12 Galactomannan variability: Published factors:False positive reactivity………..Piperacillin-tazobactamLTA of bifidobacteriaFalse negative reactivity…………N Engl J Med 2003;349:24-5Lancet 2004;363:325-7
13 Factors that influence performance Biological factorsSite of infectionAspergillus speciesMicroenvironment at site of infection (nutrients, pH, etc)Molecule structure of released GMUnderlying condition / immune suppressionExposure to antifungalsRenal clearance, hepatic metabolismPresence of GM antibodiesLancet Infect Dis 2004;4:349-57
14 Factors that influence performance-continued…. Biological factorsStorage of samplePre-treatment procedureEpidemiological factorsPatient populationPrevalence of infectionSampling strategyDefinitions (positive result (cut-off), positive patient)Lancet Infect Dis 2004;4:349-57
15 GM cut-off986 serum samples from 67 patients with hematological malignancyJ Infect Dis 2004;190:641-9
16 Effect of exposure to mould-active antifungals J Infect Dis 2004;190:641-9
17 Release of surrogate markers is a dynamic process
18 I II III Growth phases of A. fumigatus in vitro Release of markers by the fungusIIIIIICarbon source (glucose)Excretion of organic acidsDecrease of pHLogaritmic growthNo glucoseRe-use of organic acidsIncrease of pHDecreased growthNo glucoseNo acidsStable pHLysis and cannibalismArch Aller Appl Immun 1980;62:252-64
19 Concentration Release of surrogate markers I II III hours glucose 7654321IIIIIIConcentration24487296120144168192hoursglucoseDry weightGM
20 - - - - - - - - + Concentration Release of surrogate markers hours PCR 765432124487296120144168192hoursRelease of surrogate markersConcentration--------+PCR(supernatant)Need damage of fungus by host defences?
21 GM versus PCR versus BG ROC analysis: GM > PCR and GM > BG Comparative studiesGM versus PCR versus BGAdult hematology patients on mould active antifungal prophylaxisProspective study, 149 treatment episodes, 96 patientsWeekly samplingROC analysis: GM > PCR and GM > BGJ Clin Microbiol 2004;42:
22 Need for strategic studies: which test to use PCRBoth?Antigen
23 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 markersCorrelation with other diagnostics and optimal sequence of testing needs to be determinedConclusions
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