Fungal infections Flashcards
Who gets fungal infections?
○ Patients with an impaired immune system
- Patients with primary immunodeficiencies
- Patients with HIV/AIDS
- Patients with malignancies (neutropenia) & transplants
- Premature neonates (immature immune system)
○ Affecting patients with chronic lung diseases (pulmonary aspergillosis and other moulds)
- Asthma
- Cystic Fibrosis
- Chronic obstructive lung disorders
○ Affecting patients in ICU settings
What is the aetiology of Mucocutaneus candidiasis?
○ Antibiotic use ○ Moist areas ○ Inhalation steroids ○ Neonates < 3 months ○ Presenting symptom of primary immunodeficiency
Which primary immunodeficiency disorders charecteristics can Mucocutaneuous candiditis be a presenting symptom of?
- Neutropenia
- Low CD4+ T-cells
- impaired IL-17 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 mortality of invasive canditis?
40%
Where does invasive canditis commune?
The gut
What are the additional risk factors for a invasive canditis infection?
- Broad-spectrum antibiotics
- Intravascular catheters
- Total parenteral nutrition
- Abdominal surgery
How is an invasive canditis infection 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 are Aspergillus and Aspergillosis transmitted?
- sporulation
- hydrophobic conidia
- diameter 2-3 µm
- airborne / inhalation
Who gets acute invasive pulmonary aspergillosis?
® Neutropenic patients (incidence 1-10%)
® Post transplants: stem cell > solid organ (incidence up to 8%)
® Patients with defects in phagocytes
What haens in acute invasive pulmonary aspergillosis?
® Rapid and extensive hyphal growth
® Thrombosis and haemorrhage
® Angio-invasive and dissemination
® Absent or non-specific clinical signs and symptoms
® Persistent febrile neutropenia despite broad-spectrum antibiotics
® Mortality rates around 50% (but depending on immune recovery)
Who gets (sub) acute Invasive Pulmonary Aspergillosis?
Non-neutropenic host (graft-versus-host disease, neutrophil disorders)
What happens in (sub) acute Invasive Pulmonary Aspergillosis?
® 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%
How long does one have to have pulmonary aspergillosis for it to be classified as chronic?
> 3 months
Who gets chronic pulmonary aspergillosis?
Patients with underlying chronic lung conditions
What happens in chronic pulmonary aspergillosis?
® Pulmonary exacerbations (not responding to antibiotics)
® Lung function decline
® Increased respiratory symptoms as cough, decreased exercise tolerance and dyspnoea
® Positive sputum cultures for Aspergillus
◊ 50% of CF patients are infected
® High morbidity but causative mortality rates less clear
Who gets allegic aspergillosis?
® Allergic bronchopulmonary aspergillosis in CF and asthma (incidence 10-15%)
® Asthma or CF with fungal sensitisation (incidence 5-15%)
What happens in allegic aspergillosis?
® immunological responses to a variety of A. fumigatus antigens in the CF-host (10-15%) 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 Pulmonary aspergilloma?
A fungal mass that usually frows in lung cavities
When do you get Pulmonary aspergilloma?
- Sarcoidosis
- Bronchiectasis
- Bronchial cysts and bullae
- After pulmonary infections
How is pulmonary aspergillosis diagnosed 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
How is pulmonary aspergillosis diagnosed in neutropenic 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 can Cryptococcus and Cryptococcosis
be tranmitted?
Inhalation
Where can Cryptococcus and Cryptococcosis
be found?
bark of a variety of trees, bird faeces and organic matter
What happens in Cryptococcus and Cryptococcosis infections?
○ Pulmonary infection from asymptomatic to pneumonia
○ Dissemination to brain: meningoencephalitis in HIV/AIDS patients (CD4 < 100 cells/ul)
○ Clinical presentation: headache, confusion, altered behaviour, visual disturbances, coma (due to raised intracranial pressure in 60-80%)
How is Cryptococcus and Cryptococcosis diagnosed?
- Cerebrospinal fluid: Indian Ink preparation (80% sensitivity), culture, high protein and low glucose, Cryptococcus antigen (lateral flow assay)
- Blood: culture, Cryptococcus antigen
What are the outcomes of Cryptococcus and Cryptococcosis?
- Africa: 3-month mortality 70%
- US: 3-months mortality 25%
- Factors associated with mortality:
□ Delay in presentation and diagnosis
□ Lack of access to antifungals
□ Inadequate induction therapy
□ Delays in starting antiretroviral therapy
□ Immune reconstitution syndrome
What are the antifungal agents to treat infections?
○ Amphotericin B formulations (iv) - Acting on ergosterol > lysis ○ Azoles (iv, oral) - Inhibiting ergosterol synthesis ○ Echinocandins (iv) - Inhibiting glucan synthesis ○ Flucytosine (iv, oral) - Inhibiting fungal DNA synthesis
