Fungal Infections Flashcards
What are the main fungal pathogens?
- Aspergillus species
- Aspergillus fumigatus
- Candida species
- Candida albicans
- Cryptococcus species
- Cryptococcus neoformans
What are fungal pathogens in nature?
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
What are some specific fungal diseases?
What is candidiasis?
Infection due to any type of candida (type of yeast)
What kind of fungus is candida?
Yeast
What is mucocutaneous candidiasis also known as?
Thrush
What is thrush caused by?
Candida spp
What is thrush?
An immune disorder of T cells characterised by chronic infections with candida that are limited to mucosal surfaces, skin and nails
What is the presentation of thrush?
- Characterised by neutropenia, low CD4 T cells and impared IL-17 immunity
What is the treatment for thrush?
Inhaled steroids
What is invasive candidiasis?
- Gut commensal (candida), infection mostly endogenous in origin
What are risk factors for invasive candidiasis?
- Broad spectrum antibiotics
- IV catheters
- Total parenteral nutrition
- Abdominal surgery
How is invasive candidiasis diagnosed?
- Blood culture or culture from normal sterile site
How is aspergillus transmitted?
- Sporulation
- Airborne/inhalation
- Diameter 2-3um
What is a common disease caused by aspergillus?
Invasive pulmonary aspergillosis
Describe the pathogenesis of invasive pulmonary aspergillosis?
1) Sporulation
2) Inhalation
3) Germination occurs in absence of pulmonary defences
4) Causes neutropenia due to excessive hyphal growth and dessemination
What are the different classifications of pulmonary aspergillus?
-
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
What are the different classifications of host for acute invasive pulmonary aspergillosis?
- 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
Compare and contrast neutropenic and non-neutropenic hosts for acute invasive pulmonary aspergillosis?
- 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
Who does acute invasive pulmonary aspergillosis usually occur in?
- Usually occurs in neutropenic patients, post-transplant and patients with defects in phagocytes
Who does chronic pulmonary aspergillosis usually occur in?
- Occurs in patients with underlying chronic lung conditions
What is the clinical presentation for chronic pulmonary aspergillosis?
- Pulmonary exacerbations that do not respond to antibiotics
- Lung function decline
- Increased respiratory symptoms such as cough, decreased exercise tolerance and dyspnoea
Who does allergic aspergillosis usually occur in?
- Allergic bronchopulmonary aspergillosis occurs in CF and asthma patients
What is pulmonary aspergilloma?
- Fungal mass that usually grows in lung cavities
Who does pulmonary aspergilloma normally occur in?
- Occurs in patients with
- TB
- Sarcoidosis
- Bronchiectasis
- Bronchial cysts and bullae
- After pulmonary infections
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
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
What is cryptococcosis caused by?
Cryptococcus spp
How is cryptococcosis transmitted?
Transmission by inhalation:
- Found on the bark of trees, bird faeces and organic matter
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
- Clinical presentation
What is the clinical presentation of meningoencephalitis due to cryptococcosis?
- Headache
- Confusion
- Altered behaviour
- Visual disturbances
- Coma (due to increased ICP
Describe the diagnosis of cryptococcosis?
- CSF fluid
- Culture, high protein, low glucose, Cryptococcus antigen
- Blood
- Culture, Cryptococcus antigen
What are factors associated with mortality with cryptococcosis?
- Delay in presentation and diagnosis
- Lack of access to antifungals
- Delays to starting therapy
What is used to treat invasive fungal infections?
Antifungal agents
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
What is the mechanism of action of amphotercin B formulation?
- Acting on ergosterol causing lysis
- Broadest antifungal activity
What is the mechanism of action of azoles?
- Inhibiting ergosterol synthesis
What is the mechanism of action of echinocandins?
- Inhibits glucan synthesis
What is the mechanism of action of flucytosine?
- Inhibiting fungal DNA synthesis
What is the treatment for invasive candidiasis?
- Echinocandins and fluconazole
What is the treatment for invasive aspergillosis?
- Voricanazole and isavucanazole
What is the treatment for cryptococal meningitis?
- AmB and flucytosine followed by fluconazole maintainence
What drugs are given for antifungal prophylaxis?
- Itraconazole and posazonazole
Why are emerging new species of fungus creating a problem?
Emerging new species are creating an antifungal resistance problem
