Update on Antigen Detection

Paul E. Verweij, MDNijmegen University Center for

Infectious Diseases

sEukaryotic cell 2005;4:1308-16

Background

Sandwich ELISA

Detects galactofuranosyl antigen

Detection limit 1 ng/ml

Early marker of invasive aspergillosis

Variable performance reported

Factors affecting performance

Combining surrogate markers

Clinical evaluation

1

2

3

Bifidobacteria

Cross reacting lipoglycans in Gram positive cell wall

Lipoglycans containing a -1,5-galactofuranosyl chain

JCM 2005;43:3925-31

1

Bifidobacteria: reactivity with GM-ELISA

JCM 2005;43:3925-31

Measured in faeces neonates 200 – 36,320

Reactivity in faeces

JCM 2005;43:3925-31

GM and –lactam agents (31 batches analysed)

JCM 2005;43:5214-20

May 2003 – November 2004

1

GM and –lactam agents: impact on patient management

No IA

24

Possible IA

11

probable IA

0

befo

re afte

r

No IA

0

Possible IA

24

probable IA

11

Antifungal therapy

AMX based therapy 5/13

PTZ 18/22

JCM 2005;43:5214-20

J Infect Dis 2004;190:641-9

AML, MDS

Receiving antifungal prophylaxisEffect of exposure to

mould-active antifungals1

Comparative release of surrogate markers in vitro

0

5000

10000

15000

20000

25000

30000

0 2 4 6 8 10 12 14 16 18 24 32 40

time (h)

GM

0

10000

20000

30000

40000

50000

60000

70000

BG GM

BG

- - - - - - - - -- - - - -PCR

Mennink et al, submitted

2

050

100150200250300350400

15/7

22/ 7

29/ 7

19/8 6/

913

/923

/ 94/

1015

/10

11/1

1

29/ 1

1

0

2

4

6

8

10

12

14

BG

GM

GM and BG

ITZ VCZ

JCM 2005;43:5097-5101

GM and PCR

Gm positive samples

Clinical evaluation of diagnostic procedures: CT vs GM

Patients: allo HSCT (65), autol HSCT (30), chemotherapy (66)Prophylaxis: fluconazole

161 episodes in 107 patients

Weekly CT scan, twice weekly GM

CT: major sign (halo, cresent, cavity)minor sign (all other infiltrates)

GM: 0.5 in 2 consecutive samples

CID 2005;41:1143-9

3

No infiltrates

minor major GM+

No IA(109)

76 33 0 20

Possible(32)

3 26 3 21

Probl/prov(20)

1 11 8 16

CT scan

CID 2005;41:1143-9

PTZ

Factors associated with positive GM

CID 2005;41:1143-9

…the decision to administer mould-active treatment should be based on detection of new pulmonary infiltrates on CT performed early during infection, rather than on results of EIA for detection of GM….

CID 2005;41:1143-9

CT+ CT-

IA+ 8 12

IA- 0 109

GM+ GM-

IA+ 16 4

IA- 20 89

CT

GM

Sensitivity: 40%Specificity: 100%

Sensitivity: 80%Specificity: 81%

Performance

CID 2005;41:1242-50

3

Pre-emptive strategy

88 hematology patients (136 episodes, 4170 samples)

Febrile neutropenia group (117 episodes) ->

9 were treated with AmBisome

41 episodes qualified for empiric

therapy

reduction in use antifungals: 35% to

7.7%

10 non-febrile episodes of febrile episodes with

alternative explanation received antifungal therapyCID 2005;41:1242-50

Pre-emptive strategy

Breakthrough fungal infections:

C. glabrata fungemias (blood culture) – 2 cases

Disseminated zygomycoses – 1 case

CID 2005;41:1242-50

Conclusions

Increased insight in factors that are important for the performance of GM detection

Studies should focus on comparison of markers and on management strategies that incorporate surrogate markers

Differences in performance remains an important problem