Central Nervous System Mold Infections in Children with Hematological Malignancies: Advances in Diagnosis and Treatment

Abstract

The incidence of invasive mold disease (IMD) has significantly increased over the last decades, and IMD of the central nervous system (CNS) is a particularly severe form of this infection. Solid data on the incidence of CNS IMD in the pediatric setting are lacking, in which Aspergillus spp. is the most prevalent pathogen, followed by mucorales. CNS IMD is difficult to diagnose, and although imaging tools such as magnetic resonance imaging have considerably improved, these techniques are still unspecific. As microscopy and culture have a low sensitivity, non-culture-based assays such as the detection of fungal antigens (e.g., galactomannan or beta-D-glucan) or the detection of fungal nucleic acids by molecular assays need to be validated in children with suspected CNS IMD. New and potent antifungal compounds helped to improve outcome of CNS IMD, but not all agents are approved for children and a pediatric dosage has not been established. Therefore, studies have to rapidly evaluate dosage, safety and efficacy of antifungal compounds in the pediatric setting. This review will summarize the current knowledge on diagnostic tools and on the management of CNS IMD with a focus on pediatric patients.

Development of a Monoclonal Antibody and a Serodiagnostic Lateral-Flow Device Specific to Rhizopus arrhizus (Syn. R. oryzae), the Principal Global Agent of Mucormycosis in Humans

“…Cross-reactivity with other pathogenic moulds and yeasts is undesirable, especially in the setting of co-infections comprising R. arrhizus and Aspergillus , Exophiala , and Fusarium species [ 85 , 86 , 87 , 88 , 89 ], where discrimination of the infecting species is needed to optimise treatment with antifungal drugs, and to prevent breakthrough R. arrhizus infections [ 70 , 90 ]. The detection of mucormycosis is not possible using the pan-fungal (1→3)-β- d -glucan (BDG) test, since the Mucorales lack this carbohydrate in their cell walls [ 91 ].…”

An Update on the Diagnosis and Treatment of Invasive Mold Disease of the Central Nervous System in Children

“…1 A limitation of the cranial MRI is the lack of fungal-specific findings and the difficulty in evaluating the results, especially in children with granulocytopenia or immunosuppression. 1,3 The most frequently reported findings in children with CNS IMD are fungal abscesses and inflammation of the parenchyma (cerebritis). 6 Data from a pediatric case series suggested that affection of cerebral blood vessels (infections and/or perivascular micro-bleeding) might indicate poor outcomes.…”

“…6 Data from a pediatric case series suggested that affection of cerebral blood vessels (infections and/or perivascular micro-bleeding) might indicate poor outcomes. 1,6…”

“…Of importance, collection and storage specifications of samples are important, for example, to avoid the use of fixatives and to reassure the specimen’s moisturizing. 1…”

Invasive Fungal Infections in Children with Haematological Malignancies: Diagnostic and Therapeutic Challenges

“…Children with haematological malignancies and those undergoing haematopoietic stem cell transplantation (HSCT) are at risk of developing invasive fungal infections [ 1 ]. Despite improvements in diagnostic tools and therapeutic options, the morbidity and mortality related with invasive mycoses in children remains high [ 1 , 2 , 3 , 4 , 5 , 6 ].…”