LECTURE 14 (Mycology) Flashcards
What are the two types of Fungi?
Yeasts and Molds
- Yeasts = grow as single cells that reproduce by asexual budding
- Molds = grow as long filaments (HYPHAE) + form a mat (MYCELIUM)
Describe Hyphae
- Some hyphae form transverse walls (SEPTATE HYPHAE), whereas others don’t (NON-SEPTATE HYPHAE)
- NON-SEPTATE HYPHAE are multinucleated (Coenocytic)
- SEPTATE HYPHAE contain pores and septums, non-septate hyphae do not
- Growth of hyphae occurs by extension of tip of hyphae (not by cell division)
What does the term “thermally dimorphic” mean?
Form different structures at different temperatures
EXAMPLE: some fungi exist as moles in the environment at ambient temperature and as yeasts in human tissues at body temperature
Describe Fungi
- Most are obligate aerobes/facultative aerobes
- Require a preformed organic source of carbon
- Natural habitat is the environment (apart from “Candida albicans” which is part of the normal human flora)
Describe the two fungal cell structures that are important clinically
- The fungal cell wall is made of CHITIN
[bacterial cell wall is made of peptidoglycan so antibiotics (penicillin, cephalosporins, antibiotics) are not effective against fungi] - Fungal cell membrane contains ERGOSTEROL
[human cell membrane contain cholesterol so amphotericin B and azole drugs (fluconazole and ketoconazole) target fungi]
What are the two types of fungi?
- True pathogenic fungi
- Opportunistic fungi
What are the steps of pathogenesis of fungi?
1) ADHERENCE
[colonisation of mucosal surfaces of the GI and female genital tracts]
2) INVASION
[passing an initial surface barrier (skin, mucous membrane or respiratory epithelium) - may involve enzymes]
3) INJURY
[due to inflammatory and immunologic responses + NO EXOTOXINS!!!]
Describe the pathogenesis of Fungal infections
- Formation of granulomas
[cell-mediated immune response is involved in granuloma formation] - Acute suppuration
[characterised by presence of neutrophils] - NO ENDOTOXIN OR EXOTOXIN!!!!
Describe the testing for fungal infections
- Activation of the cell-mediated immune system results in a DELAYED HYPERSENSITIVITY SKIN TEST response to fungal antigens injected INTRADERMALLY
- POSITIVE SKIN TEST indicates exposure to fungal antigen
[does not imply current infection] - Skin testing with “CANDIDA” antigens used to determine normal cell-mediated immunity
[since “Candida” in part of normal flora]
What are the different Toxins and Allergies from fungi?
- Ingestion of AMANITA mushrooms causes LIVER NECROSIS due to presence of two fungal toxins, “AMANITIN” and “PHALLOIDIN” -> Amanitin inhibits the RNA polymerase that synthesises cellular mRNA
- Ingestion of peanuts and grains contaminated with ASPERGILLUS FLAVUS causes LIVER CANCER due to presence of AFLATOXIN -> AFLATOXIN EPOXIDE induces a mutation in the p53 gene resulting in loss of p53 tumour suppressor gene
- Inhalation of spores of ASPERGILLUS FUMIGATUS can cause ALLERGIC BRONCHOPULMONARY ASPERGILLOSIS -> IgE mediated immediate hypersensitivity response
What are the different types of fungal infections in humans?
- Superficial fungal infections
[OUTERMOST LAYERS of stratum corneum of skin or cuticle of hair shaft + usually cosmetic problems + rarely an immune response] - Dermatophyte infections
[affect hair, nails and skin] - Subcutaneous mycoses
[abundant in environment + low degree of infectivity + gain access to subcutaneous tissues through traumatic implantation] - Systemic mycoses
[primary site of infection is respiratory tract]
What are the only 6 agents that cause systemic mycoses?
- Histoplasma capsulatum
- Blastomyces dermatitidis
- Paracoccidiodes Brasiliensis
- Coccidiodes Immitis
- Penicillium marneffei
Describe the immune response against fungal infections
- Mucous membranes of the nasopharynx -> trap inhaled fungal spores and alveolar macrophages
- Most fungi readily killed by neutrophils
- Fungi that escape neutrophils grow slowly in macrophages + growth restricted when macrophages activated by cytokines
- Progressive fungal diseases occur in immune-compromised people
What are the different lab diagnosis for Fungal infections?
- Direct examination
[KOH, gram stain, skin biopsy] - Culture
[Sabouraud’s agar optimal for fungi] - Biochemical tests
[yeasts identified by biochemical tests (e.g urease production) + ability to form pseudohyphae] - DNA probes
- Antigen and antibody detection
What are the different Antifungal drugs?
- SERTACONAZOLE -> binds non-sterol lipids + alters cell membrane integrity
- POLYENES (amphotericin B + nystatin) -> Binds ergosterol + disrupts membrane integrity
- ECHINOCANDINS (anidulafungin, caspofungin and micafungin) -> Inhibit the glugan biosynthesis pathway
- AZOLES (flucanozole, miconazole, and sertaconazole) -> Inhibit the ergosterol biosynthesis pathway
- FLUROCYTOSINE -> Inhibit nucleic acid synthesis
ADDITIONAL INFO: most fungal infections are self-limiting and require no chemotherapy -> treatment is important for dissemination in immunocompromised people
Describe Antifungal therapy
- Most are unstable + toxic to humans
- Selective toxicity of AMPHOTERICIN B and AZOLE GROUP of drugs is based on presence of “ERGOSTEROL” in fungal cell membranes compared to cholesterol in humans
- Amphotericin B = binds to fungal cell membranes at site of ergosterol + disrupts integrity of membranes
- Azole drugs = inhibit synthesis of ergosterol
- Selective toxicity of ECHINOCANDINS based on presence of cell wall in fungi since humans have no cell wall -> inhibit synthesis of D-glucan (component of cell wall)
What are superficial fungal infections?
Primary manifestation is pigment change of skin
TWO TYPES:
- PITYRIASIS VERSICOLOR/TINEA VERSICOLOR = a chronic superficial fungal infection which leads to hypopigemented/hyperpigmented patches on the skin
[sunlight exposure around patches tan, causing patches to remain white + caused by MALASSEZIA FURFUR]
- TINEA NIGRA = superficial fungal infection that causes dark brown to black painless patches on soles of hands + feet
[caused by EXOPHIALA WERNECKII]
DIAGNOSIS:
Microscopic examination of skin scrapings mixed with KOH (KOH digests non-fungal debris -> reveal hyphae + spherical yeast) -> Malassezia can look like spaghetti (hyphae) with meatballs (spherical yeast)
TREATMENT:
- Spreading dandruff shampoo containing selenium sulphide over skin
- Topical anti fungal imidazoles
What are Cutaneous fungal infections/Dermatophytoses?
Dermatophytic fungi live in dead, horny layer of skin, hair and nails and secrete KERATINASE which digests keratin [digestion of keratin manifests as scaling of skin, loss of hair and crumbling of nails]
COMMON DERMATOPHYTES INCLUDE MOLDS:
- Microsporum
- Trichophyton
- Epidermophyton
COMMON INFECTIONS:
- TINEA CORPORIS (body) = following invasion of horny layer of skin, the fungi spreads -> forms a ring shape with a red, raised border -> expanding raised border represents areas of active inflammation with healing centre -> called “ringworm”
- TINEA CRURIS (jock itch) = patients develop itchy red patches on groin and scrotum
- TINEA PEDIS (athlete’s foot) = infection begins between toes -> causes crackling + peeling of skin. Infection requires warmth and moisture.
- TINEA CAPITIS (scalp) = primarily occurs in children + results in scaly red lesions with loss of hair
- TINEA UNGUIUM/ONYCHOMYCOSIS (nails) = nails are thickened, discoloured and brittle
DIAGNOSIS:
- Dissolve skin scrapings in potassium hydroxide (KOH) which digests keratin -> microscopic examination will reveal branched hyphae
- Direct examination of hair and skin with Wood’s light
TREATMENT:
- Topical Imidazoles (first-line drugs for treatment)
- Oral griseofulvin (used with Tinea capitis + unguium) -> becomes incorporated with newly synthesised keratin layers, inhibiting growth of fungi
What are the properties of Subcutaneous fungal infections?
- Gain entrance to the body following trauma to the skin
- Usually remain localised to subcutaneous tissue or spread along lymphatics to local nodes
- Fungi are normal soil inhabitants + low virulence
What is Sporotrichosis?
A subcutaneous fungal infection caused by Sporothrix Schenckii
EPIDEMIOLOGY:
- an occupation hazard for gardeners
- found in hay, moss, soil, decaying vegetation and various plants
MANIFESTATIONS:
Following a prick by a thorn contaminated with “SPOROTHRIX SCHENCKII”, a subcutaneous nodule gradually appears -> nodule becomes necrotic + ulcerates -> ulcer heals but new nodules pop up nearby + along lymphatic tracts up the arm
DIAGNOSIS:
- microscopic examination reveals yeast cells that reproduce by budding
- culture at 37C reveals yeast while culture at 25C reveals branching hyphae
TREATMENT:
- oral potassium iodide
- amphotericin B
What are Chromoblastomycosis?
A subcutaneous fungal infection caused by “PHIALOPHORA” and “CLADOSPORIUM” which are species of pigmented saprophytic fungi that cause cauliflower warts on skin
EPIDEMIOLOGY:
- Phialophora + Cladosporium are found on rotting wood
- Infection occurs after a puncture wound
MANIFESTATIONS:
Initially a small, violet wartlike lesion develops -> Over months to years, additional violet-coloured wartlike lesions arise nearby -> Clusters resemble cauliflower
DIAGNOSIS:
Skin scraping with KOH reveal copper-coloured sclerotic bodies
TREATMENT:
- Itraconazole
- Local excision
What are the three fungi that cause systemic disease in humans?
- Histoplasma capsulatum
- Blastomyces dermatitides
- Coccidioides immitis
CHARACTERISTICS:
- All dimorphic fungi (in natural habitat/soil they grow as mycelia + release spores into the air + when spores inhaled by humans, at 37C they grow as yeast cells)
- Grow as mycelial forms with spores at 25C on Sabouraud’s agar
- Grow as yeast form at 37C on blood agar
Describe the mechanism of disease of systemic fungal infections
1) Acquired by inhalation + spores are aerosolised from soil, bird droppings or vegetation
2) Local infection in lung is followed by bloodstream dissemination
[most fungi are destroyed at this point by cell-mediated immune system]
3) Coccidiodin + Histoplasmin injected intradermally in a previously exposed person -> yield a delayed type hypersensitivity reaction which results in localised swelling within 24-48 hours
What clinical presentations do the 3 systemic fungal infections have?
- ASYMPTOMATIC
- PNEUMONIA
[mild pneumonia can develop with fever, cough and chest X-ray infiltrates + severe pneumonia marked by weight loss, night sweats and low-grade fevers] - DISSEMINATED
[meningitis, bole lytic granulomas, skin granulomas that break down into ulcers + occur commonly in immunocompromised hosts]
Describe systemic fungal infections compared to Tuberculosis
LIKE TUBERCULOSIS:
- inhaled, primary infection in lung
- asymptomatic, mild, severe or chronic lung infections
- lung granulomas, calcifications and/or cavitations
- can disseminate hematogenously to distant sites
- skin test like PPD
UNLIKE TUBERCULOSIS:
- no person-to-person transmission
- fungi with spores NOT acid-fast bacteria
What is the diagnosis and treatment for systemic fungal infections?
DIAGNOSIS:
- Obtaining of affected tissue (skin biopsy, biopsy of lung lesions) -> tissue can be examined with silver stain for yeast or grown on Sabouraud’s agar or blood agar
- Skin tests not very helpful since many people are exposed asymptomatically -> positive test regardless
- Serologic tests (complement fixation, latex agglutination)
TREATMENT:
- Acute pulmonary histoplasmosis + Coccidoidomycosis = no treatment
- Chronic or disseminated disease = Itraconazole or amphotericin B
- All Blastomyces infections = require aggressive amphotericin B or Itraconazole treatment
What is Cryptococcosis?
A systemic fungal infection caused by “CRYPTOCOCCUS NEOFORMANS” which is a polysaccharide encapsulated yeast inhaled into lungs + infection is usually asymptomatic. Differs since causes MENINGOENCEPHALITIS not pneumonia.
EPIDEMIOLOGY & TRANSMISSION:
- fungus found in nature, especially in pigeon droppings
- following inhalation + local lung infection, often asymptomatic -> yeast spreads via blood to brain
- most cases occur in immunocompromised persons
MANIFESTATION:
- subacute chronic meningitis
[fatal without treatment since cerebral oedema progresses to eventual brainstem compression]
- headache
- nausea
- confusion
- staggering gait + cranial deficits
- fever
- pneumonia, skin ulcers and bone lesions
DIAGNOSIS:
- lumbar puncture + analysing cerebrospinal fluid
- cryptococcal antigen test
- culture
TREATMENT:
- amphotericin B + flucytosine
[require treatment for 6 months but AIDS patients require treatment for life]
What is Candidiasis?
A fungal infection caused by Candida albicans
[in normal hosts, there are 3 cutaneous infections; in immunocompromised hosts, 3 cutaneous infections can occur as well as invasive systemic disease]
NORMAL HOSTS:
- Oral thrush = patches of creamy white exudate with a reddish base cover the mucous membranes of mouth
[TREATMENT: swish and spit preparations of nystatin or amphotericin B or imidazole candies]
- VAGINITIS = vaginal itching and discharge + inflamed vaginal mucosa and patches of cottage cheese white clumps affixed to the vaginal wall (most common when takin antibiotics, contraceptives or during menses and pregnancy)
[TREATMENT: imidazole vaginal suppositories]
- DIAPER RASH = warm moist areas become red and macerated
IMMUNOCOMPROMISED HOSTS:
- ESOPHAGITIS = extension of thrush into oesophagus causes burning substernal pain worse with swallowing
- DISSEMINATED = invades bloodstream + every organ
[when Candidiasis suspected, retina must be examined with opthalmoscope -> multiple white fluffy candidal patches may be visualised]
DIAGNOSIS:
- cultured from urine, sputum and stool
- KOH preparation of skin scraping or with stains and cultures of biopsied tissue or blood
TREATMENT:
systemic infection requires amphotericin B or oral anti-fungal imidazole called FLUCONAZOLE
What is Aspergillosis?
A respiratory fungal infection caused by “ASPERGILLUS FLAVUS”
EPIDEMIOLOGY:
- Spores of Aspergillus mild are floating everywhere -> some causing an asthma-type reaction
MANIFESTATIONS:
- Type 1 hypersensitivity reaction (IgE-mediated immediate allergic reaction) = bronchospasm, increase in IgE antibodies and blood eosinophilia
- Type 4 hypersensitivity reaction (delayed type cell-mediated allergic reaction) = cell-mediated inflammation + lung infiltrates
- People with lung cavitations from tuberculosis or malignancies can grow a aspergillum fungal ball in the cavity called a “ASPERGILLOMA” -> ball can be large requiring surgical removal
- Aspergillus flavus produce AFLATOXIN (a mycotoxin) which causes liver damage and liver cancer
- Immunocompromised hosts develop invasive pneumonias + disseminated disease -> blood sputum may occur due to blood vessel wall invasion
TREATMENT:
- Systemic corticosteroids
