Fungal Infections

Question 1

Fungal pathogens are said to be opportunistic in who they infect. What makes a patient more susceptible to infection? [3]

Answer 1

> Impaired immune system (immunodeficiencies, HIV/AIDS, malignancies and transplants, neonates)
Chronic lung diseases (asthma, CF, COPD)
ICU patients

Question 2

What makes you more likely to be infected by mucocutaneous candidiasis? [4]

Answer 2

• pregnancy, high estrogen contraceptive pill
• iron deficiency
• underlying skin disease eg psoriasis, dermatitis
• local factors e.g. heat, moisture, skin maceration, topical/inhalational corticosteroids, poor dental hygiene

Question 3

Mucocutaneous candidiasis is a presenting symptom of primary immunodeficiency disorders, characterised by 3 features
Give 3 eg of primary immunodeficiency disorders

Answer 3

>Neutropenia
>Low CD4+ T cells
>Impaired IL-17 immunity 
      - AD-Hyper IgE syndrome
      - Dectin-1 deficiency
      - CARD9 deficiency

Question 4

Invasive candidiasis comes from gut commensal and is mostly endogenous of origin. How does it present [1] and what are risk factors? [5]

Answer 4

Same clinical presentation as bacterial bloodstream infection

Risk factors

• Neonates
• Broad spectrum antibiotics
• IV catheters
• Total parenteral nutrition
• Abd. surgery

Question 5

How do you diagnose invasive candidiasis?

Answer 5

> Blood culture
Culture normally sterile site
Beta-d-glucan has high NPV can exclude it
PCR assays developing as investigation

Question 6

How is Aspergillosis transmitted?

Answer 6

Inhaled. Is airborne spores. Typically affects lungs.

Question 7

What are the 3 classifications of pulmonary aspergillosis disease?

Answer 7

• Acute invasive pulmonary aspergillosis
• Chronic pulmonary aspergillosis (>3m)
• Allergic aspergillosis

Question 8

Acute invasive pulmonary aspergillosis affects neutropenic hosts (acute leukaemia/haematopoietic stem cell transplant). What are the features? [3]

Answer 8

> Thrombosis and haemorrhage
Angio-invasive and dissemination
Persistent febrile neutropenia

Question 9

Subacute invasive pulmonary aspergillosis affects non-neutropenic hosts (graft vs host disease, neutrophil disorders). What are the features?

Answer 9

>Non-angioinvasive
>Pyogranulatomous infiltrates
>Tissue necrosis
>Excessive inflammation
>Non specific clinical signs and symptoms (mild to moderate systemic illness)
>Mortality 20-50%

Question 10

What primary immunodeficiencies can lead to invasive aspergillosis presenting as a symptom?

Answer 10

> Congenital neutropenia
Chronic granulatomous disease
Hyper IgE syndrome
CARD-9 deficiency

Presentation often outside lungs eg bones, spine, brain, abdominal

Question 11

Chronic pulmonary aspergillosis affects hosts with asthma, CF, and chronic obstructive lung disorders. (high morbidity)
How do they present? [3]

Answer 11

> Pulmonary exacerbations with lung function decline
Inc respiratory symptoms as couch, dec. exercise tolerance and SOB
Positive sputum culture

Question 12

Allergic bronchopulmonary aspergillosis results from immunological responses to A. fumigatus antigens in CF hosts. What are the features of this? [5]
Clue: 3 lab tests

Answer 12

>Lung function deterioration, respiratory symptoms
>Abnormal chest imaging
>Inc. IgE level
>Positive Aspergillus skin test
>Positive Aspergillus specific IgG/IgE

Question 13

Pulmonary aspergilloma is a fungal mass that usually grows in lung cavities. When do these grow? [5]

Answer 13

• TB
• Sarcoidosis
• Bronchiectasis
• Bronchial cysts and bullae
• After pul. infections

Question 14

In non-neutropenic patients how do you diagnose Aspergillosis?

Answer 14

> Culture sputum/bronchoalveolar lavage/biopsy

>Aspergillus specific IgG/IgE

Question 15

In neutropenic patients how do you diagnose Aspergillosis?

Answer 15

> CT chest (halo sign)
Molecular markers in blood (galactomannan and PCR-Aspergillus)
BAL and biopsy if possible

Question 16

How is Cryptococcus transmitted?

Where can it be found [3]

Answer 16

Inhalation.

Can be found on bark of trees, in bird faeces, organic matter

Question 17

What does Cryptococcus cause upon dissemination to brain?

Answer 17

Meningoencephalitis in HIV/AIDS patients

Question 18

What is the clinical presentation of Cryptococcosis? [5]

Answer 18

• Headache
• Confusion
• Altered behaviour
• Visual disturbances
• Coma (raised ICP)

Question 19

How do you diagnose cryptococcal disease?

Answer 19

-India ink stain of CSF.
> CSF culture, high protein and low glucose
-Blood culture, look for cryptococcus antigen

Question 20

What are antifungal agents for invasive fungal infections?

Answer 20

• Amphotericin B formulations (IV)
• Azoles (IV, oral)
• Echinocandins (IV
• Flucytosine (IV, oral)

Question 21

What is Amphotericin B used for?

Answer 21

Broad spectrum antifungal

Question 22

What is Echinocandins and fluconazole used for?

Answer 22

Invasive candidiasis

Question 23

What is Voriconazole and Isavuconazole used for?

Answer 23

Acute invasive aspergillosis

Question 24

What is Itraconazole and Posaconazole used for?

Answer 24

Antifungal prophylaxis

Question 25

What is used for treatment of cryptococcal meningitis?

Answer 25

Amphotericin B and flucytosine folled by fluconazole maintenance

Question 26

Treatment of invasive candidiasis
In non-neutropenic patients [2 options]
In neutropenic patients [2 options]

Answer 26

Non-neutropenic patients: IV fluconazole or echinocandin

Neutropenic patients: echinocandin, lipid formulation of amphotericin

Question 27

Treatment of invasive candidiasis in neutropenic patients. First line is echinocandin, fluconazole is secondary. When can fluconazole be used in less ill patients

Answer 27

Fluconazole can be used in less ill patients with no recent azole exposure