Diagnostic parameters of modified two-tier testing in European patients with early Lyme disease

Abstract Modified two-tier testing (MTTT) for Lyme borreliosis (i.e. confirmation with an EIA instead of an immunoblot) has been shown to have improved sensitivity compared with standard two-tier testing (STTT) in samples from American patients, without losing specificity. The current study assesses the sensitivity and specificity of various algorithms of MTTT in European patients with erythema migrans (EM) as a model disease for early Lyme borreliosis, and in appropriate controls. Four different immunoassays were used in the first tier, followed by either an immunoblot or the C6-EIA, or were used as standalone single-tier test. These tests were performed on consecutively collected sera of 228 Dutch patients with physician-diagnosed EM in the setting of general practice, 231 controls from the general population, and 50 controls with potentially cross-reactive antibodies. All the variants of MTTT that were studied had significantly higher sensitivity compared with their equivalent STTT, while retaining comparable specificity. Within the MTTT algorithms, classifying equivocal results as positive yielded better diagnostic parameters than classifying equivocal results as negative. The best diagnostic parameters were found using the Enzygnost-2 assay in the first tier, followed by a C6-ELISA in the second tier (sensitivity 77.6%, 95% CI 71.7–82.9; specificity 96.1%, 95% CI 92.7–98.2). This algorithm performed significantly better than the equivalent STTT algorithm in terms of sensitivity (p < 0.001), while maintaining comparable specificity (population controls p = 0.617). Our results show that MTTT can be a useful tool for the serodiagnosis of European patients with early Lyme borreliosis.

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Geographical and genospecies distribution of Borrelia burgdorferi sensu lato DNA detected in humans in the USA

Journal of Medical Microbiology ◽

10.1099/jmm.0.073122-0 ◽

2014 ◽

Vol 63 (5) ◽

pp. 674-684 ◽

Cited By ~ 23

Author(s):

Kerry L. Clark ◽

Brian F. Leydet ◽

Clifford Threlkeld

Keyword(s):

Lyme Disease ◽

Borrelia Burgdorferi ◽

Skin Biopsy ◽

Lyme Borreliosis ◽

Erythema Migrans ◽

Skin Lesions ◽

Sensu Stricto ◽

Borrelia Burgdorferi Sensu Lato ◽

Southern States ◽

The Usa

The present study investigated the cause of illness in human patients primarily in the southern USA with suspected Lyme disease based on erythema migrans-like skin lesions and/or symptoms consistent with early localized or late disseminated Lyme borreliosis. The study also included some patients from other states throughout the USA. Several PCR assays specific for either members of the genus Borrelia or only for Lyme group Borrelia spp. (Borrelia burgdorferi sensu lato), and DNA sequence analysis, were used to identify Borrelia spp. DNA in blood and skin biopsy samples from human patients. B. burgdorferi sensu lato DNA was found in both blood and skin biopsy samples from patients residing in the southern states and elsewhere in the USA, but no evidence of DNA from other Borrelia spp. was detected. Based on phylogenetic analysis of partial flagellin (flaB) gene sequences, strains that clustered separately with B. burgdorferi sensu stricto, Borrelia americana or Borrelia andersonii were associated with Lyme disease-like signs and symptoms in patients from the southern states, as well as from some other areas of the country. Strains most similar to B. burgdorferi sensu stricto and B. americana were found most commonly and appeared to be widely distributed among patients residing throughout the USA. The study findings suggest that human cases of Lyme disease in the southern USA may be more common than previously recognized and may also be caused by more than one species of B. burgdorferi sensu lato. This study provides further evidence that B. burgdorferi sensu stricto is not the only species associated with signs and/or symptoms consistent with Lyme borreliosis in the USA.

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Scientific rationale for medical and preventive measures improvement in lyme disease endemic areas (based on the data of Udmurt Republic)

Kazan medical journal ◽

10.17816/kmj1961 ◽

2013 ◽

Vol 94 (4) ◽

pp. 517-522

Author(s):

N G Guznischeva ◽

A A Gilmanov ◽

I G Zakirov

Keyword(s):

Lyme Disease ◽

Lyme Borreliosis ◽

Preventive Measures ◽

Erythema Migrans ◽

Tick Bite ◽

Tick Bites ◽

Medical Aid ◽

Udmurt Republic ◽

Endemic Areas ◽

Scientific Rationale

Aim. To provide the scientific rationale for medical and preventive measures improvement in Lyme disease endemic areas. Methods. Epidemiologic and biostatistical analysis of preventive measures holding in Lyme disease endemic areas was performed. Results. A decrease in mean longstanding prevalence of Lyme borreliosis by 31.5% was observed in the Udmurt Republic since 1999 to 2010. The tick-invaded area has increased by 25%, there was an increase in a borrelia-harboring ticks rate by 34.6%. The number of patients seeking medical aid because of the tick bites has increased by 25.4%, which can be attributed to increased social awareness. 62.5% of patients diagnosed with Lyme borreliosis were over 41 years old, the rate of unemployed patients was 61.1%. High prevalence of Lyme borreliosis in peasants living in highly endemic areas (southern part of the Udmurt Republic) related to low medical aid appealability due to tick bites and therefore untimely medical preventive measures, was registered. The prevalence of erythema migrans-free disease has increased 4.3 times. Among the Lyme borreliosis forms associated with erythema migrans, the 1.6 times increase in multiple erythema prevalence was observed, with increase by 24 times in the areas of high disease prevalence. The most severe disease course was observed in patients over 61 years old with erythema migrans-free disease. A single oral dose of doxycycline should be used for disease prevention in all patients seeking medical aid because of the tick bite. Conclusion. The offered preventive algorithm for Lyme disease allowed to prevent the disease development in 99.7% of all cases, the economical efficacy of doxycycline prophylaxis counted on 1 borrelia-harboring tick bite was estimated as 20 400 rubles.

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Serological Follow-up of Patients with Erythema Migrans: Persistence of Antibody Response to Borrelia Burgdorferi in Lyme Disease Patients

European Journal of Inflammation ◽

10.1177/1721727x0300100204 ◽

2003 ◽

Vol 1 (2) ◽

pp. 73-77

Author(s):

I. Christova ◽

R. Komitova

Keyword(s):

Lyme Disease ◽

Antibody Response ◽

Treatment Failure ◽

Lyme Borreliosis ◽

Erythema Migrans ◽

Serum Samples ◽

Laboratory Examinations ◽

One Year ◽

Antibody Kinetics

The rate of seroconversion before treatment and antibody kinetics after treatment were analyzed and possible interpretations of serologic findings was proposed. Serum samples from 219 patients with Erythema migrans were tested by ELISA for antibodies against B. burgdorferi. Twenty-eight (28 %) to 55 % of the patients showed isolated IgM antibody response, 3–5 % showed isolated IgG response, 6–16 % showed concomitant IgM and IgG responses, and 24–63 % tested seronegative depending on number of days passed after the onset of Lyme borreliosis. One year after treatment, 38 % of the patients still had IgG response and 10% had IgM antibodies against B. burgdorferi. Furthermore, 4 of 106 seronegative patients revealed IgM response three months after treatment despite lack of signs or symptoms of active Lyme borreliosis. We concluded that persistence of antibody response is not indicative of treatment failure, although regular clinical and laboratory examinations, including PCR, should follow successful treatment.

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Epidemiology of Lyme Disease in a Highly Endemic European Zone

Medicina ◽

10.3390/medicina56030115 ◽

2020 ◽

Vol 56 (3) ◽

pp. 115 ◽

Cited By ~ 3

Author(s):

Agnė Petrulionienė ◽

Daiva Radzišauskienė ◽

Arvydas Ambrozaitis ◽

Saulius Čaplinskas ◽

Algimantas Paulauskas ◽

...

Keyword(s):

Lyme Disease ◽

Lyme Borreliosis ◽

Erythema Migrans ◽

Geographical Area ◽

Clinical Manifestations ◽

Communicable Diseases ◽

Urban Residents ◽

Tick Bites ◽

Wide Range ◽

Baseline Characteristics

Background and objective: Lyme disease, also known as Lyme borreliosis (LB), is a tick-borne infectious disease caused by the spirochete bacteria Borrelia. The risk of infection depends on the geographical area, ecological factors, and human behavior. Clinical manifestations of Lyme borreliosis have a wide range, but the most frequent clinical symptom, which is also a diagnostic symptom, is a skin rash called erythema migrans (EM). The disease is very common worldwide. In Lithuania, the disease frequency is 99.9 cases per 100,000 population (Centre for Communicable Diseases and AIDS, Lithuania, 2017). The main aim of this study was to obtain the baseline characteristics of the disease regarding the infected Lithuanian population. Materials and Methods: We analyzed data from the Centre for Communicable Diseases and AIDS about all Lyme disease (A69.2) diagnosed patients over a three-year period (from 2014 to 2016) in Lithuania. Results: In 2014–2016, 7424 (crude incidence rate 85.4) cases with LB were diagnosed in Lithuania. Most of them (4633 (62.4%)) were identified in women. Older people were more likely to suffer from LB. Urban residents were 2.6 times more often affected that those living in villages. Tick bites were primarily observed in high season months, from May to September (90%), with the highest peak in July. There was a higher number of observed tick bites (p = 0.003) in the urban residents. Erythema migrans occurred in 75.6% LB cases, while other symptoms did not exceed a quarter of all LB cases. There were 7353 (99.6%) cases where LB was confirmed via clinical symptoms and/or laboratory tests. Also, 1720 (23.2%) patients were tested for LB immunoglobulins. Conclusions: This study found a high incidence of Lyme disease in Lithuania. We elucidated the baseline characteristics regarding the infected Lithuanian population which may ease medical clinicians’ work on new Lyme diagnoses.

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Risk of Mortality (Including Sudden Cardiac Death) and Major Cardiovascular Events in Atypical and Typical Antipsychotic Users: A Study with the General Practice Research Database

Cardiovascular Psychiatry and Neurology ◽

10.1155/2013/247486 ◽

2013 ◽

Vol 2013 ◽

pp. 1-15 ◽

Cited By ~ 34

Author(s):

Tarita Murray-Thomas ◽

Meghan E. Jones ◽

Deven Patel ◽

Elizabeth Brunner ◽

Chetan C. Shatapathy ◽

...

Keyword(s):

General Practice ◽

General Population ◽

Cardiac Death ◽

General Practice Research Database ◽

Practice Research ◽

Research Database ◽

Cardiac Mortality ◽

Cardiac Events ◽

All Cause Mortality ◽

Population Controls

Objective. Antipsychotics have been associated with increased cardiac events including mortality. This study assessed cardiac events including mortality among antipsychotic users relative to nonusers. Methods. The General Practice Research Database (GPRD) was used to identify antipsychotic users, matched general population controls, and psychiatric diseased nonusers. Outcomes included cardiac mortality, sudden cardiac death (SCD), all-cause mortality (excluding suicide), coronary heart disease (CHD), and ventricular arrhythmias (VA). Sensitivity analyses were conducted for age, dose, duration, antipsychotic type, and psychiatric disease. Results. 183,392 antipsychotic users (115,491 typical and 67,901 atypical), 544,726 general population controls, and 193,920 psychiatric nonusers were identified. Nonusers with schizophrenia, dementia, or bipolar disorder had increased risks of all-cause mortality compared to general population controls, while nonusers with major depression had comparable risks. Relative to psychiatric nonusers, the adjusted relative ratios (aRR) of all-cause mortality in antipsychotic users was 1.75 (95% CI: 1.64–1.87); cardiac mortality 1.72 (95% CI: 1.42–2.07); SCD primary definition 5.76 (95% CI: 2.90–11.45); SCD secondary definition 2.15 (95% CI: 1.64–2.81); CHD 1.16 (95% CI: 0.94–1.44); and VA 1.16 (95% CI: 1.02–1.31). aRRs of the various outcomes were lower for atypical versus typical antipsychotics (all-cause mortality 0.83 (95% CI: 0.80–0.85); cardiac mortality 0.89 (95% CI: 0.82–0.97); and SCD secondary definition 0.76 (95% CI: 0.55–1.04). Conclusions. Antipsychotic users had an increased risk of cardiac mortality, all-cause mortality, and SCD compared to a psychiatric nonuser cohort.

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A Decline in C6 Antibody Titer Occurs in Successfully Treated Patients with Culture-Confirmed Early Localized or Early Disseminated Lyme Borreliosis

Clinical and Diagnostic Laboratory Immunology ◽

10.1128/cdli.12.9.1069-1074.2005 ◽

2005 ◽

Vol 12 (9) ◽

pp. 1069-1074 ◽

Cited By ~ 36

Author(s):

Mario T. Philipp ◽

Gary P. Wormser ◽

Adriana R. Marques ◽

Susan Bittker ◽

Dale S. Martin ◽

...

Keyword(s):

Lyme Disease ◽

Borrelia Burgdorferi ◽

Antibody Titer ◽

Lyme Borreliosis ◽

Antimicrobial Therapy ◽

Positive Response ◽

Erythema Migrans ◽

Response To Treatment ◽

Serum Specimen

ABSTRACT C6, a Borrelia burgdorferi-derived peptide, is used as the antigen in the C6-Lyme disease diagnostic test. We assessed retrospectively whether a fourfold decrease or a decrease to a negative value in anti-C6 antibody titer is positively correlated with a positive response to treatment in a sample of culture-confirmed patients with either early localized (single erythema migrans [EM]; n = 93) or early disseminated (multiple EM; n = 27) disease. All of these patients had been treated with antibiotics and were free of disease within 6 to 12 months of follow-up. Results show that a serum specimen taken at this time was either C6 negative or had a ≥4-fold decrease in C6 antibody titer with respect to a specimen taken at baseline (or during the early convalescent period if the baseline specimen was C6 negative) for all of the multiple-EM patients (P < 0.0001) and in 89% of the single-EM patients (P < 0.0001). These results indicate that a decline in anti-C6 antibody titer coincides with effective antimicrobial therapy in patients with early localized or early disseminated Lyme borreliosis.

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Multifactorial analysis of clinical laboratory signs, the levels of IL-17A, IL-23, IL-33, IL-35, and specific antibodies in the serum of patients with Lyme borreliosis without erythema migrans

Russian Medical Inquiry ◽

10.32364/2587-6821-2020-4-11-676-681 ◽

2020 ◽

Vol 4 (11) ◽

pp. 676-681

Author(s):

V.V. Sapozhnikova ◽

◽

A.L. Bondarenko ◽

Keyword(s):

Principal Component Analysis ◽

Lyme Borreliosis ◽

Clinical Laboratory ◽

Acute Infection ◽

Erythema Migrans ◽

Principal Component ◽

Component Analysis ◽

Control Group ◽

Multifactorial Analysis ◽

Specific Antibodies

Aim: to determine the association between clinical laboratory parameters, the production of cytokines (IL-17A, -23, -33, -35), and specific IgM and IgG in the serum of patients with Lyme borreliosis without erythema migrans. Patients and Methods: complete blood count, the concentrations of IL-17A, -23, -33, -35, and the levels of specific IgM and IgG were measured during acute infection and convalescence (n=30). The control group included age- and sex-matched healthy individuals (n=30). Statistical analysis was performed using the StatSoft Statistica v 10.0 software (parametric and non-parametric methods and multifactorial analysis, i.e., principal component analysis). Results: most (80%) patients with Lyme borreliosis without erythema migrans are the people of working age. In most patients, the combination of the specific antibodies against Borrelia afzelii and Borrelia garinii (76.7%) and severe intoxication and inflammatory process (100%) were detected. Moderate and severe disease associated with meningism was diagnosed in 90% and 10%, respectively. The mean duration of hectic period was 8.3±1.27 days. Abnormal ECG was reported in 40% of patients, i.e., conduction abnormalities in 20%, sinus bradycardia in 16.7%,and sinus tachycardia in 3.3%. The clinical laboratory signs of hepatitis without jaundice were identified in 26.7%. During treatment, the significant reduction in band and segmented neutrophil counts as well as the significant increase in platelet count were revealed compared to these parameters at admission. Abnormal cytokine levels (i.e., the increase in IL-17A, -23, -33 and the deficiency of IL-35) were detected. Conclusions: multifactorial analysis has demonstrated that the severity of immunological abnormalities in patients with Lyme borreliosis without erythema migrans is associated with fever, cardiac and liver disorders, the high levels of IL-23 and IL-33, and the lack of IL-35 and specific IgM and IgG. KEYWORDS: tick-borne borreliosis, Lyme disease without erythema migrans, clinical laboratory signs, cytokines, specific antibodies, multifactorial analysis, principal component analysis. FOR CITATION: Sapozhnikova V.V., Bondarenko A.L. Multifactorial analysis of clinical laboratory signs, the levels of IL-17A, IL-23, IL-33, IL-35, and specific antibodies in the serum of patients with Lyme borreliosis without erythema migrans. Russian Medical Inquiry. 2020;4(11):676–681. DOI: 10.32364/2587-6821-2020-4-11-676-681.

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A Case of Lyme Disease with Erythema Migrans

Nishi Nihon Hifuka ◽

10.2336/nishinihonhifu.67.599 ◽

2005 ◽

Vol 67 (6) ◽

pp. 599-603

Author(s):

Sanae KAWAI ◽

Shinya YAMANAKA ◽

Tomomi FUJISAWA ◽

Mariko SEISHIMA ◽

Hiroki KAWABATA

Keyword(s):

Lyme Disease ◽

Erythema Migrans

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Civil Religion or Nationalism? The National Day Celebrations in Norway

Religions ◽

10.3390/rel12030206 ◽

2021 ◽

Vol 12 (3) ◽

pp. 206

Author(s):

Pål Ketil Botvar

Keyword(s):

National Identity ◽

General Population ◽

Civil Religion ◽

Religious Nationalism ◽

Theoretical Concepts ◽

Role Of Religion ◽

Better Than ◽

The Way

The Norwegian National Day (17 May, also referred to as Constitution Day) stands out as one of the most popular National Day celebrations in Europe. According to surveys, around seven out of every 10 Norwegians take part in a public celebration during this day. This means that the National Day potentially has an impact on the way people reflect upon national identity and its relationship to the Lutheran heritage. In this paper, I will focus on the role religion plays in the Norwegian National Day rituals. Researchers have described these rituals as both containing a significant religious element and being rather secularized. In this article, I discuss the extent to which the theoretical concepts civil religion and religious nationalism can help us understand the role of religion, or the absence of religion, in these rituals. Based on surveys of the general population, I analyze both indicators of civil religion and religious nationalism. The two phenomena are compared by looking at their relation to such items as patriotism, chauvinism, and xenophobia. The results show that civil religion explains participation in the National Day rituals better than religious nationalism.

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