Low-Cost Genetic Test Can Distinguish Bacterial from Viral Infections

“A lot of times you can’t really tell what kind of infection someone has,” said lead author Timothy Sweeney, MD, PhD, engineering research associate, Stanford, “If someone comes into the clinic, a bacterial or a viral infection often look exactly the same.”

“The idea to look for a diagnostic test came from our previous paper in Immunity last year,” said senior author and team leader Purvesh Khatri, PhD, assistant professor, Stanford University Medical Center (Stanford, CA, USA), “In that paper, we found a common response by the human immune system to multiple viruses that is distinct from that for bacterial infections. We wondered whether we could exploit that difference to improve the diagnosis of bacterial or viral infections. But we needed a gene signature consisting of far fewer genes for the test to be clinically useful.”

The team used publicly available patient gene expression data to pinpoint 7 genes whose activity changes during an infection such that their pattern of activity can distinguish whether an infection is bacterial or viral. The 7-gene test is a vast improvement over earlier tests that look at the activity of 100s of genes. Because so few genes are involved, the new test will be cheaper and faster, while remaining accurate.

A study in Nepal co-authored by assistant professor Jason Andrews, MD, revealed that only 5% of patients who received antibiotics actually needed them, said Prof. Khatri. The Nepalese patients got antibiotic treatment because the drug was cheaper than trying to figure out if they actually needed it. “If we really want to make a difference,” Prof. Khatri said, “our test has to be more cost-effective than the drug itself.” That’s an important breakpoint.

The work is part of a global response to the need to reduce the use of antibiotics, driven in part by President Obama’s National Action Plan for Combating Antibiotic-Resistant Bacteria. Besides promoting evolution of drug-resistant microbes, antibiotics increase the risk of side effects such as tendon rupture or kidney damage, and can damage gut and other microbiomes essential to overall health.

The new test for bacterial infection faces two main hurdles before it can be made clinically available. First, it must be thoroughly tested in a clinical setting. Until now, the data and test results for this ongoing work have all come from preexisting, online digital data sets of gene expression from patients with different kinds of infections — not from current patients. The new study tested the 7-gene test on blood samples from 96 critically ill children, using a NanoString assay, and found that the test was accurate. This is a proof-of-concept but needs to be further validated in larger numbers of patients.

Second, the test needs to be incorporated into a device that can give a result in up to 1 hour. The preliminary NanoString version of the blood test takes 4-6 hours, rapid but too long for critically ill patients who, for example, have sepsis. So the researchers are working on a way to engineer the test to provide results in under an hour. The plan is to combine an 11-gene test (that they recently created a few months ago) with the newer 7-gene test. The 11-gene test reveals if the patient has an infection at all. If they do have an infection, the 7-gene test reveals if it is bacterial or viral. Both tests would be run simultaneously.

The researchers envision the two tests as a decision tree. “When you put the new 7-gene set together with the 11-gene set, we can make a decision tree that matches how a physician might think about a patient,” said Dr. Sweeney, “First we ask, ‘Is an infection present?’ Because some people present with an inflammation, a fever, a high heart rate, but it’s not due to an infection. Then we ask, ‘If so, what kind?’”

The study, by Sweeney TE et al, was published July 6, 2016, in the journal Science Translational Medicine.

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