A new tool could one day improve Lyme disease diagnosis

‘Fingerprint’ test distinguishes between two easily confused tick-borne illnesses

A new testing method can distinguish between early Lyme disease and a similar tick-borne illness, researchers report. The approach may one day lead to a reliable diagnostic test for Lyme, an illness that can be challenging to identify.

Using patient blood serum samples, the test accurately discerned early Lyme disease from the similar southern tick‒associated rash illness, or STARI, up to 98 times out of 100. When the comparison also included samples from healthy people, the method accurately identified early Lyme disease up to 85 times out of 100, beating a commonly used Lyme test’s rate of 44 of 100, researchers report online August 16 in Science Translational Medicine. The test relies on clues found in the rise and fall of the abundance of molecules that play a role in the body’s immune response.

“From a diagnostic perspective, this may be very helpful, eventually,” says Mark Soloski, an immunologist at Johns Hopkins Medicine who was not involved with the study. “That’s a really big deal,” he says, especially in areas such as the mid-Atlantic where Lyme and STARI overlap.

In the United States, Lyme disease is primarily caused by an infection with the bacteria Borrelia burgdorferi, which is spread by the bite of a black-legged tick. An estimated 300,000 cases of Lyme occur nationally each year. Patients usually develop a rash and fever, chills, fatigue and aches. Black-legged ticks live in the northeastern, mid-Atlantic and north-central United States, and the western black-legged tick resides along the Pacific coast.

An accurate diagnosis can be difficult early in the disease, says immunologist Paul Arnaboldi of New York Medical College in Valhalla, who was not involved in the study. Lyme disease is diagnosed based on the rash, symptoms and tick exposure. But other illnesses have similar symptoms, and the rash can be missed. 

A test for antibodies to the Lyme pathogen can aid diagnosis, but it works only after a patient has developed an immune response to the disease.

STARI, spread by the lone star tick, can begin with a rash and similar, though typically milder, symptoms. The pathogen responsible for STARI is still unknown, though B. burgdorferi has been ruled out. So far STARI has not been tied to arthritis or other chronic symptoms linked to Lyme, though the lone star tick has been connected to a serious allergy to red meat (SN: 8/19/17, p. 16). Parts of both ticks’ ranges overlap, adding to diagnosis difficulties.

John Belisle, a microbiologist at Colorado State University in Fort Collins, and his colleagues had previously shown that a testing method based on small molecules related to metabolism could distinguish between early Lyme disease and healthy serum samples. “Think of it as a fingerprint,” he says. 

The method takes note of differences in the abundancy of metabolites, such as sugars, lipids and amino acids, involved in inflammation.

In the new work, Belisle and colleagues measured differences in the levels of metabolites in serum samples from Lyme and STARI patients. 

The researchers then developed a “fingerprint” based on 261 small molecules to differentiate between the two illnesses. To determine the accuracy, they tested another set of samples from patients with Lyme and STARI as well as those from healthy people. “We were able to distinguish all three groups,” says Belisle.

As a diagnostic test, “I think the approach has promise,” says Arnaboldi. But more work will be necessary to see if the method can sort out early Lyme disease, STARI and other tick-borne diseases in patients with unknown illnesses.

Having information about the metabolites abundant in STARI may also help researchers learn more about this disease, says Soloski. “This is going to spur lots of future studies.”