Pulmonary aspergillus fumigatus Flashcards

1
Q

what is the most important opportunistic mould pathogen of Immuno-compromised humans

A

aspergillus fumigatus

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2
Q

who are particularly vulnerable

A

people with haematological malignancy and allogeneic bone marrow transplant

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3
Q

how many cases of invasive pulmonary aspergillosis

A

> 200,000 cases worldwide per year

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4
Q

mortality rate of invasive pulmonary aspergillosis

A

30-95%

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5
Q

chronic pulmonary aspergillosis

A

3 million cases worldwide in patients with underlying lung diseases

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6
Q

allergic bronchopulmonary aspergillosis

A

4 million cases worldwide in patients with asthma and cystic fibrosis

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7
Q

aspergilloma

A

a clump of mold which exists in a body cavity such as a paranasal sinus or an organ such as the lung.

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8
Q

immunity against aspergilloma

A
  • inactive candida are inhaled
  • candida lodge in lower respiratory tract
  • condida swell

MACROPHAGES (block the candida from germinating to hyphae)

NEUTROPHILS block hype from invading tissue and inviting blood vessels where they can disseminate

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9
Q

macrophages

A

block swelled candida from germinating to a hyphae

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10
Q

neutrophil

A

stop hyphae from invading tissue

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11
Q

if you are immunocompromised (have few macrophages and neutrophils)..

A

candida will be able to turn into hyphae, invade blood vessels and disseminate into the blood

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12
Q

diagnosing IPA

A

no single ‘gold standad’

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13
Q

what does diagnosis rely on

A

data from clinical, radiological, serological (GM and B-D gluten), molecular, histopathological and microbiological sources

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14
Q

diagnosis should conform to what writer for probable or proven detection of IPI

A

EORTC/MSG

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15
Q

what is important

A

that diagnosis is made without delay

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16
Q

serological detection of aspergillus fumigatus

A

serum shows elevated antibodies against A.fumigatus surface components

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17
Q

elevated antibody tigers shown to be due to the presence of abundnant

A

galactomannoprotein in the cell walls of the apthogen

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18
Q

which abundant galactomannoprotein is found in the cell walls of the A.fumigatus, that antibodies mount a response against

A

Afmp1p

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19
Q

Afmp1p can be detected using

A

western blotting

20
Q

diagnosis using ELISA

A

recombinant Afmp1p protein used to coat wells of microsite plate

  • sera taken from patients with aspergilloma, from patients with Invasive aspergillosis and patients with infections caused by other pathogenic fungi
  • EISa highly specific for A.fumigatus
21
Q

structure of the fungal cell wall

A

B-(1,6)- glucan on the outside and B-(1,3)- glucan makes up chitin (fungal cell wall)

  • Phospholipid bilayer with ergosterol
  • mannans and galactans
22
Q

traditional immunological test for IPA centred around

A

detection of circulating fungal cell wall - galactomannan

23
Q

what used to detect galactomannkn (GM)

A

rat mAb EB-A2 (DAS-ELISA)

24
Q

specificity of GM assay

25
negatives of GM assay
high false positives
26
reasons for GM assay false positive
cross-reactivity of EB-A2 with GM from other species cross reactivity of mAb with galacotoxylomanna from cryptococcus neoformans detection of GM in B-lactam antibiotics derived from penicillin species GM found in food products e.g. baby formulas cross-reactivity of mAb with anti-cancer drug cyclophosphamide
27
which other species have GM
Fusarium
28
anti cancer drug
cyclophosphamide
29
antibitoic
b-lactam
30
GM common in
baby milk formulas- crosses the gut into blood stream
31
another method of detection
pan-fungal detection
32
pan fungal diagnostic detects
(1-3)- B-D- glucans
33
(1-3)- B-D- glucans
glucose polymer
34
(1-3)- B-D- glucans is found in
most fungi, some bacteria, higher plants
35
(1-3)- B-D- glucans is up to
60% dry weight of fungal cell wall
36
(1-3)- B-D- gluons forms the basis of the commerical
Fungitell test
37
(1-3)- B-D- gluons - pan fungal diagnostics has a
high rate of false positives
38
Mouse mAb JF5 is what type of immunoglobulin
IgG3
39
Mouse mAb JF5 recognises
extracellular, constitutive, glycoprotein antigen
40
antigen detected by Mouse mAb JF5 is secreted during
active growth of hyphae and is not produce by dead or quiescent spores
41
Mouse mAb JF5 displays superior
specificity to mAb EB-A2 (Glucomannoproteins)
42
EB-A2 is used in
Bio-Rad Platelia GM-ELISA
43
Mouse mAb JF5 has been used to develop a
rapid, user-friendly, diagnostic test (lateral flow device) for detection of IPA
44
Immunofluorescence localises
JF5 antigens to actively growing hyphae
45
immunogold EM can be used to visualise
JF5 antigens released from growing hyphae (little dots around the structure)
46
Mouse mAb JF5 can differentiate between
A.fumigatus and S.apiospermum