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Update on Antigen Detection

s. Eukaryotic cell 2005;4:1308-16. Update on Antigen Detection. Paul E. Verweij, MD Nijmegen University Center for Infectious Diseases. Background. Sandwich ELISA Detects galactofuranosyl antigen Detection limit 1 ng/ml Early marker of invasive aspergillosis

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Update on Antigen Detection

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  1. s Eukaryotic cell 2005;4:1308-16 Update on Antigen Detection Paul E. Verweij, MD Nijmegen University Center for Infectious Diseases

  2. Background Sandwich ELISA Detects galactofuranosyl antigen Detection limit 1 ng/ml Early marker of invasive aspergillosis Variable performance reported

  3. 1 Factors affecting performance Combining surrogate markers Clinical evaluation 2 3

  4. 1 Bifidobacteria Cross reacting lipoglycans in Gram positive cell wall Lipoglycans containing a -1,5-galactofuranosyl chain JCM 2005;43:3925-31

  5. Bifidobacteria: reactivity with GM-ELISA JCM 2005;43:3925-31

  6. Reactivity in faeces Measured in faeces neonates 200 – 36,320 JCM 2005;43:3925-31

  7. GM and –lactam agents (31 batches analysed) 1 May 2003 – November 2004 JCM 2005;43:5214-20

  8. GM and –lactam agents: impact on patient management No IA 0 No IA 24 Antifungal therapy AMX based therapy 5/13 PTZ 18/22 Possible IA 24 Possible IA 11 before after probable IA 11 probable IA 0 JCM 2005;43:5214-20

  9. AML, MDS Receiving antifungal prophylaxis Effect of exposure to mould-active antifungals 1 J Infect Dis 2004;190:641-9

  10. Comparative release of surrogate markers in vitro - - - - - - - - - - - - - - PCR 2 Mennink et al, submitted

  11. GM and BG ITZ VCZ

  12. GM and PCR Gm positive samples JCM 2005;43:5097-5101

  13. Clinical evaluation of diagnostic procedures: CT vs GM 3 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

  14. CT scan PTZ CID 2005;41:1143-9

  15. Factors associated with positive GM …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

  16. Performance Sensitivity: 40% Specificity: 100% CT Sensitivity: 80% Specificity: 81% GM CID 2005;41:1143-9

  17. 3 CID 2005;41:1242-50

  18. 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 therapy CID 2005;41:1242-50

  19. Pre-emptive strategy Breakthrough fungal infections: C. glabrata fungemias (blood culture) – 2 cases Disseminated zygomycoses – 1 case CID 2005;41:1242-50

  20. 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

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