Clinical and immunological epidemiology of group B streptococcus (GBS)
Date
2016-02-22
Authors
Dangor, Ziyaad
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Abstract
Introduction: Group B Streptococcus (GBS) is a leading cause of neonatal sepsis and
meningitis. Vaccinating pregnant women against GBS may protect their infants from
invasive GBS disease. The licensure of GBS vaccines might be based on immunological
parameters should correlates of protection be established. We evaluated the burden of
invasive GBS disease, and explored the association between naturally occurring GBS
antibody concentrations and invasive GBS disease in South African infants.
Methods: Using a case-control study, we compared maternal and infant GBS serotypespecific
capsular and surface-protein IgG antibody concentrations. Neurodevelopmental
screening was performed at 3 and 6 months-of-age. Furthermore, we compared the effect
of maternal HIV-infection on GBS specific antibody concentrations and transplacental
antibody transfer.
Results: The incidence (per 1,000 live births) of invasive GBS disease within 6 days of life
was similar between HIV-exposed (1.13) and HIV-unexposed infants (1.46; p=0.487).
However, there was a 4.67-fold (95% CI: 2.24-9.74) greater risk of invasive GBS disease
at age 7-90 days in HIV-exposed infants (2.27 vs. 0.49; p<0.001). The overall case fatality
ratio among cases was 18.0%, and the adjusted odds of developing neurological sequelae
at 6 months age was 13.2-fold (95% CI: 1.4-121) greater in cases (13.2%) than controls
(0.4%).
Median antibody concentrations (μg/mL) were lower in HIV-infected than HIV-uninfected
women for serotypes Ib (p=0.033) and V (p=0.040); and for pilus island (PI)-1 (p=0.016),
PI-2a (p=0.015), PI-2b (p=0.015) and fibrinogen-binding protein A (p<0.001). For
serotypes Ia and III, cord to maternal ratios were 37.4% (p<0.001) and 32.5% (p=0.027)
lower in HIV-infected compared to HIV-uninfected mother-newborn dyads.
Using Bayesian modelling, we demonstrated >90% reduction in risk of invasive GBS
disease with maternal antibody concentrations ≥6 μg/mL and ≥3 μg/mL for serotype Ia and
III, respectively. There was no association between GBS surface-protein antibody
concentrations and invasive GBS disease.
Conclusion: The high burden of invasive GBS disease in South Africa is partly due to the
high prevalence of maternal HIV-infection (29%), which is associated with lower GBS
antibody concentrations and transplacental antibody transfer. We identified putative
correlates of protection for GBS serotype-specific capsular antibodies to serotypes Ia and
III, which could facilitate vaccine licensure.
Description
A thesis submitted to the Faculty of Health Sciences, University of the
Witwatersrand, Johannesburg, in fulfilment of the requirements for the degree of
Doctor of Philosophy
Johannesburg 2015