Mycology - Opportunistic Infections (Aspergillosis) Flashcards
What are the most common opportunistic mycoses? Give an example of a fungal pathogen that causes each. [4]
- Aspergillosis caused by Aspergillus fumigatus
- Cryptococcosis caused by Cryptococcus neoformans
- Candidiasis caused by Candida albicans
- Pneumocytosis caused by Pneumocystis jirovecii
Define primary immunodeficiency and give some examples.
Primary immunodeficiency is caused by mutations affecting any of the genes that control the immune response. Examples are:
- Severe combined immunodeficiency (SCID) - mutation in the rag gene that causes a mutation in the γ-chain of interleukin receptors: T and B cells deficient or absent.
- DiGeorge syndrome - 22q11.2 microdeletion that causes a T cell defect.
- Chronic granulomatous disease - phagocytic cells have a defect in the NADPH oxidase enzyme.
Define secondary immunodeficiency.
Secondary immunodeficiency is the consequence of other disease, secondary to environmental factors (e.g. starvation) or adverse consequences of medical intervention.
Name some predisposing factors that can lead to secondary immunodeficiency.
- Malignancies: leukaemia/lymphoma
- Drug therapies: cytotoxic cancer drugs, immunosuppressants, steroids for autoimmune disease
- Antibiotics
- HIV
- Therputic procedures: organ/bone marrow transplant, open heart surgery, indwelling catheter, artificial heart valves, radiation therapies
- Other factors: malnutrition, severe burn, diabetes, leprosy, renal failure, IV drug users, extreme age
- Aspergillus is a genus of around ___ fungi
- Belongs to the _________ phylum
- Is a ___________ fungi found ________, ubquitously
- Plays a significant role in the ___________ of plants
- Commonly found in ____, food, and air vents
- Aspergillus is a genus of around 200 fungi
- Belongs to the ascomycota phylum
- Is a filamentous fungi found worldwide, ubquitously
- Plays a significant role in the degredation of plants
- Commonly found in soil, food, and air vents
Outline the lifecycle of Aspergillus.
- Conidia are produced from the conidiosphore
- The conidia are inhaled or distributed
- They conidia germinate and form hyphae
- The hyphae extend in a dichotomous branching pattern
- This forms a mass of hyphae
What are some of the clinical manifestations of Aspergillus fumigatus?
- Allergic aspergillosis
- Aspergilloma
- Disseminated (invasive) aspergillosis
- Toxicosis
What is the allerigic agent in allergic aspergillosis?
AspF1
What do the conidia of Aspegillosis stimulate when inhaled into the lungs?
IgE
Allergic bronchopulmonary aspergillosis (ABPA) is an ________ disorder, induced by ____________ ____________. ABPA patients have:
- Positive immediate ____ reactivity
- Elevated Afu-specific ___ levels in serum
- Elevated Afu-specific ___ levels in serum
- Peripheral and pulmonary _______________
Allergic bronchopulmonary aspergillosis (ABPA) is an allergic disorder, induced by Aspergillus fumigatus. ABPA patients have:
- Positive immediate skin reactivity
- Elevated Afu-specific IgG levels in serum
- Elevated Afu-specific IgE levels in serum
- Peripheral and pulmonary eosinophillia
Define Aspergilloma.
Aspergilloma is a non-invasive disease characterised by a granulomatous mass of entwined hyphae that may measure up to 2cm in diameter.
It usually occurs in the lungs, colonising a preformed cavity caused by tuberculosis or other disease.
Erosion of other blood vessels by the expanding aspergilloma may cause severe haemoptysis.
Define invasive aspergillosis.
An infection of Aspergillus that is most commonly seen in immunocompromised patients in which the fungus disseminates haematogenously and by direct extension.
Give examples of invasive aspergillosis.
- Keratitis (eyes)
- Cerebral aspergillosis (brain)
- Endocarditis (heart)
- Myocarditis and pericarditis (heart)
What is the most potent natural carcinogen and which fungus produces it?
Aflatoxin B1 produced by Aspergillu flavus and A. parasiticus
Toxicosis has bee attributed to several _______ produced by aspergilli. The _____ is the primary target of aflatoxins. Acute aflatoxicosis (_________) results in ______, while chronic aflatoxicosis causes ______and immunosuppression.
Toxicosis has bee attributed to several toxins produced by aspergilli. The liver is the primary target of aflatoxins. Acute aflatoxicosis (hepatitis) results in death, while chronic aflatoxicosis causes cancer and immunosuppression.
Define virulence factor.
Any factor/characteristic of a pathogen that helps invasion, growth, and harm of a host, such as adherance, toxicity etc.
What are some virulence factors of Aspergillus fumigatus? [6]
- Conidia can bind to fibrinogen and laminin in the alveolae
- Produce catalase, which degrades hydrogen peroxide, which can degrade conidia
- Grows at 37ºC
- Conidia can germinate an form hyphae that secrete proteases and phospholipases that help invade the epithelium
- Can invade blood vessels and disseminate haematogenously
- Secretes gliotoxin, which is immunosuppressive as it can cause apoptosis of certain immune cells
How is aspergillosis diagnosed? [4]
- Medical history, risk factors, symptoms
- Physical examination
- Imaging (X-ray, CT scan of lungs)
-
Lab tests
- Fluid sample (sputum, blood, broncheo-alveolar lavage)
- Serology
- Microscopy
- Culture
What stains can be used to observe aspergillus species in a biopsy?
-
Sputum/broncheo-alveolar lavage
- Unstained: KOH
- Routine: Gram
- Fungal: GMS, PAS
-
Tissue
- Routine: H&E
- Fungal: GMS, PAS
How are Aspergillus species cultured?
- Isolated on SAB agar + antibiotics
- Identified using malt-extract and corn meal agar
- Incubated: 25-30ºC, aerobic, 2-6 days
What serological tests can be done to detect Aspergillus species?
Galactomannan assay to detect antigens of Asergillus species (ELISA)
How is aspergillosis treated?
- Amphotericin B: invasive and disseminated aspergillosis
- Voriconazole
- Surgery: remove aspergilloma
- Corticosteroid (benefits unclear)
