIBLE CELL INJURY IS CELL MEMBRANE DAMAGE.

  • IN FUNGAL THERAPY

    We attempt to induce cell injury by causing the cell membrane of the fungus to become permeable.

  • PROBLEM

    Finding an agent that will selectively injure fungal cell walls without damaging the host cell.

  • Cryptococcosis A sub-acute or chronic infection which may affect the lungs or skin but most commonly manifests as a meningitis

  • Cryptococcus neoformans

    Spherical5-10 micronsNarrow- baseSurrounded by polysaccharide capsule

  • Cryptococcus neoformansVirulence factorsAnti-phagocytic polysaccharide capsuleAntioxidant melaninAbility to grow at 37 C

  • Ecological NicheCryptococcus neoformans Pigeon droppings Chicken droppings

  • Cryptococcusportal of entry

    Inhalation

    inoculation

  • Typical clinical courseInhalationMild pneumoniaVision, lethargy, headacheDelirium, nuchal rigidity, comaOver a period of monthsDeath if not treated

  • Clinical SpecimensCryptococcosisCSFSputumPusBiopsy materialurine

  • Specimen of choice

    Cerebrospinal fluid

  • Serological TestsCryptococcosis Indirect fluorescent antibody Tube Ag