Abstract
Invasive mold disease (IMD) of the central nervous system (CNS) is a severe infectious complication in immunocompromised patients, but early microbiological diagnosis is difficult. As data on the value of biomarkers in the CNS are scarce, in particular in children, we retrospectively analyzed the performance of galactomannan (GM) and PCR assays in CNS samples of 15 children with proven and probable CNS IMD and of 32 immunocompromised children without fungal infection. Galactomannan in the cerebrospinal fluid (CSF) was assessed in nine of the 15 pediatric patients and was positive in five of them. Polymerase chain reaction (PCR) was performed in eight of the 15 patients and detected nucleic acids from molds in six patients. Galactomannan and PCR in CNS samples were the only positive microbiologic parameter in the CNS in three and two patients, respectively. In four patients, PCR specified the pathogen detected in microscopy. Galactomannan and PCR results remained negative in the CSF of all immunocompromised children without evidence for CNS IMD. Our data suggest that GM and PCR in CNS specimens are valuable additional tools in diagnosing CNS IMD and should be included in the work up of all pediatric patients with suspected mold disease of the CNS.
Highlights
Invasive mold disease (IMD) of the central nervous system (CNS) is a severe infectious complication in immunocompromised patients, and despite the availability of potent antifungal compounds, mortality rates remain unacceptably high[1,2,3]
Our analysis demonstrates that GM and polymerase chain reaction (PCR) in CSF or biopsies are useful tools for confirming CNS IMD in immunocompromised children, and that they are helpful to define the causative pathogen
In order to avoid major bias, it is necessary to remove patients in whom CNS GM or PCR was used as microbiological criterion to define CNS IMD [in other words: defining a study population by the test to be validated (CSF GM and CSF PCR)]14, two out of three CNS GM tests (# 5 and 12) and four out of six CNS PCR (# 1, 2, 8, 12) results indicated CNS IMD, respectively, resulting in a sensitivity of 66% for both tests
Summary
Invasive mold disease (IMD) of the central nervous system (CNS) is a severe infectious complication in immunocompromised patients, and despite the availability of potent antifungal compounds, mortality rates remain unacceptably high[1,2,3]. The difficulty to establish a microbiological diagnosis of CNS IMD might explain that data on their epidemiology are scarce, in particular in the pediatric setting. Fungal antigens [e.g., galactomannan (GM), ß-D-glucan] or fungal nucleic acids detected by polymerase chain reaction (PCR) may serve as biomarkers and are suggested by various guidelines as adjunctive diagnostic tools for confirmation of IMD7,8, these recommendations are based on limited data, in particular in pediatric patients. As the value of a diagnostic tool in children may be different relative to adults[9,13], we analyzed the performance of GM and PCR assays in CNS samples in a case series of 15 children with and in 32 children without CNS IMD
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