Rapid Genomic Diagnosis of Fungal Infections in the Age of Next-Generation Sequencing

Abstract

Next-generation sequencing (NGS) technologies have recently developed beyond the research realm and started to mature into clinical applications. Here, we review the current use of NGS for laboratory diagnosis of fungal infections. Since the first reported case in 2014, >300 cases of fungal infections diagnosed by NGS were described. Pneumocystis jirovecii is the predominant fungus reported, constituting ~25% of the fungi detected. In ~12.5% of the cases, more than one fungus was detected by NGS. For P. jirovecii infections diagnosed by NGS, all 91 patients suffered from pneumonia and only 1 was HIV-positive. This is very different from the general epidemiology of P. jirovecii infections, of which HIV infection is the most important risk factor. The epidemiology of Talaromyces marneffei infection diagnosed by NGS is also different from its general epidemiology, in that only 3/11 patients were HIV-positive. The major advantage of using NGS for laboratory diagnosis is that it can pick up all pathogens, particularly when initial microbiological investigations are unfruitful. When the cost of NGS is further reduced, expertise more widely available and other obstacles overcome, NGS would be a useful tool for laboratory diagnosis of fungal infections, particularly for difficult-to-grow fungi and cases with low fungal loads.

Rapid Diagnosis of Mycobacterium marinum Infection by Next-Generation Sequencing: A Case Report

“…In addition, it is also useful for rapid diagnosis of infections caused by slow-growing microorganisms. For example, we have recently reported its usefulness in rapid diagnosis of fungal infections (9). As for mycobacteria, NGS has been used for the diagnosis of tuberculosis and a number of non-tuberculous mycobacterial infections (10)(11)(12)(13)(14)(15).…”

Integration of Interleukin-6 Improves the Diagnostic Precision of Metagenomic Next-Generation Sequencing for Infection in Immunocompromised Children

“…Thirdly, rare or atypical pathogens in immunocompetent patients were often reported by mNGS in this population. Organisms such as Pneumocystis jirovecii, Aspergillus , and Candida , which are difficult to identify using CMT, are often reported by mNGS ( Tsang et al, 2021 ). Thus, it is a great challenge for clinicians to judge the causative role of certain pathogens as mNGS is unable to differentiate colonization and pathogenic strains ( Geng et al, 2021 ).…”

Diverse and atypical manifestations of Q fever in a metropolitan city hospital: Emerging role of next-generation sequencing for laboratory diagnosis of Coxiella burnetii

“…In the clinical setting for infectious diseases, NGS is used most often for patients who have fever without localizing features or culture-negative infections. We have recently reported its application in fungal diagnosis as well as confirming the first case of listeria meningitis in a patient with autoantibody against interferon gamma and another one with Mycobacterium marinum infection [ 17 – 19 ]. In the present cohort, case 2 and 3 both presented with fever and severe headache and were admitted to the neurology unit as suspected meningitis.…”