Overview of Fungal Infections

1. Overview of
Fungal
Infections
Dr. Hany Lotfy
Assistant Professor of Medical Microbiology & Immunology
Faculty of Medicine, Sulaiman Al Rajhi University

2. General properties:
• Fungi are eukaryotic, with all the typical cellular
organelles.
• They differ from all other eukaryotes in that they:
 Possess a rigid cell wall containing glucan, mannan and chitin.
 Have ergosterol as their major cell membrane sterol.

3. Habitat & Nutrition
• Natural habitat of almost all fungi is soil or water containing
decaying organic matters.
• An exception being Candida; part of normal flora of human
mucosa.
• All fungi are heterotrophs; must obtain its carbon in an organic
form.
• Most fungi are aerobic.
• Fungi secrete enzymes (as proteases, nucleases) into their
surrounding environment. These enzymes enable fungi to live
as saprophytes on organic matter.

4. Morphological Classification
1. Yeasts:
• Yeasts are single-celled fungi that grow by budding
(extension, constriction, and separation of new cells from the
parent).
• The buds formed in this way are called blastospores.
• On culture, yeasts form smooth, creamy colonies.
• Example: Saccharomyces cerevisae, Cryptococcus neoformans.

6. 2. Molds (filamentous fungi):
• The growth of fungi is through the development of apical tube-like
extensions generates hyphae.
• An intertwined mass of hyphae is called a mycelium.
 Most fungal hyphae has septa, cross-walls perpendicular to the cell
walls dividing the cell into subunits (septated hyphae).
 Non-septated hyphae grow as a single, continuous cell with irregularly
wide filaments and without regular cross-walls.
• Example: Aspergillus fumigatus, Aspergillus niger, Penicillium
notatum.

9. 3. Yeast-like
(Pseudohyphae):
• Like yeasts, but the bud remains
attached to the mother cell and
elongates, followed by repeated
budding, forming chains of elongated
chains known as pseudohyphae.
• Example: Candida albicans.

10. 4. Dimorphic Fungi:
• Some fungal species can grow in yeast or hyphal phase depending on
environmental conditions. These are referred to as dimorphic fungi.
• The main factor that determine the dimorphism is the temperature.
 At room temperatures (25°C), they tend to be hyphal (filamentous).
 While in the tissues (37°C), they convert to yeast or a yeast-like stage.
• This is a complex physiologic conversion that is reversible, and therefore
not a developmental process.
• Example: Histoplasma capsulatum, Sporothrix schenckii.

11. Dimorphic Fungi:

12. Difference between Fungi and Bacteria
Characteristics Fungi Bacteria
Cell type Eukaryotic Prokaryotic
Optimum pH 4-6 6.5-7.5
Optimum temperature • 25-30°C (saprophytes)
• 32-37°C (parasites)
32-37°C
Cell wall components Chitin, cellulose Peptidoglycan
Cell membrane (Sterol) Present Absent (except Mycoplasma)
O2 requirement • Strictly aerobic (moulds)
• Facultative anaerobe (Some
yeasts)
• Strict aerobes.
• Facultative anaerobes.
• Microaerophilic.
• Strict anaerobes.
Carbon source Organic Organic/ Inorganic

13. Fungal Reproduction
Fungal reproduction may be asexual or sexual.
 Asexual reproductive elements: Conidia.
 Conidia that form exogenously: Macroconidia and microconidia.
 Conidia that form within the hypha: Arthroconidia.
 Sexual reproductive elements:
 Ascospores, basidiospores and zygospores.

14. Conidia:
• Spores are formed by the
mycelium & are released in large
numbers to the environment.
• Spores are carried by air or water
to new sites, where they germinate
to form new fungi.

15. Asexual & Sexual Reproductive Elements
Arthrospores

16. Diagnosis of fungal infections
1. Sample: According to the infection sites.
2. Direct Examination:
• Scraping or biopsy treated with KOH that digests mammalian cells and
leaves the complex carbohydrate cell wall of fungi intact.
• Special stains:
 Lactophenol Cotton Blue (wet mount): It stains the chitin in the cell wall.
 Calcofluor-white: Stains Cellulose and chitin in the cell wall fluoresce.
 Gram stain: Yeasts such as Candida appears as Gram-positive.
 Silver stains: Stains the polysaccharides (glucan, mannan) of fungal cell walls.
 India ink:
 Particulate dye deposits around yeasts, does not penetrate capsular
polysaccharide, shows capsular halo.
 Insensitive test of CSF for encapsulated Cryptococcal yeasts.

17. Lactophenol cotton blue
India ink (negative stain)
Silver stain
Candida (Gram stain)

18. 2. Culture:
 Fungi are slow growing, but Sabouraud dextrose
agar (SDA) is most commonly used.
 To make it more specific, add antibiotics.
 Yeasts are further differentiated by biochemical
reactions.
 Molds are further identified by the morphology
of their conidia.
3. Serology:
 Not sufficiently specific or sensitive for use.
4. Molecular methods:
 PCR, DNA probe, FISH.. etc

19. Overview of Fungal
Infections

20. Overview of fungal infections
1. Superficial Mycosis (skin, hair and nails).
 Dermatophytosis.
 Pityriasis versicolor.
2. Subcutaneous Mycosis.
 Sporotrichosis (Madura foot, Mycetoma)
3. Systemic Mycosis:
 True (1ry) pathogens: infect healthy hosts, although disease
worsens with immunocompromized.
 Opportunistic mycosis: disease almost exclusively in
immunocompromized.

21. A. Superficial Fungal
Infections

22. 1. Dermatophytosis:
• Infections by Dermatophytes molds.
• They cause infections of the skin, hair, and nails.
• They btainin nutrients from keratinized material (they produce keratinase).
Diseases:
 Tinea corporis.
 Tinea capitis.
 Tinea barbae.
 Tinea faciei.
 Tinea cruris.
 Tinea pedis.
 Tinea manuum.
 Tinea unguum.

23. Organisms:
Fungi:
 Microsporum, Trichophyton:
 Mainly animal pathogens.
 Epidermophyton:
 A human pathogen.
Classification:
 Zoophilic: dermatophytes are mainly found in animals, and can be
transmitted to humans.
 Anthropophilic: dermatophytes are mainly found in humans and are
very infrequently transmitted to animals.
 Geophilic: dermatophytes are found mainly in soil. They infect both
humans and animals.
Microsporum Trichophyton
Epidermophyton

24. Transmission:
1. Contact with infected animals/humans.
2. Airborne hairs/scales.
3. Fomites.
4. Soil.

25. Tinea capitis
• The most common pediatric dermatophyte
infection worldwide.
• Infection in scalp hair of children.
• Areas of alopecia.
• May be suppurative (kerion).
• Draining lymph nodes may be enlarged.
Tinea corporis
• Classic “ringworm”.
• Trunk, extremities and face.
• Elevated, scaly, pruritic lesions with erythematous
edge.

26. Tinea barbae
• Beard and mustache area.
• Scaling, complicated be follicular
bacterial pustules.
• Erythema.
Tinea faciei
• Non-bearded parts of face.
• Pruritic.

27. Tinea cruris
• Affection of crural area (groin).
• Burning and pruritus.
• Red scaling lesions with raised borders.
Tinea pedis “Athlete’s foot”
• Very common in middle ages.
• Fissures, scales, and maceration in the
toe web.
• Scaling of soles.

28. Tinea manuum
• Hands.
• Palms diffusely dry, scaly, and
erythematous.
Tinea unguium (onychomycosis)
• Affects nails.
• Very common.
• The nail is thickened, discolored, broken.
• Nail plate may separate from nail bed.

30. Diagnosis
1. Wood’s lamp examination:
 Detects fluorescence.
2. Sample:
 Skin or nail scraping, Hair plucking.
3. Potassium hydroxide (KOH) & microscopy:
 Detects hyphae and conidia in skin scrapings or hair.
4. Fungal culture:
 Culture on SDA.

32. 2. Pityriasis versicolor
‘Tinea versicolor’:
• A common superficial skin infection caused by the poly-
morphic fungus (Malassezia furfur).
• Morphology: round yeast cell along curved non-branched
hyphae.
• Epidemiology:
 More commonly in men than in women.
 Middle age.
 Frequent during summer, especially in warm & humid climates.
• Clinical picture:
 A set of hypo-pigmented / hyper-pigmented patches with fine
scale over the trunk in a cape-like distribution.
Cape-like
distribution

33. Diagnosis:
1. KOH wet mount test:
• Shows “Spaghetti and Meat ball” appearance:
 Spaghetti represents the hyphal form of Malassezia.
 Meat ball represents the yeast form.
2. Wood’s lamp examination:
 Pityriasis gives the yellow-silver fluorescence.
3. Culture: is not helpful.

34. B. Subcutaneous Fungal
Infections

35. Pathogenesis:
• The disease is usually seen in field workers (e.g. farmers).
• Age: 20 - 40 years.
• The disease is acquired by inoculation of grains of fungal spores from the soil
through a fissure in the skin produced by minor trauma like a thorn-prick,
then spread via lymphatics.
• It cannot be transmitted from person-to-person.
• May reach distant organs especially bone, joints and lungs.
• Most common in non-industrialized world “Madura foot”.

37. Sporotrichosis
(Madura foot, Mycetoma,
Rose Gardner’s Disease)
• Organism: Sporothrix schenckii
 Dimorphic fungus.
 Saprophyte in soil and plants.
 Worldwide distribution.
• Clinical Syndromes:
1. Subcutaneous mycetoma (Madura foot).
2. Pulmonary sporotrichosis.
3. Disseminated sporotrichosis.

38. “Mycetoma belt” that stretches roughly
from the Equator to the Tropic of Cancer.

40. Diagnosis:
1. Specimen:
 Pus, exudate from draining sinus or biopsy material with
granules.
2. Examination:
 Direct microscopy: Presence of granules which are
diagnostic.
 Fungal granules composed of broad septate hyphae with
large number of bizzarely shaped swollen cells.
3. Culture:
 The granules are cultured on SDA + chloramphenicol,
incubated at 25°C and 37°C up to 6 weeks.
4. Histopathology:
 Stained using H&E or PAS.

41. C. Systemic fungal infections
1. “True” pathogens.
2. “Opportunistic” pathogens.

42. a) Histoplasmosis Histoplasma capsulatum
b) Coccidioidomycosis Coccidioides immitis
c) Blastomycosis Blastomyces dermatidis
They are:
• Dimorphic fungi.
• Respiratory acquisition through inhalation of fungal spores.
• Restricted geographic distribution.
• Infect normal hosts.
1. “True” pathogens:

43. Geographic distribution

44. Histoplasmosis
• Organism: Histoplasma capsulatum
• Habitat:
 Ohio-Mississippi valley; Puerto Rico, Central and South America.
 Guano of bats, birds, poultry (chicken coops and caves).
• Clinical: mimics TB.
1. Asymptomatic to acute or chronic pulmonary manifestations
(productive cough, chest pain, fever).
2. Mediastinal lymphadenopathy.
3. Nodular lesions on chest X-ray.
4. Disseminated disease:
 CNS affection.
 Ulcers on mucous membranes.

45. Coccidiodomycosis
• Organism: Coccidioides immitis
 Dimorphic soil fungus with spherules & endospores in
host and hyphal form in soil.
• Pathogenesis: inhalation of spores.
• Clinical:
 Acute self limited, flu-like symptoms.
 Lung cavities similar to TB of the lungs.
 Dissemination (pregnancy, mmunocompromised):
 Skin.
 Bone, joints.
 CNS.

46. Blastomycosis
• Organism: Blastomyces dermatidis
• Habitat: humid woodlands in Mid-Atlantic countryside.
• Pathogenesis: inhalation of spores.
• Clinical:
1. Acute or chronic lung disease
(nodular/cavitary).
1. Disseminated disease:
 Skin.
 Bone.
 Urinary tract.

47. Systemic fungal infections:
2. The “opportunists”

48. 1. Candidiasis
• Organism: Candida albicans.
(Others: C. glabrata, C. tropicalis, C. cruzi).
• Habitat: normal human flora.
• Morphology: Yeast-like
 Budding round to oval yeasts.
 Pseudohyphae: Elongated forms with
constrictions at intervals.
• Risk factors:
 Diabetes.
 Steroids.
 Antibiotic therapy.
 Oral contraceptives
 Immunosuppression.

49. Clinical settings:
1. Superficial lesion.
• Mucous membrane:
 Oral thrush characterized by discrete white patches on mucosal surface.
 Vaginal thrush: white lesion on epithelial surface of vulva, vagina and cervix.
• Skin:
 Infection in moist warm area as axilla, groin (napkin’s dermatitis), infra-
mammary folds.
• Nail:
 Infection of finger web, nail fold (onchomycosis).
2. Systemic lesion:
• Candidal esophagitis.
• Candidal endocarditis follows heart valve surgery.
• Internal organ e.g. lungs, kidney on pre-existing diseases (e.g. TB, cancer).
• Candidemia.

50. Esophagitis
Oral thrush Onchomycosis
Circum-oral candidiasis

51. Inframammary
Onchomycosis
Napkin dermatitis
Endocarditis

52. Diagnosis:
1. Sample: Swab from affected area.
2. Stain: Lactophenol stain, Gram stain.
3. Culture: on SDA; Colonies are creamy white.
Treatment:
• Topical antifungal (e.g. clotrimazole).
• Systemic antifungal: in esophagitis, endocarditis.
Gram stain
Lactophenol stain

53. 2. Aspergillosis
• Organism: Aspergillus fumigatus and
others
 A mold (filamentous).
• Habitat:
 Everywhere, worldwide.
• Pathogenesis:
 Transmission: Inhalation of spores.
 An important pathogen in patients with bone
marrow transplantation.

54. Aspergillosis
Clinical:
1. Allergic broncho-pulmonary Aspergillosis.
2. Aspergilloma (fungal ball).
3. Invasive:
 Pneumonia.
 other end-organ disease.
Treatment: Amphotricin B

55. 3. Cryptococcosis
• Organism: Cryptococcus neoformans.
 Yeast with thick polysaccharide capsule.
• Pathogenesis: inhalation of yeast.
• Clinical: Meningitis
 Acute or chronic.
 Fever, headache, stiff neck, loss of vision.
 Complicated by hydrocephalus.
• Diagnosis:
 India ink negative staining.
 Cryptococcal direct antigen detection.
 Urease test: positive.

57. 4. Mucor-mycosis
• Organism: Rhizopus and Mucor rouxii.
 Mold.
• Habitat:
 Everywhere, worldwide.
• Pathogenesis:
 Inhalation of spores.
Rhizopus
Mucor

58. Clinical:
• The most acute and fulminant fungal infection known.
• Sinusitis progressing to brain abscess.
• Orbital cellulitis and hemorrhage.
• Pneumonia progressing to infarction.

59. Mycotoxicosis
• Some fungi can generate substances with direct toxicity for
humans and animals.
• Ingestion of these toxins leads to mycotoxicosis.
• General criteria of mycotoxicosis:
1. Not transmissible among humans.
2. Seasonal.
3. Associated which foods ingestion.
4. Examination of the food reveals fungal growth.
5. No effect of antifungal in treatment.
6. The degree of toxicity depends on many host factors.

60. 10 Foods highest in mycotoxins
Sugar beets Peanuts Sugar cane
Barley Wheat
Corn

61. Sorghum Rye
Cottonseed Hard cheese

62. Type of Mycotoxins:
• There are large number of mycotoxins according to the fungus produce it.
• e.g. Aflatoxin, ochratoxins, amatoxin and phallotoxin.
Aflatoxins Produced by Aspergillus flavus.
Effects of Aflatoxin:
1. Acute:
 Gastroenteritis, abdominal pain, vomiting.
 Pulmonary edema.
 Liver necrosis.
 Could be fatal.
2. Chronic:
 Immunosuppression.
 Liver cirrhosis.
 Hepatocellular carcinoma (HBV increases the effect).
 Effect on reproductive functions.
 Could be excreted in breast milk to infants.