228 - Fungal Disease Flashcards
What do we call species that feed on dead material?
Saprophytes
Can fungi all cause infection?
No, 250,000 known but 180 cause mycosis in humans
Most opportunistic
How can a fungus damage you without actually causing an infection?
Through ingestion of mycotoxins, or allergy from spores
What investigations are used to make a diagnosis or identify a fungal infection?
Sample collected
Macroscopic exam - are there particles, caseous, purulent
Direct microscopic exam + Histology - using variety of stains (KOH, Silver)
Culture
Serology
What is the difference in culture media for fungi?
Use SAB agar or mycobiotic agar - they don’t grow on normal agar
Takes 1-3 weeks, in an aerobic 30 degree environment
What is a woods lamp?
A UV light test used to identify superficial fungal infections - they will fluoresce.
What is a dermatophytosis?
Superficial fungal infection of skin, hair, nail - keratinised tissue
What species of fungus cause dermatophytosis?
Trichophyton
Epidermophyton
Microsporum
What are dermatophyte infections otherwise known as?
Ringworms
What is the name given to dermatophyte infections in the:
Body Foot Goin Scalp Hands Nail
Body - ringworm Foot - tinea pedis / atheletes foot Groin - Tinea cruris / jock's itch Scalp - Tinea Capitis Hands - Tinea manuum Nail - Tinea unguium / onchomycosis
How are dermatophytes transmitted?
close contact or indirect contact
Need moisture
Describe pityriasis Versicolour
What causes it?
A superficial infection of the stratum corneum of skin.
Causes hyperpigmentation or depigmented macules on the trunk or proximal limbs
Malassezia furfur
What causes malassezia furfur to cause an infection rather than just being a commensal?
Associated with a change from a yeast growth form to pseudohyphal form
How can you treat pityriasis versicolor?
Ketoconazole shampoo
or oral itraconazole / fluconazole
What is superficial candidiasis?
An infection of mucous membranes - thrush
Causes soft white plaques in vagina, oral cavity, oesophagus, often following antibiotics
In immunocompromised can cause systemic candidaemia - 30% mortality
What is pneumocystis ?
Caused by pneaumocystis jiroveci / carinii
Can cause PCP : pneumonia in compromised hosts (AIDS related disease)
What makes pneumocystosis an interesting fungi?
It was originally thought to be a protozoa - as has similar morphology and same drugs work.
There is no ergosterol in their membranes (seen in other fungi) and can’t grow on fungi media
BUT has fungi ultrastructure and it’s RNA is fungal
What is cyrptococcosis?
Fungal meningitis
Caused by cryptococcus neoformans
Associated with pigeon droppings worldwide, transmitted by inhalation of fungal aerosols
Begins with an asymptomatic resp infection then gets into CNS
What is histoplasmosis?
Pneumonia from bat or bird droppings containing fungi
What is madura foot?
A fungal infection from standing on a thorn in the tropics - get painless swelling then lytic lesion on the bone - needing amputation
What is meant by a fungus that is a ‘true pathogen’?
When close contact will usually cause infection - which is often asymptomatic
eg. via inhilation of fungal spores
What are some examples of fungal true pathogens?
Histoplasmosis - bats/birds, S+N america and W africa
Coccidodomycosis - Cslifornia/W america - Pneumonia
Blastomycosis - N america - Lung, forms blastomyces sand skin lesions
Paracoccidodomycosis - S america - miliary lesions + pneumonia
Where is aspergillus fungi found?
In soil and organic matter
Globally
How is aspergillus transmitted?
Inhalation to Resp tract
What occurs when you have heavy exposure of aspergillus in a normal patient?
Hypersensitivity pneumotitis
A combo of type 3 (immune complex) and type 4 (cell mediated) hypersensitivity
What symptoms do you get with a hypersensitivity pneumonitis caused by aspergillus?
Dyspnoea Cough Fever 4-6 hours after exposure Stops when away from exposure
Name some examples of hypersensitivity pneumonitis caused by aspergillus or people who get it?
Pigeon fanciers lung Farmers Humidifyer fever Brewers/malt workers Cheese workers
What investigative findings are seen with hypersensitivity pneumonitis caused by aspergillus?
Fine crackles at end of inspiration
CXR - diffuse reticulo-nodular shaddowing
CT - Bilateral consolidation and air trapping
Restrictive lung function tests
How can you treat hypersensitivity pneumonitis caused by aspergillus?
Prevent exposure
Immunosuppression to reduce T cell response
What happens when a pt with Asthma or Cystic fibrosis is expsed to a low dose of aspergillus?
ABPA - Allergic Bronchopulmonary Aspergillosis
- colonisation of the mucous plugs found in these pts, get a thype 3 + 4 hypersensitivity reaction to them
What are the symptoms of ABPA?
Fever Cough Dyspnoea Asthma worsening Coughing up casts
How can you diagnose ABPA?
Hypae in sputum
+ve skin test
Bloods: Eosinophilia, increased IgE, +ve antibodies
BAL - broncho-alveolar lavage - +ve.
How can you treat ABPA?
Long term antifungals Oral steroids to reduce T cell response Manage asthma Physio ? Bronchoscopy to remove plugs if CXR shows collapse
What happens when a pt with pre-existing cavitating lung disease is exposed to a low dose of aspergillus?
A mycetoma forms - a fungus ball
There is not real invasion of tissue, just the cavities (eg. TB, brochiectasis)
What symptoms or complications can you get with a mycetoma caused by aspergillus invasion?
Haemoptysis - fungi releases oxalic acid which erodes vessels
Often asymptomatic or weight loss, lethergy, heamoptysis
What does the histology of a mycetoma caused by aspergillus show?
Pink necrotic center
Active hypae at rim - detected in sputum culture
Air in the cavity - as aerobic
How can you manage a mycetoma caused by aspergillus?
Monitor and observe?
Surgical resection?
Antifungals don’t work as can’t penetrate it
If an immunocompromised pt is exposed to aspergillosis what can occur?
What is seen on CXR?
Get invasive aspergillosis
- inhale it, causes invasion of blood vessels and tissues within and outside the lung
- See multiple focal opacities in CXR - with halo sign due to blood film around consolidations.
- Hypae also block vessels so get multiple lung infacts
What symptoms are seen in invasive aspergillosis?
Gravely ill
Rapid consolidation and necrosis and cavitation in lung
How can you treat invasive aspergillosis?
IV anti-fungals - amphtericin + flucytosine
What is the link between aspergillus and cancer?
Aflatoxin produced by aspergillus grows on mouldy peanuts - causes HCC - hepatocellular carcinoma
Rare in UK but more in Asia
What targets do antifungals work on?
Things we don’t also have
- Ergosterol in plasma membrane
- Proteins in cell walls
What are 3 broad ways that antifungals work by?
Inhibit membrane synthesis
Inhibit membrane function
Inhibit nucleic acid synthesis and mitosis
What are three classes of antifungal that inhibit membrane synthesis?
Azoles (block chtochrome p450 - interfeers with ergosterol - toxic metabolites build up - inhibits growth and increases membrane permeability)
Echinocandins (inhibit 1,3 B-glucan synthase - less glycan inc ell wall - weak)
Allylamines (inhibit squalene epoxidase so inhibits ergosterol synthesis)
Give examples of some Azole antifungals
Ketoconazole Clotrimazole Fluconazole Intraconasole Voriconazole
What antifungal is good for thrush?
Clotrimazole or nystatin (and lots of others)
What antifungal is good for tinea barbis?
Oral fluconazole (and lots of others)
What antifungal can you use for severe tinea pedis or onychomycosis?
Oral terbinafine
What is tinea incognito?
Tinea whose appearance has been altered by inappropriate treatment, eg. topical steroid cream
What is an example of an echinocandin antifungal?
Caspofungin - IV, needs a loading dose
- good for aspergillus and candida
What is an example of an allylamine antifungal?
Terbinaine - topical or oral
Good for dermatophytes
It is lipophilic so concentrates in skin or adipose tissue
(S/e: allergic skin reaction, rarely liver toxicity)
Name two polyene antifungals (inhibit membrane function)
Amphotericin (oral but low GI absoption. Causes pores to form in fungus - cations leak - damage)
Nystatin (topical - superficial candida)
Name one antifungal that inhibits nucleic acid synthesis
Flucytosine - used in combos to reduce resistance
Name one antifungal that inhibits nucleic acid synthesis and mitosis
Griseofulvin - interacts with microtubules
been superseded mostly now, just to be used in dermatophyte infections
What are the 2 ways that a fungus can grow?
Yeast - unicellular, budding
Filamentous - multicellular, growth by hyphae, reproduce by spores
What extra growth forms can fungi grow as?
Yeast - can switch to pseudohyphae - dimorphic growth, grow but the buds don’t fully separate - often associated with commensal becoming pathogenic - candida, malassezie furfur
Filamentous - can switch to yeast-like - some fungi are filamentous in the environment but change to yeast like when they invade the body, eg. aspergillus, dermatophytes.
Treatment for: Vulvovaginal candidiasis
Clotrimazole PV + 1% cream for externalalternative: Fluconazole
Treatment for: Fungal nail infection
Terbinafine or amorolifine or itraconazole
Treatment for: Oral Candidiasis
Nystatin oral suspensionor Fluconazole oral
Treatment for: Tinea Pedis
Clotrimazole
Treatment for: Candidaemia (non-CNS)
Fluconazole
Treatment for: Aspergillosis (non-CNS)
Voriconazole
