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Invasive group B Streptococcus disease with recurrence and in multiples: towards a better understanding of GBS Late-onset sepsis

Invasive group B Streptococcus disease with recurrence and in multiples: towards a better understanding of GBS Late-onset sepsis
Invasive group B Streptococcus disease with recurrence and in multiples: towards a better understanding of GBS Late-onset sepsis
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.
group B Streptococcus, late-onset sepsis, microbiome, multiples, recurrence
1664-3224
Freudenhammer, Mirjam
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Freudenhammer, Mirjam, Karampatsas, Konstantinos, Le Doare, Kirsty, Lander, Fabian, Armann, Jakob, Acero Moreno, Daniel, Boyle, Margaret, Buxmann, Horst, Campbell, Ruth, Chalker, Victoria, Cunney, Robert, Doherty, Lorraine, Davies, Eleri, Efstratiou, Androulla, Elling, Roland, Endmann, Matthias, Essers, Jochen, Hentschel, Roland, Jones, Christine E., Kallsen, Steffen, Kapatai, Georgia, Krüger, Marcus, Ladhani, Shamez, Lamagni, Theresa, Lindsay, Diane, Meehan, Mary, O’sullivan, Catherine P., Patel, Darshana, Reynolds, Arlene J., Roll, Claudia, Schulzke, Sven, Smith, Andrew, Stein, Anja, Von Der Wense, Axel, Voss, Egbert, Wieg, Christian, Härtel, Christoph, Heath, Paul T. and Henneke, Philipp (2021) Invasive group B Streptococcus disease with recurrence and in multiples: towards a better understanding of GBS Late-onset sepsis. Frontiers in Immunology, 12, [617925]. (doi:10.3389/fimmu.2021.617925).

Record type: Article

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.

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fimmu-12-617925 (1) - Version of Record
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Accepted/In Press date: 4 May 2021
e-pub ahead of print date: 2 June 2021
Published date: 2 June 2021
Additional Information: Funding Information: This work was supported by the Else-Kröner-Fresenius Foundation; the German Ministry of Education and Research (grants 01EO0803, 01GL1746A, 01EK1602A to PH); the German Research Council (grants HE3127/9, HE3127/12, SFB/TRR167 to PH, 413517907 as an IMM-PACT Clinician Scientist fellowship to MF) and Meningitis Now (grant 13.0189). The article processing charge was funded by the Baden-Wuerttemberg Ministry of Science, Research and Art and the University of Freiburg in the funding programme Open Access Publishing. Funding Information: We would like to acknowledge the British Pediatric Surveillance Unit, and all the pediatricians, neonatologists, and microbiologists who have assisted in the study. Additionally, we would like to acknowledge Abdelmajid Djennad and Nick Andrews for assistance with statistical multivariable analysis (Public Health England). Publisher Copyright: © 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. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
Keywords: group B Streptococcus, late-onset sepsis, microbiome, multiples, recurrence
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Identifiers

Local EPrints ID: 450794
URI: http://eprints.soton.ac.uk/id/eprint/450794
DOI: doi:10.3389/fimmu.2021.617925
ISSN: 1664-3224
PURE UUID: 6172230b-0c34-4b30-8481-8005c32eebee
ORCID for Christine E. Jones: ORCID iD orcid.org/0000-0003-1523-2368

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Date deposited: 12 Aug 2021 16:30
Last modified: 17 Mar 2024 03:45

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Contributors

Author: Mirjam Freudenhammer
Author: Konstantinos Karampatsas
Author: Kirsty Le Doare
Author: Fabian Lander
Author: Jakob Armann
Author: Daniel Acero Moreno
Author: Margaret Boyle
Author: Horst Buxmann
Author: Ruth Campbell
Author: Victoria Chalker
Author: Robert Cunney
Author: Lorraine Doherty
Author: Eleri Davies
Author: Androulla Efstratiou
Author: Roland Elling
Author: Matthias Endmann
Author: Jochen Essers
Author: Roland Hentschel
Author: Christine E. Jones ORCID iD
Author: Steffen Kallsen
Author: Georgia Kapatai
Author: Marcus Krüger
Author: Shamez Ladhani
Author: Theresa Lamagni
Author: Diane Lindsay
Author: Mary Meehan
Author: Catherine P. O’sullivan
Author: Darshana Patel
Author: Arlene J. Reynolds
Author: Claudia Roll
Author: Sven Schulzke
Author: Andrew Smith
Author: Anja Stein
Author: Axel Von Der Wense
Author: Egbert Voss
Author: Christian Wieg
Author: Christoph Härtel
Author: Paul T. Heath
Author: Philipp Henneke

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