Invasive Group B Streptococcus Disease With Recurrence and in Multiples: Towards a Better Understanding of GBS Late-Onset Sepsis

Mirjam Freudenhammer^{1

2

3}, Konstantinos Karampatsas⁴, Kirsty Le Doare⁴, Fabian Lander⁵, Jakob Armann⁵, Daniel Acero Moreno⁶, Margaret Boyle⁷, Horst Buxmann⁸, Ruth Campbell⁹, Victoria Chalker¹⁰, Robert Cunney^{11

12}, Lorraine Doherty⁹, Eleri Davies¹³, Androulla Efstratiou¹⁴, Roland Elling^{1

2}, Matthias Endmann¹⁵, Jochen Essers¹⁶, Roland Hentschel², Christine E Jones¹⁷, Steffen Kallsen¹⁸, Georgia Kapatai¹⁰, Marcus Krüger¹⁹, Shamez Ladhani^{4

20}, Theresa Lamagni¹⁴, Diane Lindsay²¹, Mary Meehan¹², Catherine P O'Sullivan⁴, Darshana Patel^{1

4}, Arlene J Reynolds²², Claudia Roll²³, Sven Schulzke²⁴, Andrew Smith^{21

25}, Anja Stein²⁶, Axel von der Wense²⁷, Egbert Voss²⁸, Christian Wieg²⁹, Christoph Härtel^{30

31}, Paul T Heath⁴, Philipp Henneke^{1

2

31}

Affiliations

¹ Institute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
² Center for Pediatrics and Adolescent Medicine, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
³ IMM-PACT Clinician Scientist Programme, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
⁴ Paediatric Infectious Diseases Research Group, Institute of Infection and Immunity, St. George's, University of London, London, United Kingdom.
⁵ Department of Pediatrics, University Hospital and Medical Faculty Carl Gustav Carus, Technische Universität (TU) Dresden, Dresden, Germany.
⁶ Department of Neonatology, Kinderkrankenhaus Amsterdamer Straße, Cologne, Germany.
⁷ Department of Health Northern Ireland, Belfast, United Kingdom.
⁸ Department of Pediatric and Adolescent Medicine, Division for Neonatology at the University Hospital Frankfurt, Frankfurt/Main, Germany.
⁹ Public Health Agency Northern Ireland, Belfast, United Kingdom.
¹⁰ Immunisation, Hepatitis and Blood Safety Department, Public Health England, London, United Kingdom.
¹¹ Health Service Executive, Health Protection Surveillance Centre, Dublin, Ireland.
¹² Irish Meningitis and Sepsis Reference Laboratory, Temple Street Children's University Hospital, Dublin, Ireland.
¹³ Public Health Wales, Cardiff, United Kingdom.
¹⁴ National Infection Service, Public Health England, London, United Kingdom.
¹⁵ Department of Pediatric and Adolescent Medicine, St. Franziskus Hospital Ahlen, Ahlen, Germany.
¹⁶ Department of Pediatrics, University of Ulm, Ulm, Germany.
¹⁷ Faculty of Medicine and Institute for Life Sciences, University of Southampton and NIHR Southampton Clinical Research Facility and NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom.
¹⁸ Department of Paediatrics and Youth Medicine, Klinikum Friedrichshafen, Friedrichshafen, Germany.
¹⁹ Department of Neonatology, München Klinik Harlaching and Schwabing, Munich, Germany.
²⁰ Immunisation and Countermeasures Division, Public Health England, London, United Kingdom.
²¹ Scottish Microbiology Reference Laboratory, Glasgow Royal Infirmary, Glasgow, United Kingdom.
²² Health Protection Scotland, Glasgow, United Kingdom.
²³ Department of Neonatology, Vest Children's Hospital Datteln, University Witten-Herdecke, Witten-Herdecke, Germany.
²⁴ Department of Neonatology, University Children's Hospital Basel UKBB, Basel, Switzerland.
²⁵ Glasgow Dental Hospital and School, University of Glasgow, Glasgow, United Kingdom.
²⁶ Department of Pediatrics, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
²⁷ Neonatology and Pediatric Intensive Care, Altonaer Children's Hospital, Altonaer Kinderkrankenhaus, Hamburg, Germany.
²⁸ Klinik Hallerwiese-Cnopfsche Kinderklinik, Nürnberg, Germany.
²⁹ Department of Neonatology, Klinikum Aschaffenburg, Aschaffenburg, Germany.
³⁰ Department of Pediatrics, University of Würzburg, Würzburg, Germany.
³¹ PRIMAL (Priming Immunity at the Beginning of Life) Consortium, Freiburg/Lübeck, Germany.

PMID: 34149682
PMCID: PMC8208644
DOI: 10.3389/fimmu.2021.617925

Invasive Group B Streptococcus Disease With Recurrence and in Multiples: Towards a Better Understanding of GBS Late-Onset Sepsis

Mirjam Freudenhammer et al. Front Immunol. 2021.

. 2021 Jun 2:12:617925.

doi: 10.3389/fimmu.2021.617925. eCollection 2021.

Authors

Affiliations

¹ Institute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
² Center for Pediatrics and Adolescent Medicine, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
³ IMM-PACT Clinician Scientist Programme, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
⁴ Paediatric Infectious Diseases Research Group, Institute of Infection and Immunity, St. George's, University of London, London, United Kingdom.
⁵ Department of Pediatrics, University Hospital and Medical Faculty Carl Gustav Carus, Technische Universität (TU) Dresden, Dresden, Germany.
⁶ Department of Neonatology, Kinderkrankenhaus Amsterdamer Straße, Cologne, Germany.
⁷ Department of Health Northern Ireland, Belfast, United Kingdom.
⁸ Department of Pediatric and Adolescent Medicine, Division for Neonatology at the University Hospital Frankfurt, Frankfurt/Main, Germany.
⁹ Public Health Agency Northern Ireland, Belfast, United Kingdom.
¹⁰ Immunisation, Hepatitis and Blood Safety Department, Public Health England, London, United Kingdom.
¹¹ Health Service Executive, Health Protection Surveillance Centre, Dublin, Ireland.
¹² Irish Meningitis and Sepsis Reference Laboratory, Temple Street Children's University Hospital, Dublin, Ireland.
¹³ Public Health Wales, Cardiff, United Kingdom.
¹⁴ National Infection Service, Public Health England, London, United Kingdom.
¹⁵ Department of Pediatric and Adolescent Medicine, St. Franziskus Hospital Ahlen, Ahlen, Germany.
¹⁶ Department of Pediatrics, University of Ulm, Ulm, Germany.
¹⁷ Faculty of Medicine and Institute for Life Sciences, University of Southampton and NIHR Southampton Clinical Research Facility and NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom.
¹⁸ Department of Paediatrics and Youth Medicine, Klinikum Friedrichshafen, Friedrichshafen, Germany.
¹⁹ Department of Neonatology, München Klinik Harlaching and Schwabing, Munich, Germany.
²⁰ Immunisation and Countermeasures Division, Public Health England, London, United Kingdom.
²¹ Scottish Microbiology Reference Laboratory, Glasgow Royal Infirmary, Glasgow, United Kingdom.
²² Health Protection Scotland, Glasgow, United Kingdom.
²³ Department of Neonatology, Vest Children's Hospital Datteln, University Witten-Herdecke, Witten-Herdecke, Germany.
²⁴ Department of Neonatology, University Children's Hospital Basel UKBB, Basel, Switzerland.
²⁵ Glasgow Dental Hospital and School, University of Glasgow, Glasgow, United Kingdom.
²⁶ Department of Pediatrics, University Hospital Essen, University Duisburg-Essen, Essen, Germany.
²⁷ Neonatology and Pediatric Intensive Care, Altonaer Children's Hospital, Altonaer Kinderkrankenhaus, Hamburg, Germany.
²⁸ Klinik Hallerwiese-Cnopfsche Kinderklinik, Nürnberg, Germany.
²⁹ Department of Neonatology, Klinikum Aschaffenburg, Aschaffenburg, Germany.
³⁰ Department of Pediatrics, University of Würzburg, Würzburg, Germany.
³¹ PRIMAL (Priming Immunity at the Beginning of Life) Consortium, Freiburg/Lübeck, Germany.

PMID: 34149682
PMCID: PMC8208644
DOI: 10.3389/fimmu.2021.617925

Abstract

Group B Streptococcus (GBS) is a common intestinal colonizer during the neonatal period, but also may cause late-onset sepsis or meningitis in up to 0.5% of otherwise healthy colonized infants after day 3 of life. Transmission routes and risk factors of this late-onset form of invasive GBS disease (iGBS) are not fully understood. Cases of iGBS with recurrence (n=25) and those occurring in parallel in twins/triplets (n=32) from the UK and Ireland (national surveillance study 2014/15) and from Germany and Switzerland (retrospective case collection) were analyzed to unravel shared (in affected multiples) or fixed (in recurrent disease) risk factors for GBS disease. The risk of iGBS among infants from multiple births was high (17%), if one infant had already developed GBS disease. The interval of onset of iGBS between siblings was 4.5 days and in recurrent cases 12.5 days. Disturbances of the individual microbiome, including persistence of infectious foci are suggested e.g. by high usage of perinatal antibiotics in mothers of affected multiples, and by the association of an increased risk of recurrence with a short term of antibiotics [aOR 4.2 (1.3-14.2), P=0.02]. Identical GBS serotypes in both recurrent infections and concurrently infected multiples might indicate a failed microbiome integration of GBS strains that are generally regarded as commensals in healthy infants. The dynamics of recurrent GBS infections or concurrent infections in multiples suggest individual patterns of exposure and fluctuations in host immunity, causing failure of natural niche occupation.

Keywords: group B Streptococcus; late-onset sepsis; microbiome; multiples; recurrence.

Copyright © 2021 Freudenhammer, Karampatsas, Le Doare, Lander, Armann, Acero Moreno, Boyle, Buxmann, Campbell, Chalker, Cunney, Doherty, Davies, Efstratiou, Elling, Endmann, Essers, Hentschel, Jones, Kallsen, Kapatai, Krüger, Ladhani, Lamagni, Lindsay, Meehan, O’Sullivan, Patel, Reynolds, Roll, Schulzke, Smith, Stein, von der Wense, Voss, Wieg, Härtel, Heath and Henneke.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

**Figure 1**
Model of pathogenesis of (recurrent) Group B streptococcus late-onset disease. Several factors (boxes) impact on the outcome of postnatal contact of the neonate with GBS: uneventful integration into microbiome *vs.* invasive GBS infection (Figure was created using BioRender.com).

See this image and copyright information in PMC

References

1. Seale AC, Bianchi-Jassir F, Russell NJ, Kohli-Lynch M, Tann CJ, Hall J, et al. . Estimates of the Burden of Group B Streptococcal Disease Worldwide for Pregnant Women, Stillbirths, and Children. Clin Infect Dis (2017) 65:S200–19. 10.1136/archdischild-2018-rcpch.284 - DOI - PMC - PubMed
1. Madrid L, Seale AC, Kohli-Lynch M, Edmond KM, Lawn JE, Heath PT, et al. . Infant Group B Streptococcal Disease Incidence and Serotypes Worldwide: Systematic Review and Meta-Analyses. Clin Infect Dis (2017) 65:S160–72. 10.1093/cid/cix656 - DOI - PMC - PubMed
1. Kohli-Lynch M, Russell NJ, Seale AC, Dangor Z, Tann CJ, Baker CJ, et al. . Neurodevelopmental Impairment in Children After Group B Streptococcal Disease Worldwide: Systematic Review and Meta-Analyses. Clin Infect Dis (2017) 65:S190–9. 10.1093/cid/cix663 - DOI - PMC - PubMed
1. Melin P. Neonatal Group B Streptococcal Disease: From Pathogenesis to Preventive Strategies. Clin Microbiol Infect (2011) 17:1294–303. 10.1111/j.1469-0691.2011.03576.x - DOI - PubMed
1. Le Doare K, O’Driscoll M, Turner K, Seedat F, Russell NJ, Seale AC, et al. . Intrapartum Antibiotic Chemoprophylaxis Policies for the Prevention of Group B Streptococcal Disease Worldwide: Systematic Review. Clin Infect Dis (2017) 65:S143–51. 10.1093/cid/cix654 - DOI - PMC - PubMed

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Invasive Group B Streptococcus Disease With Recurrence and in Multiples: Towards a Better Understanding of GBS Late-Onset Sepsis

Affiliations

Invasive Group B Streptococcus Disease With Recurrence and in Multiples: Towards a Better Understanding of GBS Late-Onset Sepsis

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

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LinkOut - more resources

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Medical