How Is Borrelia miyamotoi Diagnosed? Symptoms, Testing, and How It Differs from Lyme Disease

Borrelia miyamotoi causes a tick-borne relapsing fever illness
Diagnosis often depends on clinical evaluation and appropriate laboratory testing
Early recognition can help distinguish it from Lyme disease and other tick-borne infections

How is Borrelia miyamotoi diagnosed? Diagnosis begins with clinical suspicion based on the patient’s symptoms, possible tick exposure, and routine laboratory findings. During the acute febrile phase, polymerase chain reaction (PCR) testing of whole blood is often the most useful diagnostic test because antibodies may not yet be detectable. Although transmitted by the same Ixodes ticks that spread Lyme disease, B. miyamotoi is a different infection and is not reliably diagnosed with standard Lyme disease blood tests.

Borrelia miyamotoi belongs to the relapsing fever group of Borrelia, yet its clinical presentation often differs from classic relapsing fever. Although genetically classified as a relapsing fever borrelia, repeated episodes of fever appear to be uncommon. Many patients experience a single febrile illness rather than recurrent cycles of fever, making recognition more challenging.

Although many reported patients present with an acute febrile illness, others have less specific symptoms, making Borrelia miyamotoi difficult to distinguish from Lyme disease and other tick-borne infections.

Despite possessing the genetic machinery for antigenic variation, B. miyamotoi usually does not produce the classic pattern of repeated relapsing fevers seen with many other relapsing fever borreliae. As Sudhindra and colleagues explain, although this species has the genetic apparatus for antigenic variation, this mechanism has not been clearly demonstrated clinically or in animal models. This may help explain why many patients experience only one episode of fever rather than multiple relapses.

Why is relapsing fever uncommon in Borrelia miyamotoi infection?

Classic relapsing fever borreliae evade the immune system by repeatedly changing their surface proteins, leading to recurrent episodes of fever. Although B. miyamotoi appears capable of antigenic variation, this process has not been convincingly demonstrated in human disease or animal models.

Sudhindra from the Division of Infectious Diseases at New York Medical College notes, “Although evidence of antigenic variation, which drives the relapsing course of other relapsing fevers due to borrelia has not been demonstrated clinically or in an animal system thus far for B. miyamotoi, it has been shown that this species does have the genetic apparatus for this variation.” [3]

How is Borrelia miyamotoi diagnosed?

Borrelia miyamotoi disease can be difficult to diagnose because its symptoms overlap with Lyme disease, anaplasmosis, ehrlichiosis, babesiosis, influenza, COVID-19, and other causes of acute fever. Patients often present before antibodies have developed, making early serologic testing less reliable.

PCR testing of whole blood is generally most useful during the acute febrile phase, when the organism is circulating in the bloodstream. PCR sensitivity is highest before antibiotic treatment has begun and while fever is present. Unlike Lyme disease, routine two-tier Lyme antibody testing is not intended to diagnose B. miyamotoi infection.

Some laboratories also offer antibody testing against glycerophosphodiester phosphodiesterase (GlpQ), a protein that is absent from Borrelia burgdorferi. However, GlpQ antibodies frequently become detectable only during convalescence and therefore may be negative early in the illness. In clinical practice, positive serologic testing may raise suspicion for B. miyamotoi, but the diagnosis should always be interpreted in the context of the patient’s clinical presentation.

Because patients commonly present with fever, headache, fatigue, thrombocytopenia, leukopenia, or elevated liver enzyme levels, clinicians should also consider anaplasmosis, babesiosis, ehrlichiosis, and Lyme disease in the differential diagnosis.

All but one of the 51 individuals in the case series presented with fever. They did not, however, typically experience recurrent fevers. According to Sudhindra, “The low percentage of cases with a relapse of fever may be due to the frequent use of empiric antibiotic therapy early in the course of febrile illnesses in patients with tick exposures.” [3]

The patients exhibited symptoms similar to those seen with other tick-borne illnesses. Most reported headache, myalgias, arthralgias, fatigue, and malaise. More than half were initially suspected of having sepsis, and 24% required hospitalization, underscoring how severe B. miyamotoi infection can appear during the acute phase. [1]

The investigators identified B. miyamotoi through an active surveillance program involving acutely ill patients in Massachusetts, Rhode Island, New Jersey, and New York. Initial diagnosis was made using whole-blood PCR testing for tick-borne pathogens, while infection was confirmed by demonstrating an immune response to recombinant glycerophosphodiester phosphodiesterase (rGlpQ) protein. [1]

However, rGlpQ antibody testing was frequently negative when patients first sought medical care. Molloy explained that “Serologic testing using the rGlpQ EIA seems insensitive in diagnosing acute BMD infection given that it was positive for IgG or IgM in only 16% of the case patient samples at the time of clinical presentation.” During convalescence, 86% of patients became seropositive. [1]

Laboratory abnormalities were also common. Elevated liver enzyme levels were reported in 75% of patients, neutropenia in 60%, and thrombocytopenia in 51%. According to Molloy and colleagues, “Borrelia miyamotoi disease may be clinically similar to or be confused with human anaplasmosis.” These findings highlight the importance of considering multiple tick-borne infections in patients presenting with fever and abnormal blood counts.

Because Borrelia miyamotoi and anaplasmosis can both cause fever, headache, leukopenia, thrombocytopenia, and elevated liver enzyme levels, laboratory findings alone cannot reliably distinguish between these infections. Coinfection with other Ixodes-transmitted pathogens should also be considered in patients from endemic regions.

How does Borrelia miyamotoi differ from Lyme disease?

Although both infections are transmitted by Ixodes ticks, Borrelia miyamotoi disease differs from Lyme disease in several important ways.

• Fever is more common. Patients with B. miyamotoi are more likely to present with fever than those with early Lyme disease, while the classic expanding erythema migrans rash is uncommon.
• Routine Lyme disease blood tests are not designed to diagnose B. miyamotoi. PCR testing during acute illness and GlpQ antibody testing are generally more useful.
• Blood abnormalities are more frequent. Leukopenia, thrombocytopenia, and elevated liver enzyme levels occur much more commonly than in uncomplicated Lyme disease.
• The erythema migrans rash is uncommon. Unlike Lyme disease, most patients with B. miyamotoi infection do not develop the characteristic expanding rash.
• Neurologic complications can occur. Meningitis and meningoencephalitis have been reported, particularly in immunocompromised individuals, although these complications are uncommon.

Despite these differences, the two illnesses overlap clinically, and physicians should consider both infections—as well as other Ixodes-transmitted diseases—in patients with compatible symptoms following a tick bite.

Can Borrelia miyamotoi cause relapsing fever?

Unlike the classic soft tick-borne relapsing fevers, repeated fever relapses appear to be uncommon in B. miyamotoi disease. Most published patients experience a single febrile illness, although occasional untreated individuals have developed recurrent fever episodes.

One explanation is that many patients receive antibiotics early because clinicians suspect another tick-borne infection. Early treatment may prevent additional fever recurrences that otherwise could have occurred.

The biology may also differ from other relapsing fever borreliae. Although B. miyamotoi possesses genes associated with antigenic variation, the repeated immune evasion that characterizes classic relapsing fever has not been consistently demonstrated in humans.

An emerging tick-borne infection

Borrelia miyamotoi is now recognized as an important hard tick-borne infection transmitted by Ixodes ticks in the northeastern United States and other endemic regions. Although considerably less common than Lyme disease, physicians should include it in the differential diagnosis of patients presenting with fever, headache, fatigue, thrombocytopenia, leukopenia, or elevated liver enzyme levels after possible tick exposure.

Greater clinician awareness and increased availability of PCR testing are likely to identify additional cases. Early diagnosis can help distinguish B. miyamotoi disease from Lyme disease, anaplasmosis, babesiosis, influenza, COVID-19, and other causes of acute febrile illness.

Read more about Borrelia miyamotoi and larval tick transmission.

Frequently Asked Questions

Is Borrelia miyamotoi the same as Lyme disease?

No. Although both infections are transmitted by Ixodes ticks, Borrelia miyamotoi is a relapsing fever borrelia, whereas Lyme disease is caused primarily by Borrelia burgdorferi. The illnesses share many symptoms but differ in their laboratory findings, diagnostic testing, and typical clinical presentation.

How is Borrelia miyamotoi diagnosed?

Diagnosis begins with clinical suspicion based on the patient’s symptoms, possible tick exposure, and routine laboratory findings. PCR testing of whole blood is generally most useful during the acute febrile phase because antibody tests may be negative early in the illness. GlpQ antibody testing can support the diagnosis during convalescence, but test results should always be interpreted in the context of the patient’s clinical presentation.

Can a Lyme disease blood test diagnose Borrelia miyamotoi?

No. Standard two-tier Lyme disease blood tests are not designed to diagnose Borrelia miyamotoi infection. Some patients may have positive Lyme serology because of cross-reactivity, but PCR testing and GlpQ antibody testing are more specific for B. miyamotoi.

Can Borrelia miyamotoi be mistaken for Lyme disease?

Yes. Both infections are transmitted by Ixodes ticks and can cause fatigue, headache, muscle aches, and other nonspecific symptoms. B. miyamotoi is more likely to present with fever, thrombocytopenia, leukopenia, and elevated liver enzyme levels, while the classic erythema migrans rash is uncommon.

Clinical Takeaway

Borrelia miyamotoi is an emerging Ixodes-transmitted infection that can closely resemble Lyme disease, anaplasmosis, and other causes of acute fever. Although it belongs to the relapsing fever group of Borrelia, repeated fever episodes appear to be uncommon. Because early antibody testing may be negative, diagnosis often depends on clinical suspicion together with appropriate laboratory testing, particularly PCR during the acute phase.

Recognizing Borrelia miyamotoi early and interpreting laboratory results in the context of the patient’s clinical presentation can improve diagnosis and help distinguish it from Lyme disease and other tick-borne infections.

Related Articles

Why Lyme Disease Tests Can Be Negative
Anaplasmosis Symptoms and Diagnosis
Babesia and Babesiosis
Can One Tick Bite Transmit Multiple Diseases?
Lyme Disease Misdiagnosis

References

1. Molloy PJ, Telford SR III, Chowdri HR, Lepore TJ, Gugliotta JL, Weeks KE, Hewins ME, Goethert HK, Berardi VP. Borrelia miyamotoi Disease in the Northeastern United States: A Case Series. Ann Intern Med. 2015;163(2):91-98.
2. Telford SR III, Goethert HK, Molloy PJ, Berardi VP, Chowdri HR, Gugliotta JL, Lepore TJ. Borrelia miyamotoi Disease: Neither Lyme Disease Nor Relapsing Fever. Clin Lab Med. 2015;35(4):867-882.
3. Sudhindra P, Wang G, Schriefer ME, McKenna D, Zhuge J, Krause PJ, Marques AR, Wormser GP. Insights into Borrelia miyamotoi Infection from an Untreated Case Demonstrating Relapsing Fever, Monocytosis and a Positive C6 Lyme Serology. Diagn Microbiol Infect Dis. 2016;86(1):93-96.

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Dr. Daniel Cameron, MD, MPH
Lyme disease clinician with over 30 years of experience and past president of ILADS.

Symptoms • Testing • Coinfections • Recovery • Pediatric • Prevention