1. BASIC MYCOLOGY STRUCTURE & GROWTH @ 2 fungal cell structures :
(1) Fungal cell wall consists of chitin:
thus insensitive to antibiotics .
(2) Fungal cell membrane contains
sterols: thus selective to
amphotericin B & azole drugs,

2. @ 2 types of fungi:
yeasts and molds.
@ Yeasts grow as single cells & reproduce by asexual budding.
@ Molds grow as long filaments (hyphae) & form a mat (mycelium),
@ Some hyphae form transverse walls (septate hyphae),
@ Others non-septate, & multinucleated

3. @ Several medically important fungi are thermally dimorphic; ie, they form different structures at different temperatures.
@ They exist as molds in the saprophytic, free-living state at room temp. & as yeasts in host tissues at body temp.

4. @ Most fungi :. obligate aerobes;. some are facultative anaerobes;
@ Most fungi : * obligate aerobes; * some are facultative anaerobes; * none are obligate anaerobes.
@ Fungi require a preformed organic source of carbon, hence associated with decaying matter.
@ Natural habitat of fungi is the environment. * An exception is C. albicans - part of normal flora.

5. @ Some fungi reproduce by sexual mating & forming sexual spores, eg, zygospores, ascospores, & basidiospores
Zygospores: single large spores with thick walls;
Ascospores: formed in sac called ascus
Basidiospores: formed externally on tip of a pedestal called a basidium.
@ Fungi not forming sexual spores are classified as Fungi Imperfecti.

6. @ Fungi propagate asexually forming conidia (asexual spores)
@ Some important conidia are :
(I) arthrospores: arise by fragmentation of ends of hyphae
(2) chlamydospores: rounded, thick, resistant ;
(3) blastospores: formed by budding (yeasts)
(4) sporangiospores: formed within a sac (sporangium) on a stalk .

7. @ Fungi are used in production of bread, cheese, wine, and beer.
@ Because molds grow in a drier, more acidic, & higher osmotic pressure environment than bacteria, they are involved in spoilage of fruits, grains, vegetables, and jams.

8. @ Fungal infections form granulomas:
PATHOGENESIS
@ Fungal infections form granulomas:
histoplasmosis, and blastomycosis .
@ Cell-mediated immune response is involved in granuloma formation.
@ Acute suppuration occurs in aspergillosis & sporotrichosis.
@ Fungi have no endotoxin in their cell walls and do not produce exotoxins.

9. @ A cell-mediated positive skin test indicates exposure to the fungal antigen.
@ It does not imply current infection, because exposure may have occurred in the past.
@ A negative skin test makes diagnosis unlikely unless the patient is immunocompro­mised.

10. @ Intact skin is a host defense against Candida,& dermatophytes .
@ Fatty acids in skin inhibit dermatophyte growth, & hormone-associated skin changes at puberty limit ringworm of scalp.
@ Normal flora of skin & mucous membranes suppress fungi.
@ If normal flora inhibited (antibiotics) overgrowth of C. albicans occurs.

11. @ In respiratory tract, host defenses are mucous membranes of nasopharynx and alveolar macrophages.
@ IgG & IgM are produced during infection, have no role in protection .
@ Cell-­mediated immunity is protective & its suppression leads to opportunistic fungal infections .

12. FUNGAL TOXINS & ALLERGIES
There are 3 kinds of fungal disease:
mycotoxicoses, caused by ingested toxins,
allergies to fungal spores.
3. Mycotic infections

13. Mycotoxicosis Eating mushrooms:
These fungi produce five toxins, two of them are hepatotoxic .
2. Ergotism: caused by molds which infect grains & produces ergotamine & lysergic acid diethylamide [LSD]) that cause vascular & neurologic effects.
3. Aftatoxins: produced by Aspergillus flavus, causes liver damage & hepatic carcinoma
* Aflatoxins are ingested with spoiled grains & peanuts

14. Allergies to fungal spores,
Spores of Aspergillus cause asthma, characterized by :
bronchoconstriction (mediated by IgE), eosinophilia, and a positive skin test reaction.

15. LABORATORY DIAGNOSIS
4 methods for diagnosis :
(I) direct microscopy ,
(2) culture of organism,
(3) DNA probe tests,
(4) serologic tests.

16. Direct microscopy depends on finding asexual spores, hyphae, or yeasts in light microscope.
@ Specimen is either treated with 10% KOH to dissolve tissue material, or stained with special fungal stains. Examples are :
* capsule of Cr. neoformans in India ink .
@ Calciflor white is a fluorescent dye that binds to fungal cell walls & used to identify fungi in tissue specimens.

17. 2 DNA probes tests : identify colonies in culture before seen visually .
Hence diagnosis is made more rapidly.
@ DNA probe tests are used for Histoplasma, Blastomyces, and Cryptococcus.

18. 3. Culture: on Sabouraud's agar, inhibits bacterial growth by its low pH & added chloramphenicol & cycloheximide
@ Mycelium and asexual spores are sufficient to identify the organism.

19. 4. Serology is useful in diagnosing systemic mycoses .
@ A significant rise in antibody titer must confirm diagnosis.
@ C.F.T. is used in histoplasmosis, & blastomycosis.
@ Latex agglutination test is used in cryptococcal meningitis.

20. ANTIFUNGAL THERAPY
@ Drugs include amphotericin B and the azoles.
@ There is no clinically significant resistance to antifungal drugs.

21. Mycoses Divided into four categories: (I) cutaneous, (2) subcutaneous,
(3) systemic,
(4) opportunistic.

22. CUTANEOUS MYCOSES Dermatophytoses :
@ Caused by dermatophytes that infect skin, hair, and nails, not deeper tissues.
@ Classified into 3 genera :
* Epidermophyton, * Trichophyton,
* Microsporum.
@ Spread by direct contact .
* Microsporum also spreads by dogs &
cats.

23. @ Dermatophytoses (tinea, ringworm) infections favored by heat & humidity, eg, t.pedis & t.cruris .
@ Characterized by itchy papules, vesicles, broken hairs, and thickened nails.

24. @ Trichophyton tonsurans causes tinea capitis in children & endothrix (inside the hair) infections.
@ T. rubrum & T. schoenleinii also cause tinea capitis.

25. @ Tinea infections show positive skin tests with fungal extracts( trichophytin ).
@ Scrapings of skin or nail show hyphae under microscopy.
@ Culture on Sabouraud's agar at room temp. shows hyphae and conidia.
@ Tinea capitis caused by Microsporum detected by seeing fluorescence when exposed to UV light from a Wood's lamp.
@ Treatment: local antifungal creams
@ Prevention: keep skin dry and cool.

26. Tinea Versicolor:
@ Called pityriasis versicolor , & caused by Malassezia furfur.
@ Lesions are hypopigmented, scaly, itchy, & usually asymptomatic.
@ It occurs frequently in hot, humid weather.
@ Lesions contain both budding yeast & hyphae
@ Diagnosis is made by observing this mixture in skin scrapings. Culture is not usually done.
@ Treatment: topical miconazole, but permanent cure is difficult .

27. Tinea Nigra : @ Appears as a brownish spot on skin
@ Caused by Cladosporium wemeckii, & found in soil, transmitted on injury.
@ Diagnosis is by microscopy & culture of skin scrapings.
@ Treatment: topical salicylic acid.

28. SUBCUTANEOUS MYCOSES Sporotrichosis:
@ Cause: fungi of soil & vegetation, by trauma.
Sporotrichosis:
@ Cause: Sporothrix schellckii – dimorphic.
@ Causes a pustule, ulcer, nodules .
@ Microscopy: round or cigar-shaped budding
@ Culture: hyphae with conidia .
@ Treatment: itraconazole or potassium iodide.
@ Prevention: skin not touching plants, wood. .

29. Chromomycosis:
@ A granulomatous infection producing melanin-like pigments.
@ They are wart-like lesions with abscesses extending along lymphatics.
@ Found on bare feet and legs.
@ Laboratory: dark brown, round cells inside leukocytes or giant cells.
@ Treatment: flucytosine, thiabendazole, plus local surgery.

30. Mycetoma:
@ Soil fugus (Madurella) enters through wounds on feet, hands, or back
@ Cause abscesses, pus, sinuses.
@ Pus contains compact colored granules.
@ Nocardia cause actinomycotic mycetoma
@ Sulfonamides treat actinomycotic mycetoma .
@ Madurella treated by surgery .

31. Systemic Mycoses
@ Result from inhalation of spores of dimorphic fungi that have their saprophytic mold forms in soil.
@ Within lungs, spores form yeasts .
@ Most lung infections are asymptomatic and self-limited.

32. HISTOPLASMA @ H. capsulatum causes histoplasmosis.
Properties:
@ Dimorphic, 2 types of asexual spores :
(1) tuberculate macroconidia, with thick walls and fingerlike projections ,
(2) micro­conidia, smaller, thin, smooth-walled spores .

33. Transmission & Epidemiology:
@ Occurs in many parts of the world, & grows in soil heavily contaminated with bird droppings
@ Birds are not infected,
@ Bats are infected & can excrete organism .

34. Pathogenesis & Clinical Findings:
@ Inhaled spores are engulfed by macrophages and develop into yeast forms.
@ In tissues, H capsulatum occurs as budding yeast inside macrophages .
@ Organisms spread to liver and spleen, but most infections are asymptomatic
@ Some develop calcified granuloma, pneumonia
@ Severe disseminated histoplasmosis develops in infants & AIDS patients ( ulcers on tongue ).

35. Laboratory Diagnosis:
@ Microscopy: In tissue biopsy & bone marrow , yeast cells within macrophages.
@ Culture : show hyphae with tuberculate macroconidia.
@ Detect Histoplama antigens by RIA
@ Detect Histoplasma RNA with DNA probes .
@ 2 serologic tests are used for diagnosis:
* CFT and immunodiffusion (ID) test.
@ A titer of 1:32 in CFT is diagnostic .
@ ID test detects precipitating antibodies (precipitins) by agar-gel diffusion assay.
* ID test is more specific but less sensitive than CFT .

36. @ A skin histoplasmin test is positive within 2-3 weeks & remains positive for many years.
@ Because of false reactions , skin test is not useful for diagnosis.
@ Skin test also stimulates an antibody response & confuse the serological tests.
@ Skin test is useful for epidemiologic studies, and up to 90% of people are positive in endemic areas .

37. Treatment & Prevention:
@ No therapy is needed in asymptomatic or mild primary infections.
@ With progressive lung lesions, oral itraconazole is beneficial.
@ Disseminated disease : amphotericin B
@ In meningitis, fluconazole is used .
@ Itraconazole: for patients with AIDS.
@ Prevention: avoid infection exposure .

38. Opportunistic Mycoses
@ Fail to induce disease in most normal persons but may do so in those with impaired host defenses.

39. CANDIDA
@ C. albicans causes thrush, vaginitis, and chronic mucocutaneous candidiasis, as well as other diseases.
Properties: C albicans is an oval yeast with a single bud, & part of normal flora of URT, GIT and female genital tracts.
@ In tissues appears as yeasts or as pseudohyphae - not true hyphae.
@ Sugar fermentation differentiate it from C. tropicalis, C. krusei, and Torulopsis glabrata.

40. Transmission :
As a member of normal flora, it is not transmitted.
Pathogenesis & Clinical Findings:
C. albicans produces:
* In mouth : white patches (thrush).
* Vulvo-vaginitis with itching & discharge,
favored by high pH, diabetes, or antibiotics.
* Fingers & nails are involved when repeatedly
immersed in water .
* In immunosuppressed, Candida disseminates .
* IV drug abuse causes disseminated candidiasis,
giving right-sided endocarditis.

41. Laboratory Diagnosis:
@ In exudates or tissues, budding yeasts and pseudo hyphae are seen microscopically.
@ Such specimens grow typical yeasts when cultured.
@ Germ tubes form in serum at 37ºC, distinguish C. albicans from most other Candida species .
@ Chlamydospores are formed by C albicans only .
@ Serologic testing is rarely helpful.
@ Skin tests are positive in normal adults & used as an indicator of good cellular immunity.
@ A person who does not respond to Candida antigens in skin test has deficient cell-mediated immunity.

42. Treatment & Prevention:
@ Oropharyngeal thrush: give fluconazole
@ Skin infections: give topical nystatin.
@ Mucocutaneous candidiasis:
ketoconazole
@ Disseminated candidiasis: give either amphotericin B or fluconazole.
@ Thrush is prevented by clotrimazole or nystatin . There is no vaccine.

43. CRYPTOCOCCUS @Cryptococcus neoformans causes cryptococcal meningitis.
Properties:
C neoformans is an oval, budding yeast surrounded by a wide polysaccharide capsule . It is not dimorphic.

44. Transmission:
@ This yeast occurs widely in nature and grows in soil containing pigeon droppings.
@ Birds are not infected.
@ Human infection results from inhalation of the organism.
@ No human to human transmission.

45. Pathogenesis & Clinical Findings:
@ Lung infection is often asymptomatic or may produce pneumonia.
@ Disease occurs in AIDS patients, & organism disseminates to C.N.S. (meningitis) and other organs.

46. Laboratory Diagnosis:
@ In CSF mixed with India ink, the wide, unstained capsule is seen
@ Culture from CSF and other specimens.
@ Serologic tests can be done for both antibody and antigen.
@ In CSF , capsular antigen is detected by the latex particle agglutination test.

47. Treatment & Prevention
@ Both amphotericin B & flucytosine is used in meningitis or other disseminated disease.
@ No means of prevention.
@ Fluconazole is used in AIDS patients with cryptococcal meningitis.

48. ASPERGILLUS
@ Aspergillus fumigatus. cause infections of skin, eyes, ears, and other organs .
@ It causes "fungus ball" in lungs; and allergic bronchopulmonary aspergillosis.
Properties: Aspergillus species exist only as molds; they are not dimorphic.
@ have septate hyphae & conidia with radiating chains

49. Transmission:
@ Widely distributed in nature, & grow on decaying vegetation, producing chains of conidia.
@ Transmission is by airborne conidia.

50. Pathogenesis & Clinical Findings:
@ As. fumigatus invades abraded skin, wounds, burns, cornea, external ear, paranasal sinuses.
@ In immunosuppression, it invades lungs , producing hemoptysis & granulomas.
@ Aspergilli grow in pulmonary cavities & produce aspergilloma ("fungus ball"),
@ Allergic bronchopulmonary aspergillosis causes asthmatic symptoms and a high IgE .
@ Aspergillus flavus growing on cereals or nuts produces aflatoxins - carcinogenic or toxic.

51. Laboratory Diagnosis:
@ Biopsy show septate, branching hyphae
@ Cultures show colonies with radiating chains of conidia.
@ In patients with allergic aspergillosis high levels of IgE specific for Aspergillus antigens are detected .
@ IgG precipitins are also present.

52. Treatment & Prevention:
@ Invasive aspergillosis: give amphotericin B, but results may be poor.
@ A fungus ball growing in a sinus or in a pulmonary cavity can be surgically removed.
@ Patients with allergic aspergillosis: give steroids and antifungal agents.
@ No specific means of prevention.

53. MUCOR & RHIZOPUS
@ Zygomycosis is caused by saprophytic molds (Mucor, Rhizopus) found widely in environment.
@ Not dimorphic, transmitted by airborne asexual spores & invade low defenses patients .
@ Proliferate in blood vessels of paranasal sinuses, lungs, or gut, & cause infarction & necrosis of tissue distal to the blocked vessel.
@ Patients with diabetes , burns, or leukemias are susceptible.

54. @ In biopsy , organisms show nonseptate hyphae with broad, irregular walls and branches forming at right angles.
@ Cultures show colonies with spores contained within a sporangium.
@ Treatment: underlying disorder, plus amphotercin B and surgical removal of necrotic infected tissue .