Short summary

Group B Streptococcus (GBS) is a leading cause of sepsis and meningitis causing increased mortality and morbidity in infants. This project will: 1) describe the epidemiology of GBS and other bacteria in children under one year of age in Denmark. 2) identify genetic markers for invasive GBS by whole-genome sequencing. This knowledge on GBS is warranted to optimize pediatric infection guidelines and target screening for invasive GBS and administration of antibiotic prophylaxis in laboring women.

Rationale

Globally, Group B Streptococcus (GBS) is a leading cause of sepsis, meningitis, pneumonia and death in up to 2% of the newborns of colonized women in the absence of intrapartum antibiotic prophylaxis (IAP). GBS causes early-onset disease (EOD; age 0-6 days) and late-onset disease (LOD; age 7-90 days). The incidences of EOD and LOD differs depending on the region and time. This may be due to variations in virulence or human host factors, and further epidemiologic and genomic knowledge on GBS is warranted. Data lacks on the nationwide incidence of positive cultures including the burden of GBS in children below one year of age in relation to age at onset, preterm versus full term infants and by the specific clinical diagnosis. This knowledge will be crucial for considering the pros and cons for continuing IAP, the choice of empirical antibiotics in young infants admitted with suspected infection, and introduction of a potential vaccine. The current point-of-care test (POCT) used to screen labouring women GBS to administrate IAP identifies maternal colonization. Further genomic characterization of specific genetic markers of invasive GBS, would allow for a POCT to qualify IAP and the diagnosis and early treatment of EOD at a much higher level. This project aims to: 1) describe the incidence of positive blood cultures (and other specimen) in a nationwide cohort of children up to one year of age with particular focus on the absolute and relative (to other bacteria) occurrence of GBS; the description will include several infant characteristics which may be associated with the distribution of microbiological agents. 2) find a unique genetic marker for detection of GBS invasive isolates in EOD and LOD. GBS from EOD and LOD cases and selected carriage GBS isolates will be whole genome sequenced for the identification of specific genes.

Description of the cohort

All children under the age of one year with a positive culture from blood or cerebrospinal fluid between year 2000 and 2020 will be included.

Data and biological material

1) Data on positive cultures from blood and other clinical specimen (cerebrospinal fluid, urine, sterile fluids etc) will be retrieved from all ten Departments of Microbiology in Denmark. Information on clinical diagnosis (ICD10 codes), infant characteristics (e.g. sex, age, birthweight), maternal characteristics (sociodemographic) and mortality will be retrieved from the Danish National Patient Registry, Cause of Death Registry and Statistics Denmark. 2) Specifically for GBS, the isolates cultured from blood and cerebrospinal fluid will be retrived from all the departments of clinical mibrobiology in Denmark for the purpose of whole-genome sequencing of invasive GBS.

Collaborating researchers and departments

Department of Pediatrics, Aarhus University Hospital

• Tine Brink Henriksen, Consultant, Professor, PhD

Department of Biomedicine, Aarhus University

• Stine Yde Nielsen, MD, PhD

Neisseria and Streptococcus Reference Laboratory, The State Serume Institute

• Hans-Christian Slotved, Senior Scientist, PhD

Department of Obstetrics and Gynecology, Kolding Hospital

• Mohammed Khalil, Consultant, Associate Professor, PhD

Department of Clinical Microbiology, Vejle Hospital

• Jens Møller Kjølseth, Professor, PhD
• Stine Yde Nielsen, MD, PhD

Genomics of Pneumoniae and Meningitis, Wellcome Sanger Institute

• Dorota Jamrozy, Principal Bioinformatician