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1 Mycology Dental / Optometry Fundamentals II Stephen A. Moser, Ph.D. Stephen A. Moser, Ph.D.10/26/2011.

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Presentation on theme: "1 Mycology Dental / Optometry Fundamentals II Stephen A. Moser, Ph.D. Stephen A. Moser, Ph.D.10/26/2011."— Presentation transcript:

1 1 Mycology Dental / Optometry Fundamentals II Stephen A. Moser, Ph.D. Stephen A. Moser, Ph.D.10/26/2011

2 2 Epidemiology  Geography Endemic mycoses Endemic mycoses Worldwide mycoses Worldwide mycoses  Transmission of infection Respiratory inhalation (systemic mycoses) Respiratory inhalation (systemic mycoses) Cutaneous inoculation (sporotrichosis) Cutaneous inoculation (sporotrichosis) Systemic invasion by opportunistic normal flora (candidiasis) Systemic invasion by opportunistic normal flora (candidiasis) Contact with infected hosts (dermatophytoses) Contact with infected hosts (dermatophytoses)

3 3 Epidemiology (Cont.)  Risk factors and manifestations of disease True pathogens versus opportunists True pathogens versus opportunists Environmental risk factors for systemic fungal disease Environmental risk factors for systemic fungal disease Location and travelLocation and travel OccupationOccupation Host defenses and susceptibility to systemic fungal disease (CMI most important) Host defenses and susceptibility to systemic fungal disease (CMI most important) Congenital and acquired T cell deficiencies (including AIDS)Congenital and acquired T cell deficiencies (including AIDS) Immunosuppression (transplants and malignancies)Immunosuppression (transplants and malignancies) Diabetes mellitusDiabetes mellitus

4 4 Endemic Distribution for Blastomycosis

5 5 General Characteristics  Aerobic - obligate or facultative  Eukaryotic: membrane bound nucleus and cytoplasmic organelles (may be multinucleate)  Achlorophyllous  Morphology (unicellular or multicellular)  Saprophytic (heterotrophic)

6 6 Characteristics of Fungal Cells Cell wall: multilayered polysaccharide Cell wall: multilayered polysaccharide  Cellulose, glucans, mannans, chitin, polypeptides  Absence of teichoic acids, peptidoglycan, LPS Cell membrane Cell membrane  Phospholipid bilayer  Ergosterol (relate to chemotherapy) Cytoplasm - typical eukaryotic organelles Cytoplasm - typical eukaryotic organelles Nucleus - either uninucleate or multinucleate Nucleus - either uninucleate or multinucleate

7 7 Characteristics of Fungal Cells Capsule Capsule  Present in some species (e.G. Cryptococcus neoformans)  Amorphous polysaccharide coating  Functions and activities  Antiphagocytic  Antigenic

8 8 Growth forms Growth forms  Yeast - unicellular fungi which reproduce by budding (Cryptococcus)  Mold - hyphae (mycelium)  Septate hyphae ( Aspergillus)  Non-septate, coenocytic hyphae (Mucor)  Pseudohyphae ( Candida albicans)  Thermal dimorphism Characteristics of Fungal Cells

9 9 Differences Between Bacteria and Fungi

10 10 Examples of Yeast & Pseudohyphae Pseudohypha Blastoconidia

11 11 Blastomyces dermatitidis Thermal Dimorphism

12 12 Example of True Septate Hyphae

13 13 Non-septate Hyphae

14 14 Asexual Reproduction  Conidia (spores) – asexual structures Blastospores – formed by budding yeasts (Blastomyces) Blastospores – formed by budding yeasts (Blastomyces) Chlamydospores – terminal or intercalary cells with thick walls (Candida albicans) Chlamydospores – terminal or intercalary cells with thick walls (Candida albicans) Arthrospores – formed by fragmentation of hyphae (Coccidioides immitis) Arthrospores – formed by fragmentation of hyphae (Coccidioides immitis) Sproangiospores – formed in sporangia by cleavage (Rhizopus) Sproangiospores – formed in sporangia by cleavage (Rhizopus)

15 15 Classification Based on Sexual Phase  Ascomycetes: Aspergillus, Histoplasma, Blastomyces, Dermatophytes  Basidiomycetes: Cryptococcus, Mushrooms  Zygomycetes: Order Mucorales - Mucor, Rhizopus  Deuteromycetes (Fungi Imperfecti): Sporothrix, Coccidioides, Candida

16 16 Clinical Types of Fungal Infections

17 17 Routes of Infection  Inhalation of spores – major factor  Inoculation of spores into skin  Disease by normal flora in compromised host (Candida)  Hypersensitivity  Contact with infected host (Dermatophytes)  Mycotoxins

18 18 Laboratory Diagnosis of Fungal Infections  Microscopic Examination of tissues and body fluids Gram stain Gram stain Giemsa Giemsa India Ink India Ink Potassium hydroxide (KOH) wet prep Potassium hydroxide (KOH) wet prep Hematoxylin and Eosin stain Hematoxylin and Eosin stain Periodic-Acid Schiff stain (PAS) Periodic-Acid Schiff stain (PAS) Gomori-Methenamine Silver stain (GMS) Gomori-Methenamine Silver stain (GMS) Mucicarmine or Alcian Blue stain Mucicarmine or Alcian Blue stain

19 19 Budding Yeast - Gram Stain Staphylococcus Candida

20 20 Encapsulated Yeast - India Ink

21 21 KOH Prep - Broad-base Budding Yeast

22 22 H&E Stain - Budding Yeasts

23 23 GMS Stain - Septate Hyphae

24 24 Mucicarmine Stain - C. neoformans

25 25 Histopathological Response to Fungal Infection  Acute pyogenic abscess (Candida)  Chronic granuloma formation (Histoplasma)  Chronic, localized dermal inflammation (Dermatophytes)  Mixed pyogenic and granulomatous inflammation (Blastomyces)  Blood vessel invasion with thrombosis and infarction (Mucor, Aspergillus)  Hypersensitivity without tissue reaction (allergic bronchopulmonary aspergillosis)

26 26 Fungal Cultures  Utilize Sabouraud agar with antibiotics  Identification criteria Temperature of growth Temperature of growth Rate of growth Rate of growth Colonial and microscopic morphology Colonial and microscopic morphology Sporulation pattern Sporulation pattern Biochemical reactions (yeast) Biochemical reactions (yeast)

27 27 Fungal Serology  Generally poor and not as useful as in other pathogens such as viruses and bacteria, with some exceptions.  Cryptococcal antigen by latex agglutination: serum and CSF.  Coccidioides - early IgM response is useful for identification of acute primary disease - CSF IgG prognostic value.  Skin tests for DTH - problems: Cross-reactivity. Cross-reactivity. High positive rate in endemic areas. High positive rate in endemic areas.

28 28 Candidiasis  Clinical manifestations Mucosal Mucosal VaginitisVaginitis EsophagitisEsophagitis Oral thrushOral thrush Cutaneous Cutaneous Chronic mucocutaneous Chronic mucocutaneous Systemic Systemic FungemiaFungemia Hepato-spleenicHepato-spleenic EndophthalmitisEndophthalmitis RenalRenal Urinary tract Urinary tract

29 Oral Candidiasis 29

30 30 Wet Mount - Candidiasis

31 31 Mucocutaneous Candidiasis

32 32 Candida sp. Tissue GMS Stain

33 33 Aspergillosis  Clinical manifestations Pneumonia Pneumonia Aspergilloma Aspergilloma Allergic bronchopulmonary Allergic bronchopulmonary Disseminated multiorgan involvement Disseminated multiorgan involvement

34 34 Aspergilloma

35 35 Allergic Bronchopulmonary Aspergillosis

36 36 CNS Aspergillosis

37 37 Aspergillus sp – GMS Stain

38 38 Zygomycosis  Clinical manifestations Sinusitis Sinusitis Rhinocerebral Rhinocerebral Pulmonary Pulmonary Renal Renal

39 39 Rhinocerebral Mucormycosis in Diabetic Ketoacidosis

40 40 Postmortem – Rhinocerebral Mucormycosis

41 41 Non-septate Branching Hyphae (PAS)

42 42 Histoplasmosis  Clinical manifestations Most cases mild or sub-clinical pulmonary disease Most cases mild or sub-clinical pulmonary disease Dissemination appears to be commonDissemination appears to be common Pneumonia Pneumonia Chronic progressive pulmonary (cavitary) Chronic progressive pulmonary (cavitary) Histoplasmoma Histoplasmoma Disseminated Disseminated

43 43 Histoplasmosis – Calcified Lesions

44 44 Histoplasmosis- GMS

45 45 Histoplasmosis – Bone Marrow Histiocyte H. capsulatum

46 46 Histoplasma capsulatum In vitroIn vivo

47 Presumed Ocular Histoplasmosis  Thought to be a late stage of primary histoplasmosis.  Causes abnormal blood vessels – scar tissue.  Organism has not been found in eye.  Treated with laser surgery. 47

48 Risk Factors for Endogenous Endophthalmitis 48 Candidia species Central venous lines, neutropenia, abdominal surgery, intravenous drug abuse, broad-spectrum antibiotics Aspergillus species Neutropenia, endocarditis, intravenous drug abuse, pulmonary disease being treated with high dose steroids, organ and stem cell transplant. H. capsulatum C. immitis B. dermatitidis C. neoformans May accompany disseminated disease Fusarium speciesNeutopenia, intravenous drug abuse

49 49 Fungal Keratitis

50 50 Chemotherapy  FDA approved Polyenes (Amphotericin B, lipid encapsulated forms) Polyenes (Amphotericin B, lipid encapsulated forms) Azoles (fluconazole, itraconazole, ketoconazole, voriconazole) Azoles (fluconazole, itraconazole, ketoconazole, voriconazole) Echinocandin (Caspofungin, Micafungin, Anidulafungin) Echinocandin (Caspofungin, Micafungin, Anidulafungin) Nucleoside derivatives (5-flurocytosine) Nucleoside derivatives (5-flurocytosine) Allyamines (Terbinafine) Allyamines (Terbinafine) Microtubule disruption (Griseofulvin) Microtubule disruption (Griseofulvin)  Investigational Nikkomycins (chitin synthase inhibitors) Nikkomycins (chitin synthase inhibitors) Echinocandin/pnemocandin/lipopeptide class (inhibit glycan synthesis) Echinocandin/pnemocandin/lipopeptide class (inhibit glycan synthesis)

51 51 Antifungal Drugs for Systemic Mycoses - Amphotericin B  Mode of Action Binds to ergosterol, increases membrane permeability resulting in leakage of cytoplasmic components and cell death – Fungicidal Binds to ergosterol, increases membrane permeability resulting in leakage of cytoplasmic components and cell death – Fungicidal  Spectrum of Activity Candida, Crypto, Aspergillus, Histo, Blasto, Cocci, etc Candida, Crypto, Aspergillus, Histo, Blasto, Cocci, etc  Limitations Nephrotoxicity Nephrotoxicity

52 52 Antifungal Drugs for Systemic Mycoses - Fluconazole  Mode of Action Prevents ergosterol synthesis by inhibiting the C-14 demethylation step (cytochrome P-450 rx) Prevents ergosterol synthesis by inhibiting the C-14 demethylation step (cytochrome P-450 rx) Fungistatic Fungistatic  Spectrum of Activity Candida, Crypto, Trichsporonosis, dermatophytes Candida, Crypto, Trichsporonosis, dermatophytes  Limitations Resistance in some Candida sp – krusei and glabrata Resistance in some Candida sp – krusei and glabrata Not effective for non-dermatophyte moulds. Not effective for non-dermatophyte moulds.

53 53 Antifungal Drugs for Systemic Mycoses -Echinocandins  Mode of Action Prevents synthesis of beta 1,3-glucan required for cell wall. Prevents synthesis of beta 1,3-glucan required for cell wall. Fungistatic Fungistatic  Spectrum of activity Aspergillus, Candida Aspergillus, Candida NOT effective against Cryptococcus, zygomycetes. NOT effective against Cryptococcus, zygomycetes.

54 54 Early Diagnosis of Invasive Fungal Infections Obstacles Because of Immunosuppression typical signs and symptoms of infection are frequently absent Because of Immunosuppression typical signs and symptoms of infection are frequently absent Few clinical features are uniquely specific for systemic fungal infection Few clinical features are uniquely specific for systemic fungal infection Sputum and blood cultures are frequently negative Sputum and blood cultures are frequently negative Invasive procedures Invasive procedures – May be necessary for definitive diagnosis – Are often complicated in severely immunocompromised patient

55 55 Early Diagnosis of Invasive Fungal Infections (Continued) Benefits  Early diagnosis permits selection of a therapy of maximal effectiveness  Early intervention with antifungal therapy may help decrease the high mortality rate associated with serious systemic mycoses

56 Major Areas Covered  How fungi differ from bacteria  The major fungal infections  The epidemiology of fungal infections  Pathology of fungal infections  Mechanism of action of antifungal agents 56


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