Pulmonary aspergillus fumigatus

Question 1

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

Answer 1

aspergillus fumigatus

Question 2

who are particularly vulnerable

Answer 2

people with haematological malignancy and allogeneic bone marrow transplant

Question 3

how many cases of invasive pulmonary aspergillosis

Answer 3

> 200,000 cases worldwide per year

Question 4

mortality rate of invasive pulmonary aspergillosis

Answer 4

30-95%

Question 5

chronic pulmonary aspergillosis

Answer 5

3 million cases worldwide in patients with underlying lung diseases

Question 6

allergic bronchopulmonary aspergillosis

Answer 6

4 million cases worldwide in patients with asthma and cystic fibrosis

Question 7

aspergilloma

Answer 7

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

Question 8

immunity against aspergilloma

Answer 8

• 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

Question 9

macrophages

Answer 9

block swelled candida from germinating to a hyphae

Question 10

neutrophil

Answer 10

stop hyphae from invading tissue

Question 11

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

Answer 11

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

Question 12

diagnosing IPA

Answer 12

no single ‘gold standad’

Question 13

what does diagnosis rely on

Answer 13

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

Question 14

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

Answer 14

EORTC/MSG

Question 15

what is important

Answer 15

that diagnosis is made without delay

Question 16

serological detection of aspergillus fumigatus

Answer 16

serum shows elevated antibodies against A.fumigatus surface components

Question 17

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

Answer 17

galactomannoprotein in the cell walls of the apthogen

Question 18

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

Answer 18

Afmp1p

Question 19

Afmp1p can be detected using

Answer 19

western blotting

Question 20

diagnosis using ELISA

Answer 20

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

Question 21

structure of the fungal cell wall

Answer 21

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

Question 22

traditional immunological test for IPA centred around

Answer 22

detection of circulating fungal cell wall - galactomannan

Question 23

what used to detect galactomannkn (GM)

Answer 23

rat mAb EB-A2 (DAS-ELISA)

Question 24

specificity of GM assay

Answer 24

> 85%

Question 25

negatives of GM assay

Answer 25

high false positives

Question 26

reasons for GM assay false positive

Answer 26

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

Question 27

which other species have GM

Answer 27

Fusarium

Question 28

anti cancer drug

Answer 28

cyclophosphamide

Question 29

antibitoic

Answer 29

b-lactam

Question 30

GM common in

Answer 30

baby milk formulas- crosses the gut into blood stream

Question 31

another method of detection

Answer 31

pan-fungal detection

Question 32

pan fungal diagnostic detects

Answer 32

(1-3)- B-D- glucans

Question 33

(1-3)- B-D- glucans

Answer 33

glucose polymer

Question 34

(1-3)- B-D- glucans is found in

Answer 34

most fungi, some bacteria, higher plants

Question 35

(1-3)- B-D- glucans is up to

Answer 35

60% dry weight of fungal cell wall

Question 36

(1-3)- B-D- gluons forms the basis of the commerical

Answer 36

Fungitell test

Question 37

(1-3)- B-D- gluons - pan fungal diagnostics has a

Answer 37

high rate of false positives

Question 38

Mouse mAb JF5 is what type of immunoglobulin

Answer 38

IgG3

Question 39

Mouse mAb JF5 recognises

Answer 39

extracellular, constitutive, glycoprotein antigen

Question 40

antigen detected by Mouse mAb JF5 is secreted during

Answer 40

active growth of hyphae and is not produce by dead or quiescent spores

Question 41

Mouse mAb JF5 displays superior

Answer 41

specificity to mAb EB-A2 (Glucomannoproteins)

Question 42

EB-A2 is used in

Answer 42

Bio-Rad Platelia GM-ELISA

Question 43

Mouse mAb JF5 has been used to develop a

Answer 43

rapid, user-friendly, diagnostic test (lateral flow device) for detection of IPA

Question 44

Immunofluorescence localises

Answer 44

JF5 antigens to actively growing hyphae

Question 45

immunogold EM can be used to visualise

Answer 45

JF5 antigens released from growing hyphae (little dots around the structure)

Question 46

Mouse mAb JF5 can differentiate between

Answer 46

A.fumigatus and S.apiospermum