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Lack of Association of Group A Streptococcal Infections and Onset of Tics: European Multicenter Tics in Children
Anette-Eleonore Schrag1, Davide Martino2, Hanyuying Wang2
1From the Department of Clinical Neuroscience (A.E.S., H.W.), UCL Institute of Neurology, and Department of and Statistical Science (G.A.), University College London, UK; Department of Clinical Neurosciences (D.M.), Cumming School of Medicine and Hotchkiss Brain Institute, University of Calgary, Alberta, Canada; Child and Adolescent Psychiatry Department (N.B.-M.), Schneider Children's Medical Centre of Israel, Petah-Tikva, Affiliated to Sackler Faculty of Medicine, Tel Aviv University; Department of Biomedical Sciences and Human Oncology (M.B.), University of Bari "Aldo Moro"; Department of Human Neurosciences (F.C.), University La Sapienza of Rome; Department of Infectious Diseases (R.C.), Istituto Superiore di Sanità, Rome, Italy; WHO Global Collaborating Centre for Reference and Research on Diphtheria and Streptococcal Infections (A.E.), Reference Microbiology Division, National Infection Service, Public Health England; Evelina London Children's Hospital GSTT (T.H.), Kings Health Partners AHSC; Psychological Medicine (I.H.), Great Ormond Street Hospital NHS Foundation Trust, London, UK; Levvel (C.H.), Academic Center for Child and Adolescent Psychiatry; Amsterdam UMC (C.H.), Department of Child and Adolescent Psychiatry, the Netherlands; Unidad de Trastornos del Movimiento (P.M.), Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (P.M.), Madrid; Department of Child and Adolescent Psychiatry and Psychology (A.M.), Institute of Neurosciences, Hospital Clinic Universitari; Institut d'Investigacions Biomediques August Pi i Sunyer (A.M.), Barcelona; Centro de Investigacion en Red de Salud Mental (A.M.), Instituto Carlos III, Madrid, Spain; Institute of Laboratory Medicine (N.M., M.J.S.) and Department of Psychiatry and Psychotherapy (N.E.M.), University Hospital, LMU Munich; Department of Psychiatry, Social Psychiatry and Psychotherapy (K.R.M.-V.), Hannover Medical School, Germany; Child and Adolescent Mental Health Centre (K.v.P.), Mental Health Services, Capital Region of Denmark and University of Copenhagen; Division of Child and Adolescent Psychiatry (K.v.P.), Department of Psychiatry, Lausanne University Hospital, Switzerland; ASL BA (C.P.), Mental Health Department, Adolescence and Childhood Neuropsychiatry Unit, Bari; Child and Adolescent Neurology and Psychiatry (R.R.), Department of Clinical and Experimental Medicine, University of Catania, Italy; Department of Child and Adolescent Psychiatry (V.R.), Medical Faculty Carl Gustav Carus, TU Dresden, Germany; Vadaskert Child and Adolescent Psychiatric Hospital (Z.T.), Budapest, Hungary; Department of Child and Adolescent Psychiatry and Psychotherapy (S.W.), University of Zurich, Switzerland; and University of Groningen (A.D., P.J.H.), University Medical Centre Groningen, Department of Child and Adolescent Psychiatry, the Netherlands. a.schrag@ucl.ac.uk.
Background And Objectives:
The goal of this work was to investigate the association between group A streptococcal (GAS) infections and tic incidence among unaffected children with a family history of chronic tic disorders (CTDs).
Methods:
In a prospective cohort study, children with no history for tics who were 3 to 10 years of age with a first-degree relative with a CTD were recruited from the European Multicentre Tics in Children Study (EMTICS) across 16 European centers. Presence of GAS infection was assessed with throat swabs, serum anti-streptolysin O titers, and anti-DNAse titers blinded to clinical status. GAS exposure was defined with 4 different definitions based on these parameters. Cox regression analyses with time-varying GAS exposure were conducted to examine the association of onset of tics and GAS exposure during follow-up. Sensitivity analyses were conducted with Cox regression and logistic regression analyses.
Results:
A total of 259 children were recruited; 1 child was found to have tic onset before study entry and therefore was excluded. Sixty-one children (23.6%) developed tics over an average follow-up period of 1 (SD 0.7) year. There was a strong association of sex and onset of tics, with girls having an ≈60% lower risk of developing tics compared to boys (hazard ratio [HR] 0.4, 95% confidence interval [CI] 0.2-0.7). However, there was no statistical evidence to suggest an association of any of the 4 GAS exposure definitions with tic onset (GAS exposure definition 1: HR 0.310, 95% CI 0.037-2.590; definition 2: HR 0.561, 95% CI 0.219-1.436; definition 3: HR 0.853, 95% CI 0.466-1.561; definition 4: HR 0.725, 95% CI 0.384-1.370).
Discussion:
These results do not suggest an association between GAS exposure and development of tics.
Classification Of Evidence:
This study provides Class I evidence that group A streptococcal exposure does not associate with the development of tics in children with first-degree relatives with chronic tic disorder.
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