Study On Early Diagnosis Of Invasive Aspergillosis In Patients With Hematological Disease

Objective To evaluate the value of galactomannan(GM) detection and nest PCR for early diagnosis of invasive aspergillosis( IA) in patients with hematological disease.Methods GM ELISA and nest PCR was performed to serially screen for circulating galactomannan(GM) and DNA of Aspergillus ssp. respectively .Samples of the patients included serum twice weekly and bronchoalveolar lavage fluid(BALF). 96 patients were grouped according to case definitions of the EORTC (the European Organization for Research and Treatment of Cancer)combined with retrospective analysis standard. Sensitivity, specificity and predictive values were calculated respectively and compared.Results We wholely collected 326 sera and 12 BALF from 96 patients. According to the retrospective analysis standard,28 patients were grouped to proven IA, 20 possible IA cases ,48 excluded IA cases.(1)GM ELISA According to the receiver operator characteristic curve(ROC),using a reduced cutoff of 0.5 O.D.I of single GM test result, we can achieved the most optimal results. The sensitivity ,specificity, positive predictive value (PPV)and negative predictive value (NPV) of the ELISA test were 85.7%,91.6%,85.7%,91.6%respectively. While for the BALF samples ,a increased cutoff 1.0 maybe improve the value of this diagnosis, with sensitivity 50% and specificity 100%.Quantitive results of the serum-based GM antigen can represent the status of IA and were correlated with the prognosis Of IA. Galactomannanemia preceded the development of characteristic findings on CT about 6 days . GM test is effective when applied for direction of preemptive antifungal therapy .(2) The nest PCR assay amplifies specifically a region of the 18S rRNA gene that is highly conserved in Aspergillus species and allows detection of down to 5.0 fg/ml of Aspergillus DNA. When two-positive results were used to define an episode as'PCR positive', the sensitivity ,specificity, PPV and NPV of the PCR test were 92.9%,100%,100%,96.0% respectively. For the BALF samples, the sensitivity and specificity decreased to 75%and 60%.The frequency of the consecutively positive results of a patient were correlated with prognosis Of IA.The antifungal therapy usually causes a intermittent positive PCR results. Positve PCR results preceded the development of characteristic findings on CT about 9 days .If'eligibility'for preemptive antifungal therapy were based on two positive PCR tests, the use of treatment and excess drug toxicity could have been reduced by up to 37.5%.Conclusion (1) The cutoff 0.5 of single serum-based GM ELISA test result is the most optimal cutoff value. (2) GM ELISA test is a rapid,reliable method for early diagnosis and treatment of IA ,with good sensitivity(85.7%)and specificity(91.6%). (3) GM ELISA test is a good direction for preemptive antifungal therapy in patients with haematological disease at risk. (4) Using two-positive results to define an episode as'PCR positive', great sensitivity(92.9%)and specificity(100%) could be achieved. (5) The serum-based PCR test is useful for screening for Aspergillus spp. in patients with haematological disease at risk but without antifungal treatment.