Metagenomic next-generation sequencing (mNGS) for diagnosis of invasive fungal infectious diseases: a narrative review

Abstract

Invasive fungal diseases (IFDs) remain important causes of high morbidity and mortality in many immunosuppressed patients. Accurate etiology diagnosis coupled with subsequent initiation of effective treatment is crucial for severe or critical IFDs. As conventional diagnostic approaches require the successful culture of pathogenic organisms or suspicion of certain pathogens before testing, the implementation of non-targeted metagenomic next-generation sequencing (mNGS) is rapidly increasing in IFDs. mNGS is a high-throughput sequencing technology that provides direct information on nucleic acids from various types of specimens without relying on culture and hypothesis. It can detect all potential pathogens in theory and is especially useful for identifying unknown, rare, newly emerging or mixed infections. Currently, the clinical application of mNGS in the diagnosis of IFDs may be in the most difficult cases to diagnose or for patients who are intolerant to invasive operations, immunocompromised, or seriously ill. Studies have shown that the sensitivity and specificity of mNGS in fungal diagnosis are better than culture and histopathology. However, some hurdles to mNGS testing in the diagnosis of IFDs remain to be addressed, including high costs, influence of human host background, exogenous microbial contamination, poor detection efficiency of thickwall fungi, etc. With strategies developed to overcome these obstacles, mNGS is expected to be a routine diagnostic method of IFDs in clinical practice.