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year 3 - infection > Fungal infections > Flashcards

Fungal infections Flashcards

1
Q

How many fungal infections of humans?

A

1.5 billion

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2
Q

How many life threatening fungal infections per year?

A

> 3 million

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3
Q

What are the mortality rates typically in fungal infections?

A

> 50%

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4
Q

How many cases of blindness occur due to fungal infections per year?

A

> 400,000 cases

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5
Q

Allergens and asthma linked with fungi?

A

> 20 million

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6
Q

Example of an Aspergillus fungus species?

A

Aspergillus fumigatus

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7
Q

Example of a Candida fungal species?

A

Candida albicans

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8
Q

Example of a Cryptococcus fungal species?

A

Cryptococcus neoformans

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9
Q

Who is primary infected with fungal infections?

A

Immunocompromised:

  • HIV/AIDs
  • Neutropenia
  • Transplants
  • Premature neonates

Chronic lung diseases:

  • Asthma
  • Cystic fibrosis
  • COPD

ICU patients

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10
Q

What can Pneumocystis spp. cause?

A

1) Pneumocystis pneumonia*
2) Ophthalmic pneumocystis
3) Renal pneumocystis
4) Bone marrow infiltrates
5) Hepatosplenic infiltrates

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11
Q

What can Aspergillus spp. cause?

A

1) Allergic and invasive aspergillosis*
2) Aspergilloma*
3) Cerebral asergillosis
4) Keratitis
5) Sinusitis
6) Osteomyelitis
7) Cutaneous aspergillosis

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12
Q

What can candida spp. cause?

A

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

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13
Q

What can cryptococcus spp. cause?

A

1) Meningitis*
2) Cerebral abscess
3) Endophthalmitis
4) Pulmonary infiltrates
5) Endocarditis
6) Crptococcemia
7) Renal abscess
8) Subcutaneous abscess

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14
Q

What can cause mucocutaneous candidiasis?

A
  • Antibiotic use
  • Moist areas
  • Immunocompromised
  • Inhalation steroids
  • Neonates <3 months
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15
Q

Presenting symptom of primary immunodeficiency disorder are characterised by what?

A

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

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16
Q

What is AD-Hyper IgE syndrome?

A

AD-Hyper IgE syndrome = deficient of IL-17 producing cells

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17
Q

What is Dectin-1-deficiency?

A

Dectin-1-deficiency = Reduced levels of IL-17

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18
Q

What is CARD9 deficiency?

A

CARD9 deficiency = Low proportion of circulating IL-17 T-cells

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19
Q

What is APECED Syndrome?

A

APECED Syndrome = High titres of neutralising AB against IL-17A, IL-17F and IL-22

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20
Q

What is the most common origin of invasive candidiasis infection?

A

Endogenous of origin (Gut commensal)

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21
Q

What is the 4th most common cause of bloodstream infection is adults?

A
  • Invasive candidiasis

- 30/100,000

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22
Q

How common is invasive candidiasis in premature neonates (<1000g)?

A

150/100,000

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23
Q

How does invasive candidiasis present?

A

As bacterial bloodstream infection

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24
Q

What is the mortality rate of invasive candidiasis infection?

A

40%

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25
Q

What are the main risk factors in candidiasis infections?

A
  • Premature neonates
  • Immunocompromised
  • Broad-spectrum Abx use
  • Intravascular catheters
  • Total parenteral nutrition
  • Abdominal surgery
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26
Q

How is invasive candidiasis diagnosed?

A

1) Blood culture
2) Beta-d-glucan high NPV and performs very well to exclude invasive candidiasis
3) PCR assays

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27
Q

How is Aspergillus transmitted?

A

Sporulation, airborne hydrophobic conidia, inhaled

diameter = 2-3um

28
Q

When may acute invasive pulmonary aspergillosis occur?

A
  • Neutropenic patients (1-10%)
  • Post transplants: Stem cell > Solid organ (Up to 8%)
  • Patient with defects in phagocytes
29
Q

What is the most common cause of chronic pulmonary aspergillosis?

A

Underlying chronic pulmonary disease

30
Q

What is defined as chronic pulmonary aspergillosis?

A

> 3months

31
Q

What is allergic aspergillosis?

A
  • Allergic bronchopulmonary aspergillosis in CF and asthma (10-15%)
  • Asthma or CF with fungal sensitisation (5-15%)
32
Q

Acute invasive pulmonary aspergillosis?

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)
33
Q

(Sub) acute invasive pulmonary aspergillosis, non-neutropenic host ?

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%
34
Q

Where does invasive aspergillosis usually present in someone immunocompromised?

A

Often outside of the lungs e.g. bones, spine, brain or abdomen

35
Q

Chronic Pulmonary Aspergillosis?

occurs in: asthma, cystic fibrosis, chronic obstructive lung disorders

A

• 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

36
Q

Allergic Bronchopulmonary Aspergillosis?

A

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
37
Q

What is pulmonary aspergilloma?

A

A fungal mass that usually grows in lung cavities

38
Q

What may pulmonary aspergilloma occur after?

A
  • TB (In 22% of residual cavities)
  • Sarcoidosis
  • Bronchiectasis
  • Broncial cysts and bullae
  • After pulmonary infection s
39
Q

What is a common cause of aspergillosis in a non-neutropenic host?

A

1) Respiratory infection and insufficiency = Intubation
2) Influenza A: Oseltamivir, corticosteroids, Abx
3) Day 3: A fumigatus in sputum

40
Q

What percentage of influenza cases are associated with aspergillosis? What percentage of those died?

A

16% (23 cases), 61% of those died (14 cases)

41
Q

How is pulmonary aspergillosis diagnosed in a non-neutropenic patient?

A

1) Cultures of sputum
2) Culture of bronchoalveolar lavage
3) Culture of biopsy
4) Aspergillus specific IgG and IgE in chronic and pulmonary aspergillosis

42
Q

How is pulmonary aspergillosis diagnosed in a neutropenic patient?

A

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

43
Q

How is Cryptococcus transmitted?

A

By inhalation - It can be found on the bark of a variety of trees, bird faeces and organic matter

44
Q

In an AIDs patient with CD4 <100 cells/ul what complication of cryptococcosis is the patient at risk of?

How would they present?

A

Dissemination to the brain = Meningoencephalitis

Presentation:

  • Headache
  • Confusion
  • Altered behaviour
  • Visual disturbances
  • Coma (Due to raised intracranial pressure)
45
Q

How is cryptococcal disease diagnosed?

A

1) Cerebrospinal fluid:
- Indian ink preparations
- Culture
- High protein and low glucose
- Cryptococcus antigen (Lateral flow assays)

2) Blood cultures:
- Cryptococcus antigen

46
Q

What is the mortality risk of cryptococcal meningitis in Africa?

A

3-month mortality = 70%

47
Q

What is the mortality risk of cryptococcal meningitis in Europe?

A

3-months mortality = 25%

48
Q

Which factors are associated with increased risk of mortality in cryptococcal meningitis?

A 
> Delay in presentation/diagnosis
> Lack of access to antifungals
> Inadequate induction of therapy 
> Delays in starting antiretroviral therapy 
> Immune reconstitution syndrome
49
Q

Antifungal agents used to treat invasive fungal infections?

A

1) Amphotericin B (IV)
2) Azoles (IV or oral)
3) Echinocandins (IV)
4) Flucytosine (IV or Oral)

50
Q

Mechanism of action of amphotericin B?

A

Acting on ergosterol >lysis

51
Q

Mechanism of action of Azoles?

A

Inhibiting ergosterol synthesis

52
Q

Mechanism of action of Echinocandins?

A

Inhibiting glucan synthesis

53
Q

Mechanism of action of flucytosine?

A

Inhibiting fungal DNA synthesis

54
Q

Which anti fungal has the broadest anti fungal activity?

A

Amphotericin B

55
Q

Choice of anti fungal for invasive candidiasis?

A

Echinocandins and Fluconazole

56
Q

Choice of anti fungal for invasive aspergillosis?

A

Variconazole and Isavuconazle

57
Q

Choice of anti fungal for prophylaxis?

A

Itraconazole and Posaconazole

58
Q

Choice of anti fungal for maintenance for cryptococcal meningitis?

A

1) Amphotericin B + Flucytosine

Followed by:

2) Fluconazole

59
Q

Which anti fungal have Candida auris gained resistance to?

A

> 90% Fluconazole R

30-40% Echinocandin R

5-15% Amphotericin R

60
Q

How to treat resistant Candida auris?

A

> 2 classes of anti-fungals

Even then 10-20% have pan fungal resistance

61
Q

Which anti fungal has Aspergillus fumigatus gained resistance to?

A

Azoles

Now present in 19 countries including US, Brazil and Australia

62
Q

What are the biggest challenges in mycology presently?

A

1) Anti-fungals
2) Diagnosis
3) Understanding immunology and pathology

63
Q

Anti-fungals challenges in mycology presently?

A 
> Stativ vs cidcl
> IV vs Oral
> Toxicity 
> Drug interactions
> Resistance 
> Cost
64
Q

Diagnostic challenges in mycology presently?

A

> Sensitivity
Specificity
Portability
Cost and Feasibility

65
Q

Understanding immunology and pathology challenges in mycology presently?

A

> No vaccines

> No immunotherapies

year 3 - infection (16 decks)

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