The Karius Test is a liquid biopsy used for diagnosing infectious diseases by detecting microbial cell-free DNA (mcfDNA) from a single blood sample. It can identify over 1,000 pathogens, including bacteria, DNA viruses, fungi, and parasites. The test’s purpose is to rapidly determine the cause of an infection, assisting clinicians in complex cases or when other diagnostic methods have failed to find a cause.
The Science Behind the Test
The Karius Test analyzes microbial cell-free DNA (mcfDNA), which are fragments of genetic material released by pathogens into the bloodstream. These fragments circulate in the blood plasma and can be detected even if the infection is localized in a specific part of the body.
The test employs metagenomic next-generation sequencing (mNGS). This technique involves extracting all cfDNA from a patient’s blood sample, sequencing it, and comparing the results against a comprehensive database of pathogen genomes. This process allows for a broad, unbiased search for the genetic signature of an infecting agent.
This approach allows the test to identify pathogens even after a patient has started antimicrobial therapy. Because the test detects DNA from both living and dead microbes, a signal can persist even when the treatment has begun to work. The results quantify the amount of microbial DNA found, which can help doctors monitor treatment effectiveness.
Clinical Applications
Doctors may order the Karius Test when traditional diagnostic methods are insufficient. A primary application is for infections of unknown origin, where a patient presents with symptoms of a serious infection, but standard tests have not identified a cause. The test can help pinpoint a pathogen in cases of fever of unknown origin (FUO).
The test is frequently used for patients who are immunocompromised, such as those undergoing cancer chemotherapy, organ transplant recipients, or individuals with hematological malignancies. These patients are susceptible to a wide range of infections, and their weakened immune systems can make diagnosis challenging. For instance, in patients with febrile neutropenia, the test can rapidly identify the infectious agent.
Another application is in diagnosing deep-seated infections where obtaining a tissue sample is difficult or dangerous. This includes conditions like endocarditis and osteomyelitis. In cases of complicated pneumonia where a pathogen cannot be identified through conventional means, the Karius test can provide a diagnosis from a simple blood draw, avoiding more invasive procedures.
The Patient Experience and Results
For the patient, the process is straightforward, requiring only a standard blood draw of about 5 milliliters. The blood sample is collected and sent to a specialized laboratory for analysis. Results are often available the day after the lab receives the sample.
The test report lists any pathogens detected above a statistically significant threshold. It quantifies the amount of microbial DNA in molecules per microliter (MPM), which gives an indication of the pathogen’s abundance. The report may identify a single pathogen or multiple microbes, reflecting a polymicrobial infection.
Interpreting these results requires clinical expertise. The physician must consider the patient’s overall health and other findings to determine if a detected pathogen is the cause of the active infection or a colonizing organism. The quantitative data helps in this assessment, as a high MPM value is more likely to indicate a true infection and guides the selection of targeted antimicrobial therapy.
Comparison with Traditional Diagnostic Methods
Blood cultures, a standard method for detecting bloodstream infections, can take days or even weeks to yield results and cannot detect organisms that are difficult to grow in a lab. The Karius Test provides results much faster and can identify a broader range of pathogens, including those that are non-culturable.
Targeted Polymerase Chain Reaction (PCR) tests are fast and sensitive but are also narrow in scope, as they can only detect the specific pathogen they were designed to find. The Karius Test’s broad, untargeted approach allows it to screen for over a thousand pathogens at once from a single sample.
Compared to invasive biopsies, which involve surgically removing tissue for analysis, the Karius Test is non-invasive, requiring only a blood sample. This reduces risks for the patient, especially for those who are critically ill or have infections in hard-to-reach areas. It serves as a powerful complementary tool in complex cases where speed and a comprehensive view are needed.