Ulusakarya A, Chachaty E, Vantelon J M, Youssef A, Tancrède C, Pico J L, Bourhis J H, Fenaux P, Munck J N
Department of Medicine, Institut Gustave-Roussy, Villejuif, France.
Hematol J. 2000;1(2):111-6. doi: 10.1038/sj.thj.6200009.
The incidence of invasive fungal infections is increasing in patients with hematological malignancies. Invasive aspergillosis is one of the most frequently encountered infections with a high mortality rate. New diagnostic tests for invasive aspergillosis such as the detection of Aspergillus galactomannan antigen by a sandwich enzyme-linked immunosorbent assay (ELISA) have recently been described. The objective of this study was to evaluate this assay as a potential surrogate for invasive procedures used to diagnose IA.
We analyzed the performance of a commercially available ELISA test which we routinely use for the surveillance of galactomannan antigenemia in patients with hematological malignancies experiencing chemotherapy-induced prolonged neutropenia (ANC < 500/mm(3) for more than 7 days). Serum samples were collected on a weekly basis. Test positivity was defined in accordance with the manufacturer's recommendations.
Over the 2 year study period, we analyzed 507 samples obtained during 193 neutropenic episodes from 135 patients. Ten, six and two patients were considered to have proven, probable or possible invasive aspergillosis, respectively, based on clinical, radiological or microbiological data. Forty-four positive (Index>1.5) and 26 'undetermined' (1.5 > Index > 1.0) test results were observed in 17 and ten patients respectively. All invasive aspergillosis cases had at least a positive or an undetermined test result. Only one positive and one undetermined result were found in two patients before the onset of clinical or radiological signs suggesting invasive aspergillosis. Sensitivity was 69% and specificity 96% if only positive results are considered; when 'undetermined' test results were combined with positive results, sensitivity attained 100% and specificity 92% suggesting that the cutoff value for positivity can be lowered from 1.5 to 1.0.
Although the ELISA test did not appear to play a role in the early diagnosis of invasive aspergillosis and in the anticipation of antifungal therapy in our experience, it clarifies the diagnosis of infection in probable or possible invasive aspergillosis especially when the cutoff value is lowered and is useful for monitoring patients receiving specific therapy.
血液系统恶性肿瘤患者侵袭性真菌感染的发生率正在上升。侵袭性曲霉病是最常遇到的感染之一，死亡率很高。最近已经描述了用于侵袭性曲霉病的新诊断测试，例如通过夹心酶联免疫吸附测定（ELISA）检测曲霉半乳甘露聚糖抗原。本研究的目的是评估该测定作为用于诊断IA的侵入性程序的潜在替代方法。
我们分析了一种市售ELISA测试的性能，我们常规使用该测试来监测经历化疗引起的长期中性粒细胞减少（ANC<500/mm³超过7天）的血液系统恶性肿瘤患者的半乳甘露聚糖抗原血症。每周收集血清样本。根据制造商的建议定义测试阳性。
在为期2年的研究期间，我们分析了135例患者在193次中性粒细胞减少发作期间获得的507份样本。根据临床、放射学或微生物学数据，分别有10例、6例和2例患者被认为患有确诊、可能或疑似侵袭性曲霉病。在17例和10例患者中分别观察到44次阳性（指数>1.5）和26次“未确定”（1.5>指数>1.0）测试结果。所有侵袭性曲霉病病例至少有一次阳性或未确定的测试结果。在提示侵袭性曲霉病的临床或放射学体征出现之前，在两名患者中仅发现一次阳性和一次未确定结果。如果仅考虑阳性结果，敏感性为69%，特异性为96%；当“未确定”测试结果与阳性结果相结合时，敏感性达到100%，特异性为92%，这表明阳性临界值可以从1.5降低到1.0。
尽管根据我们的经验，ELISA测试似乎在侵袭性曲霉病的早期诊断和抗真菌治疗的预判中不起作用，但它明确了可能或疑似侵袭性曲霉病的感染诊断，特别是当临界值降低时，并且对于监测接受特定治疗的患者很有用。
