Case 17- Fungi Flashcards
Fungi
1) Type of eukaryotic organisms
2) Cell wall is made of chitin
3) Heterotrophs that do not photosynthesis
4) Saprotrophic- removal of dead matter
5) Symbiotic and parasitic
Fungal morphology
- Filamentous- when visible referred to as mould, though not all mould are fungi. They grow as multinucleate, branching hyphae forming a mycelium
- Yeast- unicellular, replicates by binary fission. They grow as ovoid or spherical single cells
- Dimorphic- able to change from one form to another depending on environmental factors
The human mycobiome
- The fungal community in and on the organism. Less then 0.1% of the human microbiome, but more significant in the ear
- Role- maintaining microbial community structure, metabolic function and immune priming
- Change in mycobiome associated with disease- CF, obesity, hepatitis
- Dysbiotic Mycobiota- imbalance in the mycobiome, including introduction of non-resident fungi, causing disease
Fungal infections in different bodies cavities
- Oral cavity- Aspergillus, Cryptococcus, Candida, Furasium
- Lungs- Aspergillus, Candida
- GI tract- Aspergillus, Candida, Cryptococcus Furasium, Pneumocystitis
- Skin- Aspergillus, Candida, Cryptococcus, Trichophyton, Microsporum
Causes of fungal dysbiosis in the mouth
Due to HIV mediated immunodeficiency, correlates with decreased number of Cd4+ T cells. Overgrowth of Candida
Causes of fungal dysbiosis in the lungs
Can be caused by cystic fibrosis- Candida spp
Causes of fungal dysbiosis in the skin
Primary immunodeficiencies that disrupt the Th17 pathway such as STAT3 mutatiobs
Causes of fungal dysbiosis in the gut
Induced by antibiotic mediated depletion of bacteria, genetic defects in antifungal immunity pathways, changes in diet, antifungal drugs and inflammation
Routes of fungal transmission
- Anthropophilic- human to human (mild)
- Zoophilic- animal to animal or animal to human
- Geophilic- animal to soil to man (rare), usually saprotrophic fungi
- Allergic fungal disease
Types of mycoses
- Superficial mycoses, body surfaces- skin, hair, nails, mouth, vagina
- Subcutaneous mycoses- nails and deeper layers of the skin
- Systemic/deep mycoses- internal organs, immunocompromised patients at greater risk
Superficical fungal infection- Ringworm
Tinea, Dermatophytosis. A common superficial presentation of a mild fungal infection which multiple causes. There are 40+ different species including Trichophyton, Microsporum or Epidermophyton. Causes an itchy, red, circular rash. Red skaly and cracked and hair loss
Different forms of ringworm- based on body location
- Tinea faciei- ringworm of the face
- Tinea capitis- ringworm of the scalp
- Tinea manus- ringworm of the hand
- Tinea corporis- ringworm of the body
- Tinea cruris- ringworm of the groin
- Tinea unguium- ringworm of the nails
- Tinea pedis- ringworm of the foot
Sources of fungal infections
- Person to person contact- sharing towels or other personal items. Physical translocation.
- Animal to person contact- common on farms, petting zoos. Pets who pick it up from other animals including humans
- Environment- damp areas like locker rooms and public showers, bare feet
Treatment for fungal infection (ring worm)
- Tinea pedia- over the counter topical antifungal (cream). Terbinafine is the most effective
- Tinea capitis- you need systemic antifungal medication, topical antifungals are not effective. For example- Griseofulvin, terbinafine, traconazole, fluconazole
- Tinea corporis/cruris- over the counter topical antifungal
Superficical yeast infection- Candidiasis
- Fungal infection by yeast in the genus Candida, most common species is C.albicans. Over 20 species
- Candidia spp. are normal commensal fungi of the skin and GI tract. Over-growth can lead to issues
- Oral candidiasis= oral thrush, most common yeast infection
Symptoms of Candidia infections of the mouth, throat and oesophagus
- White patches on the inner cheeks, tongue, roof of the mouth, and throat
- Redness or soreness
- Cottony feeling in the mouth
- Loss of taste
- Pain while eating or swallowing
- Cracking and redness at the corners of the mouth
- Can scrape off
Risk factors for Candida infections of the mouth, throat and oesophagus
- Wear dentures
- Have diabetes
- Have cancer
- Have HIV/AIDS
- Take antibiotics or corticosteroids, including inhaled corticosteroids for conditions like asthma
- Take medications that cause dry mouth or have medical conditions that cause dry mouth
- Smoke
Symptoms of vaginal Candidiasis
• Vaginal itching or soreness • Pain during sexual intercourse • Pain or discomfort when urinating • Abnormal vaginal discharge • Yeast smell Diagnosed by taking a sample of discharge and sending it to the lab
Risk factors for Vaginal Candidiasis
- Pregnant
- Uses hormonal contraceptives
- Has diabetes
- Has a weakened immune system (for example, due to HIV infection)
- Are taking or have recently taken antibiotics
Diagnosis of Vaginal Candidiasis
- Physical- often lesions are well characterised with multiple lesions present, exudative lesions are characteristic of bacterial infections
- Microscopy- potassium hydroxide (KOH) stain, may use UV light
- Culture- only if KOH tests is inconclusive, takes +3 weeks due to slow growth
Subcutaneous fungal infections
1) Sporotrichosis-rose gardeners disease
2) Mycetoma
Sporotrichosis-rose gardeners disease
- Types: Cutaneous (skin) and Pulmonary (lung- very rare), Disseminated Sporotrichosis
- Infection by the fungus Sporothrix schenckii
- Associated with the handling of plant matter
- Chronic disease, rare, slow to develop
- Initial lesion (cut), spread via lymph nodes
Mycetoma
- Subcutaneous infection
- A chronic granulomatous inflammatory disease of the deep dermis/subcutaneous tissue possibly affecting the bone i.e. Madurella mycetomatis
- Trauma mode of entry- puncture wounds such as snake bites, knives, splinters, thorns and insect bites.
Systemic fungal infections
1) Systemic Mycoses
2) Invasive Candidiasis
3) Candida auris
4) Aspergilosis
Systemic Mycoses
• Yeasts- Candida, Pneumocystitis jiroveci
• Moulds- Aspergillus, Zygomycetes (mucor)
• Dimorphic fungi- Cryptococcus neoformans, Histomplasma capsulatum, Coccidiodes immitis, Paracoccidiodes brasiliensis
In immunocompromised patients you tend to get fungal lower respiratory tract infections
Invasive Candidiasis
- Candidemia, a blood stream infection of Candida is a common infection in hospitalized patients. Often as a result of HIV
- Difficult to diagnose as hard to separate symptoms from HIV
- You get fever and chills which don’t improve after antibiotic treatment for a suspected bacterial infection.
Risk factors for invasive Candidiasis
- Patients who have a central venous catheter
- Patients in the intensive care unit (ICU)
- Immunocompromised (HIV)
- Patients on broad-spectrum antibiotics
- Neutropenia
- Kidney failure or are on haemodialysis
- Recent surgery esp. GI surgery
- Diabetes
Treatment options for oral thrush
Antifungal applied to the inside of the mouth for 7 to 14 days. Clotrimazole, Miconazole or nystatin. For unresponsive infection fluconazole by mouth
Treatment options for Vaginal Candidiasis
Antifungal applied inside the vagina or a single dose of fluconazole taken by mouth. For recurrent infections use a course of fluconazole
Treatment options for Invasive Candidiasis
Fluconazole, Echinocandin- if patients cant tolerate use of fluconazole.
Candida auris
- An emerging pathogen- first identified in Japan in 2009
- Associated with infection in immune compromised patients
- Presents as invasive candiasis
- Multidrug resistance
Aspergillosis
- Caused by Aspergills spp i.e. A.fumigatus and A.flavus
- A common mould in the environment, constant exposure, generally harmless
- People at risk- immunosuppressed
- Range of condition from mild hay fever (allergic aspergillosis) to severe (invasive aspergillosis)
Signs and symptoms of Aspergillosis
- Chest pain
- Pneumonia
- Vision difficulties
- Blood in sputum
- Headaches
- Anorexia
- Blood in urine
Pulmonary aspergilloma
- Localized pulmonary infection in people with underlying lung disease, allergic bronchopulmonary disease, allergic sinusitis, allergic alveolitis
- Pulmonary aspergilloma - colonisation of pre-existing cavities e.g. previous TB
- Can cause necrotising inflammation of the lungs: Infarction -> necrosis -> oedema -> bleeding. You get formation of granulomas and cavity wall invasion
Invasive Aspergillosis in the immune compromised i.e. HIV and transplant patients
- Pulmonary aspergilloma
- Invasive tracheobronchitis
- Invasive sinusitis
- Endocarditis
- Disseminated disease
Treatment for Aspergillosis
- Allergic forms of aspergillosis- Itraconazole, Corticosteroids may also help
- Invasive aspergillosis- usually voriconazole or Lipid amphotericin formulations, Posaconazole, Isavuconazole, Itraconazole, Caspofungin and Micafungin. If a patient is on an immunosuppressant remove the drug, Nystatin has no clinical effect on immunosuppressed patients.
Fungal meningitis- spread of fungus/yeast to spinal cord
- Cryptococcus, most common cause of meningitis in Africa
- Histoplasma, USA Midwest.
- Blastomyces USA Midwest.
- Coccidioides (Southwestern US and parts of Central and South America
- All are fungi found in soil, Cryptococcus is associated with bird droppings
- Caused by immunosuppression
Antifungal agents
- Echinocandins (beta-glucan synthesis)- works in Candida spp and Aspergilus spp. Not for dimorphics
- Polyenes (disrupts membrane integrity)- works for all except Aspergillus terreus
- Azoles (inhibits ergosterol synthesis)- works for all except candida grabrata. Fluconazole is ineffective in Candide krusei and moulds
- 5-FC (inhibits nucleic acid synthesis)- works in all yeast although resistance occurs quickly, ineffective for mould and dimorphics
Treatment for invasive candidiasis
1) Echinocandin
2) Amphotericin
Treatment for Aspergillosis
1) Voriconazole
2) Amphotericin
Treatment for Cryptococcosis
1) Amphotericin
2) Fluconazole
Treatment for mild infections- skin/head/crotch
1) Over the counter products
2) Oral azole
Treatment for Tinea capitis
1) Griseofulvin- inhibits tubulin polymerisation
2) Terbinafine
Treatment for nail infections
1) Terbinafine / Traconazole
How can anti-fungal drugs be administered
1) Topical antifungal
2) Oral antifungal
3) Intravenous antifungal
4) Intravaginal antifungal pessaries
Types of antifungal drugs
- Flucytosine- inhibits DNA and RNA synthesis
- Griseofulvin- disrupts microtubule function
- Naphthoquinone- inhibits mitochondria function
- Polyenes- disrupts membrane
- Imidazole and allylamine- inhibits ergosterol synthesis
- Polyoxins and nikkomycins- inhibits chitin synthesis
- Ethinocandines- inhibits synthesis of beta 1->3 glucans
5-Fluoroccystosine (5-FC)
Targets RNA and DNA synthesis. Usually given in conjunction with another antifungal such as Amphotericin B. 5-FC by itself has relatively weak antifungal activity and resistance readily arises.
Polyene antifungals
Interacts with ergosterol in the fungal cell membrane. Disrupts the structural integrity of the membrane. The cell leaks ions (Na+, K+) and dies. Human cells don’t have ergosterol so selective toxicity against fungi. For example, Nystatin and Amphotericin B.
Allymine antifungals
Inhibits ergosterol synthesis by inhibiting squalene epoxidase. Disrupts membrane structure and function. Inhibits fungal growth. For example, Terbinafine.
Azole antifungals
Inhibits the enzyme ‘lanosterol 14 alpha-demethylase.’ Inhibits the synthesis of ergosterol. Disrupts membrane structure and function. Inhibits fungal growth. For example, Fluconazole, Itraconazole.
Echinocandin antifungals
Used for systemic fungal infections in immunocompromised patients. Inhibits the synthesis of glucan in the cell wall via the enzyme ‘1,3-beta-glucan synthase.’ Intravenous injection, poor aqueous solubility and availability. For example, Anidulafungin and Caspofungin
