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BMC Neurology
Published in: BMC Neurology 1/2016

Open Access 01-12-2016 | Research article

Efficacy and safety of pharmacological treatments for Lyme neuroborreliosis in children: a systematic review

Authors: Rick Dersch, Tilman Hottenrott, Stefanie Schmidt, Harriet Sommer, Hans-Iko Huppertz, Sebastian Rauer, Joerg J. Meerpohl

Published in: BMC Neurology | Issue 1/2016

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Abstract

Background

Many aspects of pharmacological treatment of Lyme neuroborreliosis in children, such as choice of drug, dosage, and duration are subject to intense debates, leading to uncertainties in patients’ parents and healthcare providers alike. To assess the available evidence for pharmacological treatment for children with Lyme neuroborreliosis we conducted a systematic review.

Methods

The comprehensive systematic literature search included randomized-controlled trials (RCTs) and non-randomized studies (NRS) on treatment of Lyme neuroborreliosis in children (age <18 years). Our primary outcome was neurological symptoms after treatment. Risk of bias was assessed with the Cochrane risk of bias tools for RCTs and NRS. Quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.

Results

Two RCTs and four NRS were eligible for inclusion. Risk of bias in RCTs and NRS was generally high. Reporting of studies was generally poor. Regarding the primary outcome neurological symptoms at 1–3 months, no statistically significant difference could be found in cohort studies between doxycycline and beta-lactam antibiotics. In two RCTs comparing penicillin G and ceftriaxone, no patient experienced residual neurological symptoms at the last reported time points. Quality of evidence according to GRADE was judged very low.

Conclusions

Data is scarce and with limited quality. Several issues could not be addressed due to scarcity of information. No eligible study compared different treatment durations. According to the available evidence, there seems to be no difference between different antibiotic agents for the treatment of Lyme neuroborreliosis in children regarding neurological symptoms. We found no evidence that supports extended antibiotic regimes.

Review registration

Systematic review registration: CRD42014008839.
Appendix
Available only for authorised users
Literature
1.
Huppertz HI, Böhme M, Standaert SM, Karch H, Plotkin SA. Incidence of Lyme borreliosis in the Würzburg region of Germany. Eur J Clin Microbiol Infect Dis Off Publ Eur Soc Clin Microbiol. 1999;18(10):697–703.CrossRef
2.
Robert Koch Institut. Meldepflicht für Lyme-Borreliose in Bayern – eine erste Bilanz. Epidemiol Bull. 2015;23:56-62. (Nr. 8).
3.
Lohr B, Müller I, Mai M, Norris DE, Schöffski O, Hunfeld K-P. Epidemiology and cost of hospital care for Lyme borreliosis in Germany: lessons from a health care utilization database analysis. Ticks Tick-Borne Dis. 2015;6(1):56–62.CrossRefPubMed
4.
5.
Skogman BH, Croner S, Nordwall M, Eknefelt M, Ernerudh J, Forsberg P. Lyme neuroborreliosis in children: a prospective study of clinical features, prognosis, and outcome. Pediatr Infect Dis J. 2008;27(12):1089–94.CrossRefPubMed
6.
Wilke M, Eiffert H, Christen HJ, Hanefeld F. Primarily chronic and cerebrovascular course of Lyme neuroborreliosis: case reports and literature review. Arch Dis Child. 2000;83(1):67–71.CrossRefPubMedPubMedCentral
7.
Halperin JJ, Shapiro ED, Logigian E, Belman AL, Dotevall L, Wormser GP, et al. Practice parameter: treatment of nervous system Lyme disease (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2007;69(1):91–102.CrossRefPubMed
8.
9.
Mygland A, Ljøstad U, Fingerle V, Rupprecht T, Schmutzhard E, Steiner I, et al. EFNS guidelines on the diagnosis and management of European Lyme neuroborreliosis. Eur J Neurol. 2010;17(1):8–16. e1–4.CrossRefPubMed
10.
Dehnert M, Fingerle V, Klier C, Talaska T, Schlaud M, Krause G, et al. Seropositivity of Lyme borreliosis and associated risk factors: a population-based study in Children and Adolescents in Germany (KiGGS). PLoS One. 2012;7(8):e41321.CrossRefPubMedPubMedCentral
11.
Huppertz HI, Horneff G, Neudorf U, Karch H. Acute childhood neuroborreliosis with a selective immune response to a low molecular weight protein expressed by Borrelia garinii. Eur J Pediatr. 1994;153(12):898–902.PubMed
12.
Szer IS, Taylor E, Steere AC. The long-term course of Lyme arthritis in children. N Engl J Med. 1991;325(3):159–63.CrossRefPubMed
13.
Bensch J, Olcén P, Hagberg L. Destructive chronic borrelia meningoencephalitis in a child untreated for 15 years. Scand J Infect Dis. 1987;19(6):697–700.CrossRefPubMed
14.
Tager FA, Fallon BA, Keilp J, Rissenberg M, Jones CR, Liebowitz MR. A controlled study of cognitive deficits in children with chronic Lyme disease. J Neuropsychiatry Clin Neurosci. 2001;13(4):500–7.CrossRefPubMed
15.
Zotter S, Koch J, Schlachter K, Katzensteiner S, Dorninger L, Brunner J, et al. Neuropsychological profile of children after an episode of neuroborreliosis. Neuropediatrics. 2013;44(6):346–53.CrossRefPubMed
16.
Wormser GP, Dattwyler RJ, Shapiro ED, Halperin JJ, Steere AC, Klempner MS, et al. The clinical assessment, treatment, and prevention of lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis Off Publ Infect Dis Soc Am. 2006;43(9):1089–134.CrossRef
17.
Cameron D, Gaito A, Harris N, Bach G, Bellovin S, Bock K, et al. Evidence-based guidelines for the management of Lyme disease. Expert Rev Anti Infect Ther. 2004;2(1 Suppl):S1–S13.PubMed
18.
Holzbauer SM, Kemperman MM, Lynfield R. Death due to community-associated Clostridium difficile in a woman receiving prolonged antibiotic therapy for suspected lyme disease. Clin Infect Dis Off Publ Infect Dis Soc Am. 2010;51(3):369–70.CrossRef
19.
Patel R, Grogg KL, Edwards WD, Wright AJ, Schwenk NM. Death from inappropriate therapy for Lyme disease. Clin Infect Dis Off Publ Infect Dis Soc Am. 2000;31(4):1107–9.CrossRef
20.
21.
Hobusch D, Christen HJ, Huppertz HI, Noack R. Diagnosis and therapy of Lyme borreliosis in children. Practice guideline of the German Society for Pediatric Infectious Diseases. Klin Padiatr. 1999;211(2):70–4.CrossRefPubMed
22.
Dersch R, Freitag MH, Schmidt S, Sommer H, Rücker G, Rauer S, et al. Efficacy and safety of pharmacological treatments for neuroborreliosis--protocol for a systematic review. Syst Rev. 2014;3:117.CrossRefPubMedPubMedCentral
23.
24.
Sterne J, Higgins J, Reeves B. A Cochrane Risk Of Bias Assessment Tool: for Non-Randomized Studies of Interventions (ACROBATNRSI), Version 1.0.0 2014 [cited 2014 19.Dec]. Available from: http://​www.​riskofbias.​info
25.
Guyatt G, Oxman AD, Akl EA, Kunz R, Vist G, Brozek J, et al. GRADE guidelines: 1. Introduction-GRADE evidence profiles and summary of findings tables. J Clin Epidemiol. 2011;64(4):383–94.CrossRefPubMed
26.
Müllegger RR, Millner MM, Stanek G, Spork KD. Penicillin G sodium and ceftriaxone in the treatment of neuroborreliosis in children--a prospective study. Infection. 1991;19(4):279–83.CrossRefPubMed
27.
Millner M. Neurologic manifestations of Lyme borreliosis in children. Wien Med Wochenschr 1946. 1995;145(7-8):178–82.
28.
Jörbeck HJ, Gustafsson PM, Lind HC, Stiernstedt GT. Tick-borne Borrelia-meningitis in children. An outbreak in the Kalmar area during the summer of 1984. Acta Paediatr Scand. 1987;76(2):228–33.CrossRefPubMed
29.
Skowronek-Bała B, Wesołowska E, Gergont A, Kaciński M. Neuroboreliosis with motoric disturbations in the developmental age. Przegla̧d Lek. 2008;65(11):810–2.
30.
Thorstrand C, Belfrage E, Bennet R, Malmborg P, Eriksson M. Successful treatment of neuroborreliosis with ten day regimens. Pediatr Infect Dis J. 2002;21(12):1142–5.CrossRefPubMed
31.
Bingham PM, Galetta SL, Athreya B, Sladky J. Neurologic manifestations in children with Lyme disease. Pediatrics. 1995;96(6):1053–6.PubMed
32.
Nadelman RB, Wormser GP. Lyme borreliosis. Lancet Lond Engl. 1998;352(9127):557–65.CrossRef
33.
Cadavid D, Auwaerter P, Aucott J, Rumbaugh J. Treatment for the neurological complications of Lyme disease (Protocol). Cochrane Database Syst Rev. 2008.
34.
Dersch R, Freitag MH, Schmidt S, Sommer H, Rauer S, Meerpohl JJ. Efficacy and safety of pharmacological treatments for acute Lyme neuroborreliosis - a systematic review. Eur J Neurol. 2015;22(9):1249–59.CrossRefPubMed
35.
Stanek G, Fingerle V, Hunfeld K-P, Jaulhac B, Kaiser R, Krause A, et al. Lyme borreliosis: clinical case definitions for diagnosis and management in Europe. Clin Microbiol Infect Off Publ Eur Soc Clin Microbiol Infect Dis. 2011;17(1):69–79.
Metadata
Title
Efficacy and safety of pharmacological treatments for Lyme neuroborreliosis in children: a systematic review
Authors
Rick Dersch
Tilman Hottenrott
Stefanie Schmidt
Harriet Sommer
Hans-Iko Huppertz
Sebastian Rauer
Joerg J. Meerpohl
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Neurology / Issue 1/2016
Electronic ISSN: 1471-2377
DOI
https://doi.org/10.1186/s12883-016-0708-y

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