Fungal infections Flashcards
Please explain the grand mycological challenge:
- 1.5 billion fungal infections of humans
- > 3 million life threatening infections /year Mortality rates typically > 50%
- >400,000 cases of blindness per year
- Allergens and asthma (>20 million)
What are the three main fungal pathogens?
- Aspergillus species
- Aspergillus fumigatus
- Candida species
- Candida albicans
- Cryptococcus species
- Cryptococcus neoformans
Which patients are suspectible to fungal infection and why?
They are opportunistic in nature.
- Affecting patients with an impaired immune system
- Patients with primary immunodeficiencies
- Patients with HIV/AIDS
- Patients with malignancies (neutropenia) & transplants
- Premature neonates (immature immune system)
- Affecting patients with chronic lung diseases (pulmonary
- aspergillosis and other moulds)
- Asthma
- Cystic Fibrosis
- Chronic obstructive lung disorders
- Affecting patients in ICU settings
Who is susceptibile for mucocutaneous candidiasis?
- Antibiotic use
- Moist areas
- Inhalation steroids
- Neonates < 3 months
What are the presenting symptoms of mucocutaneous candidiasis?
- Neutropenia
- Low CD4+ T-cells
- impaired IL-17 immunity
What are notable features of candidiasis?
- Gut commensal
- Infections mostly endogenous of origin
- 4th most common bloodstream
- infection (BSI) in adults: 30/100.000 admissions
- Premature neonates (< 1000 g):
- 150/100.000 admissions
- Clinical presentation as bacterial BSI
- Mortality up to 40%
How do we diagnose invasive candidiasis?
- Blood culture or culture from normally sterile site
- β-d-glucan high NPV and performs very well to exclude invasive candidiasis
- Recent developments in PCR assays very promising
- In infants and children performance lower due to sampling issues
How is aspergillus transmissioned?
- sporulation
- hydrophobic conidia
- diameter 2-3 μm
- airborne / inhalation
What is invasive pulmonary aspergillosis?
Asperigillus infection of the ciliated cells of the lungs.
What are the classifications of aspergillus infection?
- Acute invasive pulmonary aspergillosis
- Neutropenic patients (incidence 1-10%)
- Post transplants: stem cell > solid organ (incidence up to 8%)
- Patients with defects in phagocytes
- Chronic pulmonary aspergillosis (> 3 months)
- • Patients with underlying chronic lung conditions
- Allergic aspergillosis
- Allergic bronchopulmonary aspergillosis in CF and asthma (incidence 10-15%)
- Asthma or CF with fungal sensitisation (incidence 5-15%)
Notable features and SSx of 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)
Notable features/SSx of (sub) Acute Invasive Pulmonary Aspergillosis:
non-neutropenic host (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%
How can invasive aspergillosis present as primary immunodefiency?
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
Notable features/SSx for chronic pulmonary aspergillosis?
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
What is Allergic Bronchopulmonary Aspergillosis?
Immunological responses to a variety of A. fumigatus antigens in the CF-host (10-15%) that 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
- Tuberculosis
- In 22% if residual cavities
- Sarcoidosis
- Bronchiectasis
- Bronchial cysts and bullae After pulmonary infections
How do we diagnose pulmonary aspergillosis in non-neutropenic patients?
- Cultures of sputum and/or bronchoalveolar lavage, and/or biopsy
- Aspergillus specific IgG and IgE in chronic and allergic pulmonary aspergillosis
How do we diagnose pulmonary aspergillosis in neutropenic patients?
- High resolution CT-chest
- ‘halo-sign’ and ‘air-crescent sign’
- Molecular markers in blood: galactomannan and PCR-Aspergillus (high NPV and are suited for screening purposes)
- BAL and biopsies if clinical condition allows
How is cryptococcus transmitted?
- Transmission by inhalation: can be found on the bark of a variety of trees, bird faeces and organic matter
How can cryptoccus present?
Pulmonary infection from asymptomatic to pneumonia
What is the brain risk from cryptoccocal infection?
- Dissemination to brain: meningoencephalitis in HIV/AIDS patients (CD4 < 100 cells/ul)
How does cryptococcus clinically present?
- headache, confusion, altered behaviour, visual disturbances, coma (due to raised intracranial pressure in 60-80%)
How do we diagnose cyptococcal disease?
- Cerebrospinal fluid: Indian Ink preparation (80% sensitivity), culture, high protein and low glucose, Cryptococcus antigen (lateral flow assay)
- Blood: culture, Cryptococcus antigen
What are the outcomes for cryptococcal meningitis?
- Africa: 3-month mortality 70%
- US: 3-months mortality 25%
- Factors associated with mortality:
- Delay in presentation and diagnosis
- Lack of access to antifungals
- Inadequate induction therapy
- Delays in starting antiretroviral therapy Immune reconstitution syndrome
