Diagnostic Efficacy of LAMP Assay for Human Fungal Pathogens: a Systematic Review and Meta-analysis.

Purpose: Human fungal infections particularly caused by Candida and Aspergillus have emerged as major public health burden. Long turnaround time and poor sensitivity of the conventional diagnostics are the major impediments for faster diagnosis of human fungal pathogens.

Recent findings: To overcome these issues, molecular-based diagnostics have been developed. They offer enhanced sensitivity but require sophisticated infrastructure, skilled manpower, and remained expensive. In that context, loop-mediated isothermal amplification (LAMP) assay represents a promising alternative that facilitates visual read outs. However, to eradicate fungal infections, all forms of fungi must be accurately detected. Thus, a need for alternative testing methodologies is imperative that should be rapid, accurate and facilitate widespread adoption. Therefore, the aim of the present study is to conduct a meta-analysis to assess the diagnostic efficiency of LAMP in the detection of a panel of human fungal pathogens following PRISMA guidelines using scientific databases viz. PubMed, Google Scholar, Science Direct, Scopus, BioRxiv, and MedRxiv.

Summary: From various studies reported on the diagnosis of fungi, only 9 articles were identified as eligible to meet the criteria of LAMP based diagnosis. Through this meta-analysis, it was found that most of the studies were conducted in China and Japan with sputum and blood as the most common specimens to be used for LAMP assay. The collected data underlined that ITS gene and fluorescence-based detections ranked as the most used target and method. The pooled sensitivity values of meta-analysis ranged between 0.71 and 1.0 and forest plot and SROC (summary receiver operating characteristic) curve revealed a pooled specificity values between 0.13 and 1.0 with the confidence interval of 95%, respectively. The accuracy and precision rates of eligible studies mostly varied between 70 to 100% and 68 to 100%, respectively. A quality assessment based on QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies) of bias and applicability was conducted which depicted low risk of bias and applicability concerns. Together, LAMP technology could be considered as a feasible alternative to current diagnostics considering high fungal burden for rapid testing in low resource regions.