Persistent Symptoms, Lyme Disease, and Prior Trauma

2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Fayel Mustafiz ◽  
James Moeller ◽  
Maria Kuvaldina ◽  
Clair Bennett ◽  
Brian A. Fallon
Keyword(s):  
Lyme Disease ◽  
Persistent Symptoms ◽  
Prior Trauma

scholarly journals Expectancies as predictors of symptom improvement after antimicrobial therapy for persistent symptoms attributed to Lyme disease

2021 ◽  
Author(s):  
Henriët van Middendorp ◽  
Anneleen Berende ◽  
Fidel J. Vos ◽  
Hadewych H. M. ter Hofstede ◽  
Bart Jan Kullberg ◽  
...  
Keyword(s):  
Lyme Disease ◽  
Treatment Success ◽  
Symptomatic Improvement ◽  
Post Treatment ◽  
Symptom Improvement ◽  
Persistent Symptoms ◽  
Treatment Expectancies ◽  
End Of Treatment ◽  
Pre Treatment

Abstract Introduction/Objective Expectancies about symptom improvement or deterioration are reliable predictors of symptom progression and treatment outcomes (symptom resolution or symptomatic improvement) in many (non-)pharmacological studies and treatments. This study examined predictors of symptom improvement after antimicrobial therapy for persistent symptoms attributed to Lyme disease, hypothesizing particularly pre-treatment expectancies regarding symptom improvement to be predictive. Methods A predictive study was performed on pre-treatment and post-treatment individual characteristics, including expectancies, and physical and mental health–related quality of life (HRQoL) from the PLEASE-trial comparing randomized 12-weeks of doxycycline, clarithromycin-hydroxychloroquine, or placebo following 2 weeks of intravenous ceftriaxone. At end-of-treatment (14 weeks after trial start) and follow-up (52 weeks), complete data of 231 and 170 (of initial 280) patients with persistent symptoms temporally related to a history of erythema migrans or otherwise confirmed symptomatic Lyme disease, or accompanied by B. burgdorferi IgG or IgM antibodies, were examined through hierarchical regression analyses. Results In addition to pre-treatment HRQoL, pre-treatment expectancies regarding symptom improvement were consistently associated with stronger physical and mental HRQoL improvements at both end-of-treatment and follow-up (95% CI range: .09;.54, p < .01 to .27;.92, p < .001). Post-treatment expectancies regarding having received antibiotics vs. placebo was associated with more HRQoL improvement at end-of-treatment, but not at follow-up (95% CI-range 1.00;4.75, p = .003 to −7.34; −2.22, p < .001). Conclusions The present study shows that, next to pre-treatment functioning, patients’ pre-treatment and post-treatment expectancies regarding improvement of persistent symptoms attributed to Lyme disease relate to a more beneficial symptom course. Expectancies of patients may be relevant to explain and potentially improve patient outcomes (e.g., by optimized communication about treatment success). Trial registration ClinicalTrials.gov, NCT01207739 (Registration date: 23–09-2010) Key Points• As there is currently no sufficient symptom resolution or symptomatic improvement for many patients with persistent symptoms attributed to Lyme disease, it is relevant to know which factors determine symptom progression and predict heterogeneity in treatment response.• Next to pre-treatment functioning, expectancies regarding symptom improvement and having received antimicrobial study medication are associated with a more beneficial symptom course after both shorter-term and longer-term antimicrobial treatment.• Expectancies are relevant to consider in treatment studies and may be useful in clinical settings to improve symptom course and treatment outcome (e.g., by optimized communication about treatment success).

scholarly journals A comprehensive clinical and laboratory evaluation of 224 patients with persistent symptoms attributed to presumed tick-bite exposure

PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0247384
Author(s):  
Kenneth Nilsson ◽  
Elisabet Skoog ◽  
Viktor Jones ◽  
Lisa Labbé Sandelin ◽  
Christina Björling ◽  
...  
Keyword(s):  
Lyme Disease ◽  
The Other ◽  
University Hospital ◽  
Tick Bite ◽  
Laboratory Evaluation ◽  
Disease Course ◽  
Swedish Population ◽  
Persistent Symptoms ◽  
Chronic Lyme Disease ◽  
Multifactorial Approach

BackgroundPersistent symptoms attributed to presumed tick-bite exposure constitute an unresolved medical controversy. We evaluated whether Swedish adults who met the criteria for post-treatment Lyme disease syndrome (PTLDS) exhibited characteristics distinguishable from adults who did not, but who displayed similar symptoms and disease course after suspected previous tick-bite infection (TBI).Methods and findingsDuring 2015–2018, 255 patients–referred to the Centre for Vector-borne Infections, Uppsala University Hospital, Sweden with symptoms lasting longer than six months–were recruited. Of this group, 224 completed the study. Each patient was examined by an infectious disease specialist and, besides a full medical history, underwent a panel of blood and cerebrospinal fluid laboratory tests including hematological, biochemical, microbiological and immunological analyses, and the RAND-36 scale to measure quality of life. For analysis purposes, patients were divided into five subgroups, of which one represented PTLDS. According to serological results indicating TBI and documented/ reported objective signs of Lyme disease, 85 (38%) patients fulfilled the criteria for PTLDS and were compared with the other 139 (62%) serologically classified patients. In the PTLDS group, erythema chronicum migrans (ECM) was documented/reported in 86% of patients, previous neuroborreliosis in 15%, and acrodermatitis chronica atroficans (ACA) in 3.5%. However, there were no significant differences regarding symptoms, laboratory results or disease course between patients with PTLDS and those without laboratory evidence ofBorreliaexposition. Most reported symptoms were fatigue-related (70%), musculoskeletal (79%), neurological (82%) and neurocognitive (57%). Tick bites were recalled by 74%. The RAND-36 score was significantly below that of the general Swedish population. Signs of immunological/inflammatory reactivity with myositis antibodies were detected in 20% of patients, fibrinogen levels were moderately increased in 21% and elevated rheumatoid factor in 6%.ConclusionsThe PTLDS group did not differ exclusively in any respect from the other subgroups, which either lacked previously documented/reported evidence of borreliosis or even lacked detectable serological signs of exposure to Lyme disease. The results suggest that symptoms often categorized as Chronic-Lyme-Disease (CLD) in the general debate, cannot be uniquely linked to Lyme disease. However, approximately 20% of the total group of patients showed signs of autoimmunity. Further studies are needed to elucidate the underlying causes and mechanisms of PTLDS and there is reason to consider a multifactorial approach.

scholarly journals Predicting Lyme Disease From Patients' Peripheral Blood Mononuclear Cells Profiled With RNA-Sequencing

2021 ◽  
Vol 12 ◽  
Author(s):  
Daniel J. B. Clarke ◽  
Alison W. Rebman ◽  
Allison Bailey ◽  
Megan L. Wojciechowicz ◽  
Sherry L. Jenkins ◽  
...  
Keyword(s):  
Lyme Disease ◽  
Rna Sequencing ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Enrichment Analysis ◽  
Peripheral Blood Mononuclear ◽  
Deconvolution Analysis ◽  
Persistent Symptoms ◽  
Blood Mononuclear Cells

Although widely prevalent, Lyme disease is still under-diagnosed and misunderstood. Here we followed 73 acute Lyme disease patients and uninfected controls over a period of a year. At each visit, RNA-sequencing was applied to profile patients' peripheral blood mononuclear cells in addition to extensive clinical phenotyping. Based on the projection of the RNA-seq data into lower dimensions, we observe that the cases are separated from controls, and almost all cases never return to cluster with the controls over time. Enrichment analysis of the differentially expressed genes between clusters identifies up-regulation of immune response genes. This observation is also supported by deconvolution analysis to identify the changes in cell type composition due to Lyme disease infection. Importantly, we developed several machine learning classifiers that attempt to perform various Lyme disease classifications. We show that Lyme patients can be distinguished from the controls as well as from COVID-19 patients, but classification was not successful in distinguishing those patients with early Lyme disease cases that would advance to develop post-treatment persistent symptoms.

scholarly journals Evaluation of Disulfiram Drug Combinations and Identification of Other More Effective Combinations against Stationary Phase Borrelia burgdorferi

Antibiotics ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 542 ◽  
Author(s):  
Hector Alvarez-Manzo ◽  
Yumin Zhang ◽  
Wanliang Shi ◽  
Ying Zhang
Keyword(s):  
Lyme Disease ◽  
Borrelia Burgdorferi ◽  
Stationary Phase ◽  
Drug Exposure ◽  
Drug Combinations ◽  
Persistent Symptoms ◽  
Exposure Experiment ◽  
Vector Borne ◽  
Treatment Alternatives ◽  
Possible Cause

Lyme disease, caused by Borrelia burgdorferi, is the most common vector-borne disease in USA, and 10–20% of patients will develop persistent symptoms despite treatment (“post-treatment Lyme disease syndrome”). B. burgdorferi persisters, which are not killed by the current antibiotics for Lyme disease, are considered one possible cause. Disulfiram has shown to be active against B. burgdorferi, but its activity against persistent forms is not well characterized. We assessed disulfiram as single drug and in combinations against stationary-phase B. burgdorferi culture enriched with persisters. Disulfiram was not very effective in the drug exposure experiment (survival rate (SR) 46.3%) or in combinations. Clarithromycin (SR 41.1%) and nitroxoline (SR 37.5%) were equally effective when compared to the current Lyme antibiotic cefuroxime (SR 36.8%) and more active than disulfiram. Cefuroxime + clarithromycin (SR 25.9%) and cefuroxime + nitroxoline (SR 27.5%) were significantly more active than cefuroxime + disulfiram (SR 41.7%). When replacing disulfiram with clarithromycin or nitroxoline in three-drug combinations, bacterial viability decreased significantly and subculture studies showed that combinations with these two drugs (cefuroxime + clarithromycin/nitroxoline + furazolidone/nitazoxanide) inhibited the regrowth, while disulfiram combinations did not (cefuroxime + disulfiram + furazolidone/nitazoxanide). Thus, clarithromycin and nitroxoline should be further assessed to determine their role as potential treatment alternatives in the future.

scholarly journals Update on persistent symptoms associated with Lyme disease

2015 ◽  
Vol 27 (1) ◽  
pp. 100-104 ◽  
Author(s):  
Carlos R. Oliveira ◽  
Eugene D. Shapiro
Keyword(s):  
Lyme Disease ◽  
Persistent Symptoms

scholarly journals Development and Validation of a Serologic Test Panel for Detection of Powassan Virus Infection in U.S. Patients Residing in Regions Where Lyme Disease Is Endemic

mSphere ◽  
2018 ◽  
Vol 3 (1) ◽  
Author(s):  
Angela M. Thomm ◽  
Anna M. Schotthoefer ◽  
Alan P. Dupuis ◽  
Laura D. Kramer ◽  
Holly M. Frost ◽  
...  
Keyword(s):  
Lyme Disease ◽  
Virus Infection ◽  
Clinical Symptoms ◽  
Diagnostic Testing ◽  
Chronic Fatigue ◽  
The United States ◽  
Full Spectrum ◽  
Persistent Symptoms ◽  
Powassan Virus ◽  
Tick Borne Disease

Approximately 100 cases of POWV disease were reported in the United States over the past 10 years. Most cases have occurred in the Northeast (52) and Great Lakes (45) regions (https://www.cdc.gov/powassan/statistics.html). The prevalence of POWV in ticks and mammals is increasing, and POWV poses an increasing threat in a greater geographical range. In areas of the Northeast and Midwest where Lyme disease is endemic, POWV testing is recommended for patients with a recent tick bite, patients with Lyme disease who have been treated with antibiotics, or patients with a tick exposure who have tested negative for Lyme disease or other tick-borne illnesses and have persistent symptoms consistent with posttreatment Lyme disease. Testing could also benefit patients with tick exposure and unexplained neurologic symptoms and chronic fatigue syndrome (CFS) patients with known tick exposure. Until now, diagnostic testing for Powassan virus has not been commercially available and has been limited to patients presenting with severe, neurologic complications. The lack of routine testing for Powassan virus in patients with suspected tick-borne disease means that little information is available regarding the overall prevalence of the virus and the full spectrum of clinical symptoms associated with infection. AsIxodes scapularisis the tick vector for Powassan virus and multiple other tick-borne pathogens, including the Lyme disease bacterium,Borrelia burgdorferi, the clinical presentations and long-term outcomes of Powassan virus infection and concurrent infection with other tick-borne disease pathogens remain unknown.

Antibiotic retreatment of Lyme disease in patients with persistent symptoms: A biostatistical review of randomized, placebo-controlled, clinical trials

2012 ◽  
Vol 33 (6) ◽  
pp. 1132-1142 ◽  
Author(s):  
Allison K. DeLong ◽  
Barbara Blossom ◽  
Elizabeth L. Maloney ◽  
Steven E. Phillips
Keyword(s):  
Clinical Trials ◽  
Lyme Disease ◽  
Controlled Clinical Trials ◽  
Persistent Symptoms

scholarly journals Recent Progress in Lyme Disease and Remaining Challenges

2021 ◽  
Vol 8 ◽  
Author(s):  
Jason R. Bobe ◽  
Brandon L. Jutras ◽  
Elizabeth J. Horn ◽  
Monica E. Embers ◽  
Allison Bailey ◽  
...  
Keyword(s):  
United States ◽  
Lyme Disease ◽  
Molecular Mechanisms ◽  
The United States ◽  
Persistent Symptoms ◽  
Number Of Patients ◽  
Vector Borne ◽  
The Many ◽  
Long Term Impact ◽  
Patients Experience

Lyme disease (also known as Lyme borreliosis) is the most common vector-borne disease in the United States with an estimated 476,000 cases per year. While historically, the long-term impact of Lyme disease on patients has been controversial, mounting evidence supports the idea that a substantial number of patients experience persistent symptoms following treatment. The research community has largely lacked the necessary funding to properly advance the scientific and clinical understanding of the disease, or to develop and evaluate innovative approaches for prevention, diagnosis, and treatment. Given the many outstanding questions raised into the diagnosis, clinical presentation and treatment of Lyme disease, and the underlying molecular mechanisms that trigger persistent disease, there is an urgent need for more support. This review article summarizes progress over the past 5 years in our understanding of Lyme and tick-borne diseases in the United States and highlights remaining challenges.

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