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Fungal infections of the oral
cavity

1
Medical Mycology
• Fungi were discovered before bacteria & viruses
• Most fungi cause skin or cosmetic infections
while bacteria & viruses cause fatal diseases
• Clinical Mycology has entered “Golden Age” in
modern medicine due to:

•Organ transplantation
•Immunosuppressive drugs
•Anticancer drugs
•Broad-spectrum antimicrobials
•HIV-disease

Immunosuppression

Opportunistic Fungal Infections

2
Fungi : General Characteristics
• Are eukaryotic (possess a true nucleus with nuclear
membrane & mitochondria)

Cell membrane

• Have ergosterol which is specific target for antifungal
agents (cholestrol in mammalian cells)

Cell Wall
Lacks
• Peptidoglycan
• Techoic acids
• Lipopolysaccharide

Contains
• Peptidomannan
• Glycan (target for
new antifungal agents)
3
Fungi Groups
On the basis of Morphology
1. Molds (filamentous fungi)
• Most fungi are composed of filamentous
(tubular) structures called hyphae. May be
septated OR Aseptated

Aseptate hyphae

Septate hyphae

4
Types of Hyphae
• Vegetative hyphae: penetrate the media and absorb food
• Aerial hyphae : are directed above the surface of media
• Reproductive hyphae : Aerial hyphae that carry different
spores

• Mycelium : A collection of hyphae
Reproductive
Hyphae & conidia
Mycelium
(thallus)

Surface of
media

Aerial
hyphae
Vegetative
hyphae

5
Fungi Groups
On the basis of morphology
2. Yeasts
• Unicellular (rounded or oval)
• Reproduce by budding
• The only example of pathogenic
yeast is Crptococcus

neoformans

6
Fungi Groups
On the basis of morphology

3. Yeast-Like
• Unicellular (rounded or oval)
• Reproduce by budding but buds fail to
detach and may form short chains of cells
called pseudohyphae
• Pseudohyphae are produced during
infection and have diagnostic value
• Example: Candida

7
Fungi Groups
On the basis of Morphology
4. Dimorphic Fungi
• Able to grow in two different forms
• As molds at room temperature
• As yeasts on incubation at 370C &
during infection in body
“Mold in the cold, yeast in the heat”

• Example: Histoplasma capsulatum

8
Opportunistic Infections of the URT&
LRT
• Candidiasis
• Cryptococcosis
• Aspergillosis
• Zygomycosis
***ANY fungus found in nature may
give rise to opportunistic mycoses ***

9
CANDIDIASIS
• Most commonly encountered opportunistic
mycoses worldwide
• Cellular immunity protects against
mucocutaneous candidiasis, neutrophiles protect
against invasive candidiasis
• Endogenous infection.
• Etiology: Candida spp. Most common:
 C. albicans
 C. tropicalis
10
Candida

Morphologicfal Features
• Micr. Budding yeast cells
Pseudohyphae, true hyphae
• Macr. Creamy yeast colonies (SDA)
• Germ tube
• Chlamydospore
• Identification
 Germ tube
11
Sabouraud Dextrose agar

Candida albicans

Candida albicans
Microscopic Morphology

12
Candida
Pathogenicity
• Attachment (Germ tube is more
adhesive than yeast cell)
• Adherence to plastic surfaces (catheter,
prosthetic valve..)
• Protease
• Phospholipase

13
CANDIDIASIS
Risk factors
• Physiological. Pregnancy, elderly, infancy
• Traumatic. Burn, infection
• Hematological. Cellular immune deficiency,
AIDS, chronic granulamatous disease,
aplastic anemia, leukemia, lymphoma...
• Endocrinological. DM
• Iatrogenic. Oral contraceptives, antibiotics,
steroid, chemotherapy, catheter...
14
Candidiasis
Clinical manifestations
1. CUTANEOUS and SUBCUTANEOUS
•
a)
b)
c)

Oral
Pseudomembernous (thrush)
Erythematous
Hyperplastic

• Vaginal
• Dermatitis
• Diaper rash
15
Candida albicans
Granulomatous lesions involving

Candida diaper rash

the hands.

16
Candida albicana
The white material are masses of the yeast

17
CANDIDIASIS
Clinical manifestations
2.SYSTEMIC

• Esophagitis
• Pulmonary inf.
• UTI( Cystitis)

• Osteomyelitis
• CNS (Menengitis)
• Skin lesions

• CVS

18
CANDIDIASIS
Diagnosis
• Direct micr.ic examination
Yeast cells, pseudohyphae, true hyphae
• Culture
SDA, routine bacteriological media

• Serology
Detection of mannan antigen
(ELISA, RIA, IF, latex agglutination)

19
CANDIDIASIS
Treatment
• CUTANEOUS
Topical antifungal: Ketoconazole, miconazole,
nystatin
• SYSTEMIC
Amphotericin B
Fluconazole, itraconazole

20
Aspergillosis
Causative Agent
• Aspergillus fumigatus
Systemic infection
• Aspergillus flavus
• Aspergillus niger- mostly local infection;
otomycosis
• Are molds that have septate hyphae with Vshaped branches (Fruiting body of Aspergillus)
Source of infection
• Widely distributed in environment
• Transmitted by air-borne light spores
• High environmental load is associated with sick
building syndrome & contaminated AC system

21
Aspergillus

22
Aspergillosis
Pathogenesis & Clinical features
Aspergillus can colonize and invade:
• Lungs
• Wounds, burns
• Cornea
• External ear
• Paranasal sinuses

23
Aspergillosis
In lungs can cause:
a) Hypersensitivity Reaction:
Spores colonise RT without invasion and lead to
allergic asthma, rhinitis, bronchopulmonary aspergillosis

b) Aspergilloma (fungus ball):
the spores colonise paranasal sinuses or a pre-existing
cavity in lung (TB cavity)
The radiological appearance may be similar to malignancy.

c) Invasive Aspergillosis
In immunocompromised can invade lungs causing hemoptysis
& granuloma and disseminate to other organs
Fatality rate 100% if not diagnosed and treated promptly.
24
Aspergillosis
Lab Diagnosis
Specimens : sputum, BM aspirate, biopsy
Direct Microscopy
• Shows branching septate hyphae
Cultures : Microscopy shows radiating chains of spores
Serology
• In allergic condition: high levels of specific IgE
• Galactomannan in invasive aspergillosis
Treatment
• Invasive aspergillosis
Amphotericin B
• Allergic conditions
Steroids & antifungals
25
Zygomycosis
Mucormycosis
• Causative agents; saprophtic molds
• Rhizopus, Mucor & Absidia
• Have broad, hyaline aseptate hyphae
• Have large no. of asexual spores inside a sporangium
• Risk factors
Diabetic ketoacidosis,
immunosuppression
• Pathogenesis Inhalation of sporangiospores
• Infected tissue vascular invasion,
thrombus, infarct,

26
ZYGOMYCOSIS
Clinical manifestations
I. RHINOCEREBRAL
• Nose, paranasal sinuses, eye, brain and meninges are
involved
• Orbital cellulitis
II. THORACIC
• Pulmonary lesions, parenchymal necrosis
III. LOCAL
• Posttraumatic kidney infection.
• Skin inf. following burn or surgery

27
Zygomycosis
Mucormycosis

Diseases
• Rhinocerebral zygomycosis
o Extensive cellulitis of nasal mucosa, paranasal
sinuses, orbit & brain
o Rapidly fatal
• Pulmonary & disseminated infections

28
Zygomycosis in a diabetic patient

29
Disease(s): Rhinocerebral zygomycosis

30
ZYGOMYCOSIS
Diagnosis
• Samples Sputum, BAL, biopsy of
paranasal sinuses..
• Direct exam. Nonseptate, ribbon-like
hyphae which branch at right angles,
sporangium

• Culture SDA (cotton candy appearance)
31
Image: Sporangia showing different stages of sporangiospore
development in the large sporangium, human nasal polyp,

32
Treatment
• Surgical debridement
• Amphotericin B

***High mortality rate
33
Case study
• A young Diabetic girl develops acute fatigue and
fever. Her pediatrician discovers a leukemia and
the girl is promptly treated with broad acting anticancer therapy. Two weeks after the therapy she
started to developed a severe pneumonia which
does not respond to antimicrobial antibiotics. A
biopsy from the lung was taken and plated on
Sabouraud dextrose agar containing
antibacterial antibiotics. After incubation at 250C,
a mold is seen. On further examination the girl is
treated with amphotericin B and recover. The
disease she had was
34
Questions
• What is the identity of the isolate ?

• In what patient population does this
organism normally cause infection?
• How can you investigate the patient?

35

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Fungal infections of the oral cavity

  • 1. Fungal infections of the oral cavity 1
  • 2. Medical Mycology • Fungi were discovered before bacteria & viruses • Most fungi cause skin or cosmetic infections while bacteria & viruses cause fatal diseases • Clinical Mycology has entered “Golden Age” in modern medicine due to: •Organ transplantation •Immunosuppressive drugs •Anticancer drugs •Broad-spectrum antimicrobials •HIV-disease Immunosuppression Opportunistic Fungal Infections 2
  • 3. Fungi : General Characteristics • Are eukaryotic (possess a true nucleus with nuclear membrane & mitochondria) Cell membrane • Have ergosterol which is specific target for antifungal agents (cholestrol in mammalian cells) Cell Wall Lacks • Peptidoglycan • Techoic acids • Lipopolysaccharide Contains • Peptidomannan • Glycan (target for new antifungal agents) 3
  • 4. Fungi Groups On the basis of Morphology 1. Molds (filamentous fungi) • Most fungi are composed of filamentous (tubular) structures called hyphae. May be septated OR Aseptated Aseptate hyphae Septate hyphae 4
  • 5. Types of Hyphae • Vegetative hyphae: penetrate the media and absorb food • Aerial hyphae : are directed above the surface of media • Reproductive hyphae : Aerial hyphae that carry different spores • Mycelium : A collection of hyphae Reproductive Hyphae & conidia Mycelium (thallus) Surface of media Aerial hyphae Vegetative hyphae 5
  • 6. Fungi Groups On the basis of morphology 2. Yeasts • Unicellular (rounded or oval) • Reproduce by budding • The only example of pathogenic yeast is Crptococcus neoformans 6
  • 7. Fungi Groups On the basis of morphology 3. Yeast-Like • Unicellular (rounded or oval) • Reproduce by budding but buds fail to detach and may form short chains of cells called pseudohyphae • Pseudohyphae are produced during infection and have diagnostic value • Example: Candida 7
  • 8. Fungi Groups On the basis of Morphology 4. Dimorphic Fungi • Able to grow in two different forms • As molds at room temperature • As yeasts on incubation at 370C & during infection in body “Mold in the cold, yeast in the heat” • Example: Histoplasma capsulatum 8
  • 9. Opportunistic Infections of the URT& LRT • Candidiasis • Cryptococcosis • Aspergillosis • Zygomycosis ***ANY fungus found in nature may give rise to opportunistic mycoses *** 9
  • 10. CANDIDIASIS • Most commonly encountered opportunistic mycoses worldwide • Cellular immunity protects against mucocutaneous candidiasis, neutrophiles protect against invasive candidiasis • Endogenous infection. • Etiology: Candida spp. Most common:  C. albicans  C. tropicalis 10
  • 11. Candida Morphologicfal Features • Micr. Budding yeast cells Pseudohyphae, true hyphae • Macr. Creamy yeast colonies (SDA) • Germ tube • Chlamydospore • Identification  Germ tube 11
  • 12. Sabouraud Dextrose agar Candida albicans Candida albicans Microscopic Morphology 12
  • 13. Candida Pathogenicity • Attachment (Germ tube is more adhesive than yeast cell) • Adherence to plastic surfaces (catheter, prosthetic valve..) • Protease • Phospholipase 13
  • 14. CANDIDIASIS Risk factors • Physiological. Pregnancy, elderly, infancy • Traumatic. Burn, infection • Hematological. Cellular immune deficiency, AIDS, chronic granulamatous disease, aplastic anemia, leukemia, lymphoma... • Endocrinological. DM • Iatrogenic. Oral contraceptives, antibiotics, steroid, chemotherapy, catheter... 14
  • 15. Candidiasis Clinical manifestations 1. CUTANEOUS and SUBCUTANEOUS • a) b) c) Oral Pseudomembernous (thrush) Erythematous Hyperplastic • Vaginal • Dermatitis • Diaper rash 15
  • 16. Candida albicans Granulomatous lesions involving Candida diaper rash the hands. 16
  • 17. Candida albicana The white material are masses of the yeast 17
  • 18. CANDIDIASIS Clinical manifestations 2.SYSTEMIC • Esophagitis • Pulmonary inf. • UTI( Cystitis) • Osteomyelitis • CNS (Menengitis) • Skin lesions • CVS 18
  • 19. CANDIDIASIS Diagnosis • Direct micr.ic examination Yeast cells, pseudohyphae, true hyphae • Culture SDA, routine bacteriological media • Serology Detection of mannan antigen (ELISA, RIA, IF, latex agglutination) 19
  • 20. CANDIDIASIS Treatment • CUTANEOUS Topical antifungal: Ketoconazole, miconazole, nystatin • SYSTEMIC Amphotericin B Fluconazole, itraconazole 20
  • 21. Aspergillosis Causative Agent • Aspergillus fumigatus Systemic infection • Aspergillus flavus • Aspergillus niger- mostly local infection; otomycosis • Are molds that have septate hyphae with Vshaped branches (Fruiting body of Aspergillus) Source of infection • Widely distributed in environment • Transmitted by air-borne light spores • High environmental load is associated with sick building syndrome & contaminated AC system 21
  • 23. Aspergillosis Pathogenesis & Clinical features Aspergillus can colonize and invade: • Lungs • Wounds, burns • Cornea • External ear • Paranasal sinuses 23
  • 24. Aspergillosis In lungs can cause: a) Hypersensitivity Reaction: Spores colonise RT without invasion and lead to allergic asthma, rhinitis, bronchopulmonary aspergillosis b) Aspergilloma (fungus ball): the spores colonise paranasal sinuses or a pre-existing cavity in lung (TB cavity) The radiological appearance may be similar to malignancy. c) Invasive Aspergillosis In immunocompromised can invade lungs causing hemoptysis & granuloma and disseminate to other organs Fatality rate 100% if not diagnosed and treated promptly. 24
  • 25. Aspergillosis Lab Diagnosis Specimens : sputum, BM aspirate, biopsy Direct Microscopy • Shows branching septate hyphae Cultures : Microscopy shows radiating chains of spores Serology • In allergic condition: high levels of specific IgE • Galactomannan in invasive aspergillosis Treatment • Invasive aspergillosis Amphotericin B • Allergic conditions Steroids & antifungals 25
  • 26. Zygomycosis Mucormycosis • Causative agents; saprophtic molds • Rhizopus, Mucor & Absidia • Have broad, hyaline aseptate hyphae • Have large no. of asexual spores inside a sporangium • Risk factors Diabetic ketoacidosis, immunosuppression • Pathogenesis Inhalation of sporangiospores • Infected tissue vascular invasion, thrombus, infarct, 26
  • 27. ZYGOMYCOSIS Clinical manifestations I. RHINOCEREBRAL • Nose, paranasal sinuses, eye, brain and meninges are involved • Orbital cellulitis II. THORACIC • Pulmonary lesions, parenchymal necrosis III. LOCAL • Posttraumatic kidney infection. • Skin inf. following burn or surgery 27
  • 28. Zygomycosis Mucormycosis Diseases • Rhinocerebral zygomycosis o Extensive cellulitis of nasal mucosa, paranasal sinuses, orbit & brain o Rapidly fatal • Pulmonary & disseminated infections 28
  • 29. Zygomycosis in a diabetic patient 29
  • 31. ZYGOMYCOSIS Diagnosis • Samples Sputum, BAL, biopsy of paranasal sinuses.. • Direct exam. Nonseptate, ribbon-like hyphae which branch at right angles, sporangium • Culture SDA (cotton candy appearance) 31
  • 32. Image: Sporangia showing different stages of sporangiospore development in the large sporangium, human nasal polyp, 32
  • 33. Treatment • Surgical debridement • Amphotericin B ***High mortality rate 33
  • 34. Case study • A young Diabetic girl develops acute fatigue and fever. Her pediatrician discovers a leukemia and the girl is promptly treated with broad acting anticancer therapy. Two weeks after the therapy she started to developed a severe pneumonia which does not respond to antimicrobial antibiotics. A biopsy from the lung was taken and plated on Sabouraud dextrose agar containing antibacterial antibiotics. After incubation at 250C, a mold is seen. On further examination the girl is treated with amphotericin B and recover. The disease she had was 34
  • 35. Questions • What is the identity of the isolate ? • In what patient population does this organism normally cause infection? • How can you investigate the patient? 35