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Year 3 - infection > Fungal Infections > Flashcards

Fungal Infections Flashcards

1
Q

what is the Grand Mycological Challenge?

A

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)

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2
Q

we are going to focus on hat 3 fungal pathogens?

A

Aspergillus species - Aspergillus fumigatus

Candida species - Candida albicans

Cryptococcus species - Cryptococcus neoformans

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3
Q

Fungal pathogens are opportunistic in nature affecting what kind of patients?

A

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

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4
Q

Candida and Candidiasis

A
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5
Q

What is mucocutaneous candidiasis?

A

Chronic mucocutaneous candidiasis is an immune disorder of T cells, it is characterized by chronic infections with Candida that are limited to mucosal surfaces, skin, and nails

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6
Q

Who, when and where does Mucocutaneous Candidiasis occur in?

A

Antibiotic use

Moist areas

Inhalation steroids

Neonates < 3 months

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7
Q

Mucocutaneous Candidiasis - Presenting symptom of primary immunodeficiency disorders characterised by what?

A

Neutropenia

Low CD4+ T-cells

impaired IL-17 immunity:

AD-Hyper IgE syndrome - deficit 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 titers of neutralizing Ab against IL-17A, IL-17F and/or IL-22

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8
Q

Invasive Candidiasis cause infection where?

A

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

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9
Q

What are the effects and risk factors of Invasive Candidiasis?

A

Clinical presentation as bacterial BSI

Mortality up to 40%

Additional risk-factors:

  • Broad-spectrum antibiotics
  • Intravascular catheters
  • Total parenteral nutrition
  • Abdominal surgery
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10
Q

What is the diagnosis of Invasive Candidiasis?

A

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

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11
Q

Aspergillus and Aspergillosis

A
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12
Q

how is Aspergillus transmitted?

A
  • sporulation
  • hydrophobic conidia (a spore produced asexually by various fungi at the tip of a specialized hypha)
  • diameter 2-3 µm
  • airborne / inhalation
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13
Q

what are the different classification of pulmonary Aspergillus disease?

A

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%)
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14
Q

what are the effects of Acute Invasive Pulmonary Aspergillosis in a neutropenic host (acute leukaemia, haematopoietic stem cell transplant)?

A
  • Rapid and extensive hyphal growth (fungus 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)
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15
Q

what ar ethe effects of (Sub) Acute Invasive Pulmonary Aspergillosis in a non-neutropenic host (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%

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16
Q

WHat are the effects of Chronic Pulmonary Aspergillosis in patients with 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

17
Q

Allergic Bronchopulmonary Aspergillosis:

immunological responses to a variety of A. fumigatus antigens in the CF-host (10-15%) result in:

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

18
Q

what is a Pulmonary Aspergilloma?

A

Pulmonary aspergilloma is a mass caused by a fungal infection. It usually grows in lung cavities

19
Q

a Pulmonary Aspergilloma may be seen in who?

A

Tuberculosis - In 22% if residual cavities

Sarcoidosis

Bronchiectasis

Bronchial cysts and bullae

After pulmonary infections

20
Q

Diagnosis of Pulmonary Aspergillosis in non-neutropenic patients

A
  • Cultures of sputum and/or bronchoalveolar lavage, and/or biopsy
  • Aspergillus specific IgG and IgE in chronic and allergic pulmonary aspergillosis
21
Q

Diagnosis of Pulmonary Aspergillosis in neutropenic patients

A
  • 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 (Bronchoalveolar lavage is a diagnostic method of the lower respiratory system in which a bronchoscope is passed through the mouth or nose into an appropriate airway in the lungs, with a measured amount of fluid introduced and then collected for examination)
22
Q

Cryptococcus and Cryptococcosis

A
23
Q

how is Cryptococcus transmitted?

A

Transmission by inhalation

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

24
Q

what does Cryptococcus caue?

A

Pulmonary infection from asymptomatic to pneumonia

Dissemination to brain: meningoencephalitis in HIV/AIDS patients (CD4 < 100 cells/ul)

25
Q

what is the clinical presentation of Cryptococcus?

A

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

26
Q

How is the diagnosis of cryptococcal disease made?

A

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

Blood: culture, Cryptococcus antigen

27
Q

what is the outcome of cryptococcal meningitis?

A

Africa: 3-month mortality 70%

US: 3-months mortality 25%

28
Q

what are some factors associated with mortality in cryptococcal meningitis?

A

Delay in presentation and diagnosis

Lack of access to antifungals

Inadequate induction therapy

Delays in starting antiretroviral therapy

Immune reconstitution syndrome

29
Q

what are some antifungal agents to treat invasive fungal infections?

A
  • Amphotericin B formulations (iv) - Acting on ergosterol > lysis
  • Azoles (iv, oral) - Inhibiting ergosterol synthesis
  • Echinocandins (iv) - Inhibiting glucan synthesis
  • Flucytosine (iv, oral) - Inhibiting fungal DNA synthesis
30
Q

Grand Mycological Challenge - we urgently need better what and what are the current problems?

A

Year 3 - infection (14 decks)

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