Fungal Infections Flashcards
What does pneumocystis spp. cause?
Pneumocystitis
Pneumonia
What does aspergillus spp. cause?
Allergic and invasive pulmonary aspergillosis
Aspergilloma
What does candida spp. cause?
Thrush
Candidemia
What does Cryptococcus spp. cause?
Meningitis
Renal abscess
Who especially gets mucocutaneous candidiasis?
Neonates < 3 months
Causes of mucocutaneous candidiasis
Antibiotic use
Inhalation steroids
Where is mucocutaneous candidiasis found?
Nappy rash
Flexural/intertriginous e.g. behind knee
Interdigital candidiasis of the hands
Presenting symptom of primary immunodeficiency disorders characterised by…..
Neutropenia
Low CD4+ cells
Impaired IL-17 immunity
Risk factors for invasive candidiasis
Premature neonates Broad spectrum antibiotics Intravascular catheters Total parenteral nutrition Abdominal surgery
Presentation of invasive candidiasis
As bacterial bloodstream infection
Investigations for invasive candidiasis
Blood culture or culture from normally sterile site
B-d-glucan high NPV
How is aspergillus transmitted?
Sporulation - hydrophobic conidia
Airborne - inhalation
Pathology of invasive pulmonary aspergillosis
- sporulation
- inhalation of airborne conidia
- Conidial germination in absence of sufficient pulmonary defences
- Corticosteriod induced immunosuppression; PMN recruitment and tissue damage and neutropenia; excessive hyphal growth and dissemination
Types of pulmonary aspergillus disease
Acute invasive pulmonary aspergillosis
Chronic pulmonary aspergillosis
Allergic aspergillosis
Who gets acute invasive pulmonary aspergillosis?
Neutropenic patients
Post transplants; stem cell > solid organ
Patients with defects in phagocytes
Definition of neutropenia
Abnormally low concentration of neutrophils (type of white blood cells) in the blood
Who gets chronic pulmonary aspergillosis?
Patients with underlying chronic lung conditions
Types of allergic aspergillosis
Allergic bronchopulmonary aspergillosis in CF and asthma
Asthma or CF with fungal sensitisation
Pathology of acute invasive pulmonary aspergillosis
- Rapid and extensive hyphal growth
- Thrombosis and haemorrhage
- Angio-invasive + dissemination
What could cause a host to be neutropenic?
Acute leukaemia
Haematopoietic stem cell transplant
Presentation of acute invasive pulmonary aspergillosis
Absent or non-specific clinical signs and symptoms
Persistent febrile neutropenia despite broad spectrum antibiotics
Prognosis of acute invasive pulmonary aspergillosis
Mortality rates 50%
Although depends on immune recovery
Who gets (sub) acute invasive pulmonary aspergillosis?
Non-neutropenic hosts
- graft vs host disease
- neutrophil disorders
Pathology of (sub) acute invasive pulmonary aspergillosis
Non-angioinvasive Limited fungal growth Pyogranulomatous infiltrates Tissue necrosis Excessive inflammation
Presentation of (sub) acute invasive pulmonary aspergillosis
Non-specific clinical signs and symptoms
Mild to moderate systemic illness
Prognosis of (sub) acute invasive pulmonary aspergillosis
mortality 20-50%
Invasive aspergillosis can be a presenting symptom of what?
Primary immunodeficiency
Causes of primary immunodeficiency
Congenital neutropenia
Chronic granulomatous disorder (phagocytic disorder)
Hyper IgE syndrome
CARD-9 deficiency
Presentation of invasive aspergillosis as a presentation of primary immunodeficiency
Often outside of the lungs e.g.
- bones, spine, brain, abdominal
What conditions does chronic pulmonary aspergillus affect?
Asthma
Cystic Fibrosis
Chronic obstructive lung disorders
Presentation of chronic pulmonary aspergillosis
Pulmonary exacerbations (not responding to antibiotics) Lung function decline Increased respiratory symptoms Cough Decreased exercise tolerance Dyspnoea
Investigations for chronic pulmonary aspergillosis
Positive sputum culture for aspergillosis
Are a proportion of CF patients infected with aspergillosis?
Yes - 50% are infected
Pathology of allergic bronchopulmonary aspergillosis
immunological responses to a variety of A. fumigatus antigens in the CF- host (10-15%) results in multiple presentations
Symptoms/signs of allergic bronchopulmonary aspergillosis
Acute/subacute deterioration of lung function and respiratory symptoms
New abnormalities of chest imaging
Elevated 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 conditions does pulmonary aspergilloma grow in?
TB Sarcoidosis Bronchiectasis Bronchial cysts and bullae After pulmonary infections
Investigations for pulmonary aspergillosis
Non-neutropenic patients
- cultures of sputum and/or bronchoalveolar lavage, and/or biopsy
- aspergillosis specific IgG and IgE in chronic and allergic pulmonary aspergillus
Neutropenic patients
- High resolution CT chest (halo sign and air crescent sign)
- molecular markers in the blood (galactomannan and PCR)
- BAL and biopsies if clinical conditions allow
Cryptococcus has caused a huge global burden of what disease?
HIV-associated cryptococcal meningitis
Transmission of cryptococcal infection is done by…
Inhalation
Bark of a variety of trees
Bird faeces
Organic matter
Presentation of cryptococcal infection
pulmonary infection - asymptomatic to pneumonia dissemination to brain - meningoencephalitis in HIV/AIDs patients Headache confusion altered behaviour visual disturbances coma (due to raised ICP in 60-80%)
Investigations for cryptococcal disease
CSF
Blood culture
Factors associated with mortality of cryptococcal meningitis
Delay in presentation or diagnosis Lack of access to antifungals Inadequate induction therapy Delays in starting anti-retrovirals Immune reconstitution syndrome
Who is affected by fungal pathogens that are opportunistic in nature?
Impaired immune system - primary immunodeficiencies - HIV/AIDs - malignancies (neutropenia) and transplants - premature neonates (immature immune system) Chronic lung disease - CF - chronic obstructive lung disorders - asthma ICU settings
Antifungals that treat invasive fungal infections
Amphotericin B (IV)
Azoles (IV, oral)
Echinocandins (IV)
Flucytosine (IV, oral)
Which antifungal drug has the broadest anti-fungal activity?
Amphotericin B
