Invasive mould infection in children - advances made or obstacles remaining?

Abstract

BACKGROUND: Invasive mould infection (IMI) is a major cause of morbidity and mortality in immunocompromised children. Outcomes for paediatric patients with IMI remain poor, due in part to the limitations of available diagnostic tools and therapeutic agents. OBJECTIVES: To summarize current and emerging modalities for diagnosis and treatment of IMI in immunocompromised children, focusing on recent advances and remaining barriers. SOURCES: A comprehensive literature search of tools for diagnosis and management of IMI in children was conducted using PubMed, including clinical and preclinical studies, relevant consensus guidelines, and reviews. CONTENT: Initial diagnosis of IMI, particularly for invasive aspergillosis (IA), often relies on computed tomography imaging of the chest, yet imaging findings are not specific to mould infection and cannot differentiate between IA and nonaspergillus moulds. Fluorodeoxyglucose-positron emission tomography imaging may have advantages, but diagnostic sampling remains essential. Traditional microbiological and histopathological work up of blood, fluid and tissue samples are the mainstay of laboratory diagnosis of IMI in children, yet limitations related to test sensitivity, turnaround time, as well as potential complications associated with invasive sampling remain. Nonculture-based biomarkers, including galactomannan for IA, have a role in diagnosis of paediatric IMI, although interpretation requires consideration of test limitations and patient factors. Molecular assays have shown promise and will be an important diagnostic tool in future. Novel antifungal agents, including isavuconazole, olorofim, fosmanogepix, and ibrexafungerp, have significantly broadened the range of agents with activity against IMI, yet paediatric data are required to facilitate use in children. Similarly, immunotherapeutic approaches have potential to improve outcomes in paediatric IMI, yet data in children remain limited. IMPLICATIONS: There has been much progress in IMI management with recent development of novel diagnostic methods, new antifungals, and immunotherapeutic approaches. Ongoing paediatric studies are required to inform optimal implementation of these tools into clinical practice.