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Streptococcal Infections and Exacerbations in PANDAS

A Systematic Review and Meta-analysis

Nielsen, Marie Ødum, MD*; Köhler-Forsberg, Ole, MD*,†,‡; Hjorthøj, Carsten, PhD*,§; Benros, ME, MD, PhD*,§; Nordentoft, Merete, MD, PhD*,§; Orlovska-Waast, Sonja, MD*,§

The Pediatric Infectious Disease Journal: February 2019 - Volume 38 - Issue 2 - p 189–194
doi: 10.1097/INF.0000000000002218
Review Article

Background: The pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS) hypothesis suggests an association between group A beta-hemolytic streptococcus (GABHS) infections and subsequent onset or exacerbation of neuropsychiatric symptoms, such as obsessive-compulsive disorder or tic disorders.

Methods: We performed a systematic review and meta-analysis including longitudinal, prospective studies on exacerbations of neuropsychiatric symptoms associated with GABHS infections in children with PANDAS. We searched PubMed and EMBASE through August 14, 2017. Two independent reviewers extracted data and we used random-effects analysis to calculate rate ratios (RR).

Results: Three studies were included with a total of 82 PANDAS cases and 127 control children with obsessive-compulsive disorder or chronic tic disorder. PANDAS cases had a nonsignificantly increased RR of 2.33 [95% confidence interval [CI]: 0.63–8.70, P = 0.21, I 2 = 28.3%] for exacerbations of neuropsychiatric symptoms in temporal proximity to a GABHS infection and no increased risk of GABHS infections (RR = 0.99, 95% CI: 0.56–1.73, P = 0.97, I 2 = 45%) compared with the control children. However, PANDAS cases had an increased risk of neuropsychiatric exacerbations in general with a RR of 1.54 (95% CI: 1.12–2.11, P = 0.008, I 2 = 0%) compared with the control children. The studies had methodologic heterogeneity, high risk of selection bias and differed concerning case definition and infection measures.

Conclusions: Our findings did not show significant evidence concerning higher rates of temporally associated GABHS infections and exacerbations of neuropsychiatric symptoms in children with PANDAS. The included studies were small and limited by low GABHS rates and exacerbations. Future studies with large population sizes and routine evaluations are needed to thoroughly examine the PANDAS hypothesis.

From the *Mental Health Centre Copenhagen, Copenhagen University Hospital, Copenhagen, Denmark

Psychosis Research Unit, Aarhus University Hospital, Risskov, Denmark

Department of Clinical Medicine, Aarhus University Hospital, Denmark

§iPSYCH The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus University, Aarhus, Denmark.

Accepted for publication September 3, 2018.

The project was supported by an unrestricted grant from the Lundbeck Foundation. However, the sponsor had no role in the planning of the study, acquisition and analysis of the data, interpretation of the results or the decision to publish this manuscript.

The authors have no conflicts of interest to disclose.

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Address for correspondence: Marie Ødum Nielsen, MD, Mental Health Centre Copenhagen, Copenhagen University Hospital, Kildegaardsvej 28, Entrance 15, 4th Floor, 2900 Hellerup, Denmark. E-mail:

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