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Original Research |

Borrelia miyamotoi Disease in the Northeastern United States: A Case SeriesBorrelia miyamotoi Disease in the Northeastern United States

Philip J. Molloy, MD; Sam R. Telford III, ScD; Hanumara Ram Chowdri, MD; Timothy J. Lepore, MD; Joseph L. Gugliotta, MD; Karen E. Weeks, BS; Mary Ellen Hewins, BS; Heidi K. Goethert, ScD; and Victor P. Berardi
[+] Article, Author, and Disclosure Information

This article was published online first at www.annals.org on 9 June 2015.


From IMUGEN, Norwood, Massachusetts; Cummings School of Veterinary Medicine, Tufts University, North Grafton, Massachusetts; Hawthorn Medical Associates and South Coast Hospital System, New Bedford, Massachusetts; Nantucket Cottage Hospital, Nantucket, Massachusetts; Hunterdon Medical Center, Flemington, New Jersey; and Robert Wood Johnson Medical School, New Brunswick, New Jersey.

Acknowledgment: The authors thank Dr. Allen C. Steere for reading the manuscript and providing useful suggestions on its focus and content.

Financial Support: This research was internally funded by IMUGEN. Drs. Telford and Goethert are funded, in part, by grants from the National Institutes of Health (R41 AI 078631), the Evelyn Lilly Lutz Foundation, the Dorothy Harrison Egan Foundation, and the Tufts Innovation Institute.

Disclosures: Dr. Molloy reports that he is the paid medical director of IMUGEN. Dr. Telford reports personal fees from IMUGEN, Immunetics, Meridian Bioscience, and Fuller Laboratories outside the submitted work. Dr. Chowdri reports employment as a clinical consultant for IMUGEN. Ms. Weeks reports board membership, employment as vice-president and laboratory manager, and stock ownership at IMUGEN. Ms. Hewins reports board membership, employment as vice-president and laboratory manager, and stock ownership at IMUGEN. Dr. Goethert reports that she is a part-time employee of IMUGEN. Mr. Berardi reports board membership, employment as president/CEO and associate director of laboratory science, and stock ownership at IMUGEN. Authors not named here have disclosed no conflicts of interest. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M15-0333.

Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that she has no financial relationships or interests to disclose. Darren B. Taichman, MD, PhD, Executive Deputy Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Deborah Cotton, MD, MPH, Deputy Editor, reports that she has no financial relationships or interest to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Catharine B. Stack, PhD, MS, Deputy Editor for Statistics, reports that she has stock holdings in Pfizer.

Reproducible Research Statement:Study protocol and statistical code: Available from Mr. Berardi (e-mail, vberardi@imugen.com). Data set: Not available.

Requests for Single Reprints: Victor Berardi, IMUGEN Reference Diagnostics Division, 315 Norwood Park South, Norwood, MA 02062; e-mail, vberardi@imugen.com.

Current Author Addresses: Dr. Molloy, Ms. Weeks, Ms. Hewins, and Mr. Berardi: IMUGEN, 315 Norwood Park South, Norwood, MA 02062.

Drs. Telford and Goethert: Department of Infectious Disease and Global Health, Cummings School of Veterinary Medicine, Tufts University, 200 Westboro Road, North Grafton, MA 01536.

Dr. Chowdri: Hawthorn Medical Associates, 275 Allen Street, Unit 3, New Bedford, MA 02740.

Dr. Lepore: Nantucket Cottage Hospital, 57 Prospect Street, Nantucket, MA 02554.

Dr. Gugliotta: Hunterdon Medical Center Infectious Diseases, 1100 Wescott Drive, Suite 306, Flemington, NJ 08822.

Author Contributions: Conception and design: P.J. Molloy, H.R. Chowdri, J.L. Gugliotta, K.E. Weeks, H.K. Goethert, V.P. Berardi.

Analysis and interpretation of the data: P.J. Molloy, S.R. Telford, H.R. Chowdri, J.L. Gugliotta, H.K. Goethert, V.P. Berardi.

Drafting of the article: P.J. Molloy, S.R. Telford, H.R. Chowdri, J.L. Gugliotta, H.K. Goethert.

Critical revision of the article for important intellectual content: P.J. Molloy, S.R. Telford, H.R. Chowdri, H.K. Goethert, V.P. Berardi.

Final approval of the article: P.J. Molloy, S.R. Telford, H.R. Chowdri, J.L. Gugliotta, H.K. Goethert.

Provision of study materials or patients: P.J. Molloy, H.R. Chowdri, T.J. Lepore, J.L. Gugliotta.

Statistical expertise: S.R. Telford.

Administrative, technical, or logistic support: M.E. Hewins, H.K. Goethert, V.P. Berardi.

Collection and assembly of data: P.J. Molloy, H.R. Chowdri, T.J. Lepore, J.L. Gugliotta, K.E. Weeks, M.E. Hewins, H.K. Goethert.


Ann Intern Med. 2015;163(2):91-98. doi:10.7326/M15-0333
Text Size: A A A

Background: The first recognized cases of Borrelia miyamotoi disease (BMD) in North America were reported in the northeastern United States in 2013.

Objective: To further describe the clinical spectrum and laboratory findings for BMD.

Design: Case series.

Setting: Patients presenting to primary care offices, emergency departments, or urgent care clinics in 2013 and 2014.

Participants: Acutely febrile patients from the northeastern United States in whom the treating health care providers suspected and ordered testing for tick-transmitted infections.

Measurements: Whole-blood polymerase chain reaction (PCR) testing was performed for the presence of specific DNA sequences of common tickborne infections (including BMD). Serologic testing for B. miyamotoi was performed using a recombinant glycerophosphodiester phosphodiesterase (rGlpQ) protein. Clinical records were analyzed to identify the major features of acute disease.

Results: Among 11 515 patients tested, 97 BMD cases were identified by PCR. Most of the 51 case patients on whom clinical histories were reviewed presented with high fever, chills, marked headache, and myalgia or arthralgia. Twenty-four percent were hospitalized. Elevated liver enzyme levels, neutropenia, and thrombocytopenia were common. At presentation, 16% of patients with BMD were seropositive for IgG and/or IgM antibody to B. miyamotoi rGlpQ. Most (78%) had seropositive convalescent specimens. Symptoms resolved after treatment with doxycycline, and no chronic sequelae or symptoms were observed.

Limitation: Findings were based on specimens submitted for testing to a reference laboratory, and medical records of only 51 of the 97 case patients with BMD were reviewed.

Conclusion: Patients with BMD presented with nonspecific symptoms, including fever, headache, chills, myalgia, and arthralgia. Laboratory confirmation of BMD was possible by PCR on blood from acutely symptomatic patients who were seronegative at presentation. Borrelia miyamotoi disease may be an emerging tickborne infection in the northeastern United States.

Primary Funding Source: IMUGEN.

Figures

Grahic Jump Location
Figure 1.

Seasonal distribution of acute Borrelia miyamotoi incident infections.

The months of acute blood collection are presented for 97 samples submitted in 2013–2014 that were determined by active case detection or retrospectively to contain B. miyamotoi DNA.

Grahic Jump Location
Grahic Jump Location
Figure 2.

Acute and convalescent antibody responses to rGlpQ in sera from Borrelia miyamotoi incident infections, expressed as kinetic OD ratios.

The shaded area indicates nonreactivity. OD = optical density; rGlpQ = recombinant glycerophosphodiester phosphodiesterase.

Grahic Jump Location

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