JC virus PCR assay reporting for PML: promises, perils, and pitfalls

Area of Science:

• Neurovirology
• Infectious Diseases
• Clinical Diagnostics

Background:

• Progressive multifocal leukoencephalopathy (PML) is a severe central nervous system infection caused by the JC virus (JCV).
• PML is a known complication in immunosuppressed patients, including those undergoing transplants, chemotherapy, or taking specific immunomodulatory drugs like natalizumab or rituximab.
• Current diagnostic standards rely on detecting JCV DNA in cerebrospinal fluid (CSF) via PCR, alongside clinical and MRI evidence.

Purpose of the Study:

• To highlight a critical flaw in current JC virus (JCV) PCR reporting for progressive multifocal leukoencephalopathy (PML) diagnosis.
• To advocate for the mandatory inclusion of assay metrics like limit of quantitation (LOQ) and limit of detection (LOD) in JCV PCR reports.
• To improve diagnostic transparency and prevent missed or delayed PML diagnoses.

Main Methods:

• Analysis of current practices in JCV PCR reporting for PML diagnosis.
• Identification of omitted critical assay metrics (LOQ, LOD) in standard reports.
• Evaluation of the impact of missing data on diagnostic certainty and patient care.

Main Results:

• Standard JCV PCR reports for PML diagnosis are often reported as 'positive or negative' without essential quantitative data.
• The absence of Limit of Quantitation (LOQ) and Limit of Detection (LOD) data creates a false sense of diagnostic security.
• This reporting deficiency can lead to delayed or missed diagnoses of early-stage PML, particularly when viral loads are low.

Conclusions:

• The current reporting of JCV PCR results presents a significant diagnostic shortcoming.
• Mandatory inclusion of LOQ and LOD data in CSF JCV PCR reports is essential for diagnostic transparency.
• Implementing this change will provide clinicians with critical information, improving the accuracy and timeliness of PML diagnosis and patient management.