Clinical and immunological epidemiology of group B streptococcus (GBS)

• Main Author: Dangor, Ziyaad
• Format: Others
• Language: en
• Published: 2016
• Online Access: http://hdl.handle.net/10539/19678

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 === 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.