| 1. |
- Appelgren, Daniel, et al.
(author)
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Neutrophil Extracellular Traps (NETs) in the Cerebrospinal Fluid Samples from Children and Adults with Central Nervous System Infections.
- 2020
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In: Cells. - : MDPI AG. - 2073-4409. ; 9:1
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Journal article (peer-reviewed)abstract
- 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 (rs = 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.
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| 2. |
- Borgstrom, Malin, et al.
(author)
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Fecal disimpaction in children with enuresis and constipation does not make them dry at night
- 2022
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In: Journal of Pediatric Urology. - : Elsevier. - 1477-5131 .- 1873-4898. ; 18:4, s. 446.e1-446.e7
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Journal article (peer-reviewed)abstract
- BACKGROUND: Constipation, daytime incontinence and nocturnal enuresis often overlap. Treatment of constipation has been shown to be an important aspect of therapy for children with daytime incontinence. However, the value of fecal disimpaction, as a part of constipation therapy, in children with enuresis has not been evaluated.AIM: Our aim was to evaluate the antienuretic effect of fecal disimpaction in children with enuresis and concomitant constipation.METHODS: The bladder and bowel function was assessed noninvasively in children aged six to ten years who sought help for enuresis for the first time. If they were constipated according to the Rome IV criteria or had a rectal diameter exceeding 30 mm, as assessed by ultrasound, they were given standard evacuation with mini-enemas and macrogol therapy for at least two weeks. Enuresis frequency was documented 14 nights preceding and following therapy.RESULTS: In total, 66 children (20 girls, 46 boys) were evaluated, 23 (35%) of whom were constipated. There were no differences in age, sex or baseline bladder function between the two groups. The enuresis frequency per two weeks was 9.8 ± 4.1 nights before and 9.3 ± 5.1 nights after constipation therapy (p = 0.43).DISCUSSION: This study found that fecal disimpaction in children with enuresis who are also constipated did not alleviate nocturnal enuresis. Bowel problems may still need to be addressed but the child should not be given the false hope that this approach alone will make them dry at night. It might be that evidenced based therapies, such as the enuresis alarm and desmopressin, could be less efficient in children with enuresis and constipation unless their bowel disturbance is first properly addressed.CONCLUSIONS: Fecal disimpaction in children with enuresis and concomitant constipation will, by itself, not make the children dry at night.
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| 3. |
- Borgström, Malin, et al.
(author)
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Daytime urotherapy in nocturnal enuresis : a randomised, controlled trial
- 2022
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In: Archives of Disease in Childhood. - : BMJ Publishing Group Ltd. - 0003-9888 .- 1468-2044. ; 107:6, s. 570-574
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Journal article (peer-reviewed)abstract
- OBJECTIVE: According to international guidelines, children with enuresis are recommended urotherapy, or basic bladder advice, before treatment with evidence-based alternatives such as the enuresis alarm is given. The efficacy of this strategy has, however, not been supported by controlled studies. We wanted to test if basic bladder advice is useful in enuresis.DESIGN: Randomised, controlled trial.SETTING: Paediatric outpatient ward, regional hospital.PATIENTS: Treatment-naïve enuretic children aged ≥6 years, with no daytime incontinence.INTERVENTIONS: Three groups, each during 8 weeks: (A) basic bladder advice-that is, voiding and drinking according to a strict schedule and instructions regarding toilet posture, (B) enuresis alarm therapy and (C) no treatment (control group).MAIN OUTCOME MEASURES: Reduction in enuresis frequency during week 7-8 compared with baseline.RESULTS: The median number of wet nights out of 14 before and at the end of treatment were in group A (n=20) 12.5 and 11.5 (p=0.44), in group B (n=22) 11.0 and 3.5 (p<0.001) and in group C (n=18) 12.5 and 12.0 (p=0.55). The difference in reduction of enuresis frequency between the groups was highly significant (p=0.002), but no difference was found between basic bladder advice and controls.CONCLUSIONS: Urotherapy, or basic bladder advice, is ineffective as a first-line treatment of nocturnal enuresis. Enuretic children who are old enough to be bothered by their condition should be offered treatment with the alarm or desmopressin.TRIAL REGISTRATION NUMBER: NCT03812094.
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| 4. |
- Bruinsma, R. A., et al.
(author)
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Clinical manifestations of Lyme neuroborreliosis in children : a review
- 2023
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In: European Journal of Pediatrics. - : Springer. - 0340-6199 .- 1432-1076. ; 182:5, s. 1965-1976
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Research review (peer-reviewed)abstract
- Lyme neuroborreliosis (LNB) is a manifestation of Lyme disease involving the central and peripheral nervous system. It is caused by the spirochete Borrelia burgdorferi, transmitted by tick bites to a human host. Clinical signs of LNB develop after the dissemination of the pathogen to the nervous system. The infection occurs in children and adults, but the clinical manifestations differ. In adults, painful meningoradicultis is the most common manifestation of LNB, while children often present with facial nerve palsy and/or subacute meningitis. Subacute headache can be the only manifestation of LNB in children, especially during the summer months in Lyme disease-endemic regions. Non-specific symptoms, such as loss of appetite, fatigue or mood changes, may also occur, especially in young children. A high level of suspicion and early recognition of the various clinical manifestations presented by children with LNB is essential to minimize delay in diagnosis and optimize management. This review provides an overview of the spectrum of clinical manifestations, and discusses diagnosis, antibiotic treatment, and clinical outcome of LNB in children.
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| 5. |
- Fredriksson, Tobias, et al.
(author)
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Diagnostic patterns of serum inflammatory protein markers in children with Lyme neuroborreliosis
- 2024
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In: Ticks and Tick-borne Diseases. - : Elsevier. - 1877-959X .- 1877-9603. ; 15:4
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Journal article (peer-reviewed)abstract
- Definite diagnosis of Lyme neuroborreliosis (LNB) requires investigation of serum and cerebrospinal fluid (CSF). Thus, lumbar puncture is necessary, and requires administration of sedating drugs in children. This study aimed to investigate if a pattern of different inflammatory biomarkers in serum could contribute to the selection of children for lumbar puncture in suspected LNB. Patients were included from a cohort of children who was previously investigated for LNB including serum and CSF sampling during the years 2010-2014. The multiplex proximity extension assay (PEA) inflammation panel Target 96 (Olink Bioscience, Uppsala, Sweden) was used to examine 92 biomarkers in serum. Based on the presence of CSF pleocytosis and Borrelia-specific antibodies, patients were divided into a definite LNB group (n=61) and a non-LNB control group (n=58). Following PEA and statistical analysis with multivariate logistic regression, five biomarkers remained significant (p < 0.001), which were included in a calculation of protein index. The index biomarkers were CST5, IL-15RA, CXCL10, DNER and CX3CL1. A receiver operating characteristic curve was constructed from the index, which showed an 80 % sensitivity and 81 % specificity. Area under the curve was 0.889. We offer evidence that, with further refinements, patterns of serum biomarkers might help identify those children more or less likely to have LNB, perhaps ultimately decreasing the need for lumbar punctures.
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| 6. |
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| 7. |
- Hedin Skogman, Barbro, 1967-
(author)
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Neuroborreliosis in childhood : Clinical, immunological and diagnostic aspects
- 2008
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Doctoral thesis (other academic/artistic)abstract
- Lyme Borreliosisis is a multi-organ infectious disease caused by the spirochete Borrelia burgdorferi. The spirochete is transmitted to humans by tick bites. Neuroborreliosis (NB) is a disseminated form of the disease, in which the spirochetes invade the nervous system. In children, subacute meningitis and facial nerve palsy are typical clinical manifestations of NB.The aim of this thesis was to study clinical, immunological and laboratory characteristics in children being evaluated for NB in a Lyme endemic area of Sweden, in order to identify factors of importance for prognosis and clinical recovery. A total of 250 patients and 220 controls were included during 1998-2005, with a prospective and a retrospective part.Less than half (41%) of children with signs and symptoms indicative of NB get the diagnosis confirmed by detection of Borrelia specific flagella antibodies in CSF (clinical routine method). Surprisingly few patients were diagnosed as having other infectious or neurologic diseases and consequently, many patients ended up with an uncertain diagnosis. However, four new Borrelia antigens (DbpA, BBK32, OspC, IR6) were evaluated and performed well in laboratory diagnostics. If they were combined in a panel, together with the flagella antigen, the sensitivity was 82% and the specificity 100%, leading to improved diagnostic accuracy in children with NB, as compared to using the routine flagella antibody test alone.Clinical recovery at the 6-month follow-up (n=177) was generally good and nonspecific symptoms, such as headache and fatigue, were not more frequently reported in patients than in controls. No patient was found to have recurrent or progressive neurologic symptoms.However, permanent facial nerve palsy was found in 22% of patients at the 2-year follow-up, with consequences such as eye-closing problems, excessive tear secretion, pronunciation difficulties and cosmetic complaints.When cellular immune responses were investigated, the number of Borrelia-specific IL-4 and IFN-γ secreting cells in CSF was found to be more prominent in children with NB than in controls. Furthermore, a much stronger IL-4 response in CSF was seen in children as compared to adults with NB. This cytokine profile of children with NB is believed to represent an effective and balanced type1/type2 response in a relevant compartment, and could contribute to the less severe course of the disease seen in children as compared to adults with NB.No prognostic factors were found to influence the outcome in patients with “Confirmed NB” or facial nerve palsy. Nor was any specific cytokine profile, or antibody response to new Borrelia antigens in CSF, correlated to a less favorable clinical outcome.An NB prediction score test, based on clinical variables at admission, is suggested to help physicians to determine whether to start early antibiotic treatment, before results from Borrelia antibody tests are available.Results in this thesis support the notion that mononuclear pleocytosis in CSF, in patients being evaluated for NB, indicates that they are true NB cases despite the fact that an antibody response cannot yet be visualized. with the routine flagella test. Consequently, early antibiotic treatment in NB seems to be the correct course of action and over-treatment is not a substantial problem.
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| 8. |
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| 9. |
- Jonsson Henningsson, Anna, et al.
(author)
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Laboratory Methods for Detection of Infectious Agents and Serological Response in Humans With Tick-Borne Infections : A Systematic Review of Evaluations Based on Clinical Patient Samples
- 2021
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In: Frontiers In Public Health. - : Frontiers Media S.A.. - 2296-2565. ; 9
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Research review (peer-reviewed)abstract
- Background: For the most important and well-known infections spread by Ixodes ticks, Lyme borreliosis (LB) and tick-borne encephalitis (TBE), there are recommendations for diagnosis and management available from several health authorities and professional medical networks. However, other tick-borne microorganisms with potential to cause human disease are less known and clear recommendations on diagnosis and management are scarce. Therefore, we performed a systematic review of published studies and reviews focusing on evaluation of laboratory methods for clinical diagnosis of human tick-borne diseases (TBDs), other than acute LB and TBE. The specific aim was to evaluate the scientific support for laboratory diagnosis of human granulocytic anaplasmosis, rickettsiosis, neoehrlichiosis, babesiosis, hard tick relapsing fever, tularemia and bartonellosis, as well as tick-borne co-infections and persistent LB in spite of recommended standard antibiotic treatment.Methods: We performed a systematic literature search in 11 databases for research published from 2007 through 2017, and categorized potentially relevant references according to the predefined infections and study design. An expert group assessed the relevance and eligibility and reviewed the articles according to the QUADAS (diagnostic studies) or AMSTAR (systematic reviews) protocols, respectively. Clinical evaluations of one or several diagnostic tests and systematic reviews were included. Case reports, non-human studies and articles published in other languages than English were excluded.Results: A total of 48 studies fulfilled the inclusion criteria for evaluation. The majority of these studies were based on small sample sizes. There were no eligible studies for evaluation of tick-borne co-infections or for persistent LB after antibiotic treatment.Conclusions: Our findings highlight the need for larger evaluations of laboratory tests using clinical samples from well-defined cases taken at different time-points during the course of the diseases. Since the diseases occur at a relatively low frequency, single-center cross-sectional studies are practically not feasible, but multi-center case control studies could be a way forward.
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| 10. |
- Lindström, Björn E., et al.
(author)
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Borrelia Ocular Infection : A Case Report and a Systematic Review of Published Cases
- 2022
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In: Ophthalmic Research. - : S. Karger. - 0030-3747 .- 1423-0259. ; 65:2, s. 121-130
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Research review (peer-reviewed)abstract
- INTRODUCTION: Lyme borreliosis can cause many diverse manifestations, also ocular disease where the diagnosis of ocular borreliosis is challenging. The primary aim was to report on the evidence of Borrelia spirochetes in the ocular tissue in presumed ocular borreliosis.METHODS: A systematic review of pathological eye conditions was performed where Borrelia has been suspected in relevant ocular tissue, together with a case report of diagnosed uveitis with polymerase chain reaction (PCR)-confirmed Borrelia afzelii in the vitreous. The evidence for clinical and laboratory diagnosis was evaluated systematically. As a secondary aim, the treatment of ocular Borrelia infection was also evaluated for confirmed cases.RESULTS: Thirteen includable studies were found, and after the removal of case duplicates, eleven unique cases were extracted. Apart from the present case report, 4 other cases reported strong evidence for the detection of B. spirochetes in ocular tissue. Four cases presented reasonable evidence for assumed detected Borrelia, while three additional cases showed only weak diagnostic credibility that Borrelia was detected.CONCLUSION: This systematic review, including all reported cases and our case report, supports evidence of ocular infection of Borrelia species. Furthermore, in case of suspicion of infection and seronegativity, it is justified to look for Borrelia in eye tissue samples. In addition, microscopy without using PCR is not sufficient to confirm the diagnosis of borreliosis on ocular tissue. In the articles studied, there was no unambiguous recommendation of treatment.
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