The Discovery of New Borrelia Species

A recent discovery by researchers at Mayo Clinic demonstrates the complexity of tick-borne organisms. Pathologists at the institution have described a new Borrelia burgdorferi sensu lato genospecies in six patients. The new species, provisionally named Borrelia mayonii, was found in the Upper Midwest but it may be elsewhere. Symptoms are similar to those seen with an infection from Borrelia burgdorferi, the agent causing Lyme disease.

“Five of the six patients with atypical PCR [polymerase chain reaction] results had presented with fever, four had diffuse or focal rash, three had symptoms suggestive of neurological inclusion, and two were admitted to the hospital. The sixth patient presented with knee pain and swelling.” All of the patients were diagnosed with a PCR test.

This discovery represents the first new Borrelia species identified in North America in decades. The clinical presentation overlaps significantly with standard Lyme disease, making differentiation impossible without molecular testing. Fever occurs more commonly in B. mayonii infection than in typical B. burgdorferi Lyme disease, and bacteremia levels can be higher—occasionally visible on blood smear examination, a finding rarely seen with B. burgdorferi.

Borrelia bissettii in the Southern United States

Meanwhile, researchers have successfully cultivated Borrelia burgdorferi and Borrelia bissettii-like spirochete from 24 individuals in the Southern U.S. Rudenko and colleagues described 11 individuals from Georgia and ten from Florida with “severe headache, nausea, muscle and joint pain, numbness and tingling sensations in extremities, neck pain, back pain, panic attacks, depression, dizziness, vision problems, sleep problems, and shortness of breath.”

The investigators used a modified Kelly-Pettenkofer medium to culture the specimens, rather than a Barbour-Stoenner-Kelly-H (BSK-H) medium. The positive cultures were further characterized by DNA purification, PCR amplification, sequencing, sequence analysis and multilocus sequence analysis (MLSA) followed by transmission electron microscopy.

The successful cultivation of B. bissettii-like organisms from patients in Georgia and Florida—states not considered endemic for Lyme disease—demonstrates that tick-borne Borrelia infections occur far beyond traditionally recognized geographic boundaries. The symptom profile is indistinguishable from B. burgdorferi Lyme disease, yet standard two-tier serology designed for B. burgdorferi may not detect B. bissettii infection.

Borrelia miyamotoi: Relapsing Fever Spirochete

Borrelia miyamotoi, a relatively new bacterium that can cause relapsing fever and symptoms similar to Lyme disease, has been identified in patients using a blood smear, direct detection of spirochetes in cerebrospinal fluid and follow-up PCR, and molecular detection of B. miyamotoi DNA in acute whole blood from patients.

Unlike B. burgdorferi, which belongs to the Lyme borreliosis group, B. miyamotoi belongs to the relapsing fever group of Borrelia species. It’s transmitted by the same Ixodes ticks that carry Lyme disease but causes distinct clinical syndrome including fever (often relapsing), thrombocytopenia, and leukopenia—features uncommon in typical Lyme disease. Standard Lyme serology does not detect B. miyamotoi, requiring separate molecular or serologic testing.

The Diagnostic Gap: No Commercial Tests Available

The investigators did not address the availability of the tests. The investigators described laboratory developed tests that are non-FDA-approved. In Scientific American, infectious disease physician and researcher John Aucott cautioned on the availability of tests. “These tests require physicians to send samples to the Mayo Clinic … that just may not happen.”

This accessibility problem is fundamental. Laboratory-developed tests performed at specialized research institutions like Mayo Clinic are not available through commercial laboratories that most clinicians use. Physicians must know these organisms exist, suspect them based on clinical presentation, and have the knowledge and resources to send samples to specific research labs for testing. In routine practice, this rarely happens.

Even when samples reach appropriate laboratories, insurance may not cover research testing. Results may take weeks. Most importantly, the vast majority of clinicians remain unaware these organisms exist or that testing is theoretically available.

Two-Tier Testing Failures

Nor did the investigators address the poor reliability of current tests, such as the well-known two-tier test. Molins from the Centers for Disease Control and Prevention, Division of Vector-Borne Diseases, found that the “existing two-tier serology-based assays yield low sensitivities (29 – 40%) for early infection.”

This compounds the diagnostic challenge. Not only do we lack commercial tests for emerging Borrelia species, but standard testing for B. burgdorferi—the organism we’ve studied for decades—has abysmal sensitivity in early infection when treatment is most effective.

The two-tier algorithm (ELISA followed by Western blot) was designed for surveillance purposes, favoring specificity over sensitivity to avoid false-positive case reports. It was never intended as a clinical diagnostic tool for individual patient care. Yet it has become the de facto standard, missing 60-71% of early Lyme disease cases.

When standard testing fails to detect the organism we know best, and no commercial tests exist for newly discovered organisms, vast numbers of patients with tick-borne illness go undiagnosed.

Clinical Diagnosis Becomes Essential

Without reliable commercial tests, patients suffering from these newly discovered diseases run the risk of being misdiagnosed, unless the physician uses clinical judgment.

This statement underscores the critical importance of clinical diagnosis in tick-borne disease. When laboratory confirmation is unavailable or unreliable, diagnosis must rest on:

Clinical presentation compatible with tick-borne illness. Geographic exposure to tick-endemic areas. Symptom patterns consistent with known tick-borne infections. Exclusion of alternative diagnoses. Response to empiric antibiotic therapy.

Physicians who insist on laboratory confirmation before diagnosis or treatment will miss most cases of emerging tick-borne diseases—and a substantial fraction of standard Lyme disease cases given the poor sensitivity of two-tier testing.

Frequently Asked Questions

Are there commercial tests for Borrelia mayonii?
No. B. mayonii can be detected through laboratory-developed PCR tests at specialized institutions like Mayo Clinic, but no FDA-approved commercial tests are available. Most clinicians cannot access these tests for routine patient care.

Can standard Lyme tests detect Borrelia bissettii?
Possibly not. Standard two-tier serology was designed for B. burgdorferi and may not detect B. bissettii infection. Specialized culture or molecular testing is required, but these are not commercially available.

How is Borrelia miyamotoi diagnosed?
Through blood smear examination (when bacteremia is high), PCR detection of DNA in blood or CSF, or specialized serologic testing. Standard Lyme disease tests do not detect B. miyamotoi because it’s a relapsing fever spirochete, not a Lyme borreliosis organism.

What is the sensitivity of two-tier Lyme testing?
Only 29-40% in early infection according to CDC research. This means standard testing misses 60-71% of early Lyme disease cases when treatment is most effective.

How should doctors diagnose emerging tick-borne diseases without commercial tests?
Through clinical judgment based on symptoms, geographic exposure, tick contact, and clinical presentation compatible with tick-borne illness. Waiting for laboratory confirmation will miss most cases given the lack of available testing.

Clinical Takeaway

The discovery of new Borrelia species highlights a fundamental diagnostic crisis in tick-borne disease: we’re identifying organisms faster than we’re developing commercially available tests to detect them. Borrelia mayonii was discovered at Mayo Clinic in six patients from the Upper Midwest. Five presented with fever, four with rash, three with neurologic symptoms, two requiring hospitalization. One had knee pain and swelling. All were diagnosed by PCR—a laboratory-developed test not commercially available. Symptoms are indistinguishable from standard B. burgdorferi Lyme disease, making diagnosis impossible without molecular testing. Borrelia bissettii-like organisms were successfully cultured from 24 patients in Georgia and Florida—states not considered Lyme-endemic. Patients presented with severe headache, nausea, muscle and joint pain, numbness and tingling, neck and back pain, panic attacks, depression, dizziness, vision and sleep problems, shortness of breath. Modified Kelly-Pettenkofer culture medium enabled detection where standard BSK-H medium might have failed. Borrelia miyamotoi, a relapsing fever spirochete transmitted by Ixodes ticks, causes fever, thrombocytopenia, leukopenia—clinical syndrome distinct from Lyme disease. Standard Lyme serology doesn’t detect it. Diagnosis requires blood smear, PCR, or specialized serologic testing—none commercially available to most clinicians. The accessibility problem is severe. Infectious disease physician John Aucott noted that tests for these organisms “require physicians to send samples to the Mayo Clinic … that just may not happen.” Laboratory-developed tests performed at research institutions aren’t available through commercial labs most clinicians use. Physicians must know organisms exist, suspect them clinically, and have resources to send samples to specific research facilities. Insurance may not cover research testing. Results take weeks. Most clinicians remain unaware these organisms exist or testing is theoretically available. Compounding this, standard two-tier testing for B. burgdorferi—the organism we’ve studied for decades—has only 29-40% sensitivity in early infection according to CDC research. This means current testing misses 60-71% of early Lyme cases when treatment is most effective. The two-tier algorithm was designed for surveillance, favoring specificity to avoid false positives. It was never intended for clinical diagnosis of individual patients, yet has become the de facto standard. The implications are clear: without reliable commercial tests for emerging Borrelia species, and with poor sensitivity of standard testing for known organisms, patients with tick-borne illness will be misdiagnosed unless physicians use clinical judgment. Diagnosis must rest on clinical presentation, geographic exposure, symptom patterns, exclusion of alternatives, and response to empiric therapy. Insisting on laboratory confirmation before treatment will miss most cases of emerging diseases and substantial fraction of standard Lyme disease. Clinical diagnosis becomes not just preferred but essential when laboratory infrastructure cannot keep pace with emerging pathogen discovery.