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Systems: Infection AB > Fungal Infections > Flashcards

Fungal Infections Flashcards

1
Q

Give 3 examples of fungal pathogens.

A

Aspergillus species -Aspergillus fumigatus

Candida species
-Candida albicans 

Cryptococcus species
-Cryptococcus neoformans

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2
Q

Why type of nature do fungal pathogens have?

A

Opportunistic nature

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3
Q

Why are fungal pathogens said to be opportunistic?

A
  • Affect patients with impaired immune system
  • Affect patients with chronic lung disease
  • Affect patients in ICU settings
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4
Q

Give an example of a condition associated with the pneumocystic species.

A

Pneumocystis pneumonia

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5
Q

Give an example of a condition associated with the aspergillus species.

A

Allergic and invasive pulmonary aspergillosis

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6
Q

Give examples of conditions associated with the candida species.

A
  • Thrush

- Candidemia

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7
Q

Give an example of a condition associated with the Cryptococcus species.

A

Meningitis

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8
Q

What are the prime conditions for mucocutaneous candidiasis to occur?

A
  • Antibiotic use
  • Moist areas
  • Inhalation steroids
  • Neonates < 3 months
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9
Q

What is mucocutaneous candidiasis the presenting symptom of?

A

Primary immunodeficiency disorders

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10
Q

How are primary immunodeficiency disorders characterised?

A
  • Neutropenia
  • Low CD4 T cells
  • Impaired IL17 immunity
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11
Q

Give examples of impaired IL17 immunity

A

AD-Hyper IgE syndrome
-Deficit of IL-17 producing cells 

Dectin-1 deficiency
-Reduced levels of IL-17

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

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

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12
Q

What is the origin of invasive candidiasis?

A
  • Gut commensal
  • Infections mostly endogenous of origin
  • 4th most common bloodstream infection (BSI) in adults: 30/100.000 admissions
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13
Q

What are the risk factors for invasive candidiasis?

A
  • Broad spectrum antibiotics
  • Intravascular catheters
  • Total parenteral nutrition
  • Abdominal surgery
  • Premature neonates
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14
Q

How is invasive candidiasis diagnosed?

A
  • Blood culture or culture from normally sterile site 
  • β-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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15
Q

How is aspergillus transmitted?

A
  • Sporulation
  • Hydrophobic conidia
  • Diameter 2-3um
  • Airborne/inhalation
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16
Q

What plays a central role in invasive pulmonary aspergillosis?

A

Neutrophils

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17
Q

How can aspergillus disease be classified?

A
  • Acutee aspergillosis
  • Chronic pulmonary aspergillosis (3 months)
  • Allergic aspergiloosis
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18
Q

Who is usually affected by acute invasive pulmonary aspergillosis?

A
  • Neutropenic patients (incidence 1-10%)
  • Post transplants: stem cell > solid organ (incidence up to 8%)
  • Patients with defects in phagocytes
19
Q

Who is usually affected by chronic pulmonary aspergillosis?

A

Patients with underlying lung conditions

20
Q

Who is usually affected by allergic aspergillosis?

A
  • Allergic bronchopulmonary aspergillosis in CF and asthma (incidence 10-15%)
  • Asthma or CF with fungal sensitisation (incidence 5-15%)
21
Q

How does acute invasive pulmonary aspergillosis present?

A

-Rapid and extensive hyphal growth
-Thrombosis and hemorrhage
-Angio-invasive and dissemination-
Absent or non-specific clinical signs and symptom
-Persistent febrile neutropenia despite broad-spectrum antibiotics
-Mortality rates around 50% (but depending on immune recovery)

22
Q

Who is the host in acute invasive pulmonary aspergillosis?

A

Neutropenic host (acute leukaemia, haematopoietic stem cell transplant)

23
Q

Who is the host in (Sub( acute invasive pulmonary aspergillosis?

A

Non-neutropenia host (graft versus host disease, neutrophil disorders)

24
Q

How does sub-acute invasive pulmonary aspergillosis present?

A
  • Non-angioinvasive
  • Limited fungal growth
  • Pyogranulomatous infiltrates 
  • Tissue necrosis 
  • Excessive inflammation 
  • Non-specific clinical signs and symptoms
  • Mild to moderate systemic illness
  • Mortality 20-50%
25
Q

What primary immunodeficiency conditions can invasive aspergillosis be the presenting symptom of?

A

Congenital neutropenia 

Chronic granulomatous disease 
-Phagocytic disorder

Hyper IgE syndrome (Job’s syndrome)
-Phagocytic disorder and impaired IL-17 pathway 

CARD-9 deficiency
-Innate immune pathways, killing defec

26
Q

How does chronic aspergillosis present?

A

Pulmonary exacerbations (not responding to antibiotics) 

  • Lung function decline
  • Increased respiratory symptoms as cough, decreased exercise tolerance and dyspnea 
  • Positive sputum cultures for Aspergillus 
  • High morbidity but causative mortality rates less clear
27
Q

In allergic bronchopulmonary aspergillosis in a CF host, what can the immunological response to A. fumigatus result in?

A
  • Acute/subacute deterioration of lung function and respiratory symptoms
  • New abnormalities chest imaging
  • Elevated immunoglobulin E (IgE) level
  • Increased Aspergillus specific IgE or positive skin-test 
  • Positive Aspergillus specific IgG
28
Q

What is a pulmonary aspergilloma?

A

A fungal mass that usually grows in lung cavities

29
Q

What predisposes people to pulmonary aspergillomas?

A
  • TB
  • Sarcoidosis
  • Bronchiectasis
  • Bronchial cysts and bullae
  • After pulmonary infections
30
Q

How is pulmonary aspergillosis diagnosed in non-neutropenic hosts?

A
  • Cultures of sputum and/or bronchoalveolar lavage, and/or biopsy
  • Aspergillus specific IgG and IgE in chronic and allergic pulmonary aspergillosis
31
Q

How is pulmonary aspergillosis diagnosed in neutropenia patients?

A

-High resolution CT-chest (‘halo-sign’ and ‘air-crescent sign’)
-Molecular markers in blood: galactomannan and PCR-Aspergillus (high NPV and are suited for screening purposes)
BAL and biopsies if clinical condition allows

32
Q

How is Cryptococcus transmitted?

A

By inhalation, it can be found on the bark of a variety of trees, bird faeces and organic matter

33
Q

How can Cryptococcus infection manifest?

A
  • Pulmonary infection from asymptomatic to pneumonia

- Dissemination to brain: meningoencephalitis in HIV/AIDs patients

34
Q

How does Cryptococcus present?

A
  • Headache
  • Altered behaviour
  • Visual disturbances
  • Coma (due to raised intracranial pressure)
35
Q

How is cryptococcal disease diagnosed?

A

-Cerebrospinal fluid: Indian Ink preparation (80% sensitivity), culture, high protein and low glucose,
Cryptococcus antigen (lateral flow assay)
-Blood: culture, Cryptococcus antigen

36
Q

What is the prognosis for cryptococcal meningitis?

A
  • In Africa 3 month mortality is 70%

- In the US 3-month mortality is 25%

37
Q

What factors are associated with mortality in cryptococcal meningitis?

A
  • Delay in presentation and diagnosis 
  • Lack of access to antifungals 
  • Inadequate induction therapy 
  • Delays in starting antiretroviral therapy
  • Immune reconstitution syndrome
38
Q

What antifungals are used to treat invasive infections?

A

Amphotericin B formulations (iv)
-Acting on ergosterol> lysis
Azoles (iv, oral)
-Inhibiting ergosterolsynthesis

Echinocandins (iv)
-Inhibiting glucan synthesis

Flucytosine (iv, oral)
-Inhibiting fungal DNA synthesis

39
Q

What antifungal has the broadest treatment?

A

Amphotericin B

40
Q

What antifungals are used for invasive candidiasis?

A

Echinocandins and fluconazole

41
Q

What antifungals are used for (acute) invasive aspergillosis?

A

Voriconazole and isavuconazole

42
Q

What antifungals are used for antifungal prophylaxis?

A

Itraconazole and posaconazole

43
Q

How is Cryptococcal meningitis treated?

A

Amphotericin B and flucytosine followed by fluconazole maintenance

44
Q

What antifungals have been associated with resistance?

A
  • Fluconazole
  • Echinocandin
  • Amphotericin B

Systems: Infection AB (12 decks)

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