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Updated: Jun 28, 2025

Author Spotlight: Controlled Human Exposure Model for Tick Research and Lyme Disease Studies
Published on: December 1, 2023
Emerging Tick-borne Infections in the Upper Midwest and Northeast United States Among Patients With Suspected
Megan E Reller1, Emily G Clemens1,2,3, Johan S Bakken2
1Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Background:
Emerging tick-transmitted illnesses are increasingly recognized in the United States (US). To identify multiple potential tick-borne pathogens in patients from the Upper Midwest and Northeast US with suspected anaplasmosis, we used state-of-the-art methods (polymerase chain reaction [PCR] and paired serology) to test samples from patients in whom anaplasmosis had been excluded.
Methods:
Five hundred sixty-eight patients without anaplasmosis had optimal samples available for confirmation of alternative tick-borne pathogens, including PCR and/or paired serology (acute-convalescent interval ≤42 days).
Results:
Among 266 paired serology evaluations, for which the median acute-convalescent sampling interval was 28 (interquartile range, 21-33) days, we identified 35 acute/recent infections (24 [9%] Borrelia burgdorferi; 6 [2%] Ehrlichia chaffeensis/Ehrlichia muris subsp eauclairensis [EC/EME]; 3 [1%] spotted fever group rickettsioses [SFGR], and 2 [<1%] Babesia microti) in 33 (12%) patients. Two had concurrent or closely sequential infections (1 B burgdorferi and EC/EME, and 1 B burgdorferi and SFGR). Using multiplex PCR and reverse-transcription PCR, we identified 7 acute infections (5/334 [1%] Borrelia miyamotoi and 2/334 [1%] B microti) in 5 (1%) patients, including 2 with B microti-B miyamotoi coinfection, but no Borrelia mayonii, SFGR, Candidatus Anaplasma capra, Heartland virus, or Powassan virus infections. Thus, among 568 patients with ruled-out anaplasmosis, 38 (6.7%) had ≥1 agent of tick-borne illness identified, with 33 patients (35 infections) diagnosed by paired serology and 5 additional patients (7 infections) by PCR.
Conclusions:
By identifying other tick-borne agents in patients in whom anaplasmosis had been excluded, we demonstrate that emerging tick-borne infections will be identified if specifically sought.
Insights
Emerging tick-borne illnesses are a growing concern. Testing patients negative for anaplasmosis revealed other tick-borne pathogens, highlighting the need for comprehensive diagnostics.
Area of Science:
- Medical Entomology
- Infectious Diseases
- Molecular Diagnostics
Background:
- Tick-transmitted illnesses are increasingly recognized in the United States.
- Anaplasmosis is a significant tick-borne disease, but other pathogens can cause similar symptoms.
Purpose of the Study:
- To identify alternative tick-borne pathogens in patients from the Upper Midwest and Northeast US with suspected anaplasmosis, after anaplasmosis was excluded.
- To evaluate the utility of advanced diagnostic methods for detecting a range of tick-borne agents.
Main Methods:
- Utilized polymerase chain reaction (PCR) and paired serology on samples from 568 patients.
- Samples were from patients with suspected anaplasmosis but negative results for the disease.
- Acute-convalescent serum intervals were analyzed, with a median of 28 days.
Main Results:
- Identified 35 infections in 33 patients via serology, including Borrelia burgdorferi, Ehrlichia chaffeensis/Ehrlichia muris subsp eauclairensis, spotted fever group rickettsioses, and Babesia microti.
- Detected 7 infections in 5 patients via PCR, including Borrelia miyamotoi and B. microti, with two coinfections.
- Overall, 38 patients (6.7%) had at least one tick-borne agent identified.
Conclusions:
- Tick-borne infections other than anaplasmosis are frequently identified in patients with suspected anaplasmosis.
- Comprehensive diagnostic approaches are crucial for recognizing emerging tick-borne diseases.
- Specific testing for a broader range of tick-borne pathogens is warranted.

