Fungal Infections Flashcards
What are the three main fungal pathogens?
Aspergillus species (aspergillus fumigatus)
Candida species (candida albicans)
Cryptococcus species (cryptococcus neoformans)
What types of patients do fungal pathogens often attack?
Impaired immune systems
Patients with chronic lung diseases
Patients in ICU settings
Give examples of patients with impaired immune systems
Patients with primary immunodeficiencies
Patients with HIV/AIDS
Malignancies (neutropenia) and transplants
Premature neonates (immature immune system)
What chronic lung disease might fingal infections attack?
Asthma
Cystif fibrosis
Chronic obstructive lung disorders
(pulmonary aspergillosis and other moulds)
What organism is responsible for pneumocystis pneumonia?
Pneumocystis spp
What fungal speces can cause meningitis?
Cryptococcus
What can cause mucocutaneous candidiasis?
Antibiotic use
Inhalation steroids
When might mucocutaneous candidiasis suggest presenting symptoms of immunodeficiency?
In the presence of neutropenia
Low CD4+ T cells
Impaired IL-17 immunity
Where do most invasive candidiasis infections arise from?
Mostly endogenous origin - candida is a commensal of the gut
Candidiasis is the 4th most common blood stream infection
What are additional risk factors for invasive candidiasis infections?
Broad spectrum antibiotics
Intravascular catheters
Total parenteral nutrition
Abdominal surgery
How do we diagnose invasive candidiasis?
- Blood culture or culture from normally sterile site
- β-d-glucan high NPV (negative predicitve value) and performs very well to exclude invasive candidiasis (B-d glucan is an antigen that is found in candida spp, aspergillus spp and pneumocystis jirovecii
- Recent developments in PCR assays very promising
- In infants and children performance lower due to sampling issues
How does aspergillus transmit?
Sporulation
Hydrophobic conidia
Conidia is a non-motile spore of a fungus, they allow the asexual reproduction of ascomycetes
Diameter of 2-3 micrometres
Airborne/inhalation
What are the stages of invasive pulmonmary aspergillosis?
Sporulation
Inhalation of conidia
Conidial germination in absence of sufficient pulmonary defences
If there is corticosteroid induced immunosuprpession - Peripheral mononucleocyte recruitment and tissue damage
If there is neutropenia - excessive hyphal growth and dissemination
In what patients is acute invasive pulmonary aspergillois common?
Neutropenic patients
Post transplant (stem cell is more common than solid tissue)
Patients with defects in phagocytes
In what patients is chronic pulmonary aspergillosis common?
Patients with chronic underlying lung conditions
What patients are more likely to get allergic aspergillosis?
CF or Asthma
What are the feaures of invasive pulmonary aspergillosis in a neutropenic host?
Rapid and extensive hyphal growth
Thrombosis and hemorrhage
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)
What are the features of (sub) acute invasive pulmonary aspergillosis?
This is seen in non-neutropenic patients (graft-versus host disease, neutrophil disorders)
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 disorders might be underlying an invasive aspergillosis infection?
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 defect)
Clinical presentation often outside the lungs; e.g.
bones, spine, brain, abdominal
What are the clinical features of pulmonary aspergillosis?
Doesn’t respond to antibiotics
Decline in lung function
Increased respiratory symptoms such as cough, dyspnoea and decreased exercise tolerance
POsitive sputum cultures for aspergillus (50% of CF patients are infected)
High morbidity but causative mortality is not clear)
When does allergic bronchopulmonary aspergillosis occur?
Immunological response to a variety of A fumigatus antigens in the CF host
What does the immunological response by a CF host to A.Fumigatus antigens cause?
What are the tests?
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 grow in lung cavities
What is the pathogenesis of aspergilloma?
Inhaled Aspergillus may lodge and germinate in areas of damaged lung tissue, forming a fungal ball or ‘aspergil- loma’
Often form in tuberculosis cavities
Other causes include damage from a lung abscess cavity, bronchiectatic space, pulmonary infarct, sarcoidosis, ankylosing spondylitis or even a cavitated tumour.
