Fungal Infections Flashcards
1
Q
What are the main fungal pathogens?
A
- Aspergillus species
- Aspergillus fumigatus
- Candida species
- Candida albicans
- Cryptococcus species
- Cryptococcus neoformans
2
Q
What are fungal pathogens in nature?
A
Fungal pathogens are opportunistic in nature:
- Affects patients with impaired immune systems
- Primary immunodeficiency’s
- Patients with HIV/AIDS
- Patients with malignancies
- Premature neonates
- Patients with transplants
- Affects patients with chronic lung diseases
- Asthma
- Cystic fibrosis
- Chronic obstructive lung disorders
- Patients in ICU
3
Q
What are some specific fungal diseases?
A
4
Q
What is candidiasis?
A
Infection due to any type of candida (type of yeast)
5
Q
What kind of fungus is candida?
A
Yeast
6
Q
What is mucocutaneous candidiasis also known as?
A
Thrush
7
Q
What is thrush caused by?
A
Candida spp
8
Q
What is thrush?
A
An immune disorder of T cells characterised by chronic infections with candida that are limited to mucosal surfaces, skin and nails
9
Q
What is the presentation of thrush?
A
- Characterised by neutropenia, low CD4 T cells and impared IL-17 immunity
10
Q
What is the treatment for thrush?
A
Inhaled steroids
11
Q
What is invasive candidiasis?
A
- Gut commensal (candida), infection mostly endogenous in origin
12
Q
What are risk factors for invasive candidiasis?
A
- Broad spectrum antibiotics
- IV catheters
- Total parenteral nutrition
- Abdominal surgery
13
Q
How is invasive candidiasis diagnosed?
A
- Blood culture or culture from normal sterile site
14
Q
How is aspergillus transmitted?
A
- Sporulation
- Airborne/inhalation
- Diameter 2-3um
15
Q
What is a common disease caused by aspergillus?
A
Invasive pulmonary aspergillosis
16
Q
Describe the pathogenesis of invasive pulmonary aspergillosis?
A
1) Sporulation
2) Inhalation
3) Germination occurs in absence of pulmonary defences
4) Causes neutropenia due to excessive hyphal growth and dessemination
17
Q
What are the different classifications of pulmonary aspergillus?
A
-
Acute invasive pulmonary aspergillosis
- Usually occurs in neutropenic patients, post-transplant and patients with defects in phagocytes
- Neutropenic host:
- Rapid and extensive hyphal growth
- Thrombosis and haemorrhage
- Angio-invasive and dissemination
- Non-specific clinical signs and symptoms
- Non-neutropenic host
- Non-angiovasive
- Limited fungal growth
- Tissue necrosis and excessive inflammation
- Non-specific clinical signs and symptoms
-
Chronic pulmonary aspergillosis (>3 months)
- Occurs in patients with underlying chronic lung conditions
- Pulmonary exacerbations that do not respond to antibiotics
- Lung function decline
- Increased respiratory symptoms such as cough, decreased exercise tolerance and dyspnoea
- Positive sputum culture for aspergillus
-
Allergic aspergillosis
- Allergic bronchopulmonary aspergillosis occurs in CF and asthma patients
- Immunological response to variety of A. Fumigatus antigens causing
- Acute/subacute deterioration of lung function and respiratory symptoms
- Elevated immunoglobulin E (IgE) levels
- Positive aspergillus specific IgG
-
Pulmonary aspergilloma
- Fungal mass that usually grows in lung cavities
- Occurs in patients with
- TB
- Sarcoidosis
- Bronchiectasis
- Bronchial cysts and bullae
- After pulmonary infections
18
Q
What are the different classifications of host for acute invasive pulmonary aspergillosis?
A
- Neutropenic host:
- Rapid and extensive hyphal growth
- Thrombosis and haemorrhage
- Angio-invasive and dissemination
- Non-specific clinical signs and symptoms
- Non-neutropenic host
- Non-angiovasive
- Limited fungal growth
- Tissue necrosis and excessive inflammation
- Non-specific clinical signs and symptoms
19
Q
Compare and contrast neutropenic and non-neutropenic hosts for acute invasive pulmonary aspergillosis?
A
- Neutropenic host:
- Rapid and extensive hyphal growth
- Thrombosis and haemorrhage
- Angio-invasive and dissemination
- Non-specific clinical signs and symptoms
- Non-neutropenic host
- Non-angiovasive
- Limited fungal growth
- Tissue necrosis and excessive inflammation
- Non-specific clinical signs and symptoms
20
Q
Who does acute invasive pulmonary aspergillosis usually occur in?
A
- Usually occurs in neutropenic patients, post-transplant and patients with defects in phagocytes
21
Q
Who does chronic pulmonary aspergillosis usually occur in?
A
- Occurs in patients with underlying chronic lung conditions
22
Q
What is the clinical presentation for chronic pulmonary aspergillosis?
A
- Pulmonary exacerbations that do not respond to antibiotics
- Lung function decline
- Increased respiratory symptoms such as cough, decreased exercise tolerance and dyspnoea
23
Q
Who does allergic aspergillosis usually occur in?
A
- Allergic bronchopulmonary aspergillosis occurs in CF and asthma patients
24
Q
What is pulmonary aspergilloma?
A
- Fungal mass that usually grows in lung cavities
25
Who does pulmonary aspergilloma normally occur in?
* Occurs in patients with
* TB
* Sarcoidosis
* Bronchiectasis
* Bronchial cysts and bullae
* After pulmonary infections
26
Invasive aspergillosis is often a presenting symptom of what?
Invasive aspergillosis is often presenting symptoms of primary immunodeficiency, such as:
* Congenital neutropenis
* Chronic granulomatous disease
* Phagocytic disorder
* Hyper IgE syndrome
* Phagocytic disorder and impaired IL-17 pathway
* CARD-9 deficiency
* Innate immune pathways
27
Describe the diagnosis of pulmonary aspergillosis?
* In non-neutropenic patients
* Cultures of sputum and/or bronchoalveolar lavage and/or biopsy
* Aspergillus specific IgG and IgE in chronic and allergic pulmonary aspergillosis
* In neutropenic patients
* High resolution CT chest
* Molecular markers in blood
* Galactomannan and PCR-aspergillus
* BAL and biopsies if clinical conditions allow
28
What is cryptococcosis caused by?
Cryptococcus spp
29
How is cryptococcosis transmitted?
Transmission by inhalation:
* Found on the bark of trees, bird faeces and organic matter
30
What does cryptococcosis cause?
Causes pulmonary infection from asymptomatic to pneumonia:
* Dissemination to brain causing meningoencephalitis in HIV/AIDs patients
* Clinical presentation
* Headache
* Confusion
* Altered behaviour
* Visual disturbances
* Coma (due to increased ICP
31
What is the clinical presentation of meningoencephalitis due to cryptococcosis?
* Headache
* Confusion
* Altered behaviour
* Visual disturbances
* Coma (due to increased ICP
32
Describe the diagnosis of cryptococcosis?
* CSF fluid
* Culture, high protein, low glucose, Cryptococcus antigen
* Blood
* Culture, Cryptococcus antigen
33
What are factors associated with mortality with cryptococcosis?
* Delay in presentation and diagnosis
* Lack of access to antifungals
* Delays to starting therapy
34
What is used to treat invasive fungal infections?
Antifungal agents
35
What are different classes of antifungal agents?
* Amphotericin B formulation (IV)
* Acting on ergosterol causing lysis
* Broadest antifungal activity
* Azoles (IV, oral)
* Inhibiting ergosterol synthesis
* Echinocandins (IV)
* Inhibits glucan synthesis
* Flucytosine (IV, oral)
* Inhibiting fungal DNA synthesis
36
What is the mechanism of action of amphotercin B formulation?
* Acting on ergosterol causing lysis
* Broadest antifungal activity
37
What is the mechanism of action of azoles?
* Inhibiting ergosterol synthesis
38
What is the mechanism of action of echinocandins?
* Inhibits glucan synthesis
39
What is the mechanism of action of flucytosine?
* Inhibiting fungal DNA synthesis
40
What is the treatment for invasive candidiasis?
* Echinocandins and fluconazole
41
What is the treatment for invasive aspergillosis?
* Voricanazole and isavucanazole
42
What is the treatment for cryptococal meningitis?
* AmB and flucytosine followed by fluconazole maintainence
43
What drugs are given for antifungal prophylaxis?
* Itraconazole and posazonazole
44
Why are emerging new species of fungus creating a problem?
Emerging new species are creating an antifungal resistance problem
