Fungal infections Flashcards
How many fungal infections of humans?
1.5 billion
How many life threatening fungal infections per year?
> 3 million
What are the mortality rates typically in fungal infections?
> 50%
How many cases of blindness occur due to fungal infections per year?
> 400,000 cases
Allergens and asthma linked with fungi?
> 20 million
Example of an Aspergillus fungus species?
Aspergillus fumigatus
Example of a Candida fungal species?
Candida albicans
Example of a Cryptococcus fungal species?
Cryptococcus neoformans
Who is primary infected with fungal infections?
Immunocompromised:
- HIV/AIDs
- Neutropenia
- Transplants
- Premature neonates
Chronic lung diseases:
- Asthma
- Cystic fibrosis
- COPD
ICU patients
What can Pneumocystis spp. cause?
1) Pneumocystis pneumonia*
2) Ophthalmic pneumocystis
3) Renal pneumocystis
4) Bone marrow infiltrates
5) Hepatosplenic infiltrates
What can Aspergillus spp. cause?
1) Allergic and invasive aspergillosis*
2) Aspergilloma*
3) Cerebral asergillosis
4) Keratitis
5) Sinusitis
6) Osteomyelitis
7) Cutaneous aspergillosis
What can candida spp. cause?
1) Thrush*
2) Candidemia*
3) Cerebral abcess
4) Oesophagitis
5) Hepatic abscess
6) Renal abscess
7) Urinary candidiasis
8) Vulvovaginal candidiasis
9) Osteomyelitits
10) Cutaneous candidiasis
11) Onychomycosis
What can cryptococcus spp. cause?
1) Meningitis*
2) Cerebral abscess
3) Endophthalmitis
4) Pulmonary infiltrates
5) Endocarditis
6) Crptococcemia
7) Renal abscess
8) Subcutaneous abscess
What can cause mucocutaneous candidiasis?
- Antibiotic use
- Moist areas
- Immunocompromised
- Inhalation steroids
- Neonates <3 months
Presenting symptom of primary immunodeficiency disorder are characterised by what?
1) Neutropenia
2) Low CD4+ T-cells
3) Impaired IL-17 immunity:
- AD-Hyper IgE syndrome = deficient of IL-17 producing cells
- Dectin-1-deficiency = Reduced levels of IL-17
- CARD9 deficiency = Low proportion of circulating IL-17 T-cells
- APECED Syndrome = High titres of neutralising AB against IL-17A, IL-17F and IL-22
What is AD-Hyper IgE syndrome?
AD-Hyper IgE syndrome = deficient of IL-17 producing cells
What is Dectin-1-deficiency?
Dectin-1-deficiency = Reduced levels of IL-17
What is CARD9 deficiency?
CARD9 deficiency = Low proportion of circulating IL-17 T-cells
What is APECED Syndrome?
APECED Syndrome = High titres of neutralising AB against IL-17A, IL-17F and IL-22
What is the most common origin of invasive candidiasis infection?
Endogenous of origin (Gut commensal)
What is the 4th most common cause of bloodstream infection is adults?
- Invasive candidiasis
- 30/100,000
How common is invasive candidiasis in premature neonates (<1000g)?
150/100,000
How does invasive candidiasis present?
As bacterial bloodstream infection
What is the mortality rate of invasive candidiasis infection?
40%
What are the main risk factors in candidiasis infections?
- Premature neonates
- Immunocompromised
- Broad-spectrum Abx use
- Intravascular catheters
- Total parenteral nutrition
- Abdominal surgery
How is invasive candidiasis diagnosed?
1) Blood culture
2) Beta-d-glucan high NPV and performs very well to exclude invasive candidiasis
3) PCR assays
How is Aspergillus transmitted?
Sporulation, airborne hydrophobic conidia, inhaled
diameter = 2-3um
When may acute invasive pulmonary aspergillosis occur?
- Neutropenic patients (1-10%)
- Post transplants: Stem cell > Solid organ (Up to 8%)
- Patient with defects in phagocytes
What is the most common cause of chronic pulmonary aspergillosis?
Underlying chronic pulmonary disease
What is defined as chronic pulmonary aspergillosis?
> 3months
What is allergic aspergillosis?
- Allergic bronchopulmonary aspergillosis in CF and asthma (10-15%)
- Asthma or CF with fungal sensitisation (5-15%)
Acute invasive pulmonary aspergillosis?
- 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)
(Sub) acute invasive pulmonary aspergillosis, non-neutropenic host ?
• 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%
Where does invasive aspergillosis usually present in someone immunocompromised?
Often outside of the lungs e.g. bones, spine, brain or abdomen
Chronic Pulmonary Aspergillosis?
occurs in: asthma, cystic fibrosis, chronic obstructive lung disorders
• Pulmonary exacerbations (not responding to antibiotics)
• Lung function decline
• Increased respiratory symptoms as cough,
decreased exercise tolerance and dyspnea
• Positive sputum cultures for Aspergillus (50% of CF patients are infected)
• High morbidity but causative mortality rates less clear
Allergic Bronchopulmonary Aspergillosis?
Immunological responses to a variety of A. fumigatus antigens in the CF-host (10-15%) result in:
- 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 grows in lung cavities
What may pulmonary aspergilloma occur after?
- TB (In 22% of residual cavities)
- Sarcoidosis
- Bronchiectasis
- Broncial cysts and bullae
- After pulmonary infection s
What is a common cause of aspergillosis in a non-neutropenic host?
1) Respiratory infection and insufficiency = Intubation
2) Influenza A: Oseltamivir, corticosteroids, Abx
3) Day 3: A fumigatus in sputum
What percentage of influenza cases are associated with aspergillosis? What percentage of those died?
16% (23 cases), 61% of those died (14 cases)
How is pulmonary aspergillosis diagnosed in a non-neutropenic patient?
1) Cultures of sputum
2) Culture of bronchoalveolar lavage
3) Culture of biopsy
4) Aspergillus specific IgG and IgE in chronic and pulmonary aspergillosis
How is pulmonary aspergillosis diagnosed in a neutropenic patient?
1) High resolution chest CT = Halo sign and air crescent sign
2) Molecular markers in the blood: Galactomannan and PCR-Aspergillus
3) Bronchoalveolar lavage and biopsies if clinical condition allows
How is Cryptococcus transmitted?
By inhalation - It can be found on the bark of a variety of trees, bird faeces and organic matter
In an AIDs patient with CD4 <100 cells/ul what complication of cryptococcosis is the patient at risk of?
How would they present?
Dissemination to the brain = Meningoencephalitis
Presentation:
- Headache
- Confusion
- Altered behaviour
- Visual disturbances
- Coma (Due to raised intracranial pressure)
How is cryptococcal disease diagnosed?
1) Cerebrospinal fluid:
- Indian ink preparations
- Culture
- High protein and low glucose
- Cryptococcus antigen (Lateral flow assays)
2) Blood cultures:
- Cryptococcus antigen
What is the mortality risk of cryptococcal meningitis in Africa?
3-month mortality = 70%
What is the mortality risk of cryptococcal meningitis in Europe?
3-months mortality = 25%
Which factors are associated with increased risk of mortality in cryptococcal meningitis?
> Delay in presentation/diagnosis > Lack of access to antifungals > Inadequate induction of therapy > Delays in starting antiretroviral therapy > Immune reconstitution syndrome
Antifungal agents used to treat invasive fungal infections?
1) Amphotericin B (IV)
2) Azoles (IV or oral)
3) Echinocandins (IV)
4) Flucytosine (IV or Oral)
Mechanism of action of amphotericin B?
Acting on ergosterol >lysis
Mechanism of action of Azoles?
Inhibiting ergosterol synthesis
Mechanism of action of Echinocandins?
Inhibiting glucan synthesis
Mechanism of action of flucytosine?
Inhibiting fungal DNA synthesis
Which anti fungal has the broadest anti fungal activity?
Amphotericin B
Choice of anti fungal for invasive candidiasis?
Echinocandins and Fluconazole
Choice of anti fungal for invasive aspergillosis?
Variconazole and Isavuconazle
Choice of anti fungal for prophylaxis?
Itraconazole and Posaconazole
Choice of anti fungal for maintenance for cryptococcal meningitis?
1) Amphotericin B + Flucytosine
Followed by:
2) Fluconazole
Which anti fungal have Candida auris gained resistance to?
> 90% Fluconazole R
30-40% Echinocandin R
5-15% Amphotericin R
How to treat resistant Candida auris?
> 2 classes of anti-fungals
Even then 10-20% have pan fungal resistance
Which anti fungal has Aspergillus fumigatus gained resistance to?
Azoles
Now present in 19 countries including US, Brazil and Australia
What are the biggest challenges in mycology presently?
1) Anti-fungals
2) Diagnosis
3) Understanding immunology and pathology
Anti-fungals challenges in mycology presently?
> Stativ vs cidcl > IV vs Oral > Toxicity > Drug interactions > Resistance > Cost
Diagnostic challenges in mycology presently?
> Sensitivity
Specificity
Portability
Cost and Feasibility
Understanding immunology and pathology challenges in mycology presently?
> No vaccines
> No immunotherapies
