scholarly journals Post-treatment Lyme Disease as a Model for Persistent Symptoms in Lyme Disease

2020 ◽  
Vol 7 ◽  
Author(s):  
Alison W. Rebman ◽  
John N. Aucott
Author(s):  
Henriët van Middendorp ◽  
Anneleen Berende ◽  
Fidel J. Vos ◽  
Hadewych H. M. ter Hofstede ◽  
Bart Jan Kullberg ◽  
...  

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).


mBio ◽  
2016 ◽  
Vol 7 (1) ◽  
Author(s):  
Jerome Bouquet ◽  
Mark J. Soloski ◽  
Andrea Swei ◽  
Chris Cheadle ◽  
Scot Federman ◽  
...  

ABSTRACT Lyme disease is a tick-borne illness caused by the bacterium Borrelia burgdorferi , and approximately 10 to 20% of patients report persistent symptoms lasting months to years despite appropriate treatment with antibiotics. To gain insights into the molecular basis of acute Lyme disease and the ensuing development of post-treatment symptoms, we conducted a longitudinal transcriptome study of 29 Lyme disease patients (and 13 matched controls) enrolled at the time of diagnosis and followed for up to 6 months. The differential gene expression signature of Lyme disease following the acute phase of infection persisted for at least 3 weeks and had fewer than 44% differentially expressed genes (DEGs) in common with other infectious or noninfectious syndromes. Early Lyme disease prior to antibiotic therapy was characterized by marked upregulation of Toll-like receptor signaling but lack of activation of the inflammatory T-cell apoptotic and B-cell developmental pathways seen in other acute infectious syndromes. Six months after completion of therapy, Lyme disease patients were found to have 31 to 60% of their pathways in common with three different immune-mediated chronic diseases. No differential gene expression signature was observed between Lyme disease patients with resolved illness to those with persistent symptoms at 6 months post-treatment. The identification of a sustained differential gene expression signature in Lyme disease suggests that a panel of selected human host-based biomarkers may address the need for sensitive clinical diagnostics during the “window period” of infection prior to the appearance of a detectable antibody response and may also inform the development of new therapeutic targets. IMPORTANCE Lyme disease is the most common tick-borne infection in the United States, and some patients report lingering symptoms lasting months to years despite antibiotic treatment. To better understand the role of the human host response in acute Lyme disease and the development of post-treatment symptoms, we conducted the first longitudinal gene expression (transcriptome) study of patients enrolled at the time of diagnosis and followed up for up to 6 months after treatment. Importantly, we found that the gene expression signature of early Lyme disease is distinct from that of other acute infectious diseases and persists for at least 3 weeks following infection. This study also uncovered multiple previously undescribed pathways and genes that may be useful in the future as human host biomarkers for diagnosis and that constitute potential targets for the development of new therapies.


2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S403-S403
Author(s):  
Kalpana D Shere-Wolfe ◽  
Rachel Silk ◽  
Carla Alexander

Abstract Background Controversy and confusion surround the terminology for patients who have persistent symptoms after treatment for Lyme disease (LD) or may have been misdiagnosed with Lyme disease. While Infectious Diseases (ID) use the term Post treatment Lyme disease syndrome (PTLDS), patients tend to use the term Chronic Lyme disease (CLD) to describe the syndrome associated with persistent symptoms post treatment of LD. Many ID physicians are reluctant to see patients who identify themselves as having “Chronic Lyme” disease in some part due to reluctance to prescribe repeated courses of antibiotics. The purpose of this inquiry was to assess belief regarding Lyme disease and treatment. Methods Patients at the Integrated Lyme Program at the University of Maryland completed clinical intake forms which included questions on their familiarity and beliefs surrounding Lyme disease. Results We evaluated 146 patient records from our Lyme Program Registry which began in December 2018. There were 57 (34.5%) males and 108 (65.5%)females with mean age of 51 years. Forty seven percentage of patients were referred by a physician and 53 % were self-referred. Approximately 50% (71/146) were treated with less 30 days of antibiotics, 37% (54/146) were treated with 1-6 months of antibiotics and 11.6% (17/146) were treated with &gt;6months of antibiotics prior to their initial evaluation in our Lyme program. Sixty eight percentage of patients were familiar with the term CLD but only 44% percentage were familiar with term PTLDS. Approximately half of the patients ( 52%) believed that they currently had Lyme disease and 63% believed that their current symptoms were due to Lyme disease. Despite this only 18% believed that they needed antibiotics for Lyme disease at the time completing the form. Conclusion Patient referred to our Lyme center were more familiar with term CLD vs PTLDS. Many of them believed that they currently had LD and their symptoms were due to Lyme disease. Despite this, the majority did not feel that they needed antibiotics for Lyme Disease at the time of their clinical visit. More research is needed to better understand patient beliefs and understanding regarding Lyme disease. Disclosures All Authors: No reported disclosures


2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Fayel Mustafiz ◽  
James Moeller ◽  
Maria Kuvaldina ◽  
Clair Bennett ◽  
Brian A. Fallon

PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0247384
Author(s):  
Kenneth Nilsson ◽  
Elisabet Skoog ◽  
Viktor Jones ◽  
Lisa Labbé Sandelin ◽  
Christina Björling ◽  
...  

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.


2021 ◽  
Vol 12 ◽  
Author(s):  
Daniel J. B. Clarke ◽  
Alison W. Rebman ◽  
Allison Bailey ◽  
Megan L. Wojciechowicz ◽  
Sherry L. Jenkins ◽  
...  

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.


2018 ◽  
Vol 66 (2) ◽  
pp. 445-451
Author(s):  
Maria Elena Di Battista ◽  
Carola Dell’Acqua ◽  
Luciana Baroni ◽  
Chiara Fenoglio ◽  
Daniela Galimberti ◽  
...  

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