Diagnostic Performance of Galactomannan Antigen Testing in Cerebrospinal Fluid

Abstract

e Testing cerebrospinal fluid (CSF) for the presence of galactomannan (GM) antigen may help in diagnosing cerebral aspergillosis (CA). However, the use of the CSF GM test as a diagnostic test has been little studied. We evaluated its diagnostic performance by comparing the CSF GM optical density indexes (ODI) at different cutoffs in patients with probable and proven CA to those in patients without CA. Patients from 2 tertiary referral hospitals with suspected CA between 2004 and 2014 and in whom CSF GM ODI had been determined were selected. European Organization for Research and Treatment of Cancer/Invasive Infectious Diseases Study Mycoses Group (EORTC/MSG) definitions of invasive aspergillosis and CA were used, but with the exclusion of the test to be validated (i.e., the CSF GM test) as a microbiological EORTC/MSG criterion. The study population consisted of 44 patients (4 with proven CA, 13 with probable CA, and 27 with no CA). Of the 17 patients with CA, 15 had a CSF GM ODI of >2.0. Of 27 patients without CA, 26 had a CSF GM ODI of <0.5 and 1 had a CSF GM ODI of 8.2. When a GM CSF ODI cutoff of 1.0 was used, the sensitivity, specificity, and positive and negative predictive values were 88.2%, 96.3%, 93.8%, and 92.9%, respectively. The same results were found when a CSF GM ODI cutoff of 0.5 or 2.0 was used. Testing GM in CSF has a high diagnostic performance for diagnosing CA and may be useful to diagnose or virtually rule out the infection without the need for a cerebral biopsy. C erebral aspergillosis (CA) is a rare and often fatal invasive fungal disease (IFD) (1, 2). The diagnosis is challenging, as radiological findings are nonspecific and cerebrospinal fluid (CSF) cultures are positive only in less than one-third of cases (3, 4). Moreover, obtaining brain tissue for histopathological examination, the diagnostic gold standard, is frequently not feasible. Galactomannan (GM) antigen detection in CSF is one of the microbiological criteria in the revised European Organization for Research and Treatment of Cancer/Invasive Infectious Diseases Study Mycoses Group (EORTC/MSG) criteria (5). However, its diagnostic performance has been studied very little. To date, only 3 studies including a total of 25 patients have described the value of CSF GM, only 2 of which were carried out with patients with suspected CA (3, 6, 7). In these 2 studies, CSF GM optical density indexes (ODI) were higher in patients with CA than in those without CA, and sensitivity and specificity were 80% and 100% (6, 7). Based on these limited data, the GM antigen test in CSF seems promising, even though no positive and negative predictive values (PPV and NPV) were determined and no formal cutoff was established. This study evaluated the diagnostic performance of the Platelia GM antigen test (Bio-Rad, Marnes-la-Coquette) in CSF of patients with suspected CA.(This information was presented at the 7th Trends in Medical Mycology, Lisbon, Portugal, 9 to 12 October 2015 [8].) MATERIALS AND METHODSThis retrospective study was performed at the Erasm...

Retrospective study on the incidence and outcome of proven and probable invasive fungal infections in high‐risk pediatric onco‐hematological patients

“…In patients with a positive blood or tissue culture or tissue histopathology, other organ involvement was based on clinical or radiological evidence (CT scan, MRI, ultrasound exam). Galactomannan test was considered positive with an optical density index of 1.0 on a single serum sample, or of 0.5 on two consecutive serum samples, or of 1.0 on BAL sample or cerebro‐spinal fluid . Serum B‐ d ‐glucan and fungal DNAemia detection by polymerase chain reaction were not included as criteria of probable IFI due to the paucity of pediatric data available, the lack of consensus on their use, and the limited experience by participating centers with these tests in daily practice …”

“…Galactomannan test was considered positive with an optical density index of 1.0 on a single serum sample, or of 0.5 on two consecutive serum samples, 19 or of 1.0 on BAL sample or cerebro-spinal fluid. 20 Serum Bd-glucan and fungal DNAemia detection by polymerase chain reaction were not included as criteria of probable IFI due to the paucity of pediatric data available, the lack of consensus on their use, and the limited experience by participating centers with these tests in daily practice. 16 According to the stage of treatment of the underlying disease at the time of diagnosis of PP-IFI, we distinguished three groups: (i) chemotherapy for disease relapse, or after HSCT.…”

Diagnosis of invasive fungal diseases in haematology and oncology: 2018 update of the recommendations of the infectious diseases working party of the German society for hematology and medical oncology (AGIHO)

“…In addition, a lateral flow assay may be performed at the bedside for rapid diagnosis of IPA from BAL. Aspergillus GM may be useful in diagnosis of cerebral aspergillosis, but only few data are available on its diagnostic value …”

“…In addition, a lateral flow assay may be performed at the bedside for rapid diagnosis of IPA from BAL. Aspergillus GM may be useful in diagnosis of cerebral aspergillosis, but only few data are available on its diagnostic value 89. Empiric antifungal therapy in patients with antibacterialrefractory fever of unknown origin may be withheld until further signs of invasive aspergillosis (eg, lung infiltrate on chest computed tomography) emerge, as shown in a prospective clinical trial[A]…”

Infectious Etiologies of Stroke

“…84 Additionally, CSF GM has a reported sensitivity 88% and specificity of 96% in 44 patients studied by Chong et al in 2016. 85 Despite these findings, CSF PCR and GM are not yet part of the IDSA guidelines due to lack of validation of commercially available assays and variability of techniques used in published studies. 81…”