Fungal Infections

Question 1

What are the global burdens from fungal infections?

Answer 1

> 3 million life threatening infections/ year
Mortality rates typically > 50%
400 000 cases of blindness per year

Question 2

What are the 3 fungal organisms causing the majority of infections?

Answer 2

Aspergillus fumigatus
Candida albicans
Cryptococcus neoformans

Question 3

Since fungal pathogens are opportunistic, who do they affect most commonly?

Answer 3

Patients with impaired immune system: immunodeficiencies, HIV, malignancies, transplants, premature neonates

Patients with chronic lung diseases: asthma, cystic fibrosis, COPD

Question 4

What is mucocutaneous candidiasis?

Answer 4

Superficial infections of the skin and mucous membrane

It is an immune disorder of T cells + therefore body is less able to fight fungal infections

Question 5

Risk factors for mucocutaneous candidiasis?

Answer 5

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

Question 6

What symptoms is primary immunodeficiency disorders characterised by:

Answer 6

Neutropenia

Low CD4+ T cells

Question 7

What molecule is impaired in mucocutaenous candidiasis?

Answer 7

IL-17 (interleukin) is inhibited

Question 8

What is invasive candidiasis?

Answer 8

Infections from gut commensal
Is a common bloodstream infection
Has mortality up to 40%

Question 9

What patient risk factors are there for invasive candidiasis?

Answer 9

Broad-spectrum antibiotic use
Intravascular catheters
Total parenteral nutrition
Abdominal surgery

Question 10

How do you diagnose invasive candidiasis?

Answer 10

Blood culture

PCR assays

Question 11

How is invasive candidiasis transmitted?

Answer 11

Sporulation

Airborne/ inhalation

Question 12

What are the types of invasive pulmonary aspergillum disease?

Answer 12

Acute invasive pulmonary aspergillosis
Chronic pulmonary aspergillosis
Allergic aspergillosis

Question 13

Describe the features of acute invasive pulmonary aspergillosis?

Who are at risk?

Answer 13

At risk groups:
Neutropenic patients (e.g. leukaemia)
Post-transplants
Patients with defective phagocytes

Absent or non-specific clinical signs

Complications:
thrombosis and haemorrhage
Angio-Invasive
Mortality rate ~ 50%

Question 14

Describe the features of Chronic Pulmonary Aspergillosis?

Who are at risk?

Answer 14

Pulmonary exacerbations
Lung function decline
Increased respiratory symptoms

Positive sputum cultures for aspergillosis
High morbidity

Risk groups:
patients with underlying lung conditions

Question 15

What is Allergic Pulmonary Aspergillosis?

Who are at risk?

Answer 15

Immunological response to Aspergillosis fumigatus

Symptoms:
Deterioration of lung function
Respiratory symptoms (cough, wheeze)

There is an elevated IgE level
Positive Aspergillus specific IgG

Risk groups:
Asthma or CF

Question 16

What is pulmonary Aspergilloma?

Answer 16

A fungal mass that usually grows in lung cavities

e.g.
Tuberculosis
Sarcoidosis
Bronchiectasis

Question 17

How do you diagnose Pulmonary Aspergillosis?

Answer 17

In non-neutropenic patients:
cultures of sputum
+/- biopsy
Aspergillum specific IgG and IgE

In neutropenic patients:
CT chest
Molecular markers in blood (PCR aspergillus)

Question 18

What is the treatment for Pulmonary Aspergillosis?

Answer 18

For respiratory insufficiency: Intubation in ICU

Oseltamivir: antiviral to treat influenza A
Corticosteroids
Antibiotics

Question 19

What is the
-transmission
-symptoms
for Cryptococcus and Cryptococcosis?

Answer 19

Transmission by inhalation
It is a pulmonary infection from asymptomatic to pneumonia

Presents: headache, confusion altered behaviour, visual disturbances, coma (due to raised ICP)
Dissemination to brain can occur

Question 20

How is Cryptococcus and Cryptococcosis diagnosed?

Answer 20

CSF: indian ink, high protein
Blood: culture + Cryptococcus antigen

Question 21

What is the prognosis for Cryptococcus and Cryptococcosis?

Answer 21

Africa= 3 month mortality 70% US= 3 month mortality 25%

Factors associated with mortality: delay in diagnosis, lack of access to antifungals, delays in starting therapy

Question 22

What antifungal agents are there?

What are they used for?

Answer 22

Amphotericin B (broadest anti fungal agent)
Azoles (IV, oral)
Enchinocandins = for invasive aspergillosis
Flucytosine= cryptococcal meningitis

Question 23

There are emerging species of antifungal resistance, what are they resisted to?

Answer 23

> 90% fluconazole resistant
30-40% enchinocandin resistant
5-15% amphotericin resistant

Question 24

What improvements are needed for tackling fungal infections?

Answer 24

Better antifungals: lower-toxicity, drug interactions, resistance, cost

Diagnostics current problems:
sensitivity, specificity, portability, cost

Understanding immunology: currently no vaccines, no immunotherapies