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Flashcards in Fungal Infections Deck (41)
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1
Q

What are the three main fungal pathogens?

A

Aspergillus species (aspergillus fumigatus)

Candida species (candida albicans)

Cryptococcus species (cryptococcus neoformans)

2
Q

What types of patients do fungal pathogens often attack?

A

Impaired immune systems

Patients with chronic lung diseases

Patients in ICU settings

3
Q

Give examples of patients with impaired immune systems

A

Patients with primary immunodeficiencies

Patients with HIV/AIDS

Malignancies (neutropenia) and transplants

Premature neonates (immature immune system)

4
Q

What chronic lung disease might fingal infections attack?

A

Asthma

Cystif fibrosis

Chronic obstructive lung disorders

(pulmonary aspergillosis and other moulds)

5
Q

What organism is responsible for pneumocystis pneumonia?

A

Pneumocystis spp

6
Q

What fungal speces can cause meningitis?

A

Cryptococcus

7
Q

What can cause mucocutaneous candidiasis?

A

Antibiotic use

Inhalation steroids

8
Q

When might mucocutaneous candidiasis suggest presenting symptoms of immunodeficiency?

A

In the presence of neutropenia

Low CD4+ T cells

Impaired IL-17 immunity

9
Q

Where do most invasive candidiasis infections arise from?

A

Mostly endogenous origin - candida is a commensal of the gut

Candidiasis is the 4th most common blood stream infection

10
Q

What are additional risk factors for invasive candidiasis infections?

A

Broad spectrum antibiotics

Intravascular catheters

Total parenteral nutrition

Abdominal surgery

11
Q

How do we diagnose invasive candidiasis?

A
  • Blood culture or culture from normally sterile site
  • β-d-glucan high NPV (negative predicitve value) and performs very well to exclude invasive candidiasis (B-d glucan is an antigen that is found in candida spp, aspergillus spp and pneumocystis jirovecii
  • Recent developments in PCR assays very promising
  • In infants and children performance lower due to sampling issues
12
Q

How does aspergillus transmit?

A

Sporulation

Hydrophobic conidia

Conidia is a non-motile spore of a fungus, they allow the asexual reproduction of ascomycetes

Diameter of 2-3 micrometres

Airborne/inhalation

13
Q

What are the stages of invasive pulmonmary aspergillosis?

A

Sporulation

Inhalation of conidia

Conidial germination in absence of sufficient pulmonary defences

If there is corticosteroid induced immunosuprpession - Peripheral mononucleocyte recruitment and tissue damage

If there is neutropenia - excessive hyphal growth and dissemination

14
Q

In what patients is acute invasive pulmonary aspergillois common?

A

Neutropenic patients

Post transplant (stem cell is more common than solid tissue)

Patients with defects in phagocytes

15
Q

In what patients is chronic pulmonary aspergillosis common?

A

Patients with chronic underlying lung conditions

16
Q

What patients are more likely to get allergic aspergillosis?

A

CF or Asthma

17
Q

What are the feaures of invasive pulmonary aspergillosis in a neutropenic host?

A

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)

18
Q

What are the features of (sub) acute invasive pulmonary aspergillosis?

This is seen in non-neutropenic patients (graft-versus host disease, neutrophil disorders)

A

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%

19
Q

What primary immunodeficiency disorders might be underlying an invasive aspergillosis infection?

A

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)

Clinical presentation often outside the lungs; e.g.

bones, spine, brain, abdominal

20
Q

What are the clinical features of pulmonary aspergillosis?

A

Doesn’t respond to antibiotics

Decline in lung function

Increased respiratory symptoms such as cough, dyspnoea and decreased exercise tolerance

POsitive sputum cultures for aspergillus (50% of CF patients are infected)

High morbidity but causative mortality is not clear)

21
Q

When does allergic bronchopulmonary aspergillosis occur?

A

Immunological response to a variety of A fumigatus antigens in the CF host

22
Q

What does the immunological response by a CF host to A.Fumigatus antigens cause?

What are the tests?

A

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

23
Q

What is pulmonary aspergilloma?

A

A fungal mass that usually grow in lung cavities

24
Q

What is the pathogenesis of aspergilloma?

A

Inhaled Aspergillus may lodge and germinate in areas of damaged lung tissue, forming a fungal ball or ‘aspergil- loma’

Often form in tuberculosis cavities

Other causes include damage from a lung abscess cavity, bronchiectatic space, pulmonary infarct, sarcoidosis, ankylosing spondylitis or even a cavitated tumour.

25
Q

How is diagnosis of pulmonary aspergillosis achieved if the patient is non-neutropenic?

A

Cultures of sputum and/or bronchoalveolar lavage, and/or biopsy

Aspergillus specific IgG and IgE in chronic and allergic pulmonary aspergillosis

26
Q

How is diagnosis of pulmonary aspergillosis achieved in neutropenic patients?

A

High resolution CT of chest (halo sign and air-crescent sign)

Molecular markers in the blood (galactomannan and PCR aspergillus)

bronchoalveolar lavage and biopsies if clinical condition allows

27
Q

What causes transmission of cryptococcus?

A

Transmission by inhalation

28
Q

Where is cryptococcus found?

A

On the bark of a variety of trees, bird faeces and organic matter

29
Q

What are the manifestations of cryptocccus?

A

Pulmonary infection (asymptomatic - pneumonia)

Dissemination to brain (meningoencephalitis in HIV/AIDS patients (CD4 less than 100 cells/ul)

30
Q

What is the clinical presentation of cryptocccus / cryptococcosis?

A

Clinical presentation: headache, confusion, altered behaviour, visual disturbances, coma (due to raised intracranial pressure in 60-80%)

31
Q

What is the diagnosis of cryptococcal disease?

A

CSF - indian ink preparation, culture, high protein, low glucose, cryptococcus antigen

Blood: culture - cryptococcus antigen

32
Q

What factors are assocaited with mortality from cryptococcal meningitis?

A

Delay in presentation and diagnosis

Lack of access to antifungals

Inadequate induction therapy

Delays in starting anti-retroviral therapy

Immune reconstitution syndrome

33
Q

What are the actions of the following anti-fungal drugs used to treat invasive anti-fungal infections?

Amphotericin B

Azoles

Echinocandins

Flucytosine

A

Amphotericin B - acting on ergosterol - lysis

Azoles - inhibiting ergosterol synthesis

Echinocandins - inhibiting glucan synthesis

Flucytosine - inhibiting fungal DNA synthesis

34
Q

What drug has the broadest antifungal actvity?

A

Amphotericin B

35
Q

What is used to treat invasive candidiasis?

A

Echinocandins and fluconazole

36
Q

What dugs are used for treatment of invasive aspergillosis?

A

Voriconazole and isavuconazole

37
Q

What drugs are used for antifungal prophylaxis?

A

Itraconazole and posaconazole

38
Q

What is used for maintenance therapy of cryptococcal meningitis?

A

Amphotericin B and flucytosine followed by fluconazole

39
Q

Cerebrospinal fluid: Indian Ink preparation (80% sensitivity), culture, high protein and low glucose, Cryptococcus antigen (lateral flow assay)

Blood: culture, Cryptococcus antigen

A
40
Q

Candida auris has recently attracted attention because of its multi-drug resistance - to what drugs is it resistant?

A

>90% fluconazole R

30-40% echinocandin R

5-15% amphotericin R

50% MDR (≥ 2 classes of antifungals)

~10-20% pan-fungal R

41
Q

A.fumigatus resistance is assocaited with what drug?

A

Azoles