Case 17- Fungi Flashcards

1
Q

Fungi

A

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

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2
Q

Fungal morphology

A
  • 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
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3
Q

The human mycobiome

A
  • 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
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4
Q

Fungal infections in different bodies cavities

A
  • Oral cavity- Aspergillus, Cryptococcus, Candida, Furasium
  • Lungs- Aspergillus, Candida
  • GI tract- Aspergillus, Candida, Cryptococcus Furasium, Pneumocystitis
  • Skin- Aspergillus, Candida, Cryptococcus, Trichophyton, Microsporum
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5
Q

Causes of fungal dysbiosis in the mouth

A

Due to HIV mediated immunodeficiency, correlates with decreased number of Cd4+ T cells. Overgrowth of Candida

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6
Q

Causes of fungal dysbiosis in the lungs

A

Can be caused by cystic fibrosis- Candida spp

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7
Q

Causes of fungal dysbiosis in the skin

A

Primary immunodeficiencies that disrupt the Th17 pathway such as STAT3 mutatiobs

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8
Q

Causes of fungal dysbiosis in the gut

A

Induced by antibiotic mediated depletion of bacteria, genetic defects in antifungal immunity pathways, changes in diet, antifungal drugs and inflammation

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9
Q

Routes of fungal transmission

A
  • 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
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10
Q

Types of mycoses

A
  • 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
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11
Q

Superficical fungal infection- Ringworm

A

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

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12
Q

Different forms of ringworm- based on body location

A
  • 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
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13
Q

Sources of fungal infections

A
  • 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
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14
Q

Treatment for fungal infection (ring worm)

A
  • 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
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15
Q

Superficical yeast infection- Candidiasis

A
  • 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
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16
Q

Symptoms of Candidia infections of the mouth, throat and oesophagus

A
  • 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
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17
Q

Risk factors for Candida infections of the mouth, throat and oesophagus

A
  • 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
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18
Q

Symptoms of vaginal Candidiasis

A
• 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
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19
Q

Risk factors for Vaginal Candidiasis

A
  • Pregnant
  • Uses hormonal contraceptives
  • Has diabetes
  • Has a weakened immune system (for example, due to HIV infection)
  • Are taking or have recently taken antibiotics
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20
Q

Diagnosis of Vaginal Candidiasis

A
  • 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
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21
Q

Subcutaneous fungal infections

A

1) Sporotrichosis-rose gardeners disease

2) Mycetoma

22
Q

Sporotrichosis-rose gardeners disease

A
  • 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
23
Q

Mycetoma

A
  • 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.
24
Q

Systemic fungal infections

A

1) Systemic Mycoses
2) Invasive Candidiasis
3) Candida auris
4) Aspergilosis

25
Q

Systemic Mycoses

A

• 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

26
Q

Invasive Candidiasis

A
  • 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.
27
Q

Risk factors for invasive Candidiasis

A
  • 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
28
Q

Treatment options for oral thrush

A

Antifungal applied to the inside of the mouth for 7 to 14 days. Clotrimazole, Miconazole or nystatin. For unresponsive infection fluconazole by mouth

29
Q

Treatment options for Vaginal Candidiasis

A

Antifungal applied inside the vagina or a single dose of fluconazole taken by mouth. For recurrent infections use a course of fluconazole

30
Q

Treatment options for Invasive Candidiasis

A

Fluconazole, Echinocandin- if patients cant tolerate use of fluconazole.

31
Q

Candida auris

A
  • An emerging pathogen- first identified in Japan in 2009
  • Associated with infection in immune compromised patients
  • Presents as invasive candiasis
  • Multidrug resistance
32
Q

Aspergillosis

A
  • 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)
33
Q

Signs and symptoms of Aspergillosis

A
  • Chest pain
  • Pneumonia
  • Vision difficulties
  • Blood in sputum
  • Headaches
  • Anorexia
  • Blood in urine
34
Q

Pulmonary aspergilloma

A
  • 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
35
Q

Invasive Aspergillosis in the immune compromised i.e. HIV and transplant patients

A
  • Pulmonary aspergilloma
  • Invasive tracheobronchitis
  • Invasive sinusitis
  • Endocarditis
  • Disseminated disease
36
Q

Treatment for Aspergillosis

A
  • 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.
37
Q

Fungal meningitis- spread of fungus/yeast to spinal cord

A
  • 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
38
Q

Antifungal agents

A
  • 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
39
Q

Treatment for invasive candidiasis

A

1) Echinocandin

2) Amphotericin

40
Q

Treatment for Aspergillosis

A

1) Voriconazole

2) Amphotericin

41
Q

Treatment for Cryptococcosis

A

1) Amphotericin

2) Fluconazole

42
Q

Treatment for mild infections- skin/head/crotch

A

1) Over the counter products

2) Oral azole

43
Q

Treatment for Tinea capitis

A

1) Griseofulvin- inhibits tubulin polymerisation

2) Terbinafine

44
Q

Treatment for nail infections

A

1) Terbinafine / Traconazole

45
Q

How can anti-fungal drugs be administered

A

1) Topical antifungal
2) Oral antifungal
3) Intravenous antifungal
4) Intravaginal antifungal pessaries

46
Q

Types of antifungal drugs

A
  • 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
47
Q

5-Fluoroccystosine (5-FC)

A

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.

48
Q

Polyene antifungals

A

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.

49
Q

Allymine antifungals

A

Inhibits ergosterol synthesis by inhibiting squalene epoxidase. Disrupts membrane structure and function. Inhibits fungal growth. For example, Terbinafine.

50
Q

Azole antifungals

A

Inhibits the enzyme ‘lanosterol 14 alpha-demethylase.’ Inhibits the synthesis of ergosterol. Disrupts membrane structure and function. Inhibits fungal growth. For example, Fluconazole, Itraconazole.

51
Q

Echinocandin antifungals

A

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