21. Oral Fungal Infections Flashcards
Fungi are simple …
Some can form …
And some transition between …
- eukaryotes
- multicellular structures like mushrooms, pin moulds
- yeast and hyphal forms (e.g candida spp.)
Yeasts are … with … bodies
- unicellular
- spherical or ovoid
Hyphae are what?
- thread-like tubes containing fungal cytoplasm and organelles `
Moulds are … with a variety of …
- mutlicellular
- specialised structures to perform specific functions
Define ‘mycelium’
mass of hyphae that forms mould colony
Fungi are …, … cells
With what two defining components?
- larger, eukaryotic cells
- with membrane-bound nucleus and mitochondria
Fungi for medicine are classified into …
- yeasts
- filamentous fungi
- dimorphic fungi
Diameter of fungi
Relation to animal and bacteria
- around 3-6 micrometres
- smaller than animal, larger than bacteria
Fungi are slow/fast growing
Hetero/homotrophic?
slow
hetero
Fungi have a similarity with … cells of human host
mammalian
Fungi cell walls have what main component?
chitin
Cell walls in fungal cells
- thick and rigid surrounding plasma membrane
- two layers
- contains ergosterol instead of cholesterol
- outer amorphous layer of glycoproteins, carbohydrates, mannans
- inner layers of polysacchardies e.g glucans/chitins
Role of fungal cell walls
- antigenicity
- adherance to host cells
Are fungi normally in mouth?
yes
- part of normal oral microbiota
Incidence of oral Candida carriage?
35-80% in healthy individuals
What’s the most predominant fungi in mouth?
candida species
Explain the genus ‘Candida’
- over 400 species
- mainly non-pathogenic
- C.albicans over 90% of oral isolates
- carried naturally but overgrowth can be infection (enumeration is important)
- dimorphic fungi (yeasts and hyphaes)
Specifications about candida albicans
- typically grows as spherical to oval budding yeast cells 3-5 x5-10 micrometres in size
- indigenous to oral cavity, GI tract, female genital tract and skin
Explain the yeast to hyphae transition
- hyphal form invades epithelia
- certain cell surface receptors are only present in hyphae
- morphotype switching is under complex regulation circuit
What controls the morphotype switching of yeast to hyphae?
- osmotic shock
- temp fluctuations
- pH
- nutrients
- cell density
- salivary factors like statherin
- oral bacteria
How does oral bacteria interact with candida albicans?
- grow alongside each other in mixed community
- oral bacteria modulate morphology and physiology of C.albicans
- some species synergistic whilst others tend to compete with Candida spp.
- on the whole, oral strep benefit from candida but lactobacillus spp. tend to inhibit
List candida species that cause infection?
- albicans
- glabarta
- krusei
- topicalis
- guilliermondii
- kefyr
- dubliniensis
How does the genus candida go from normal to infectious?
- normal, harmless commensal
- change in env or systemic conditions
- conditions favour candida prolieferation
- pathogenic disease causing infection
Candida infections are … and depends on …
- opportunistic
- underlying predisposition (sometimes termed ‘disease of the diseased’)
How to grow candida in agar?
- culture on Sabouraud Dextrose agar (sometimes with antibiotics)
- selects candida over bacteria due to low pH
- microscopy used to identify (e.g germ tube test, chlamydospore production)
Instead of using a microscope to identify candida, how could you?
- biochemical tests
- e.g carbohydrate utilisation
- used more for quick and accurate assessments
- or molecular methods for epidemiology to track clones
List types of virulence factors on candida
- morphology - hyphae formation
- phenotypic switching
- hydrolytic enzymes
- candidalysin
How is candida morphology a virulence factor?
- can be dimorphic or polymorphic
- C.albicans and C.dubliniensis can grow as yeast cells, pseudohyphae and hyphae
- hyphae formation promotes oral epithelium invasion, reduces likelihood of phagocytosis, allows phagocytosed yeast to escape phagocyte
- mutants unable to form hyphae are less virulent
- responds to environment for example producing hyphae in response to elevated temp, CO2 conc, alkaline pH, presence of serum, limited nutrients
How is phenotypic switching a virulence factor for candida?
- ability to rapidly change cell morphology
- responsive to environment
- associated with altered gene expression affecting antigenicity, adhesion, phagocytosis and drug susceptibility
2 hydrolytic enzymes in candida that aid virulence
- aspartyl proteinases
- phospholipases
Role of aspartyl proteinases in candida
- expressed under different conditions (10 genes)
- some expressed during hyphal development
- nutrition
- adapting cell morphology
- break down tissue barrier
- cleave immune proteins
- facilitate adherance
- host cell and extracellular matrix damage
Role of phospholipases in candida
- hydrolyse phospholipids
- damage host cells - host cell membrane damage, promoting cell lysis or exposure to receptors to facilitate adherance
How is candidalysin a virulence factor for candida?
- peptide toxin
- candidalysin helps c. albicans penetrate host epithelial cells
Human infections caused by fungi are characterised how?
- superficial
- subcutaneous
- systemic
How do we defend against oropharyngeal candidiasis?
- damage mediated by C. albicans hyphal penetration and secretion of proteolytic enzymes
- host responds with Th1 and Th17 adaptive immune response
How do we defend against hematogenously disseminated candidiasis?
- induced by biofilm formation on tissue or abiotic surfaces
- damage is mediated by C.albicans hyphal invasion and secreted proteolytic enzymes
- host responds with Th1 and Th17 adaptive immune response
Intra-abdominal candidiasis is triggered by … and results in …
- C.albicans invasion of abdominal organs
- formation of abscesses
Explain denture stomatitis
- induced by C. albicans formation on dentures
- damage is initiated by hyphal invasion of host tissue
- further damage is mediated and propagated by host innate immune response, mainly neutrophils
Explain gastro-intestinal candidiasis
- induced by C. albicans overgrowth in GI tract
- in immunocompromised hosts, damage is mediated by mucosal invasion and disruption of epithelial barrier
- at other end of host response spectrum, C. albicans overgrowth can be a predisposing dactor for inflammatory diseases of Gi tract like colitis
Explain vulvovaginal candidiasis
- onset initiated by C. albicans hyphal transition and subsequent invasion of vaginal mucosa
- triggers innate immune response
- damage is mediated and propagated by host innate immune response, mainly neutrophils
What determines the particular form of oral candidosis?
- combination of host factors and microbial factors
What is likely to influence proliferation of candida?
- change in environment
- change in host immunity
Local factors that predispose patients to oral candidosis?
- denture wearing
- inhaled corticosteroids
- reduced salivary flow
- carbohydrate rich diet
Systemic factors that predispose patients to oral candidosis?
- systemic corticosteroids, immunosuppressants, cytotoxics, broad-spectrum antibiotics
- extremes of age
- endocrine disorders (like diabetes)
- anaemia
- patients with nutritional deficiencies
- salivary gland hypofunction
- immunosuppression (and from linked conditions like leukaemias, malignancy or HIV)
How to diagnose oral candidosis?
- clinical appearance (size/site, can white plaques be scraped off?)
- lab tests (blood tests, microbiology - oral rinse and swab - and histology - biopsy)
4 primary forms of oral candidosis
- acute pseudomembranous
- acute erythematous
- chronic erythematous
- chronic hyperplastic
Acute pseudomembranous candidosis is …
oral thrush
Acute erythematous candidosis is …
- antibiotic sore mouth/stomatitis
Chronic erythematous candisosis is …
- denture stomatitis
Management of denture stomatitis
- clean dentures thoroughly
- soak them in chlorhexidine mouthwash or sodium hypochlorite for 15 mins twice daily
- chemical and mechanical cleansing of dentures twice daily
- leave them out as often as possible
- denture replacement or adjustment
- antifungal therapy if continues
Chronic hyperplastic candidosis is …
candidal leukoplasia
List types of secondary oral candidosis
- angular cheilitis
- median rhomboid glossitis
- chronic mucocutaneous candidosis
Give cause and treatment for angular cheilitis
- infection with candida or staphlo/streptococcus
- consider cause e.g denture wearer and then miconazole cream or sodium fusidate (fusidic acid) ointment
Explain causes of median rhomboid glossitis
- symmetrical-shaped area in midline of dorsum of tongue
- chronic infection with atrophy of filiform papillae
- infection linked to smoking and inhaled steroids
Explain chronic mucocutaneous candidosis
- skin, mucous membranes and nails
- associated with rare congenital disorders
- key predisposing factor impaired cellular immunity against Candida
Treatment of oral candidosis
- rectify any local factors, identify risk factors and treat systemic disease
- antifungal meds like topical (suspension, gel, lozenges) or systemic (tablets)
3 main groups of antifungal meds
- polyenes
- azoles
- DNA analogues
Examples, mode of action and administration of polyenes
- nystatin, amphotericin
- disrupt fungal cell membrane (interact with ergosterol)
- topical
Examples, mode of action and administration of azoles
- fluconazole, clotrimazole, miconazole, ketoconazole, itraconazole
- inhibit ergosterol biosynthesis (interfere with lanosterol demethylase)
- topical or systemic
Examples, mode of action and administration of 5-flucytosine
- inhibit DNA and protein synthesis (enter fungal cells through cytosine permease and is converted to %-fluorouracil)
- systemic (often given with amphotericin)
Examples, mode of action and administration of eschinocandins
- caspofungin, microfungin
- inhibit beta 1,3 D-glucan synthesis
- intravenous
