Fungal Infections

Question 1

What are the three main fungal pathogens?

Answer 1

Aspergillus species; aspergillus fumigatus

Candida species; candida albicans

Cryptococcus species; cryptococcus neoformans

Question 2

Why are fungal infections classed as ‘opportunistic’?

Answer 2

They cause no real problems in otherwise healthy hosts but in immunocompromised, chronic lung disease or in ICU

Question 3

Describe invasive candidiasis

Answer 3

Gut commensal, infections most commonly endogenous of origin

4th most common bloodstream infection

Clinical presentation as bacterial BSI

Question 4

What are the risk factors for invasive candidiasis?

Answer 4

Risk factors;

• broad spectrum Abs
• intravascular catheters
• total parenteral nutrition
• abdo surgery

Question 5

How is invasive candidiasis diagnosed?

Answer 5

Blood culture or culture from normally sterile site (many false negatives)

Beta-d-glucan performs well to exclude invasive candidiasis

Question 6

Describe aspergillus transmission

Answer 6

• sporulation
• hydrophobic conidida
• diameter 2-3 um
• airborne/inhalation

Question 7

What are the types of invasive pulmonary aspergillosis?

Answer 7

Acute invasive PA; neutropenic patients, post-transplant, patients with defects in phagocytes

Chronic PA; underlying chronic lung conditions

Allergic aspergillosis

*aspergillosis can be can be a presenting symptom of primary immunodeficiency

Question 8

Describe acute invasive pulmonary aspergillosis

Answer 8

Rapid and extensive hyphal growth

Thrombosis and haemorrhage

Angio-invasive and dissemination

Absent or non-specific clinical signs and symptoms

Persistent febrile neutropenia despite BS Abs

Question 9

Describe subactue invasive pulmonary aspergillosis

Answer 9

Non-angioinvasive

Limited fungal growth

Pyrogranulomatous infiltrates

Tissue necrosis

Excessive inflammation

Non-specific clinical signs and symptoms

Mild to moderate systemic illness

Question 10

Describe cryptococcal meningitis

Answer 10

Most commonly sub-Saharan Africa

Transmission by inhalation, pulmonary infection from asymptomatic to pneumonia

Headache, confusion, altered behaviour, visual disturbances, coma

Question 11

What is meningoencephalitis?

Answer 11

Dissemination of meningitis to the brain

Question 12

Describe diagnosis of cryptococcal meningitis

Answer 12

CSF

• Indian ink preparation
• Culture
• High protein
• Low glucose
• cryptococcus antigen

Blood; culture antigen

Question 13

Describe antifungals

Answer 13

Amphotericin B formulations (IV); act on ergosterol > lysis

Azoles (IV, oral); inhibit ergosterol synthesis

Echinocandins (IV); inhibiting glucan synthesis

Flucystosine (IV, oral); inhibiting fungal DNA synthesis

Question 14

What are risk factors for mucocutaneous candidiasis

Answer 14

Antibiotic use, moist areas, inhalation steroids, neonates < 3 months

Question 15

Describe mucocutaneous candidiasis presentation

Answer 15

• Neutropenia
• Low CD4+ T cells
• impaired IL-17 immunity

Question 16

What does BSI stand for?

Answer 16

bloodstream infection

Question 17

Describe chronic pulmonary aspergillosis

Answer 17

Those with chronic lung condition

Pulmonary exacerbations (not responding to ABs)

Lung function decline, increased cough, decreased exercise tolerance and dyspnoea

Positive sputum cultures for aspergillus (50% CF patients are infected)

Question 18

Describe allergic bronchopulmonary aspergillosis

Answer 18

Immunological responses to variety of A.fumigatus antigens in CF host result in

• deterioration lung function and resp symptoms
• new abnormalities on chest imaging
• elevated IgE level
• increased aspergillus specific IgE on positive skin test
• positive aspergillus specific IgG

Question 19

Describe pulmonary aspergilloma

Answer 19

Fungal mass that grows in lung cavities

Question 20

Describe diagnosis of pulmonary aspergillosis in non-neutropenic patients

Answer 20

Cultures of sputum and/or bronchoalveolar lavage, and/or biopsy

Aspergillus specific IgG and IgE and allergic pulmonary aspergillosis

Question 21

Describe diagnosis of pulmonary aspergillosis in neutropenic patients

Answer 21

High resolution CT-chest
- halo sign, air crescent sign

molecular markers in blood; galactomannan and PCR aspergillus

BAL and biopsies if clinical condition allows

Question 22

Factors associated with mortality in cryptococcal meningitis

Answer 22

Delay in presentation and diagnosis

Lack of access to antifungals

inadequate induction therapy

Delays in starting antiretroviral therapy

Immune reconstitution syndrome

Question 23

What is immune reconstitution syndrome?

Answer 23

Paradoxical worsening of known condition or appearance of new condition following starting antiretroviral therapy in HIV infected patients

This is due to restoration of immunity to certain antigens

Question 24

What treatment is given for invasive candidiasis?

Answer 24

Echinocandins and fluconazole

Question 25

What is treatment for (acute) invasive aspergillosis?

Answer 25

Voriconazole and isavuconazole

Question 26

What is used in antifungal prophylaxis?

Answer 26

Itraconazole and posaconazole

Question 27

What is treatment for cryptococcal meningitis?

Answer 27

AmB + flucytosine followed by fluconazole maintenance