Persistent Lyme Disease: Evidence for Ongoing Infection and Symptoms
Persistent symptoms remain a major clinical challenge
Researchers continue to debate the causes of ongoing illness
Studies are investigating persistent infection and other mechanisms
Persistent Lyme disease remains one of the most debated topics in medicine. Some researchers believe persistent symptoms primarily reflect immune or inflammatory changes after infection, while others propose that persistent Borrelia infection may explain ongoing illness in at least a subset of patients. Laboratory, animal, and clinical studies continue to investigate these competing hypotheses.
Several National Institutes of Health (NIH)-funded clinical trials enrolled patients with persistent symptoms lasting months or years after standard antibiotic treatment.2-4 These studies demonstrated that some participants remained significantly ill despite previous antibiotic therapy. Participants reported severe fatigue, impaired cognitive function, chronic pain, and reduced quality of life. In one trial, patients had been ill for an average of approximately 9 years before enrollment.5
Across these NIH-sponsored studies, persistent symptoms following treatment highlighted that standard antibiotic therapy does not eliminate illness in every patient.2-5 The reasons remain an area of ongoing investigation and debate. Proposed explanations include persistent infection, immune dysregulation, residual tissue injury, autoimmunity, co-infections, and other biological mechanisms.
Some physicians have dismissed the possibility that a persistent tick-borne infection contributes to chronic illness,6 while others believe that persistent Borrelia infection may explain ongoing symptoms in at least some patients.7
Shor and colleagues summarized several biologically plausible mechanisms that could contribute to persistent Borrelia infection.7
“Potential survival mechanisms of Lyme disease persistence include immune evasion, immune modulation, and the presence of subpopulations of persister cells. Physical seclusion—within cells, collagen-rich tissues, and immunologically protected sites (CNS, joints, and eyes)—is one method of immune evasion. Biofilm generation is another recognized form of physical seclusion. Published reports document that Borrelia burgdorferi can produce biofilm in vitro and examination of infected human tissues demonstrated B. afzelii and B. burgdorferi embedded in biofilm.”7
Additional laboratory, animal, and human tissue studies have reported findings consistent with the persistence of Borrelia after antibiotic treatment, while other investigators interpret the available evidence differently. Continued research is needed to better define which patients, if any, harbor persistent infection and which mechanisms account for long-term symptoms.
For a broader discussion of persistent symptoms following treatment, see our guide to Post-Treatment Lyme Disease Syndrome (PTLDS). For proposed biological mechanisms, visit Persistent Lyme Disease Mechanisms. If you are wondering what recovery may look like, see Can You Recover From Lyme Disease?.
Editor’s perspective: Many patients with persistent symptoms report difficulty finding physicians willing to evaluate whether ongoing infection, immune dysfunction, co-infections, or other mechanisms may be contributing to their illness.
Frequently Asked Questions
Can Lyme disease remain in the body after antibiotics?
The possibility of persistent Borrelia infection remains controversial. Laboratory and animal studies have demonstrated persistence under some experimental conditions, while the significance of these findings in humans continues to be debated.
Can Lyme disease symptoms return years later?
Some patients experience symptoms months or years after treatment. Possible explanations include persistent infection, immune dysregulation, tissue injury, reinfection, or other medical conditions. Careful clinical evaluation is important.
Does persistent Lyme disease always mean active infection?
No. Experts disagree on the underlying mechanisms. Proposed explanations include persistent infection, immune-mediated inflammation, nervous system injury, persistent immune activation, or a combination of factors.
What evidence suggests Borrelia may persist after antibiotic treatment?
Evidence includes laboratory studies, animal models, human tissue studies, and clinical observations. Although these findings support continued investigation, experts differ in how they interpret the available data and its implications for patient care.
Clinical Takeaway
Persistent symptoms after Lyme disease remain an active area of scientific investigation. While experts continue to debate the underlying mechanisms, multiple clinical studies demonstrate that some patients remain significantly ill despite standard antibiotic treatment.
Future research into persistent infection, immune dysregulation, tissue injury, and related mechanisms will continue to refine how persistent Lyme disease is diagnosed and managed.
Related Articles
What Is Chronic Lyme Disease?
Persistent Lyme Disease Mechanisms
Post-Treatment Lyme Disease Syndrome (PTLDS)
Can You Recover From Lyme Disease?
References
- Logigian EL, Kaplan RF, Steere AC. Chronic neurologic manifestations of Lyme disease. N Engl J Med. 1990;323(21):1438-1444.
- Klempner MS, Hu LT, Evans J, et al. Two controlled trials of antibiotic treatment in patients with persistent symptoms and a history of Lyme disease. N Engl J Med. 2001;345(2):85-92.
- Krupp LB, Hyman LG, Grimson R, et al. Study and treatment of post-Lyme disease (STOP-LD): a randomized double-masked clinical trial. Neurology. 2003;60(12):1923-1930.
- Fallon BA, Keilp JG, Corbera KM, et al. A randomized, placebo-controlled trial of repeated IV antibiotic therapy for Lyme encephalopathy. Neurology. 2008;70(13):992-1003.
- Rebman AW, Aucott JN, Weinstein ER, Bechtold KT, Smith KC, Leonard L. Living in Limbo: Contested Narratives of Patients With Chronic Symptoms Following Lyme Disease. Qual Health Res. 2017;27(4):534-546.
- Wormser GP, McKenna D, Karmen CL, et al. Prospective Evaluation of the Frequency and Severity of Symptoms in Lyme Disease Patients With Erythema Migrans Compared With Matched Controls at Baseline, 6 Months, and 12 Months. Clin Infect Dis. 2020.
- Shor S, Green C, Szantyr B, et al. Chronic Lyme Disease: An Evidence-Based Definition by the ILADS Working Group. Antibiotics (Basel). 2019;8(4):269.
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
