Fungal Infections

Question 1

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

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?

Answer 2

• Antibiotic use
• Moist areas
• Inhalation steroids
• Neonates <3m

Question 3

Mucocutaneous candidiasis is a presenting symptom of primary immunodeficiency disorders, characterised by what?

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 and what are risk factors?

Answer 4

Presents 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 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 different 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?

Answer 8

>Thrombosis and haemorrhage
>Angio-invasive and dissemination
>Absent/non-specific clinical signs and victims
>Persistent febrile neutropenia
>Mortality rates 50%

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. How do they present?

Answer 11

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

Question 12

Allergic bronchopulmonary aspergillosis results from immunological responses to A. fumigatus antigens in 10-15% CF hosts. What are the features of this?

Answer 12

>Lung function deterioration, respiratory symptoms
>Abnormal chest imaging
>Inc. immunoglobulin E 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?

Answer 13

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

Question 14

What groups of people are emerging as non-nutropenic osts of Aspergillosis?

Answer 14

• Resp insufficiency

- Influenza A virus

Question 15

In non-neutropenic patients how do you diagnose Aspergillosis?

Answer 15

> Culture sputum/bronchoalveolar lavage/biopsy

>Aspergillus specific IgG/IgE

Question 16

In neutropenic patients how do you diagnose Aspergillosis?

Answer 16

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

Question 17

How is Cryptococcus transmitted?

Answer 17

Inhalation. Can be found on bark of trees, in bird faeces

Question 18

What does Cryptococcus cause upon dissemination to brain?

Answer 18

Meningoencephalitis in HIV/AIDS patients

Question 19

What is the clinical presentation of Cryptococcosis?

Answer 19

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

Question 20

How do you diagnose cryptococcal disease?

Answer 20

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

Question 21

What factors are associated with mortality in cryptococcal meningitis?

Answer 21

• Delay in presentation/diagnosis
• Lack of access to antifungals
• Inadequate induction therapy
• Delays in starting ART
• Immune reconstitution syndrome

Question 22

What are antifungal agents for invasive fungal infections?

Answer 22

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

Question 23

What is Amphotericin B used for?

Answer 23

Broad spectrum antifungal

Question 24

What is Echinocandins and fluconazole used for?

Answer 24

Invasive candidiasis

Question 25

What is Voriconazole and Isavuconazole used for?

Answer 25

Acute invasive aspergillosis

Question 26

What is Itraconazole and Posaconazole used for?

Answer 26

Antifungal prophylaxis

Question 27

What is used for treatment of cryptococcal meningitis?

Answer 27

Amphotericin B and flucytosine folled by fluconazole maintenance