Fungal Infections Flashcards
What are the global burdens from fungal infections?
> 3 million life threatening infections/ year
Mortality rates typically > 50%
400 000 cases of blindness per year
What are the 3 fungal organisms causing the majority of infections?
Aspergillus fumigatus
Candida albicans
Cryptococcus neoformans
Since fungal pathogens are opportunistic, who do they affect most commonly?
Patients with impaired immune system: immunodeficiencies, HIV, malignancies, transplants, premature neonates
Patients with chronic lung diseases: asthma, cystic fibrosis, COPD
What is mucocutaneous candidiasis?
Superficial infections of the skin and mucous membrane
It is an immune disorder of T cells + therefore body is less able to fight fungal infections
Risk factors for mucocutaneous candidiasis?
- Antibiotic use
- Moist areas
- Inhalation steroids
- Neonates < 3 months
What symptoms is primary immunodeficiency disorders characterised by:
Neutropenia
Low CD4+ T cells
What molecule is impaired in mucocutaenous candidiasis?
IL-17 (interleukin) is inhibited
What is invasive candidiasis?
Infections from gut commensal
Is a common bloodstream infection
Has mortality up to 40%
What patient risk factors are there for invasive candidiasis?
Broad-spectrum antibiotic use
Intravascular catheters
Total parenteral nutrition
Abdominal surgery
How do you diagnose invasive candidiasis?
Blood culture
PCR assays
How is invasive candidiasis transmitted?
Sporulation
Airborne/ inhalation
What are the types of invasive pulmonary aspergillum disease?
Acute invasive pulmonary aspergillosis
Chronic pulmonary aspergillosis
Allergic aspergillosis
Describe the features of acute invasive pulmonary aspergillosis?
Who are at risk?
At risk groups:
Neutropenic patients (e.g. leukaemia)
Post-transplants
Patients with defective phagocytes
Absent or non-specific clinical signs
Complications:
thrombosis and haemorrhage
Angio-Invasive
Mortality rate ~ 50%
Describe the features of Chronic Pulmonary Aspergillosis?
Who are at risk?
Pulmonary exacerbations
Lung function decline
Increased respiratory symptoms
Positive sputum cultures for aspergillosis
High morbidity
Risk groups:
patients with underlying lung conditions
What is Allergic Pulmonary Aspergillosis?
Who are at risk?
Immunological response to Aspergillosis fumigatus
Symptoms: Deterioration of lung function Respiratory symptoms (cough, wheeze)
There is an elevated IgE level
Positive Aspergillus specific IgG
Risk groups:
Asthma or CF
What is pulmonary Aspergilloma?
A fungal mass that usually grows in lung cavities
e.g.
Tuberculosis
Sarcoidosis
Bronchiectasis
How do you diagnose Pulmonary Aspergillosis?
In non-neutropenic patients:
cultures of sputum
+/- biopsy
Aspergillum specific IgG and IgE
In neutropenic patients:
CT chest
Molecular markers in blood (PCR aspergillus)
What is the treatment for Pulmonary Aspergillosis?
For respiratory insufficiency: Intubation in ICU
Oseltamivir: antiviral to treat influenza A
Corticosteroids
Antibiotics
What is the
-transmission
-symptoms
for Cryptococcus and Cryptococcosis?
Transmission by inhalation
It is a pulmonary infection from asymptomatic to pneumonia
Presents: headache, confusion altered behaviour, visual disturbances, coma (due to raised ICP)
Dissemination to brain can occur
How is Cryptococcus and Cryptococcosis diagnosed?
CSF: indian ink, high protein
Blood: culture + Cryptococcus antigen
What is the prognosis for Cryptococcus and Cryptococcosis?
Africa= 3 month mortality 70% US= 3 month mortality 25%
Factors associated with mortality: delay in diagnosis, lack of access to antifungals, delays in starting therapy
What antifungal agents are there?
What are they used for?
Amphotericin B (broadest anti fungal agent) Azoles (IV, oral) Enchinocandins = for invasive aspergillosis Flucytosine= cryptococcal meningitis
There are emerging species of antifungal resistance, what are they resisted to?
> 90% fluconazole resistant
30-40% enchinocandin resistant
5-15% amphotericin resistant
What improvements are needed for tackling fungal infections?
Better antifungals: lower-toxicity, drug interactions, resistance, cost
Diagnostics current problems:
sensitivity, specificity, portability, cost
Understanding immunology: currently no vaccines, no immunotherapies
