Neuroborreliosis in Swedish Children: A Population-based Study on Incidence and Clinical Characteristics

Södermark, Liv; Sigurdsson, Gudmundur Vignir; Näs, Wilhelmina; Wall, Pernilla; Trollfors, Birger

doi:10.1097/inf.0000000000001653

Cited by 39 publications

(28 citation statements)

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“…We found that the incidence was highest in children younger than 10 years; this is in agreement with a recent study on Lyme neuroborreliosis in children younger than 15 years in the south-western part of Sweden, where the incidence rate was lower in 10–14 year-olds compared with those younger than 10 years [15]. A similar age distribution with a higher incidence of Lyme neuroborreliosis in 5–10 year-old children and people older than 55 years was seen during an evaluation of the national surveillance system in Denmark [6].…”

Section: Discussionsupporting

confidence: 93%

Lyme neuroborreliosis epidemiology in Sweden 2010 to 2014: clinical microbiology laboratories are a better data source than the hospital discharge diagnosis register

et al. 2019

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Background In a study from 2013 that prioritised communicable diseases for surveillance in Sweden, we identified Lyme borreliosis as one of the diseases with highest priority. In 2014, when the present study was designed, there were also plans to make neuroborreliosis notifiable within the European Union. Aim We compared possibilities of surveillance of neuroborreliosis in Sweden through two different sources: the hospital discharge register and reporting from the clinical microbiology laboratories. Methods We examined the validity of ICD-10 codes in the hospital discharge register by extracting personal identification numbers for all cases of neuroborreliosis, defined by a positive cerebrospinal fluid–serum anti- Borrelia antibody index, who were diagnosed at the largest clinical microbiology laboratory in Sweden during 2014. We conducted a retrospective observational study with a questionnaire sent to all clinical microbiology laboratories in Sweden requesting information on yearly number of cases, age group and sex for the period 2010 to 2014. Results Among 150 neuroborreliosis cases, 67 (45%) had received the ICD-10 code A69.2 (Lyme borreliosis) in combination with G01.9 (meningitis in bacterial diseases classified elsewhere), the combination that the Swedish National Board of Health and Welfare recommends for neuroborreliosis. All 22 clinical laboratories replied to our questionnaire. Based on laboratory reporting, the annual incidence of neuroborreliosis in Sweden was 6.3 cases per 100,000 in 2014. Conclusion The hospital discharge register was unsuitable for surveillance of neuroborreliosis, whereas laboratory-based reporting was a feasible alternative. In 2018, the European Commission included Lyme neuroborreliosis on the list of diseases under epidemiological surveillance.

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Section: Discussionsupporting

confidence: 93%

Lyme neuroborreliosis epidemiology in Sweden 2010 to 2014: clinical microbiology laboratories are a better data source than the hospital discharge diagnosis register

et al. 2019

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“…Lyme neuroborreliosis (LNB), which is caused by a complex of Gram-negative spirochaetes called Borrelia burgdorferi sensu lato and transmitted to humans by the Ixodes ricinus tick, is the most serious manifestation of Lyme disease (LD) [1]. Borrelia constitutes a common cause of bacterial infection of the central nervous system (CNS) among children and adults in Sweden [2][3][4][5] and Finland [6]. According to the diagnostic criteria for LNB [7], mononuclear pleocytosis must be present in the cerebrospinal fluid (CSF), and this is an indicator of an active infection.…”

Section: Introductionmentioning

confidence: 99%

“…Neutrophils and their activation products are important early during infection, and they most likely affect the course and outcome of many diseases. With LNB, children tend to seek medical care earlier than adults owing to their having higher frequencies of meningeal symptoms and facial nerve palsy [3,4,21]. Therefore, we systematically evaluated whether NETs could be detected (using two different assays) in the CSF samples of children and adults with LNB, as well as in CSF samples from other infections and disorders affecting the CNS.…”

Section: Introductionmentioning

confidence: 99%

Neutrophil Extracellular Traps (NETs) in the Cerebrospinal Fluid Samples from Children and Adults with Central Nervous System Infections

Söderberg

Enocsson

Skogman

et al. 2019

Cells

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Neutrophils operate as part of the innate defence in the skin and may eliminate the Borrelia spirochaete via phagocytosis, oxidative bursts, and hydrolytic enzymes. However, their importance in Lyme neuroborreliosis (LNB) is unclear. Neutrophil extracellular trap (NET) formation, which is associated with the production of reactive oxygen species, involves the extrusion of the neutrophil DNA to form traps that incapacitate bacteria and immobilise viruses. Meanwhile, NET formation has recently been studied in pneumococcal meningitis, the role of NETs in other central nervous system (CNS) infections has previously not been studied. Here, cerebrospinal fluid (CSF) samples from clinically well-characterised children (N = 111) and adults (N = 64) with LNB and other CNS infections were analysed for NETs (DNA/myeloperoxidase complexes) and elastase activity. NETs were detected more frequently in the children than the adults (p = 0.01). NET presence was associated with higher CSF levels of CXCL1 (p < 0.001), CXCL6 (p = 0.007), CXCL8 (p = 0.003), CXCL10 (p < 0.001), MMP-9 (p = 0.002), TNF (p = 0.02), IL-6 (p < 0.001), and IL-17A (p = 0.03). NETs were associated with fever (p = 0.002) and correlated with polynuclear pleocytosis (r s = 0.53, p < 0.0001). We show that neutrophil activation and active NET formation occur in the CSF samples of children and adults with CNS infections, mainly caused by Borrelia and neurotropic viruses. The role of NETs in the early phase of viral/bacterial CNS infections warrants further investigation. supervision, C.S., D.N. and L.E.M.; project administration, J.S.; funding, D.A., B.H.S., D.N., L.E.M. and C.S.; acquisition, D.A., L.E.M., C.S. and J.S. All authors have read and agreed to the published version of the manuscript.

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“…Lyme neuroborreliosis (LNB) is the second most frequent LB manifestation and most commonly caused by B. garinii [ 1 – 3 ]. The incidence of LNB in Sweden is 2.8/10.000 children [ 8 ]. The Borrelia spirochetes in the skin may spread into the central nervous system in two alternative ways: either through the bloodstream or along peripheral nerves [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

“…Facial nerve palsy is the most commonly occurring clinical manifestation of LNB in children and it is often present at the ipsilateral side of the tick bite or EM [ 10 ]. Headache, fever and/or fatigue are common unspecific symptoms in LNB [ 8 , 11 ] and occasionally, LNB presents with normal neurological examination [ 12 ]. Thus, the LNB diagnosis requires both clinical signs and symptoms attributable for LNB and laboratory testing, according to European guidelines [ 2 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

Occurrence of erythema migrans in children with Lyme neuroborreliosis and the association with clinical characteristics and outcome – a prospective cohort study

Backman

Skogman

2018

BMC Pediatr

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BackgroundErythema migrans (EM) is the most common manifestation of Lyme borreliosis (LB), caused by the spirochete Borrelia burgdorferi sensu lato. The infection can disseminate into the nervous system and cause Lyme neuroborreliosis (LNB), the second most frequent LB manifestation in children. The aim of this prospective cohort study is to describe the occurrence of EM among children with LNB and to evaluate possible differences in clinical characteristics or outcome between LNB patients with and without EM.MethodChildren being evaluated for LNB in southeast Sweden during the period 2010–2014 underwent a clinical examination, laboratory testing and filled out a questionnaire regarding duration and nature of symptoms, EM and the child’s health. Children were classified according to European guidelines for LNB. Clinical recovery was evaluated at a 2-month follow-up.ResultsThe occurrence of EM among children with LNB was 37 out of 103 (36%). Gender, age, observed tick bite, clinical features, duration of neurological symptoms or clinical outcome did not differ significantly between LNB patients with or without EM. However, facial nerve palsy was significantly more common among children with EM in the head and neck area.ConclusionEM occurred in 36% of children with LNB and the location on the head and neck was more common among children with facial nerve palsy. EM was not associated with other specific clinical characteristics or outcome. Thus, the occurrence of EM in children with LNB cannot be useful as a prognostic factor for clinical outcome. This aspect has not previously been highlighted but seems to be relevant for the paediatrician in a clinical setting.Electronic supplementary materialThe online version of this article (10.1186/s12887-018-1163-2) contains supplementary material, which is available to authorized users.

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Neuroborreliosis in Swedish Children: A Population-based Study on Incidence and Clinical Characteristics

Cited by 39 publications

References 32 publications

Lyme neuroborreliosis epidemiology in Sweden 2010 to 2014: clinical microbiology laboratories are a better data source than the hospital discharge diagnosis register

Lyme neuroborreliosis epidemiology in Sweden 2010 to 2014: clinical microbiology laboratories are a better data source than the hospital discharge diagnosis register

Neutrophil Extracellular Traps (NETs) in the Cerebrospinal Fluid Samples from Children and Adults with Central Nervous System Infections

Occurrence of erythema migrans in children with Lyme neuroborreliosis and the association with clinical characteristics and outcome – a prospective cohort study

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