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.
How is diagnosis of pulmonary aspergillosis achieved if the patient is non-neutropenic?
Cultures of sputum and/or bronchoalveolar lavage, and/or biopsy
Aspergillus specific IgG and IgE in chronic and allergic pulmonary aspergillosis
How is diagnosis of pulmonary aspergillosis achieved in neutropenic patients?
High resolution CT of chest (halo sign and air-crescent sign)
Molecular markers in the blood (galactomannan and PCR aspergillus)
bronchoalveolar lavage and biopsies if clinical condition allows
What causes transmission of cryptococcus?
Transmission by inhalation
Where is cryptococcus found?
On the bark of a variety of trees, bird faeces and organic matter
What are the manifestations of cryptocccus?
Pulmonary infection (asymptomatic - pneumonia)
Dissemination to brain (meningoencephalitis in HIV/AIDS patients (CD4 less than 100 cells/ul)
What is the clinical presentation of cryptocccus / cryptococcosis?
Clinical presentation: headache, confusion, altered behaviour, visual disturbances, coma (due to raised intracranial pressure in 60-80%)
What is the diagnosis of cryptococcal disease?
CSF - indian ink preparation, culture, high protein, low glucose, cryptococcus antigen
Blood: culture - cryptococcus antigen
What factors are assocaited with mortality from cryptococcal meningitis?
Delay in presentation and diagnosis
Lack of access to antifungals
Inadequate induction therapy
Delays in starting anti-retroviral therapy
Immune reconstitution syndrome
What are the actions of the following anti-fungal drugs used to treat invasive anti-fungal infections?
Amphotericin B
Azoles
Echinocandins
Flucytosine
Amphotericin B - acting on ergosterol - lysis
Azoles - inhibiting ergosterol synthesis
Echinocandins - inhibiting glucan synthesis
Flucytosine - inhibiting fungal DNA synthesis
What drug has the broadest antifungal actvity?
Amphotericin B
What is used to treat invasive candidiasis?
Echinocandins and fluconazole
What dugs are used for treatment of invasive aspergillosis?
Voriconazole and isavuconazole
What drugs are used for antifungal prophylaxis?
Itraconazole and posaconazole
What is used for maintenance therapy of cryptococcal meningitis?
Amphotericin B and flucytosine followed by fluconazole
Cerebrospinal fluid: Indian Ink preparation (80% sensitivity), culture, high protein and low glucose, Cryptococcus antigen (lateral flow assay)
Blood: culture, Cryptococcus antigen
Candida auris has recently attracted attention because of its multi-drug resistance - to what drugs is it resistant?
>90% fluconazole R
30-40% echinocandin R
5-15% amphotericin R
50% MDR (≥ 2 classes of antifungals)
~10-20% pan-fungal R
A.fumigatus resistance is assocaited with what drug?
Azoles
