Fungal Infections Flashcards
What are the three main fungal pathogens?
Aspergillus species; aspergillus fumigatus
Candida species; candida albicans
Cryptococcus species; cryptococcus neoformans
Why are fungal infections classed as ‘opportunistic’?
They cause no real problems in otherwise healthy hosts but in immunocompromised, chronic lung disease or in ICU
Describe invasive candidiasis
Gut commensal, infections most commonly endogenous of origin
4th most common bloodstream infection
Clinical presentation as bacterial BSI
What are the risk factors for invasive candidiasis?
Risk factors;
- broad spectrum Abs
- intravascular catheters
- total parenteral nutrition
- abdo surgery
How is invasive candidiasis diagnosed?
Blood culture or culture from normally sterile site (many false negatives)
Beta-d-glucan performs well to exclude invasive candidiasis
Describe aspergillus transmission
- sporulation
- hydrophobic conidida
- diameter 2-3 um
- airborne/inhalation
What are the types of invasive pulmonary aspergillosis?
Acute invasive PA; neutropenic patients, post-transplant, patients with defects in phagocytes
Chronic PA; underlying chronic lung conditions
Allergic aspergillosis
*aspergillosis can be can be a presenting symptom of primary immunodeficiency
Describe 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 BS Abs
Describe subactue invasive pulmonary aspergillosis
Non-angioinvasive
Limited fungal growth
Pyrogranulomatous infiltrates
Tissue necrosis
Excessive inflammation
Non-specific clinical signs and symptoms
Mild to moderate systemic illness
Describe cryptococcal meningitis
Most commonly sub-Saharan Africa
Transmission by inhalation, pulmonary infection from asymptomatic to pneumonia
Headache, confusion, altered behaviour, visual disturbances, coma
What is meningoencephalitis?
Dissemination of meningitis to the brain
Describe diagnosis of cryptococcal meningitis
CSF
- Indian ink preparation
- Culture
- High protein
- Low glucose
- cryptococcus antigen
Blood; culture antigen
Describe antifungals
Amphotericin B formulations (IV); act on ergosterol > lysis
Azoles (IV, oral); inhibit ergosterol synthesis
Echinocandins (IV); inhibiting glucan synthesis
Flucystosine (IV, oral); inhibiting fungal DNA synthesis
What are risk factors for mucocutaneous candidiasis
Antibiotic use, moist areas, inhalation steroids, neonates < 3 months
Describe mucocutaneous candidiasis presentation
- Neutropenia
- Low CD4+ T cells
- impaired IL-17 immunity
What does BSI stand for?
bloodstream infection
Describe chronic pulmonary aspergillosis
Those with chronic lung condition
Pulmonary exacerbations (not responding to ABs)
Lung function decline, increased cough, decreased exercise tolerance and dyspnoea
Positive sputum cultures for aspergillus (50% CF patients are infected)
Describe allergic bronchopulmonary aspergillosis
Immunological responses to variety of A.fumigatus antigens in CF host result in
- deterioration lung function and resp symptoms
- new abnormalities on chest imaging
- elevated IgE level
- increased aspergillus specific IgE on positive skin test
- positive aspergillus specific IgG
Describe pulmonary aspergilloma
Fungal mass that grows in lung cavities
Describe diagnosis of pulmonary aspergillosis in non-neutropenic patients
Cultures of sputum and/or bronchoalveolar lavage, and/or biopsy
Aspergillus specific IgG and IgE and allergic pulmonary aspergillosis
Describe diagnosis of pulmonary aspergillosis in neutropenic patients
High resolution CT-chest
- halo sign, air crescent sign
molecular markers in blood; galactomannan and PCR aspergillus
BAL and biopsies if clinical condition allows
Factors 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 is immune reconstitution syndrome?
Paradoxical worsening of known condition or appearance of new condition following starting antiretroviral therapy in HIV infected patients
This is due to restoration of immunity to certain antigens
What treatment is given for invasive candidiasis?
Echinocandins and fluconazole
What is treatment for (acute) invasive aspergillosis?
Voriconazole and isavuconazole
What is used in antifungal prophylaxis?
Itraconazole and posaconazole
What is treatment for cryptococcal meningitis?
AmB + flucytosine followed by fluconazole maintenance
