Rare Infectious Diseases: Detection and Clinical Implications

Rare infectious diseases are infections that are uncommon, have a low incidence, and are caused by newly emerging pathogens, cross-species or ectopic infections, or host immunodeficiencies. The detection and diagnosis of rare infections is one of the main reasons for misdiagnosis and missed diagnosis. Traditional detection techniques such as microbial cultivation and isolation or polymerase chain reaction often fail to meet the clinical demands for timeliness, accuracy, and sensitivity. Metagenomic next-generation sequencing involves pan-nucleic acid testing conducted directly using specimens to facilitate rapid identification of rare or unidentified pathogens. Despite the availability of various techniques, advanced methods in clinical practice are necessary to achieve timely clinical diagnosis of rare infections. In this review, we summarize the definition and clinical significance of rare infectious diseases as well as the current detection methods, limitations, and future research areas for their detection.