Lyme arthritis in Southern Norway - an endemic area for Lyme Borreliosis

Background: Despite Southern Norway is an endemic area for Lyme borreliosis there is a lack of data on Lyme arthritis (LA). In the literature controversies exist if acute LA can develop into chronic arthritis. Our objective was to identify and characterize patients with LA in Southern Norway and explore disease course after antibiotic treatment.Methods: Patients aged 20 years or older with arthritis and a positive serology for Borrelia burgdorferi infection (IgG and/or IgM) suspected of having LA were consecutively recruited either from general practitioners or from hospital departments.Results: From January 2007 to December 2010 a total of 27 patients were assessed. Mean (range) age was 56 years (41-80) and mean symptom duration prior to inclusion was 11.2 weeks (1 day - 2 years). Definite LA was diagnosed in 16 patients, probable LA in 5 patients and 6 patients were concluded to have other arthritis disorders. Among the 21 LA patients 20 had mono-arthritis (knee 18, ankle 2) and 1 had polyarthritis.All LA patients responded favourable to antibiotic treatment and none of the patients developed chronic arthritis after long term follow up, not even in LA patients who had intraarticular glucocorticosteroid (GC) injection prior to antibiotic treatment.Conclusions: Our data shows that LA in Southern Norway is a benign disease which successfully can be treated with antibiotics even in patients treated with GC prior to antibiotics

The B-lymphocyte chemokine CXCL13 in the cerebrospinal fluid of children with Lyme neuroborreliosis: associations with clinical and laboratory variables

Background: The B-lymphocyte chemokine CXCL13 is increasingly considered as a useful early phase diagnostic marker of Lyme neuroborreliosis (LNB). However, the large variation in level of CXCL13 in the cerebrospinal fluid (CSF) observed in LNB patients is still unexplained. We aimed to identify factors associated with the level of CXCL13 in children with LNB, possibly improving the interpretation of CXCL13 as a diagnostic marker of LNB. Methods: Children with confirmed and probable LNB were included in a prospective study on CXCL13 in CSF as a diagnostic marker of LNB. The variables age, sex, facial nerve palsy, generalized inflammation symptoms (fever, headache, neck-stiffness and/or fatigue), duration of symptoms, Borrelia antibodies in CSF, Borrelia antibody index (AI), CSF white blood cells (WBC), CSF protein and detection of the genospecies Borrelia garinii by PCR were included in simple and multivariable regression analyses to study the associations with the CXCL13 level. Results: We included 53 children with confirmed and 17 children with probable LNB. CXCL13 levels in CSF were positively associated with WBC, protein and Borrelia antibodies in CSF in both simple and multivariable analyses. We did not find any associations between CXCL13 and age, sex, clinical symptoms, duration of symptoms, AI or the detection of Borrelia garinii. Conclusions: High levels of CSF CXCL13 are present in the early phase of LNB and correlate with the level of CSF WBC and protein. Our results indicate that CSF CXCL13 in children evaluated for LNB can be interpreted independently of clinical features or duration of symptoms

Does more favourable handling of the cerebrospinal fluid increase the diagnostic sensitivity of <i>Borrelia burgdorferi</i> sensu lato-specific PCR in Lyme neuroborreliosis?

<p><b>Background:</b> Tests for direct detection of <i>Borrelia burgdorferi</i> sensu lato <i>(Bb)</i> in Lyme neuroborreliosis (LNB) are needed. Detection of <i>Bb</i> DNA using PCR is promising, but clinical utility is hampered by low diagnostic sensitivity. We aimed to examine whether diagnostic sensitivity can be improved by the use of larger cerebrospinal fluid (CSF) volumes and faster handling of samples.</p> <p><b>Methods:</b> Patients who underwent CSF examination for LNB were included. We collected two millilitres of CSF for PCR analysis, extracted DNA from the pellets within 24 h and analysed the eluate by two real-time PCR protocols (16S rRNA and OspA). Patients who fulfilled diagnostic criteria for LNB were classified as LNB cases and the rest as controls.</p> <p><b>Results:</b><i>Bb</i> DNA in CSF was detected by PCR in seven of 28 adults with LNB. Two were <i>Bb</i> antibody negative. No <i>Bb</i> DNA was detected in CSF from 137 controls. Diagnostic sensitivity was 25% and specificity 100%. There was a non-significant trend towards larger CSF sample volume, faster handling of the sample, shorter duration of symptoms, and higher CSF cell count in the PCR-positive cases.</p> <p><b>Conclusion:</b> We did not find that optimized handling of CSF increased diagnostic sensitivity of PCR in adults with LNB. However, our case series is small and we hypothesize that the importance of these factors will be clarified in further studies with larger case series and altered study design. PCR for diagnosis of LNB may be useful in cases without <i>Bb</i> antibodies due to short duration of symptoms.</p

Molecular detection of Borrelia burgdorferi sensu lato – An analytical comparison of real-time PCR protocols from five different Scandinavian laboratories

Introduction: Lyme borreliosis (LB) is the most common tick transmitted disease in Europe. The diagnosis of LB today is based on the patient´s medical history, clinical presentation and laboratory findings. The laboratory diagnostics are mainly based on antibody detection, but in certain conditions molecular detection by polymerase chain reaction (PCR) may serve as a complement. Aim: The purpose of this study was to evaluate the analytical sensitivity, analytical specificity and concordance of eight different real-time PCR methods at five laboratories in Sweden, Norway and Denmark. Method: Each participating laboratory was asked to analyse three different sets of samples (reference panels; all blinded) i) cDNA extracted and transcribed from water spiked with cultured Borrelia strains, ii) cerebrospinal fluid spiked with cultured Borrelia strains, and iii) DNA dilution series extracted from cultured Borrelia and relapsing fever strains. The results and the method descriptions of each laboratory were systematically evaluated. Results and conclusions: The analytical sensitivities and the concordance between the eight protocols were in general high. The concordance was especially high between the protocols using 16S rRNA as the target gene, however, this concordance was mainly related to cDNA as the type of template. When comparing cDNA and DNA as the type of template the analytical sensitivity was in general higher for the protocols using DNA as template regardless of the use of target gene. The analytical specificity for all eight protocols was high. However, some protocols were not able to detect Borrelia spielmanii, Borrelia lusitaniae or Borrelia japonica

Results from panel III consisting of DNA extracted from 15 <i>Borrelia</i> strains and five specificity controls containing two relapsing fever strains (<i>B</i>. <i>hermsii</i> and <i>B</i>. <i>miyamotoi</i>), <i>Treponema phagedenis</i> and <i>Leptospira</i>.

<p>Results from panel III consisting of DNA extracted from 15 <i>Borrelia</i> strains and five specificity controls containing two relapsing fever strains (<i>B</i>. <i>hermsii</i> and <i>B</i>. <i>miyamotoi</i>), <i>Treponema phagedenis</i> and <i>Leptospira</i>.</p

Results from panel I consisting of cDNA transcribed from total nucleic acid extracted from RNase-free water spiked with different concentrations of <i>B</i>. <i>afzelii</i> Lu81, <i>B</i>. <i>garinii</i> Lu59 and <i>B</i>. <i>burgdorferi</i> s.s. B31.

<p>Results from panel I consisting of cDNA transcribed from total nucleic acid extracted from RNase-free water spiked with different concentrations of <i>B</i>. <i>afzelii</i> Lu81, <i>B</i>. <i>garinii</i> Lu59 and <i>B</i>. <i>burgdorferi</i> s.s. B31.</p

Results from panel II consisting of cerebrospinal fluid spiked with different concentrations of <i>B</i>. <i>afzelii</i> Lu81, <i>B</i>. <i>garinii</i> Lu59 and <i>B</i>. <i>burgdorferi</i> s.s. B31.

<p>Protocol 8 was excluded due to lack of resources.</p