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Fungal Infections Flashcards

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1
Q

name the main fungal pathogens

A

aspergillus sp - aspergillus fumigatus
candida sp - candida albicans
cryptococcus sp - cryptococcus neoformans

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2
Q

fungal pathogens are what in nature?

A

opportunistic

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3
Q

fungal pathogens affect what groups of people?

A

impaired immune system: primary immunodeficiences, HIV/AIDS, malignancies, transplants, premature neonates

chronic lung disease: asthma, CF, chronic obstructive lung disorders

Patients in ICU

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4
Q

name common infections caused by: pneumocystis spp

A

pneumocystis pneumonia

ophthalmic pneumocystosis
hepatosplenic infiltrates
renal pneumocystosis
bone marrow infiltrates

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5
Q

name common infections caused by: aspergillus spp

A

allergic and invasive pulmonary aspergillosis
aspergilloma

cerebral aspergillosis
keratitis
sinusitis
osteomyeliti
cutaeneous aspergillosis
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6
Q

name common infections caused by: candida spp

A

thrush
candidaemia

cerebral abscess
oesophagitis
endocardinitis
hepatic abscess
renal abscess
urinary candidiasis
vulvovaginal candidiasis
osteomyelitis
cutaneous candidiasis
onchomycosis
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7
Q

name common infections caused by: cryptococcus spp

A

meningitis

cerebral absecc
endophathlamitis
pulmonary infiltrates
endocarditis
crytococcaemia
renal abscess
subcutaneous abscess
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8
Q

what is mucocutaneous candidiasis associated with?

A

antibiotic use

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9
Q

where is mucocutaneous candidiasis found?

A

moist areas

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10
Q

oral candidiasis is associated with?

A

inhalation steroids

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11
Q

what age group are vulnerable to mucocutaneous candidiasis?

A

< 3 months

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12
Q

presenting symptoms of primary immunodeficiency disorders

A

neutropenia
low CD4+ T cells
impaired IL-17 immunity

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13
Q

what are the 4 types of impaired IL-17 immunity?

A

AD-hyper IgE syndrome - deficit of IL-17 producing cells

Dectin-1 deficiency - reduced IL=17 producing cells

CARD9 deficiency - low proportion of circulating IL-17 T cells

APECED syndrome - high titers of neutralising Ab against IL-17A, IL-17F and/or IL-22

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14
Q

most invasive candidiasis infections are what in origin and why?

A

endogenous because gut commensal

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15
Q

what can invasive candidiasis present as?

A

bacterial blood stream infection

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16
Q

what is the mortality rate of invasive candidiasis?

A

up to 40%

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17
Q

risk factors for developing invasive candidiasis

A

broad spectrum antibiotics
intravascular catheters
TPN
abdominal surgery

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18
Q

how can you diagnose invasive candidiasis?

A

Take a blood culture or culture from a normally sterile site. B-d-glucan high NPV and performs very well to exclude invasive candidiasis. Recent developments in PCR assays very promising. In infants and children performance lower due to sampling issues.

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19
Q

how is aspergillus spread?

A

airborne

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20
Q

describe aspergillus spores

A

hydrophobic conidia

diameter approx 2-3um

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21
Q

name the classification of pulmonary aspergillus disease

A

acute invasive pulmonary aspergillosis
chronic pulmonary aspergillosis
allergic aspergillosis

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22
Q

who gets acute invasive pulmonary aspergillosis?

A

neutropenic patients
post transplant: stem cell > solid organ
patients with defects in phagocytes

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23
Q

who gets chronic pulmonary aspergillosis?

A

patients with underlying chronic lung conditions

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24
Q

when does aspergillosis pulmonary become chronic?

25
who gets allergic aspergillosis ?
allergic bronchopulmonary aspergillosis in CF ans asthma | asthma or CF with fungal sensitisation
26
describe effects acute invasive pulmonary aspergillosis
rapid and extensive hyphal growth thrombosis and haemorrhage angioinvasive and dissemination
27
acute invasive pulmonary aspergillosis signs and symptoms
absent or non specigic | persistent febrile neutropenia despite broad spectrum antibiotics
28
acute invasive pulmonary aspergillosis mortality
50%
29
effects of sub acute invasive pulmonary aspergillosis
``` non-angioinvasive limited fungal growth pyogranulomatous infiltrates tissue necrosis excessive inflammation ```
30
who does sub acute invasive pulmonary aspergillosis affect?
non-neutropenic host (graft vs host disease, neutrophil disorders)
31
signs and symptoms of sub acute invasive pulmonary aspergillosis
non-specific | mild-moderate systemic illness
32
sub acute invasive pulmonary aspergillosis mortality
20-50%
33
discuss invasive aspergillosis as a presenting symptom of primary immunodeficiency
``` • Congenital neutropenia • Chronic granulomatous disease o Phagocytic disorder • Hyper IgE syndrome (Job’s syndrome) o Phagocytic disorder and impaired IL-17 pathway • CARD-9 deficiency o Innate immune pathways, killing defect ``` Clinical presentation is often outside the lungs; e.g. bones, spine, brain, abdomen.
34
discuss chronic pulmonary aspergillosis
• Asthma, cystic fibrosis, chronic obstructive lung disorders • Pulmonary exacerbations (not responding to antibiotics) • Lung function decline • Increased respiratory symptoms as cough, decreased exercise tolerance and dyspnoea • Positive sputum cultures for aspergillus o 50% of CF patients are infected • High morbidity but causative mortality rates less clear
35
discuss allergic bronchopulmonary aspergillosis
Immunological responses to a variety of A. fumigatus antigens in the CF-host (10-15%) result in: • Acute/subacute deterioration of lung function and respiratory symptoms • New abnormalities chest imaging • Elevated IgE level • Increases aspergillus specific IgE or positive skin test • Positive aspergillus specific IgG
36
pulmonary aspergilloma who does it affect?
``` tuberculosis sarcoidosis bronchiectasis bronchial cysts and bullae after pulmonary infections ```
37
emerging non-neutropenic hosts vulnerable to aspergillus?
* Respiratory insufficiency > intubation ICU * Influenza A > Th: oseltamivir, corticosteroids, antibiotics * A. fumigatus in sputum by day 3
38
diagnosis of pulmonary aspergillosis in the non-neutropenic host
cultures of sputum and/or bronchoalveolar lavage, and/or biopsy aspergillus specific IgG or IgE in chronic and allergic
39
diagnosis of pulmonary aspergillosis in the neutropenic host
high resolution CT chest - halo sign, air crescent sign molecular markers in blood: galactomannan and PCR aspergillus BAL and biopsies if clinical condition allows
40
how cryptococcus is spread?
inhalational
41
where can cryptococcus be found?
bark on a variety of trees bird faeces organic matter
42
what can cryptococcus cause?
pulmonary infection ranging from asymptomatic to pneumonia
43
cryptococcus can disseminate to the brain causing?
meningoencephalitis in HIV and AIDS patients
44
clinical presentation of cryptococcus
``` headache confusion altered behaviour visual disturbances coma due to raised ICP in 60-80% ```
45
diagnosis of cryptococcal disease: CSF
Indian Ink preparation culture high protein and low glucose cryptococcus antigen
46
diagnosis of cryptococcal disease: blood
culture | cryptococcus antigen
47
mortality of cryptococcal meningitis
africa - 3 month mortality 70% | US - 3 month mortality 25%
48
what factors are associated with mortality in cryptococcal meningitis?
``` delay in presentation and diagnosis lack of access to antifungals inadequate induction therapy delays in starting antiretroviral therapy immune reconstitution syndrome ```
49
what antifungals can be used to treat invasive fungal infections? inc route
amphotericin B formulation (IV) azoles (IV, oral) ehinocandins (IV) flucytosine (IV, oral)
50
how does amphotericin B work>
acting on ergosterol causing lysis
51
how do azoles work?
inhibit ergosterol synthesis
52
how do echinocandins work?
inhibit glucan synthesis
53
how does flucytosine work?
inhibit fungal DNA synthesis
54
what antifungal has the broadest activity?
AmB
55
what can be used to treat invasisive candidiasis?
echinocandins and fluconazole
56
what can be used to treat (acute) invasive aspergillosis?
voriconazole and isavuconazole
57
what can be used for antifungal prophylaxis?
itraconazole and posaconazole
58
what can be used for the maintenance of cryptococcal meningitis?
AmB + flucytosine followed by fluconazole

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