Clinical and Analytical Validation | Karius

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Clinical and Analytical Validation of the Karius Test

The clinical and analytical validation of the Karius Test addresses the challenges of bringing a metagenomic infectious disease diagnostic test to clinicians.

 

The Karius Test is a non-invasive blood test based on next-generation sequencing of microbial cell-free DNA. It can identify over 1,000 clinically relevant pathogens including bacteria, DNA viruses, fungi, and parasites. Applications include complicated pneumonia, endocarditis, invasive fungal infections, and sepsis.

 

The study on the clinical and analytical validation of the Karius Test was published in Nature Microbiology1.  

 

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To access and download the publication, click here

Clinical Validation

This study presented the clinical validity of microbial cell-free DNA sequencing in plasma as a means of identifying infecting pathogens in patients with suspected sepsis. The validation showed that the Karius Test:

  • can identify a broad range of pathogens in patients with suspected sepsis from a single blood draw
  • has improved diagnostic yield, with more causal pathogens identified than all microbiological testing combined
  • can potentially provide faster results than conventional testing

Analytical Validation

This study demonstrated the accuracy, precision and robustness of the Karius Test through a rigorous validation process.  

A combination of laboratory and bioinformatics experiments were performed using:

  • 580 clinical samples with known infection status
  • 350+ contrived infections modeling the most challenging or rare scenarios
  • 2,600+ simulated data sets. 

 

Clinical Validity and Diagnostic Performance

The SEP-SEQ Study (NCT02730468) compared the performance of the Karius Test to the standard-of-care diagnostic workup in sepsis. The accuracy of the Karius Test was demonstrated in sepsis as this is a challenging clinical scenario caused by a breadth of pathogens which often fail to grown in culture. The study involved 350 patients with suspected sepsis presenting to the Stanford Emergency Department.

The performance of the Karius Test was compared to a composite reference standard which included a combination of:

  • Initial blood culture
  • Additional microbiological testing
    • Urine culture
    • Respiratory culture
    • Serology
    • PCR testing
    • Subsequent blood culture
  • Clinical adjudication of test results including radiology results and discharge summaries

 

Increase in diagnostic yield compared to blood culture and other microbiological testing


 

 

 

High agreement with existing diagnostic tests


Positive and negative agreement of the Karius Test vs. Composite Reference Standard

Note on specificity: Microorganisms related to chronic infections or viral reactivations such as HPV, EBV, CMV, and HHV6, reported by Karius, were deemed unlikely causes of sepsis and therefore categorized as Composite Reference Standard Negative (-). 

 

Positive Karius Test results include fastidious bacteria, viruses, and eukaryotic pathogens. Unlike conventional culture techniques, the Karius Test detects cell-free DNA and therefore is able to identify pathogens even when prior antimicrobial treatment has sterilized blood cultures.

 

Faster identification of etiology of sepsis than the standard-of-care diagnostic workup

Comparison of the time to test results for both test methodologies. 

 

 

 

 

Median time from specimen collection to positive findings

55.4 hours | Karius Test

85.4 hours | Conventional microbiological testing

 

The Karius Test can detect over 1,000 pathogens from a single non-invasive blood draw. Results are reported next day for >85% of specimens received by 8:30 am Monday-Saturday.

 

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Analytical Validation

 

Highly accurate - analytical sensitivity and specificity


 

Proven performance across a diverse set of over 1,000 microorganisms


Performance was determined using a reference panel of 13 microorganisms representing superkingdoms, GC-content, and genome length reflective of the diverse set of microorganisms that the Karius Test can detect.

 

Comparison of superkingdom makeup

 

Our proprietary pathogen database is carefully curated for sequence quality and clinical relevance. This database is always evolving. Click below to see the latest version.  

Pathogen List

 


For a copy of the publication, please email us at help@kariusdx.com.

Blauwkamp, et al. Nat Microbiol 2019 April, 4(4):663-674. doi: 10.1038/s41564-018-0349-6.