Fungal Infections Flashcards
Give 3 examples of fungal pathogens.
Aspergillus species -Aspergillus fumigatus
Candida species
-Candida albicans
Cryptococcus species
-Cryptococcus neoformans
Why type of nature do fungal pathogens have?
Opportunistic nature
Why are fungal pathogens said to be opportunistic?
- Affect patients with impaired immune system
- Affect patients with chronic lung disease
- Affect patients in ICU settings
Give an example of a condition associated with the pneumocystic species.
Pneumocystis pneumonia
Give an example of a condition associated with the aspergillus species.
Allergic and invasive pulmonary aspergillosis
Give examples of conditions associated with the candida species.
- Thrush
- Candidemia
Give an example of a condition associated with the Cryptococcus species.
Meningitis
What are the prime conditions for mucocutaneous candidiasis to occur?
- Antibiotic use
- Moist areas
- Inhalation steroids
- Neonates < 3 months
What is mucocutaneous candidiasis the presenting symptom of?
Primary immunodeficiency disorders
How are primary immunodeficiency disorders characterised?
- Neutropenia
- Low CD4 T cells
- Impaired IL17 immunity
Give examples of impaired IL17 immunity
AD-Hyper IgE syndrome
-Deficit of IL-17 producing cells
Dectin-1 deficiency
-Reduced levels of IL-17
CARD9 deficiency
-Low proportion of circulating IL-17 T-cells
APECED syndrome
-High titers of neutralizing Ab against IL-17A, IL-17F and/or IL-22
What is the origin of invasive candidiasis?
- Gut commensal
- Infections mostly endogenous of origin
- 4th most common bloodstream infection (BSI) in adults: 30/100.000 admissions
What are the risk factors for invasive candidiasis?
- Broad spectrum antibiotics
- Intravascular catheters
- Total parenteral nutrition
- Abdominal surgery
- Premature neonates
How is invasive candidiasis diagnosed?
- Blood culture or culture from normally sterile site
- β-d-glucan high NPV and performs very well to exclude invasive candidiasis
- Recent developments in PCR assays very promising
- In infants and children performance lower due to sampling issues
How is aspergillus transmitted?
- Sporulation
- Hydrophobic conidia
- Diameter 2-3um
- Airborne/inhalation
What plays a central role in invasive pulmonary aspergillosis?
Neutrophils
How can aspergillus disease be classified?
- Acutee aspergillosis
- Chronic pulmonary aspergillosis (3 months)
- Allergic aspergiloosis
Who is usually affected by acute invasive pulmonary aspergillosis?
- Neutropenic patients (incidence 1-10%)
- Post transplants: stem cell > solid organ (incidence up to 8%)
- Patients with defects in phagocytes
Who is usually affected by chronic pulmonary aspergillosis?
Patients with underlying lung conditions
Who is usually affected by allergic aspergillosis?
- Allergic bronchopulmonary aspergillosis in CF and asthma (incidence 10-15%)
- Asthma or CF with fungal sensitisation (incidence 5-15%)
How does acute invasive pulmonary aspergillosis present?
-Rapid and extensive hyphal growth
-Thrombosis and hemorrhage
-Angio-invasive and dissemination-
Absent or non-specific clinical signs and symptom
-Persistent febrile neutropenia despite broad-spectrum antibiotics
-Mortality rates around 50% (but depending on immune recovery)
Who is the host in acute invasive pulmonary aspergillosis?
Neutropenic host (acute leukaemia, haematopoietic stem cell transplant)
Who is the host in (Sub( acute invasive pulmonary aspergillosis?
Non-neutropenia host (graft versus host disease, neutrophil disorders)
How does sub-acute invasive pulmonary aspergillosis present?
- Non-angioinvasive
- Limited fungal growth
- Pyogranulomatous infiltrates
- Tissue necrosis
- Excessive inflammation
- Non-specific clinical signs and symptoms
- Mild to moderate systemic illness
- Mortality 20-50%
What primary immunodeficiency conditions can invasive aspergillosis be the presenting symptom of?
Congenital neutropenia
Chronic granulomatous disease
-Phagocytic disorder
Hyper IgE syndrome (Job’s syndrome)
-Phagocytic disorder and impaired IL-17 pathway
CARD-9 deficiency
-Innate immune pathways, killing defec
How does chronic aspergillosis present?
Pulmonary exacerbations (not responding to antibiotics)
- Lung function decline
- Increased respiratory symptoms as cough, decreased exercise tolerance and dyspnea
- Positive sputum cultures for Aspergillus
- High morbidity but causative mortality rates less clear
In allergic bronchopulmonary aspergillosis in a CF host, what can the immunological response to A. fumigatus result in?
- Acute/subacute deterioration of lung function and respiratory symptoms
- New abnormalities chest imaging
- Elevated immunoglobulin E (IgE) level
- Increased Aspergillus specific IgE or positive skin-test
- Positive Aspergillus specific IgG
What is a pulmonary aspergilloma?
A fungal mass that usually grows in lung cavities
What predisposes people to pulmonary aspergillomas?
- TB
- Sarcoidosis
- Bronchiectasis
- Bronchial cysts and bullae
- After pulmonary infections
How is pulmonary aspergillosis diagnosed in non-neutropenic hosts?
- Cultures of sputum and/or bronchoalveolar lavage, and/or biopsy
- Aspergillus specific IgG and IgE in chronic and allergic pulmonary aspergillosis
How is pulmonary aspergillosis diagnosed in neutropenia patients?
-High resolution CT-chest (‘halo-sign’ and ‘air-crescent sign’)
-Molecular markers in blood: galactomannan and PCR-Aspergillus (high NPV and are suited for screening purposes)
BAL and biopsies if clinical condition allows
How is Cryptococcus transmitted?
By inhalation, it can be found on the bark of a variety of trees, bird faeces and organic matter
How can Cryptococcus infection manifest?
- Pulmonary infection from asymptomatic to pneumonia
- Dissemination to brain: meningoencephalitis in HIV/AIDs patients
How does Cryptococcus present?
- Headache
- Altered behaviour
- Visual disturbances
- Coma (due to raised intracranial pressure)
How is cryptococcal disease diagnosed?
-Cerebrospinal fluid: Indian Ink preparation (80% sensitivity), culture, high protein and low glucose,
Cryptococcus antigen (lateral flow assay)
-Blood: culture, Cryptococcus antigen
What is the prognosis for cryptococcal meningitis?
- In Africa 3 month mortality is 70%
- In the US 3-month mortality is 25%
What factors are associated with mortality in cryptococcal meningitis?
- Delay in presentation and diagnosis
- Lack of access to antifungals
- Inadequate induction therapy
- Delays in starting antiretroviral therapy
- Immune reconstitution syndrome
What antifungals are used to treat invasive infections?
Amphotericin B formulations (iv)
-Acting on ergosterol> lysis
Azoles (iv, oral)
-Inhibiting ergosterolsynthesis
Echinocandins (iv)
-Inhibiting glucan synthesis
Flucytosine (iv, oral)
-Inhibiting fungal DNA synthesis
What antifungal has the broadest treatment?
Amphotericin B
What antifungals are used for invasive candidiasis?
Echinocandins and fluconazole
What antifungals are used for (acute) invasive aspergillosis?
Voriconazole and isavuconazole
What antifungals are used for antifungal prophylaxis?
Itraconazole and posaconazole
How is Cryptococcal meningitis treated?
Amphotericin B and flucytosine followed by fluconazole maintenance
What antifungals have been associated with resistance?
- Fluconazole
- Echinocandin
- Amphotericin B
