City Research Online

Abstract

Introduction: Invasive Group B streptococcal disease (iGBS) remains among the most common causes of sepsis and meningitis among neonates and young infants. Risk factors of the late-onset form of iGBS disease (LOGBS) are not fully understood. Establishing a correlate of protection (CoP) through natural immunity studies will facilitate and accelerate vaccine licensure to prevent both early and late-onset iGBS disease.

Methods: Three studies were undertaken: 1) A systematic review of clinical risk factors associated with LOGBS. 2) An epidemiological study of cases with recurrence and in multiples from the United Kingdom (UK) and Republic of Ireland (national surveillance study 2014/15) and Germany and Switzerland (retrospective case collection). 3) A UK pilot cohort study (iGBS feasibility; 2018-2020) followed by a large-scale seroepidemiological study (iGBS3; still underway) to define protective levels of anti-GBS capsular polysaccharide (CPS) immunoglobulin G (IgG).

Results: 1) The odds ratios (OR) of LOGBS in infants born <37 weeks or to colonised women were 7.79 (95% CI, 6.56–9.24) and 2.18 (1.78–2.68), respectively. 2) The incidence in infants of multiple births with an affected sibling was 17%. Very low birth weight and a course of antibiotics <10 days were associated with recurrence (aOR 10.0 (2.7-37.4), P<0.001; and 4.5 (1.3-17.5), P=0.02, respectively). 3) The half-life of protective transplacental anti-GBS IgG was 27.4 (23.5-32.9) days. For serotype III, IgG geometric mean concentrations were higher in the cord sera of healthy infants compared to acute sera from cases (0.1 vs 0.01 μg/mL; P<0.001). The threshold associated with 90% disease risk reduction was 2.28 (1.16-7.03) μg/mL.

Conclusions: Prematurity, low birth weight and maternal colonisation are important risk factors for LOGBS. Persistent mucosal colonisation and acute horizontal transmission are the two most likely mechanisms underpinning recurrent iGBS disease and LOGBS in general. Relatively low levels of naturally acquired anti-GBS CPS IgG protect most infants against serotype III-associated iGBS disease.

Publication Type:	Thesis (Doctoral)
Subjects:	Q Science > QR Microbiology > QR180 Immunology R Medicine > RA Public aspects of medicine > RA0421 Public health. Hygiene. Preventive Medicine R Medicine > RJ Pediatrics
Departments:	School of Health & Medical Sciences > Infection and Immunity Research Institute School of Health & Medical Sciences > School of Health & Medical Sciences Doctoral Theses Doctoral Theses

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