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Fungal Infections Flashcards

1
Q

What are the 3 main fungal species?

A

Aspergillus species Candida species Cryptococcus species

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2
Q

Fungal pathogens are _______ in nature.

A

Opportunistic

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3
Q

Give examples of patients who may be more affected by fungal infections

A

Those with impaired immune systems (AIDS, primary immunodeficiencies, malignancies, transplants, premature neonates)

Those with chronic lung dx (CF, asthma, chronic obstructive lung disorders)

Those in ICU

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4
Q

What is candida a type of?

A

Yeast

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5
Q

What is the most common cause of fungal infections worldwide?

A

Candida

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6
Q

What is candidiasis?

A

Candida infection (due to any type of candida)

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7
Q

What is the most common cause of candidiasis?

A

Candida albicans

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8
Q

Most candida are harmless - when do they pose a threat to someone’s health?

A

When mucosal barriers are disrupted/immune system is impaired they can invade and cause disease

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9
Q

What are the risk factors for mucocutaneous candidiasis?

A

Post-antibiotic use

Moist areas

Inhalational steroids (oral thrush)

Neonates (<3m)

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10
Q

Why are neonates more prone to candiasis?

A

As they have an immature immune system

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11
Q

Why are you more prone to candidiasis after a course of antibiotics?

A

Antibiotics lead to imbalance in local flora which allows candida to thrive

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12
Q

Mucocutaneous candidiasis is the presenting symptom of primary immunodeficiency disorders characterised by what things?

A

Neutropenia

Low CD4 T-cells

Impaired IL17 immunity

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13
Q

What is IL-17?

A

Pro-inflammatory cytokine produced by T-helper 17 cells

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14
Q

True or false:

Candida is a respiratory commensal

A

FALSE - it is a gut commensal

Found in low numbers on skin, GI, GU tracts, mouth

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15
Q

What is the most common pathogenesis of invasive candidiasis?

A

Local mucocutaneous infection –> breach of skin/mucosal barrier or translocation (e.g. IV catheterisation) –> direct invasion into bloodstream (candidaemia) –> spread to visceral tissues –> disseminated organ infection

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16
Q

What is the mortality of invasive candidiasis?

A

Up to 40%

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17
Q

What is the clinical presentation of invasive candidiasis?

A

Classical presentation as bacterial bloodstream infection (may vary from fever –> sepsis)

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18
Q

What are the risk factors for invasive candidiasis?

A
  • Broad spectrum antibiotics
  • IV catheters
  • TPN
  • Abdominal surgery
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19
Q

How do you diagnose invasive candidiasis?

A

Blood culture/culture from normally sterile site

?Developments in PCR

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20
Q

Lack of ____________ is a good negative predictor to exclude invasive candidiasis.

A

Beta-d-glucan (naturally occuring polysaccharide in the cell wall of fungi)

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21
Q

How do you treat invasive candidiasis?

A

Enchocandins or fluconazole

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22
Q

Aspergillus is a type of _______.

A

Mould

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23
Q

Aspergillus spores are _______ but do not usually cause infection in patients who are ___________.

A

Ubiquitous

Immunocompetent

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24
Q

Describe the process of sporulation in A. fumigatus

A

A. fumigatus produces a small, hydrophobic conidia (asexual, non-motile fungal spore) which are easily dispersed in air currents

25
How are aspergillus spores spread?
Through inhalation of airborne spores
26
What is the most common aspergillus species to cause disease in the immunodeficient?
Aspergillus fumigatus
27
Describe the pathogenesis of invasive pulmonary aspergillosis
Sporulation of a microbe --\> conidia inhaled into alveola --\> conidial germination (grows into mould) in absence of pulmonary defences
28
What occurs in those with invasive pulmonary aspergillosus due to corticosteroid induced immunodeficiency?
Polymorphonuclear neutrophils are recruited and tissue is damaged
29
What occurs in those with invasive pulmonary aspergillosus due to neutropenia?
Excessive hyphal growth and dissemination
30
Describe what hyphi of aspergillus look like
Long, branching form of aspergillus
31
What are the three classifications of pulmonary aspergillus disease?
Acute invasive pulmonary aspergillosis Chronic pulmonary aspergillosis (\>3m, tends to be those with chronic lung disease) Allergic aspergillosis (e.g. in those with CF, asthma)
32
What are the clinical consequences of acute invasive pulmonary aspergillosis in the neutropenic host?
* Thrombosis and haemorrhage * Angio-invasive and dissemination *
33
What are the clues in someone's presentation that may indicate an acute invasive pulmonary aspergillosis?
Persistent febrile neutropenia despite broad-spectrum antibiotics Absent/non-specific clinical signs and symptoms
34
How do you treat acute invasive aspergillosis?
Voriconazole or isavuconazole
35
What is the presentation of sub-acute invasive pulmonary aspergillosis?
* Non-angioinvasive * Limited fungal growth * Polygranulomatous infiltrates * Tissue necrosis * Excessive inflammation
36
What primary immunodeficiencies may present as invasive aspergillosis?
Congenital neutropenia Chronic granulomatous disease Hyper IgE syndrome CARD-9 deficiency In these groups, the presentation is often outside the lungs, e.g. bone, spine, brain
37
When should you be suspicious of chronic pulmonary aspergillosis?
Pulmonary exacerbations not responding to antibiotics with lung function decline & increased respiratory symptoms Positive sputum cultures for aspergillus
38
What is allergic bronchopulmonary aspergillosis?
Immunological response to A. fumigatus antigens in the CF host resulting in acute/subacute deterioriation of lung function & respiratory symptoms, new abnormalities in chest imaging, elevated IgE levels (incl. IgE specific for aspergillus/+ve skin prick test), positive IgG for aspergillus
39
How do you diagnose pulmonary aspergillosis in non-neutropenic patients?
Cultures of sputum and/or bronchoalveolar lavage and/or biopsy Aspergillus specific IgG and IgE in chronic and allergic pulmonary aspergillosis
40
How do you diagnose pulmonary aspergillosis in neutropenic patients?
High resolution chest CT (halo sign/air crescent sign) Molecular markers in blood - galactomannan and PCR-aspergillosis Bronchoalveolar lavage and biopsies if patient well enough
41
What is glactomannan?
Component of cell wall of aspergillus (released during its growth)
42
What is bronchoalveolar lavage?
When a bronchoscope is put through the nose/mouth into the lungs and fluid is squirted into a small part of the lung and re-collected for examination
43
What are cryoptococci types of?
Yeast
44
Which of the cyrptococci is the main pathogen?
Cyrptococcus neoforms
45
Extrapulmonary cryptococcal infection is what kind of disease?
AIDS defining illness
46
How is cryptococcus transmitted and where can it be found?
Inhalation Found on trees, bird faeces, organic matter
47
What is the clinical presentation of cryptococcosis?
Pulmonary infection, varies from asymptomatic to pneumonia Dissemination to bring (meningoencephalitis in those with HIV/AIDS) Clinical presentation: headache, confusion, altered behaviour, visual disturbances, coma
48
At what CD4 count do most cases of cryptococcal meningitis occur in those with HIV?
\<100
49
How do you diagnose cryptococcal disease?
CSF - india ink preparation or culture (high protein, low glucose, cryptococcus antigen) Blood - culture, cryptococcal antigen
50
What factors are associated with higher mortality in those with cryptococcal meningitis?
* Delay in presentation and diagnosis * Lack of access to antifungals * Inadequate induction therapy * Delays in starting anti-retroviral therapy * Immune reconstitution syndrome
51
How do you treat cryptococcal meningitis?
AmB + Flucytosine Followed by fluconazole maintenance
52
How does amphotericin B work?
Acts on ergosterol to cause lysis Ergosterol is a component of the fungi cell membrane
53
Which anti-fungal has the broadest anti-fungal activity?
Amphotericin B
54
How do azoles work?
Inhibit ergosterol synthesis
55
How do echocandins work?
Inhibit glucan synthesis These can be used for invasive candidiasis
56
How does flucytosine work?
Inhibits fungal DNA synthesis
57
What are risk factors for invasive asperigllosis?
HIV Leukaemia Following broad spectrum antibiotics
58

Infection (22 decks)

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