Fungal Infections Flashcards
name the main fungal pathogens
aspergillus sp - aspergillus fumigatus
candida sp - candida albicans
cryptococcus sp - cryptococcus neoformans
fungal pathogens are what in nature?
opportunistic
fungal pathogens affect what groups of people?
impaired immune system: primary immunodeficiences, HIV/AIDS, malignancies, transplants, premature neonates
chronic lung disease: asthma, CF, chronic obstructive lung disorders
Patients in ICU
name common infections caused by: pneumocystis spp
pneumocystis pneumonia
ophthalmic pneumocystosis
hepatosplenic infiltrates
renal pneumocystosis
bone marrow infiltrates
name common infections caused by: aspergillus spp
allergic and invasive pulmonary aspergillosis
aspergilloma
cerebral aspergillosis keratitis sinusitis osteomyeliti cutaeneous aspergillosis
name common infections caused by: candida spp
thrush
candidaemia
cerebral abscess oesophagitis endocardinitis hepatic abscess renal abscess urinary candidiasis vulvovaginal candidiasis osteomyelitis cutaneous candidiasis onchomycosis
name common infections caused by: cryptococcus spp
meningitis
cerebral absecc endophathlamitis pulmonary infiltrates endocarditis crytococcaemia renal abscess subcutaneous abscess
what is mucocutaneous candidiasis associated with?
antibiotic use
where is mucocutaneous candidiasis found?
moist areas
oral candidiasis is associated with?
inhalation steroids
what age group are vulnerable to mucocutaneous candidiasis?
< 3 months
presenting symptoms of primary immunodeficiency disorders
neutropenia
low CD4+ T cells
impaired IL-17 immunity
what are the 4 types of impaired IL-17 immunity?
AD-hyper IgE syndrome - deficit of IL-17 producing cells
Dectin-1 deficiency - reduced IL=17 producing cells
CARD9 deficiency - low proportion of circulating IL-17 T cells
APECED syndrome - high titers of neutralising Ab against IL-17A, IL-17F and/or IL-22
most invasive candidiasis infections are what in origin and why?
endogenous because gut commensal
what can invasive candidiasis present as?
bacterial blood stream infection
what is the mortality rate of invasive candidiasis?
up to 40%
risk factors for developing invasive candidiasis
broad spectrum antibiotics
intravascular catheters
TPN
abdominal surgery
how can you diagnose invasive candidiasis?
Take a blood culture or culture from a normally sterile site. B-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 spread?
airborne
describe aspergillus spores
hydrophobic conidia
diameter approx 2-3um
name the classification of pulmonary aspergillus disease
acute invasive pulmonary aspergillosis
chronic pulmonary aspergillosis
allergic aspergillosis
who gets acute invasive pulmonary aspergillosis?
neutropenic patients
post transplant: stem cell > solid organ
patients with defects in phagocytes
who gets chronic pulmonary aspergillosis?
patients with underlying chronic lung conditions
when does aspergillosis pulmonary become chronic?
3 months
who gets allergic aspergillosis ?
allergic bronchopulmonary aspergillosis in CF ans asthma
asthma or CF with fungal sensitisation
describe effects acute invasive pulmonary aspergillosis
rapid and extensive hyphal growth
thrombosis and haemorrhage
angioinvasive and dissemination
acute invasive pulmonary aspergillosis signs and symptoms
absent or non specigic
persistent febrile neutropenia despite broad spectrum antibiotics
acute invasive pulmonary aspergillosis mortality
50%
effects of sub acute invasive pulmonary aspergillosis
non-angioinvasive limited fungal growth pyogranulomatous infiltrates tissue necrosis excessive inflammation
who does sub acute invasive pulmonary aspergillosis affect?
non-neutropenic host (graft vs host disease, neutrophil disorders)
signs and symptoms of sub acute invasive pulmonary aspergillosis
non-specific
mild-moderate systemic illness
sub acute invasive pulmonary aspergillosis mortality
20-50%
discuss invasive aspergillosis as a presenting symptom of primary immunodeficiency
• Congenital neutropenia • Chronic granulomatous disease o Phagocytic disorder • Hyper IgE syndrome (Job’s syndrome) o Phagocytic disorder and impaired IL-17 pathway • CARD-9 deficiency o Innate immune pathways, killing defect
Clinical presentation is often outside the lungs; e.g. bones, spine, brain, abdomen.
discuss 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 dyspnoea
• Positive sputum cultures for aspergillus
o 50% of CF patients are infected
• High morbidity but causative mortality rates less clear
discuss 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 IgE level
• Increases aspergillus specific IgE or positive skin test
• Positive aspergillus specific IgG
pulmonary aspergilloma who does it affect?
tuberculosis sarcoidosis bronchiectasis bronchial cysts and bullae after pulmonary infections
emerging non-neutropenic hosts vulnerable to aspergillus?
- Respiratory insufficiency > intubation ICU
- Influenza A > Th: oseltamivir, corticosteroids, antibiotics
- A. fumigatus in sputum by day 3
diagnosis of pulmonary aspergillosis in the non-neutropenic host
cultures of sputum and/or bronchoalveolar lavage, and/or biopsy
aspergillus specific IgG or IgE in chronic and allergic
diagnosis of pulmonary aspergillosis in the neutropenic host
high resolution CT chest - halo sign, air crescent sign
molecular markers in blood: galactomannan and PCR aspergillus
BAL and biopsies if clinical condition allows
how cryptococcus is spread?
inhalational
where can cryptococcus be found?
bark on a variety of trees
bird faeces
organic matter
what can cryptococcus cause?
pulmonary infection ranging from asymptomatic to pneumonia
cryptococcus can disseminate to the brain causing?
meningoencephalitis in HIV and AIDS patients
clinical presentation of cryptococcus
headache confusion altered behaviour visual disturbances coma due to raised ICP in 60-80%
diagnosis of cryptococcal disease: CSF
Indian Ink preparation
culture
high protein and low glucose
cryptococcus antigen
diagnosis of cryptococcal disease: blood
culture
cryptococcus antigen
mortality of cryptococcal meningitis
africa - 3 month mortality 70%
US - 3 month mortality 25%
what factors are associated with mortality in cryptococcal meningitis?
delay in presentation and diagnosis lack of access to antifungals inadequate induction therapy delays in starting antiretroviral therapy immune reconstitution syndrome
what antifungals can be used to treat invasive fungal infections? inc route
amphotericin B formulation (IV)
azoles (IV, oral)
ehinocandins (IV)
flucytosine (IV, oral)
how does amphotericin B work>
acting on ergosterol causing lysis
how do azoles work?
inhibit ergosterol synthesis
how do echinocandins work?
inhibit glucan synthesis
how does flucytosine work?
inhibit fungal DNA synthesis
what antifungal has the broadest activity?
AmB
what can be used to treat invasisive candidiasis?
echinocandins and fluconazole
what can be used to treat (acute) invasive aspergillosis?
voriconazole and isavuconazole
what can be used for antifungal prophylaxis?
itraconazole and posaconazole
what can be used for the maintenance of cryptococcal meningitis?
AmB + flucytosine followed by fluconazole
