Presentation on theme: "Paul E. Verweij, MD Department of Medical Microbiology Nijmegen University Center of Infectious Diseases, UMC St Radboud Advances in the diagnosis of invasive."— Presentation transcript:
Paul E. Verweij, MD Department of Medical Microbiology Nijmegen University Center of Infectious Diseases, UMC St Radboud Advances in the diagnosis of invasive aspergillosis
Advances……… Understanding release and kinetics of surrogate markers Comparison of surrogate markers Comparison of strategies
Galactomannan variability: Published factors: False positive reactivity……….. Piperacillin-tazobactam LTA of bifidobacteria False negative reactivity………… N Engl J Med 2003;349:24-5 Lancet 2004;363:325-7
Factors that influence performance Biological factors Site of infection Aspergillus species Microenvironment at site of infection (nutrients, pH, etc) Molecule structure of released GM Underlying condition / immune suppression Exposure to antifungals Renal clearance, hepatic metabolism Presence of GM antibodies Lancet Infect Dis 2004;4:349-57
Factors that influence performance-continued…. Biological factors Storage of sample Pre-treatment procedure Epidemiological factors Patient population Prevalence of infection Sampling strategy Definitions (positive result (cut-off), positive patient) Lancet Infect Dis 2004;4:349-57
J Infect Dis 2004;190:641-9 GM cut-off 986 serum samples from 67 patients with hematological malignancy
J Infect Dis 2004;190:641-9 Effect of exposure to mould-active antifungals
Release of surrogate markers is a dynamic process
Growth phases of A. fumigatus in vitro I Carbon source (glucose) Excretion of organic acids Decrease of pH Logaritmic growth II No glucose Re-use of organic acids Increase of pH Decreased growth III No glucose No acids Stable pH Lysis and cannibalism Arch Aller Appl Immun 1980;62: Release of markers by the fungus
Concentration hours Release of surrogate markers glucoseDry weightGM III III
Concentration hours Release of surrogate markers PCR (supernatant) Need damage of fungus by host defences?
Comparative studies GM versus PCR versus BG Adult hematology patients on mould active antifungal prophylaxis Prospective study, 149 treatment episodes, 96 patients Weekly sampling ROC analysis: GM > PCR and GM > BG J Clin Microbiol 2004;42:
PCR Antigen Need for strategic studies: which test to use Both?
Conclusions PCR,GM and BG may be useful for the early detection of invasive mycoses when intensive sampling is achieved. Some progress has been made in understanding the kinetics of surrogate markers Correlation with other diagnostics and optimal sequence of testing needs to be determined