1. Introduction to Medical Mycology

2. Medical Mycology
Medical mycology is the study of mycoses of man and their eitiologic agents .It is an integral part of general mycology as well as an important specialty in medicine.
The mycoses are disease caused by fungi. fungal invasion of human tissue was recognized in the early 1800s before the science of bacteriology was developed.

3. What is a Fungus ? Eukaryotic – a true nucleus
Do not contain chlorophyll
Have cell walls
Produce filamentous structures
Produce spores

4. Kingdom Fungi Eukaryocytes
Ascomycota
Basidiomycota
Zygomycota
Mitosporic Fungi
(Fungi Imperfecti)

5. MYCOTIC DISEASES (Four Types)
Hypersensitivity
Allergy
Mycotoxicosis
Production of toxin
Mycetismus (mushroom poisoning)
Pre-formed toxin
Infection

6. PATHOGENIC FUNGI NORMAL HOST IMMUNOCOMPROMISED HOST
Systemic pathogens - 25 species
Cutaneous pathogens - 33 species
Subcutaneous pathogens - 10 species
IMMUNOCOMPROMISED HOST
Opportunistic fungi species

7. PATHOGENICITY OF FUNGI
Thermotolerance
Ability to survive in tissue environment
Ability to withstand host defenses

9. MORPHOLGY Yeasts Hyphae (filamentous fungi, mycelium) Dimorphic
Septate
Coenocytic (non-septate)
Dimorphic
Yeast
Mycelium

10. Budding Yeast/Germ Tubes

11. Hyphae Tubular Hard wall of chitin
Cross walls may form compartments (± cells)
Multinucleate
Grow at tips
Chitin is the same material used by Arthropods (Insects, crabs, etc.) in their exoskeletonsa
Nuclei of fungi are hard to see without stains

13. Dimorphic Fungi Yeast Form Mycelial Form Parasitic form Tissue form
Cultured at 37 C
Mycelial Form
Saprophytic form
Cultured at 25 C

14. Dimorphic nature of true fungal pathogens
Figure 22.2

15. SPORES ASEXUAL Arthrospore Blastospore Chamydospore Conidia
Microconidia
Macroconidia

16. Asexual Spores
Chlamydospore - thick-walled asexual spore formed by direct differentiation of the mycelium (concentration of protoplasm and nutrients).
Sporangiospore - an asexual spore contained in a sporangium at the end of a sporangoiphore.

17. Sexual spores - exhibit fusion of nuclei.
Ascospore - spore formed in a sac-like cell known as an ascus. Often eight (8) spores formed. (Ascomycetes)
Basidiospore - sexual spore produced on a specialized club-shaped structure, called a basidium. (Basidiomycetes)
Zygospore - a thick-walled spore formed during sexual reproduction (Phycomycetes)

18. Sexual spores

20. Miscellanous terms:
Conidiophore - a specialized branch of hypha on which conidia are developed.
Dematiaceous - pigmented, dark in color, usually gray to black
Sterigmata - a specialized structure that arises from a basidium and supports basidiospores .

22. Miscellanous terms: (continued)
Pseudohyphae - a chain of elongated budding cells that have failed to detach (not true hyphae).
Rhizoids - root-like structures.
Sporangiophore - a special aerial hypha or stalk bearing a sporangium.
Sporangium - a sac or cell containing spores produced asexually.

25. Immunology of Mycosis Antibody mediated immunity (B-cell, humoral)
Antibodies are often produced in response to a fungal infection, but do not confer immunity.
Serological tests for identification of fungal diseases detect these antibodies.
Cellular mediated immunity (T-cell)
T-cell immunity is effective in resistance to fungal infections.

26. Classifications of Fungi
Geographic grouping - where they exist.
Epidemiologic grouping - how organism is transmitted.
Taxonomy grouping - according to morphologic and cultural characteristics.
Topographic Grouping - type of mycosis produced.

27. EPIDEMIOLOGY MOST MYCOTIC AGENTS ARE SOIL SAPRPHYTES
Mycotic Diseases Are NOT Contagious

28. ESTABLISHMENT OF INFECTION WITH A MYCOTIC AGENT DEPENDS ON
Inoculum size
Resistance of the host , rather than virulence of fungus

29. Topographic Grouping of Fungi
most often used
Superficial - Confined to the outer most layers of the skin and hair. No host cellular or inflammatory response due to organisms being remote from living tissue. Essentially no pathology; the disease is recognized purely on cosmetic basis.
Cutaneous - in the keratin of the skin, nails, and hair. These organisms prefer non-living cornified layers. The disease is called a dermatophytosis or dermatomycosis. Host response is patchy scaling or eczema eruptions. They are classified according to the area of the body that is involved.

30. Topographic Grouping of Fungi: (continued)
Subcutaneous - Involve the deeper layers of skin and often muscle tissue. Man is an accidental host following inoculation of fungal spores via some form of trauma. This type of infection is often identified by the presence of a characteristic tissue reaction or granule.
Systemic - Attack the deep tissues and organ systems; often creating symptoms that resemble other diseases.

31. Categories of systemic disease:
Those caused by truly pathogenic fungi with the ability to cause disease in the normal human host when the inoculum is of sufficient size (Histoplasma capsulatum, Blastomyces dermatitidis, Coccidioides immitis, Paracoccidioides braziliensis).
Those caused by opportunistic fungi, low virulence organisms, which require the patient's defenses to be lowered before the infection is established (Aspergillus spp. Candida albicans, Cryptococcus neoformans).

32. COLONIZATION
MOUTH
RESPIRATORY TRACT
EYE
Multiplication of an organism at a given site without harm to the host
SKIN
UROGENITAL TRACT
ANUS

33. INFECTION
MOUTH
RESPIRATORY TRACT
EYE
Invasion and multiplication of organisms in body tissue resulting in local cellular injury.
SKIN
UROGENITAL TRACT
ANUS

34. Diagnosis 1. Wet Mount (KOH) 2. Skin test (dermal hypersensitivity) 3
Diagnosis 1. Wet Mount (KOH) 2. Skin test (dermal hypersensitivity) 3. Serology (Latex agglutination , Complement fixation ….) 4. Fluorescent antibody 5. Biopsy and histopathology(pyogenic , granulomatous ,or necrotic) 6. Culture (Sabouraud dextrose agar) 7. DNA probes

35. KOH Wet Mount

38. ISOLATION MEDIA(culture)
SABOURAUD DEXTROSE AGAR
(pH ~ 5.6)
Plain
With antibiotics
With cycloheximide

39. INCUBATION TEMPERATURE
37 C - Body temperature
25 C - Room temperature

40. DNA Probes
Rapid (1-2 Hours)
Species specific
Expensive

41. 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.

42. IN FUNGAL THERAPY
We attempt to induce cell injury by causing the cell membrane of the fungus to become permeable.

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

44. ALL EUKARYOTIC CELLS CONTAIN STEROLS
Mammalian cells – cholesterol
Fungal cells - ergosterol

46. PRIMARY ANTI-FUNGAL AGENTS
Polyene derivatives
Amphotericin B
Nystatin
Azoles
Ketoconazole
Fluconazole
Itraconazole
Voriconazole
Posaconazole

47. PRIMARY ANTI-FUNGAL AGENTS
3. Griseofulvin
4. 5-fluorocytosine (5-FC)
5. Allylamines
-Terbinafine (Lamasil)
6. Echinocandins
- Caspofungin

48. AMPHOTERICIN B Mechanism of Action
Amphotericin B binds to sterols
Ergosterol is a constituent of the fungal cell wall
AMB has a greater avidity for ergosterol than for the cholesterol in the human cell wall
Binding to the fungal cell wall alters the permeability and the intracellular contents leak

49. AMPHOTERICIN B Disadvantages
Intravenous administration
Thrombophlebitis
Nephrotoxic
Fever
Chills
Anemia
Long term administration

50. Azoles
There are a few rare serious side effects from Itraconazole and Fluconazole

51. Griseofulvin
A slow acting drug used for skin and nail infections. It accumulates in the stratum corneum and prevent hyphal penetration through these layers

52. 5-fluorocytosine (5-FC)
Interferes With RNA Synthesis

53. MECHANISMS OF ACTION Polyenes Azoles Griseofulvin 5 - FC
Ergosterol in cell membrane
Interfere with ergosterol synthesis
Forms a barrier to fungal growth
Inhibits RNA synthesis

54. End of
Introduction