Skip directly to site content Skip directly to page options Skip directly to A-Z link Skip directly to A-Z link Skip directly to A-Z link
Volume 27, Number 10—October 2021

Relapsing Fever Infection Manifesting as Aseptic Meningitis, Texas, USA

Lisa Ellis, Michael W. Curtis, Sarah M. Gunter, and Job E. LopezComments to Author 
Author affiliations: Austin Infectious Disease Consultants, Austin, Texas, USA (L. Ellis); Baylor College of Medicine, Houston, Texas (M.W. Curtis, S.M. Gunter, J.E. Lopez)

Cite This Article


CME Logo


In support of improving patient care, this activity has been planned and implemented by Medscape, LLC and Emerging Infectious Diseases. Medscape, LLC is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.

Medscape, LLC designates this Journal-based CME activity for a maximum of 1.00 AMA PRA Category 1 Credit(s). Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to 1.0 MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program. Participants will earn MOC points equivalent to the amount of CME credits claimed for the activity. It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting ABIM MOC credit.

All other clinicians completing this activity will be issued a certificate of participation. To participate in this journal CME activity: (1) review the learning objectives and author disclosures; (2) study the education content; (3) take the post-test with a 75% minimum passing score and complete the evaluation at; and (4) view/print certificate.

Release date: September 20, 2021; Expiration date: September 20, 2022
Learning Objectives

Upon completion of this activity, participants will be able to:

  • Describe clinical presentation and course in a case of neuroborreliosis in Austin, Texas, that was initially thought to be Lyme disease (LD)

  • Determine retrospective serological analysis and other laboratory findings in a case of neuroborreliosis in Austin, Texas, that was initially thought to be LD

  • Identify clinical and public health implications of findings in this case of neuroborreliosis in Austin, Texas, that was initially thought to be LD.

CME Editor

Terie A. Grant, BS, Copyeditor, Emerging Infectious Diseases. Disclosure: Amy J. Guinn, BA, MA, has disclosed no relevant financial relationships.

CME Author

Laurie Barclay, MD, freelance writer and reviewer, Medscape, LLC. Disclosure: Laurie Barclay, MD, has disclosed no relevant financial relationships.


Disclosures: Lisa C. Ellis, MD; Michael W. Curtis, PhD; Sarah M. Gunter, PhD, MPH; and Job E. Lopez, PhD, have disclosed no relevant financial relationships.



Tickborne relapsing fever spirochetes are an overlooked cause of disease around the globe. We report a case of tickborne relapsing fever in a patient in Texas, USA, who had a single febrile episode and gastrointestinal and neurologic symptoms. Immunoblot analysis using recombinant Borrelia immunogenic protein A implicated Borrelia turicatae as the causative agent.

Tickborne relapsing fever (TBRF) spirochetes are globally neglected pathogens. Borrelia turicatae is found in the southwestern and eastern United States into Latin America (1), and high-risk populations include military personnel, outdoor enthusiasts, and impoverished undocumented immigrants (24). However, evidence indicates the presence of endemic foci of B. turicatae in metropolitan cities of Texas, USA (4,5).

TBRF is often misdiagnosed because of the nonspecific manifestations of the disease. More than 90% of patients experience recurrent febrile episodes, rigors, headache, and myalgia (6). Previous work suggests that B. turicatae is similar to Old World species, manifesting with neurologic complications (7). However, these diagnoses were made on the basis of a priori assumptions, and the causative agents were never confirmed.

We report a case of neuroborreliosis in Austin, Texas, USA, that was initially suspected to be Lyme disease (LD). A retrospective serologic analysis was performed using the diagnostic antigen, Borrelia immunogenic protein A (BipA). This antigen is absent from LD-causing spirochetes and might be a species-specific antigen for North American TBRF Borrelia (8,9).

The Study

The patient was a previously healthy 30-year-old man residing in Austin near a creek greenbelt that he frequented (Figure 1); he had no recent travel outside the city. On March 5, 2020, he experienced acute dizziness, headache, myalgia, vomiting, chills, and fever of 37.8°C (reference 36.1°C–37.2°C). Symptoms were attributed to a foodborne illness, and he improved after several days. However, he continued to experience dizziness, headache, fatigue, myalgia, and intermittent severe night sweats, with no report of further fever.

Within 2 weeks, he had Bell’s palsy on his left side, and the primary care physician ordered a blood analysis. Results for complete blood count, electrolytes, blood urea nitrogen, creatinine, and liver enzymes were unremarkable. Erythrocyte sedimentation rate was 62 mm/h (reference <15 mm/h), and C-reactive protein was 97.5 mg/L (reference <8.0 mg/L). Valacyclovir (1 g orally 3×/d for 7 d) and prednisone (20 mg orally 2×/d for 5 d) were prescribed, with partial improvement. Subsequent blood testing showed the erythrocyte sedimentation rate declined to 41 mm/h, and C-reactive protein declined to 43.2 mg/L.

Two weeks later, he had Bell’s palsy on his right side, blurred vision, tinnitus, and cervical lymph node enlargement. Dizziness, headache, and fatigue continued. Results of complete blood count and metabolic panel were unremarkable. The patient underwent magnetic resonance imaging of the brain with contrast, which revealed faint nonspecific enhancement in the right internal auditory canal. High-resolution imaging of the 7th and 8th cranial nerves was not performed.

The patient’s wife reported removing ticks from herself and a pet 4 weeks before the patient’s illness began, and LD was suspected. A 2-tiered antibody test was performed. The enzyme immunoassay result was 2.43 (>1.09 considered positive). The LD IgM immunoblot was positive for the 23 kDa and 39 kDa bands, but the IgG immunoblot was negative.

The patient was referred to an infectious disease specialist who suspected TBRF and ordered a lumbar puncture. Clear, colorless cerebrospinal fluid (CSF) was recovered, and the analysis revealed 124 leukocytes/UL (reference <5 leukocytes/UL) with 85% lymphocytes, 10% monocytes, 5% large mononuclear cells, and 0% erythrocytes/UL. CSF protein was 103 mg/dL (reference 15.0–45.0 mg/dL), and glucose was 52 mg/dL (reference 40–70 mg/dL). CSF was analyzed by the Associated Regional and University Pathologists laboratory for LD and TBRF spirochete DNA, the Venereal Disease Research Laboratory test for neurosyphillis, and the Biofire Filmarray Meningitis/Encephalitis (bioMérieux, panel that detects 6 bacterial and 7 viral pathogens. All test results were negative.

Given the patient’s clinical history, intravenous ceftriaxone was administered (2 g/d for 14 d), and he showed considerable improvement within 4 days of treatment. Upon completion of antibiotics, all symptoms were resolved except for minimal lower right facial weakness. Deidentified serum samples and CSF collected 5 weeks after the onset of illness were sent to Baylor College of Medicine (Houston, TX, USA) for additional testing.

No spirochetes were recovered from the CSF nor was DNA detected; therefore, we performed serologic tests using recombinant BipA (rBipA) (8,9). We generated expression constructs for B. turicatae, B. parkeri, and B. hermsii rBipA by using GenScript (GenScript, in the pET19b vector. We purified recombinant proteins and performed immunoblotting and ELISA, as previously described (8). For immunoblots, we used protein lysates from B. turicatae 91E135, B. hermsii DAH, and B. parkeri SLO. We probed immunoblots with the patient’s serum sample and CSF diluted 1:200. Only the serum sample was diluted 2-fold from 1:200 to 1:256,000 for the ELISA because the CSF was depleted in prior assays. The secondary antibody was goat anti-human IgA, IgG, and IgM (Millipore, We repeated serologic assays twice.

Serologic assays indicated likely exposure to B. turicatae. Strong responses were detected with the serum sample and CSF to B. turicatae protein lysates and rBipA (Figure 2, panels A and B upper). Antibodies in the patient’s serum and CSF cross-reacted with protein lysates from B. parkeri and B. hermsii, but reactivity to rBipA from these species was undetectable (Figure 2, panels A, B, top images). In addition, reactivity to B. burgdorferi protein lysates was undetectable (Figure 2, panels A, B, top images). A negative control serum sample from a subject without history of TBRF failed to detect proteins (Figure 2, panel C, top image). Reprobing immunoblots with a monoclonal antibody for the histidine residues fused to rBipA demonstrated that protein was electrophoresed and transferred to membranes (Figure 2, bottom images). ELISA further indicated infection attributable to B. turicatae with antibody titers to B. turicatae rBipA between 1:400 to 1:800, and responses to B. parkeri and B. hermsii rBipA were undetectable.


This study reports a case of neurologic TBRF likely caused by B. turicatae. The hallmark of TBRF is recurrent febrile episodes (6), but this patient had a single febrile episode, nausea, and predominantly neurologic symptoms. B. turicatae has been suspected to cause neurologic symptoms including facial paralysis, vertigo, hearing loss, delirium, and hallucinations (10). However, past diagnoses were attributed solely on the basis of the geographic range of the probable pathogen and were not empirically confirmed.

This study demonstrated that rBipA could aid in the identification of the TBRF species causing infection. It was unlikely that the patient was exposed to B. hermsii and B. parkeri because of his travel history, but we used this opportunity to assess serologic crossreactivity to rBipA from these 2 species. Similar to prior work with B. turicatae–infected laboratory animals (8), we detected no crossreactive patient antibodies to B. hermsii rBipA. This finding was expected given that the proteins share ≈35% amino acid identity (11). Of note, rBipA could differentiate between infections caused by B. parkeri and B. turicatae, which share ≈75% amino acid identity (11).

In summary, B. turicatae is often misdiagnosed, and healthcare providers should understand the pathogen’s circulation (2,5,11). Endemic foci have been identified in Florida, USA, and within and around the 4 largest cities of Texas (Austin, San Antonio, Dallas, and Houston) (13,5,7). With urban expansion and the incorporation of greenbelts into metropolitan areas, B. turicatae should be considered in cases of fever with neurologic symptoms when the Lyme antibody test is positive but prevalence of LD is not epidemiologically supported.



We thank Aparna Krishnavajhala and Alexander Kneubehl for critical review of this manuscript and Tom Schwan for originally providing B. hermsii, B. turicatae, and B. parkeri isolates for serology.

This work was supported by funding from National Institutes of Health grant no. AI144187 (JEL). Michael W. Curtis was supported through the Infection and Immunity T32 Fellowship at Baylor College of Medicine (grant no. T32AI055413).



  1. Lopez  JE, Krishnavahjala  A, Garcia  MN, Bermudez  S. Tick-borne relapsing fever spirochetes in the Americas. Vet Sci. 2016;3:118. DOIPubMedGoogle Scholar
  2. Rawlings  JA. An overview of tick-borne relapsing fever with emphasis on outbreaks in Texas. Tex Med. 1995;91:569.PubMedGoogle Scholar
  3. Christensen  AM, Pietralczyk  E, Lopez  JE, Brooks  C, Schriefer  ME, Wozniak  E, et al. Diagnosis and management of Borrelia turicatae infection in febrile soldier, Texas, USA. Emerg Infect Dis. 2017;23:8834. DOIPubMedGoogle Scholar
  4. Campbell  SB, Klioueva  A, Taylor  J, Nelson  C, Tomasi  S, Replogle  A, et al. Evaluating the risk of tick-borne relapsing fever among occupational cavers-Austin, TX, 2017. Zoonoses Public Health. 2019;66:57986. DOIPubMedGoogle Scholar
  5. Bissett  JD, Ledet  S, Krishnavajhala  A, Armstrong  BA, Klioueva  A, Sexton  C, et al. Detection of tickborne relapsing fever spirochete, Austin, Texas, USA. Emerg Infect Dis. 2018;24:20039. DOIPubMedGoogle Scholar
  6. Dworkin  MS, Schwan  TG, Anderson  DE Jr, Borchardt  SM. Tick-borne relapsing fever. [viii.]. Infect Dis Clin North Am. 2008;22:44968, viii. DOIPubMedGoogle Scholar
  7. Gillespie  JO. Relapsing fever in the United States. JAMA. 1935;104:187881. DOIGoogle Scholar
  8. Lopez  JE, Wilder  HK, Boyle  W, Drumheller  LB, Thornton  JA, Willeford  B, et al. Sequence analysis and serological responses against Borrelia turicatae BipA, a putative species-specific antigen. PLoS Negl Trop Dis. 2013;7:e2454. DOIPubMedGoogle Scholar
  9. Lopez  JE, Schrumpf  ME, Nagarajan  V, Raffel  SJ, McCoy  BN, Schwan  TG. A novel surface antigen of relapsing fever spirochetes can discriminate between relapsing fever and Lyme borreliosis. Clin Vaccine Immunol. 2010;17:56471. DOIPubMedGoogle Scholar
  10. Cadavid  D, Barbour  AG. Neuroborreliosis during relapsing fever: review of the clinical manifestations, pathology, and treatment of infections in humans and experimental animals. Clin Infect Dis. 1998;26:15164. DOIPubMedGoogle Scholar
  11. Wilder  HK, Wozniak  E, Huddleston  E, Tata  SR, Fitzkee  NC, Lopez  JE. Case report: A retrospective serological analysis indicating human exposure to tick-borne relapsing fever spirochetes in Texas. PLoS Negl Trop Dis. 2015;9:e0003617. DOIPubMedGoogle Scholar




Follow Up

Earning CME Credit

To obtain credit, you should first read the journal article. After reading the article, you should be able to answer the following, related, multiple-choice questions. To complete the questions (with a minimum 75% passing score) and earn continuing medical education (CME) credit, please go to Credit cannot be obtained for tests completed on paper, although you may use the worksheet below to keep a record of your answers.

You must be a registered user on If you are not registered on, please click on the “Register” link on the right hand side of the website.

Only one answer is correct for each question. Once you successfully answer all post-test questions, you will be able to view and/or print your certificate. For questions regarding this activity, contact the accredited provider, For technical assistance, contact American Medical Association’s Physician’s Recognition Award (AMA PRA) credits are accepted in the US as evidence of participation in CME activities. For further information on this award, please go to The AMA has determined that physicians not licensed in the US who participate in this CME activity are eligible for AMA PRA Category 1 Credits™. Through agreements that the AMA has made with agencies in some countries, AMA PRA credit may be acceptable as evidence of participation in CME activities. If you are not licensed in the US, please complete the questions online, print the AMA PRA CME credit certificate, and present it to your national medical association for review.

Article Title: 
Relapsing Fever Infection Manifesting as Aseptic Meningitis, Texas, USA
CME Questions
  • Your patient is a 64-year-old man presenting with fever and myalgias after possible tick exposure. According to the case report by Ellis and colleagues, which of the following statements about clinical presentation and course in a case of neuroborreliosis in Austin, Texas, that was initially thought to be Lyme disease (LD) is correct?

    • Initial symptoms were vomiting, diarrhea, chills, and fever without headache (HA) or other neurologic symptoms

    • Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were not elevated

    • Cerebrospinal fluid (CSF) and LD immunoglobulin (Ig) M immunoblot were negative

    • Ceftriaxone 2 g intravenous (IV) daily for 14 days led to significant improvement within 4 days and resolution of all symptoms at treatment completion except for minimal right lower facial weakness

  • According to the case report by Ellis and colleagues, which of the following statements about retrospective serologic analysis and other laboratory findings in a case of neuroborreliosis in Austin, Texas, that was initially thought to be LD is correct?

    • CSF collected 5 weeks after illness onset showed Borrelia spirochetes and DNA

    • Strong responses were detected to B. turicatae protein lysates and recombinant Borrelia immunogenic protein (rBipA) in serum and CSF, indicating likely exposure to B. turicatae

    • CSF was strongly reactive to rBipA from B. parkeri and B. hermsii

    • Enzyme-linked immunosorbent assay (ELISA) antibody titers to B. hermsii rBipA were between 1081:400 and 1:800

  • According to the case report by Ellis and colleagues, which of the following statements about clinical and public health implications of findings in this case of neuroborreliosis in Austin, Texas, that was initially thought to be LD is correct?

    • Endemic foci of B. turicatae have been identified in Colorado and Wyoming

    • B. turicatae is easy to diagnose from classical presentation and history of tick exposure

    • B. turicatae should be considered in cases of fever with neurologic symptoms when the Lyme antibody test is positive, but prevalence of LD is not epidemiologically supported

    • The findings suggest that BipA is not specific to North American TBRF Borrelia


Cite This Article

DOI: 10.3201/eid2710.210189

Related Links

Table of Contents – Volume 27, Number 10—October 2021

EID Search Options
presentation_01 Advanced Article Search – Search articles by author and/or keyword.
presentation_01 Articles by Country Search – Search articles by the topic country.
presentation_01 Article Type Search – Search articles by article type and issue.



Please use the form below to submit correspondence to the authors or contact them at the following address:

Job Lopez, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA

Send To

10000 character(s) remaining.


Page created: August 18, 2021
Page updated: September 20, 2021
Page reviewed: September 20, 2021
The conclusions, findings, and opinions expressed by authors contributing to this journal do not necessarily reflect the official position of the U.S. Department of Health and Human Services, the Public Health Service, the Centers for Disease Control and Prevention, or the authors' affiliated institutions. Use of trade names is for identification only and does not imply endorsement by any of the groups named above.