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Chronic Lyme

Neuropathogenicity of non-viable Borrelia burgdorferi ex vivo
Parthasarathy G, Gadila SKG. Neuropathogenicity of non-viable Borrelia burgdorferi ex vivo. Sci Rep. 2022 Jan 13;12(1):688. doi: 10.1038/s41598-021-03837-0. PMID: 35027599; PMCID: PMC8758786.
“As neuroinflammation is the basis of many neurological disorders, lingering inflammation in the brain due to these unresolved fragments could cause long term health consequences,” Parthasarathy said.

  • Some patients with Lyme disease continue to experience symptoms even after treatment, a condition known as Post-Treatment Lyme Disease Syndrome (PTLDS).
  • Brain scans show that PTLDS likely have glial activation which indicates persistent neuroinflammatory processes.
  • They discovered that these remnants triggered high levels of inflammation, sometimes even more than live bacteria, particularly for certain inflammatory markers like IL-6, CXCL8, and CCL2. The response was stronger in brain tissue compared to nerve tissue.
Lyme Borreliosis and Associations With Mental Disorders and Suicidal Behavior: A Nationwide Danish Cohort Study

Lyme Borreliosis and Associations With Mental Disorders and Suicidal Behavior: A Nationwide Danish Cohort Study. Brian A. Fallon, M.D., M.P.H., Trine Madsen, Ph.D., Annette Erlangsen, Ph.D., Michael E. Benros, M.D., Ph.D. Published Online:28 Jul 2021 https://doi.org/10.1176/appi.ajp.2021.20091347

“Having more than one episode of Lyme borreliosis was associated with increased incidence rate ratios for mental disorders, affective disorders, and suicide attempts, but not for death by suicide. Individuals diagnosed with Lyme borreliosis in the hospital setting had an increased risk of mental disorders, affective disorders, suicide attempts, and suicide. Although the absolute population risk is low, clinicians should be aware of potential psychiatric sequelae of this global disease.”

Depressive Symptoms and Suicidal Ideation Among Symptomatic Patients With a History of Lyme Disease vs Two Comparison Groups
Doshi S, Keilp JG, Strobino B, McElhiney M, Rabkin J, Fallon BA. Depressive Symptoms and Suicidal Ideation Among Symptomatic Patients With a History of Lyme Disease vs Two Comparison Groups. Psychosomatics. 2018 Sep-Oct;59(5):481-489. doi: 10.1016/j.psym.2018.02.004. Epub 2018 Mar 1. PMID: 29606281; PMCID: PMC6119532.

The study reveals that depression is reported in 8-45% of post-treatment Lyme disease syndrome (PTLDS) patients, with limited knowledge of suicidal tendencies. A comparison of depression and suicidality between PTLDS, HIV/AIDS patients, and a non-patient group shows a significant increase in suicidal tendencies among depressed individuals. Depression levels in PTLDS and HIV/AIDS patients are statistically similar. The study emphasizes that one in five PTLDS patients reported suicidal thoughts, underscoring the need for screening depression and suicidality to enhance patient care.

Borrelia burgdorferi adhere to blood vessels in the dura mater and are associated with increased meningeal T cells during murine disseminated borreliosis

li Divan, Timothy Casselli, S. Anand Narayanan, Sanjib Mukherjee, David C. Zawieja, John A. Watt, Catherine A. Brissette, M. Karen Newell-Rogers, Published: May 3, 2018. https://doi.org/10.1371/journal.pone.0196893

Traditionally, mice haven’t shown neuroborreliosis, mirroring human symptoms, but this study achieved colonization of the central nervous system in mice. Using two strains of B. burgdorferi, researchers infected mice through the skin, consistently detecting spirochetes in the brain membranes 75 days post-infection. Live spirochetes were present, adhering to blood vessels, indicating long-term infection. The presence of CD3+ T cells suggested an immune response. These findings provide new avenues for studying neuroborreliosis and may offer insights into potential treatments for patients.

Expression of C-Reactive Protein and Serum Amyloid A in Early to Late Manifestations of Lyme Disease
Uhde M, Ajamian M, Li X, Wormser GP, Marques A, Alaedini A. Expression of C-Reactive Protein and Serum Amyloid A in Early to Late Manifestations of Lyme Disease. Clin Infect Dis. 2016 Dec 1;63(11):1399-1404. doi: 10.1093/cid/ciw599. Epub 2016 Sep 1. PMID: 27585799; PMCID: PMC5106611.

The immune response to invasive microbes involves two main components: the innate and adaptive response. C-reactive protein (CRP) and serum amyloid A (SAA) are proteins elevated during inflammation. In Lyme disease, CRP is elevated in early stages with erythema migrans but normal in neurological symptoms and arthritis. However, post-treatment Lyme disease syndrome (PTLDS) shows higher CRP, indicating persistent inflammation. SAA is elevated only in patients with erythema migrans. These findings suggest that lingering symptoms post-antibiotic therapy in Lyme disease are associated with elevated CRP, warranting further study on long-term inflammatory processes.

Correlates of Perceived Health-Related Quality of Life in Post-Treatment Lyme Encephalopathy
Chandra AM, Keilp JG, Fallon BA. Correlates of perceived health-related quality of life in post-treatment Lyme encephalopathy. Psychosomatics. 2013 Nov-Dec;54(6):552-9. doi: 10.1016/j.psym.2013.04.003. Epub 2013 Jul 9. PMID: 23845316; PMCID: PMC5507690.

A significant portion of Lyme disease-treated patients experiences persistent symptoms for months or even years, including pain, fatigue, and neurocognitive issues, collectively referred to as post-treatment Lyme disease syndrome. Determining whether ongoing infection is present remains challenging with current technology, raising an open question. Alternatively, a post-infectious immune-mediated process could be responsible for sustained symptoms.

As fatigue and depression significantly impact the reported decline in both physical and mental functioning in patients with PTLDS, clinicians should thoroughly evaluate these symptoms. It is advisable to consider addressing these issues when selecting treatment interventions. Subsequent controlled studies should investigate the efficacy of such approaches for patients dealing with PTLDS.

Increased IFNα Activity and Differential Antibody Response in Patients with a History of Lyme Disease and Persistent Cognitive Deficits
Jacek E, Fallon BA, Chandra A, Crow MK, Wormser GP, Alaedini A. Increased IFNα activity and differential antibody response in patients with a history of Lyme disease and persistent cognitive deficits. J Neuroimmunol. 2013 Feb 15;255(1-2):85-91. doi: 10.1016/j.jneuroim.2012.10.011. Epub 2012 Nov 8. PMID: 23141748; PMCID: PMC3557545.
The increase in IFNα activity is suggestive of a mechanism contributing to the ongoing neuropsychiatric symptoms.
Clinical and diagnostic manifestations of tickborne mixed infection in combination with COVID-19
Shutikova AL, Leonova GN, Popov AF, Shchelkanov MY. Clinical and diagnostic manifestations of tickborne mixed infection in combination with COVID-19. Klin Lab Diagn. 2021 Nov 29;66(11):689-694. English. doi: 10.51620/0869-2084-2021-66-11-689-694. PMID: 34882355.
  • The study investigated the coexistence of pathogens in a patient, focusing on the relationship between laboratory diagnostics and clinical manifestations during SARS-CoV-2 infection in a case of chronic encephalitis-borreliosis.
  • Blood samples collected over a year revealed Lyme disease diagnosed through IgG antibodies to Borrelia, with joint pain and erythema migrans. Subsequently, the patient contracted SARS-CoV-2 during a Lyme disease exacerbation.
  • Treatment improved the underlying disease but led to TBEV activation, possibly due to immune system focus on SARS-CoV-2. Despite TBEV activation, clinical manifestations were absent, suggesting weak virulence. Etiotropic treatment suppressing borreliosis led to TBEV activation, highlighting the dominance of B. burgdorferi in tick-borne infections.