Aspergillus meningitis: A rare clinical manifestation of central nervous system aspergillosis. Case report and review of 92 cases

Antinori, Spinello; Corbellino, Mario; Meroni, Luca; Resta, F.; Sollima, Salvatore; Tonolini, Massimo; Tortorano, Anna Maria; Milazzo, Laura; Bello, Lorenzo; Furfaro, Elisa; Galli, Massimo; Viscoli, Claudio

doi:10.1016/j.jinf.2012.11.003

Cited by 97 publications

(101 citation statements)

References 88 publications

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“…Zhu et al [5] have reported that there was no decline in immune function in a patient infected with Aspergillus, in spite of the presence of brain-occupying lesions caused by Aspergillus infection. The clinical manifestations of this case resemble those of another 93 cases reported by Antinori et al, [6] of which 55.9% (52 cases) showed no decline in immune function and no predisposing factors. Therefore, fungal infections can also occur in people with normal immune function.…”

Section: Diagnosis Of Central Nervous System Parasitic and Fungal Infsupporting

confidence: 80%

Diagnosis and therapy of rare central nervous system infections

Qi¹

2014

Neuroimmunol Neuroinflammation

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Section: Diagnosis Of Central Nervous System Parasitic and Fungal Infsupporting

confidence: 80%

Diagnosis and therapy of rare central nervous system infections

Qi¹

2014

Neuroimmunol Neuroinflammation

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“…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.…”

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confidence: 99%

“…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).…”

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confidence: 99%

Diagnostic Performance of Galactomannan Antigen Testing in Cerebrospinal Fluid

et al. 2016

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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...

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“…Although other filamentous fungi have been documented as causes of human meningitis and/or encephalitis, most of these infections have been diagnosed postmortem (19, 20). Furthermore, the sensitivity of fungus culture for detection of molds in CSF is very low (13,18). A PCR method for detecting A. fumigatus in CSF has been proposed by Hummel et al; however, its performance has not been well established since only a small number of cases have been evaluated (13,21).…”

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confidence: 99%

“…Recently, an outbreak of fungal meningitis caused by A. fumigatus was reported in post-tsunami Sri-Lanka and linked to the use of contaminated material during spinal anesthesia (14,15). Among filamentous fungi, A. fumigatus is the most common cause of invasive fungal infections in clinical settings, so most of the available fungal detection methods target this organism and often rely on culture, antigen, and/or radiological findings (16)(17)(18). Although other filamentous fungi have been documented as causes of human meningitis and/or encephalitis, most of these infections have been diagnosed postmortem (19,20).…”

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Detection of Fungal DNA in Human Body Fluids and Tissues during a Multistate Outbreak of Fungal Meningitis and Other Infections

et al. 2013

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Exserohilum rostratum was the major cause of an outbreak of fungal infections linked to injections of contaminated methylprednisolone acetate. Because almost 14,000 persons were exposed to product that was possibly contaminated with multiple fungal pathogens, there was unprecedented need for a rapid throughput diagnostic test that could detect both E. rostratum and other unusual agents of fungal infection. Here we report development of a novel PCR test that allowed for rapid and specific detection of fungal DNA in cerebrospinal fluid (CSF), other body fluids and tissues of infected individuals. The test relied on direct purification of free-circulating fungal DNA from fluids and subsequent PCR amplification and sequencing. Using this method, we detected Exserohilum rostratum DNA in 123 samples from 114 case-patients (28% of 413 case-patients for whom 627 samples were available), and Cladosporium DNA in one sample from one case-patient. PCR with novel Exserohilum-specific ITS-2 region primers detected 25 case-patients with samples that were negative using broad-range ITS primers. Compared to fungal culture, this molecular test was more sensitive: of 139 case-patients with an identical specimen tested by culture and PCR, E. rostratum was recovered in culture from 19 (14%), but detected by PCR in 41 (29%), showing a diagnostic sensitivity of 29% for PCR compared to 14% for culture in this patient group. The ability to rapidly confirm the etiologic role of E. rostratum in these infections provided an important contribution in the public health response to this outbreak. In late September 2012, the Centers for Disease Control and Prevention (CDC) began to investigate an outbreak of fungal meningitis associated with epidural injections of contaminated methylprednisolone acetate solution purchased from a single compounding pharmacy (1-5). By 15 January 2013, 678 cases of fungal infections, including meningitis, spinal, paraspinal, or peripheral joint infections, had been reported from 19 states, and 44 people had died. Although Aspergillus fumigatus was isolated from the index patient (1), and several fungal species were identified in patients during the outbreak, the vast majority of laboratory-confirmed infections were caused by Exserohilum rostratum, which was detected in cerebrospinal fluid (CSF) and tissues of patients (3, 6).E. rostratum (teleomorph Setophaeria rostrata) is a dematiaceous (brown-black) filamentous fungus, which is common in the environment and occasionally causes opportunistic infections in humans (7-9). In healthy individuals, exposure to E. rostratum can cause allergic sinusitis or cutaneous and subcutaneous infections (7, 10, 11). Invasive fungal infections due to E. rostratum are rare and limited to persons with severely impaired immune systems (7, 10, 12). To our knowledge, no cases of fungal meningitis or encephalitis due to this fungus had been described prior to this outbreak. In addition, no genome or animal models had been developed to study E. rostratum, which also complicated the deve...

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Aspergillus meningitis: A rare clinical manifestation of central nervous system aspergillosis. Case report and review of 92 cases

Abstract: Aspergillus meningitis may occur in both immunocompetent and immunocompromised patients and run an acute or chronic course. The findings of this systematic review extend the information on this life-threatening infection and could assist physicians in achieving an improved outcome.

Cited by 97 publications

References 88 publications

Diagnosis and therapy of rare central nervous system infections

Diagnosis and therapy of rare central nervous system infections

Diagnostic Performance of Galactomannan Antigen Testing in Cerebrospinal Fluid

Detection of Fungal DNA in Human Body Fluids and Tissues during a Multistate Outbreak of Fungal Meningitis and Other Infections

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