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 29, Number 5—May 2023

Borrelia miyamotoi Infection in Immunocompromised Man, California, USA, 2021

Luis Alberto RubioComments to Author , Anne M. Kjemtrup, Grace E. Marx, Shanna Cronan, Christopher Kilonzo, Megan E.M. Saunders, Jamie L. Choat, Elizabeth A. Dietrich, Kelly A. Liebman, and Sarah Y. Park
Author affiliations: University of California, San Francisco, San Francisco, California, USA (L.A. Rubio); California Department of Public Health, Sacramento, California, USA (A.M. Kjemtrup); Centers for Disease Control and Prevention, Fort Collins, Colorado, USA (G.E. Marx, J.L. Choat, E.A. Dietrich); County of Marin Department of Health and Human Services, San Rafael, California, USA (S. Cronan); California Department of Public Health, Richmond, California, USA (C. Kilonzo, M.E.M. Saunders); Marin-Sonoma Mosquito and Vector Control District, Cotati, California, USA (K.A. Liebman); Karius, Incorporated, Redwood City, California, USA (S.Y. Park)

Cite This Article


Infection with Borrelia miyamotoi in California, USA, has been suggested by serologic studies. We diagnosed B. miyamotoi infection in an immunocompromised man in California. Diagnosis was aided by plasma microbial cell–free DNA sequencing. We conclude that the infection was acquired in California.

Borrelia miyamotoi is a relapsing fever spirochete; infection is recognized in Europe, Japan, and the northeastern United States as an emerging human infectious disease (1,2). First identified in Japan in 1995 in Ixodes persulcatus ticks, B. miyamotoi has since been detected in other species of Ixodes ticks, including I. ricinus in Europe, I. scapularis in eastern North America, and I. pacificus in western North America (1). In California, USA, I. pacificus ticks can harbor 2 spirochetes capable of causing human disease: B. miyamotoi and Borrelia burgdorferi, the agent that causes Lyme disease (3). Prevalence of B. miyamotoi in I. pacificus ticks in California is estimated to be 0.8% in adult ticks and 1.4% in nymphal ticks, similar to other parts of the world that have Ixodes spp. ticks and reported human cases of B. miyamotoi infection (1).

In California, tick-borne relapsing fever is usually ascribed to infection with B. hermsii, transmitted by soft ticks (Ornithodoros hermsi), found in high-elevation habitats (4). Although infection with B. miyamotoi in California has been suggested by serologic studies, clinical human cases of B. miyamotoi infection acquired in the western United States have not been reported in the literature (1,3,4). We describe B. miyamotoi infection, confirmed through plasma microbial cell–free DNA (mcfDNA) sequencing, in a California man with relapsing fevers. Our investigation was determined to be exempt from human subjects research by the Office of Human Research Protections of the California Health and Human Services Agency (Federalwide Assurance no. 00000681).

The Case

In December 2021, an adult man receiving ocrelizumab (anti-B lymphocyte CD20 monoclonal antibody) for multiple sclerosis diagnosed in 2018 sought care at a neurology clinic in San Francisco, California, USA. The patient reported having experienced new fevers up to 38.7°C beginning in October 2021. The febrile episodes typically lasted 1 day, occurred every 10–14 days, and were associated with night sweats, mild vision changes, and nausea. Results of a physical examination were unremarkable, and the patient was sent home with a recommendation to return for evaluation if fever recurred.

Given continued intermittent fevers, the neurologist referred the patient to a local hospital in Greenbrae, California, USA, 3 days later for an expedited evaluation. Although the patient was again afebrile and results of physical examination were unremarkable, laboratory results were notable for thrombocytopenia (96,000 cell/mL [reference range 150,000–400,000 cells/mL]), elevated C-reactive protein level (47.2 mg/L [reference <5.0 mg/L]), and elevated procalcitonin level (1.89 ng/mL [reference <0.10 ng/mL]). No abnormalities were noted on chest radiographs or computed tomography scans of the abdomen and pelvis. Peripheral blood cultures were without growth, and the patient was discharged to home with a referral to the infectious disease clinic in San Francisco. At that clinic, serologic evaluation for certain bacteria, fungi, and viruses was notable only for positive Epstein-Barr viral capsid and nuclear antigen IgG. Serologic test results for Borrelia burgdorferi, brucellosis, and leptospirosis were negative, and results of a peripheral blood smear were unremarkable (Table 1).

Given the patient’s immunocompromised status and relapsing fever history, suspicion for infection remained high and plasma mcfDNA sequencing (Karius test, was ordered. Results were positive for B. miyamotoi (56 DNA molecules/μL [reference <10 molecules/μL]). The Centers for Disease Control and Prevention performed confirmatory Borrelia PCR testing, results of which were also positive for B. miyamotoi (5), and multilocus sequence typing (MLST), which indicated that the sequence was 100% identical in >6,040 nucleotides to a B. miyamotoi isolate from an I. pacificus tick collected in Marin County, California (Table 2) (6,7). The sequence was distinct from B. miyamotoi isolates from other geographic regions, displaying 99.3% identity (44 nt differences) to isolates from the eastern United States.

After B. miyamotoi infection was diagnosed, a 4-week course of doxycycline was prescribed. The patient reported having 1 additional febrile episode (38.9°C) after the first dose, but fevers subsequently resolved, and all other signs/symptoms improved. After consultation with the patient’s neurologist, cerebrospinal fluid testing was not performed, given resolution of visual symptoms and absence of other focal neurologic deficits. The patient returned to the clinic 1 month after having completed the course of doxycycline without any fever recurrence; laboratory testing showed resolution of thrombocytopenia and normalization of inflammatory markers. Ocrelizumab infusions were resumed after B. miyamotoi treatment, and symptom recurrence has not been reported.

The patient was a resident of Marin County, California, and reported having traveled 2 months before fever onset to Ohio and within California to Mendocino and Monterey Counties but reported no travel outside the United States for the previous 2 years. He reported hiking and swimming in freshwater lakes while traveling and near home but did not recall any insect or tick bites. He reported often spending time outdoors near home. He owned 2 domestic indoor cats not receiving regular tick prevention and reported no other animal exposures.

The California Department of Public Health Vector-Borne Disease Section collaborated with Marin-Sonoma Vector Control Agency to collect and test ticks from areas around the patient’s residence. The habitat consisted of coastal redwood grove and understory grass and shrub vegetation. Questing ticks were collected by dragging a 1-m2 white flannel cloth along the ground cover. A total of 19 I. pacificus ticks (12 adults, 7 nymphs) from the patient’s yard and nearby trails were collected and stored in 70% ethanol until DNA extraction. PCR testing did not identify any ticks positive for B. miyamotoi infection but identified 1 adult tick infected with B. burgdorferi sensu lato (8).


Although B. miyamotoi has been identified in ticks in California for >20 years, locally acquired human cases within the western United States have not been described (1). Our environmental investigation identified multiple I. pacificus ticks near this patient’s residence and recreation areas in California, all in locations where B. miyamotoi has been documented in I. pacificus ticks (1). The B. miyamotoi sequence recovered from the patient was most closely related to an isolate recovered from an I. pacificus tick in California (7). Of note, the patient’s travel to Ohio was during August, when seasonal activity of Ixodes spp. ticks in the region is low, and was to a location where B. miyamotoi has not been identified (9).

For patients with high or relapsing fever during seasons of Ixodes tick activity, particularly in areas where B. miyamotoi has been reported in local tick populations, clinicians should consider the possibility of B. miyamotoi infection along with other Borrelia spp. Laboratory confirmation of B. miyamotoi infection can be challenging because the spirochetes share many proteins with B. burgdorferi and B. hermsii, resulting in cross-reacting antibodies, and because few laboratories offer specific molecular diagnostic testing for B. miyamotoi (10). For this case, B. miyamotoi infection was diagnosed through molecular testing with unbiased plasma mcfDNA sequencing, an increasingly used tool for evaluating patients with fever of unknown etiology (11,12). The patient’s immunocompromised status may have contributed to the infection chronicity, increasing our ability to detect the organism (11,13). PCR and sequencing confirmed the diagnosis.

Our study suggests that B. miyamotoi is an emerging human pathogen in California. Human infection is probably rare, given low seroprevalence in blood donors, even in counties to which I. pacificus ticks are endemic, and low prevalence of B. miyamotoi in ticks that is rarely >2% (1,3). Given limitations of serologic testing, clinicians should maintain an index of suspicion for B. miyamotoi in patients with relapsing fever without a clear etiology, should ask about potential tick exposure, and should consider molecular diagnostic testing.

Dr. Rubio is an assistant clinical professor at University of California, San Francisco, and provides clinical care there and at the Zuckerberg San Francisco General Hospital and Trauma Center. His interests include general infectious diseases, latent tuberculosis infection, HIV primary care, and medical education.



We thank Lindsey Termini for the case investigation.

The findings and conclusions in this article are those of the authors and do not necessarily represent the views or opinions of the California Department of Public Health, the California Health and Human Services Agency, County of Marin Department of Public Health, or the Centers for Disease Control and Prevention.



  1. Padgett  K, Bonilla  D, Kjemtrup  A, Vilcins  IM, Yoshimizu  MH, Hui  L, et al. Large scale spatial risk and comparative prevalence of Borrelia miyamotoi and Borrelia burgdorferi sensu lato in Ixodes pacificus. PLoS One. 2014;9:e110853. DOIPubMedGoogle Scholar
  2. Sato  K, Takano  A, Konnai  S, Nakao  M, Ito  T, Koyama  K, et al. Human infections with Borrelia miyamotoi, Japan. Emerg Infect Dis. 2014;20:13913. DOIPubMedGoogle Scholar
  3. Brummitt  SI, Kjemtrup  AM, Harvey  DJ, Petersen  JM, Sexton  C, Replogle  A, et al. Borrelia burgdorferi and Borrelia miyamotoi seroprevalence in California blood donors. PLoS One. 2020;15:e0243950. DOIPubMedGoogle Scholar
  4. Krause  PJ, Carroll  M, Fedorova  N, Brancato  J, Dumouchel  C, Akosa  F, et al. Human Borrelia miyamotoi infection in California: Serodiagnosis is complicated by multiple endemic Borrelia species. PLoS One. 2018;13:e0191725. DOIPubMedGoogle Scholar
  5. Dietrich  EA, Replogle  AJ, Sheldon  SW, Petersen  JM. Simultaneous detection and differentiation of clinically relevant relapsing fever Borrelia with semimultiplex real-time PCR. J Clin Microbiol. 2021;59:e0298120. DOIPubMedGoogle Scholar
  6. Margos  G, Gatewood  AG, Aanensen  DM, Hanincová  K, Terekhova  D, Vollmer  SA, et al. MLST of housekeeping genes captures geographic population structure and suggests a European origin of Borrelia burgdorferi. Proc Natl Acad Sci U S A. 2008;105:87305. DOIPubMedGoogle Scholar
  7. Kingry  LC, Replogle  A, Dolan  M, Sexton  C, Padgett  KA, Schriefer  ME. Chromosome and large linear plasmid sequences of a Borrelia miyamotoi strain isolated from Ixodes pacificus ticks from California. Genome Announc. 2017;5:e0096017. DOIPubMedGoogle Scholar
  8. Barbour  AG, Bunikis  J, Travinsky  B, Hoen  AG, Diuk-Wasser  MA, Fish  D, et al. Niche partitioning of Borrelia burgdorferi and Borrelia miyamotoi in the same tick vector and mammalian reservoir species. Am J Trop Med Hyg. 2009;81:112031. DOIPubMedGoogle Scholar
  9. Krause  PJ, Fish  D, Narasimhan  S, Barbour  AG. Borrelia miyamotoi infection in nature and in humans. Clin Microbiol Infect. 2015;21:6319. DOIPubMedGoogle Scholar
  10. Fleshman  AC, Foster  E, Maes  SE, Eisen  RJ. Reported county-level distribution of seven human pathogens detected in host-seeking Ixodes scapularis and Ixodes pacificus (Acari: Ixodidae) in the contiguous United States. J Med Entomol. 2022;59:132835. DOIPubMedGoogle Scholar
  11. Wright  WF, Simner  PJ, Carroll  KC, Auwaerter  PG. Progress report: next-generation sequencing, multiplex polymerase chain reaction, and broad-range molecular assays as diagnostic tools for fever of unknown origin investigations in adults. Clin Infect Dis. 2022;74:92432. DOIPubMedGoogle Scholar
  12. Haidar  G, Singh  N. Fever of unknown origin. N Engl J Med. 2022;386:46377. DOIPubMedGoogle Scholar
  13. Boden  K, Lobenstein  S, Hermann  B, Margos  G, Fingerle  V. Borrelia miyamotoi–associated neuroborreliosis in immunocompromised person. Emerg Infect Dis. 2016;22:161720. DOIPubMedGoogle Scholar




Cite This Article

DOI: 10.3201/eid2905.221638

Original Publication Date: April 12, 2023

Table of Contents – Volume 29, Number 5—May 2023

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:

Luis Alberto Rubio, 2nd Fl, Box 0620, Division of Infections Disease, University of California San Francisco, 521 Parnassus Ave, San Francisco, CA 94143, USA

Send To

10000 character(s) remaining.


Page created: April 12, 2023
Page updated: April 19, 2023
Page reviewed: April 19, 2023
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.