血清半乳甘露聚糖检测血液病患者侵袭性曲霉菌病的价值

The value of serum galactomannan antigen for detection of invasive aspergillosis in hematological patients

目的侵袭性曲霉菌病（IA）在血液病患者发病逐年增多，且伴随很高的病死率。本研究旨在评价血清半乳甘露聚糖（GM）抗原检测作为早期诊断和评价IA疗效的价值。方法81例中性粒细胞减少伴发热（T〉38．5℃），经广谱抗生素治疗无效的血液病患者被纳入研究。每周采集患者血液标本2次，共测定标本302份。GM检测采用双夹心酶联免疫吸附法，GM实验阳性定义为连续2次不同时点检测，A值〉1．5。对GM实验阳性的患者给予两性霉素B或伊曲康唑抢先抗曲霉治疗。结果81例患者中27例GM实验阳性（33．0％），其中11例临床确诊IA，GM实验在该11例中检出7例阳性（敏感性63．6％），14患者临床排除IA，GM实验在该14例中检出12例阴性（特异性85．7％），同时GM实验显示可早于真菌培养结果3～30d预测曲霉感染。27例GM实验阳性患者中，19例完成针对曲霉的抢先治疗，12例有效，7例无效死亡，病死率为36．8％。治疗有效组GM值下降到正常，治疗无效组GM值反而上升（P〈0．0005）。结论研究提示：血清GM抗原检测用于早期诊断IA是一种有效的方法，在高危血液病患者以GM实验阳性为起点抢先抗曲霉治疗可降低IA病死率，监测GM值的动态变化具有评价疗效的价值。

Objective The incidence of invasive aspergillosis （IA） is increasing in patients with hematological disorders and it may lead to a high mortality rate. This study was to evaluate serum aspergillus galactomannan （GM） antigen assay as a potential early diagnosis and follow-up of IA. Methods From October 2004 to October 2005, 302 blood samples were obtained from 81 neutropenic hematological patients with fever over 38. 5℃ and shown to have no response to broad-spectrum antibiotics treatment. Blood samples were collected twice a week. The detection of aspergillus GM antigen was carried out with a sandwich enzyme-linked immunosorbent assay and a GM positivity was defined as A index 〉 1.5 in two consecutive measuration. Furthermore, the patients with positive GM test received preemptive antifungal therapy with amphotericin B or itraconazole. Results Twenty seven patients （33. 0% ） were considered GM test positive from a total of 81 cases and 11 patients were diagnosed as proven or probable IA. The GM test correctly identified 7 of the 11 patients who had aspergillus antigen （63.6% sensitivity）. When 14 patients without signs or symptoms of invasive fungal infection （IFI） were tested, the test correctly identified 12 of the 14 （85.7% specificity） as not having the antigen. GM positivity allowed also the anticipation of IA diagnosis （from 3 to 30 days before mycological culture）. 19 of 27 GM test positive patients were given preemptive antiaspergillus therapy and there was a good response in 12 patients but no response in 7 cases with 36. 8% mortality. After treatment, GM antigen decreased to normal with a good response. Otherwise, an elevated value hinted a unsatisfactory result as judged with Wilcoxon signed rank test （ P 〈 0. 0005 ）. Conclusions It is suggested that serum GM antigen detection may be a useful test for early diagnosis of IA and GM test-based preemptive antifungal therapy in hematological patients at high risk can decrease mortality of IA substantively. Moreover, the dynamic change of GM test value can be useful for assessing therapeutic response.