Group B streptococcal infections in the newborn infant and the potential value of maternal vaccination

Abstract

Group B Streptococcus (GBS) is a leading cause of neonatal bacterial infections in developed countries. Early-onset disease (EOD) occurs at day 0–6 and late-onset disease occurs at day 7–89. Currently, the prevention of EOD relies upon intrapartum antibiotic prophylaxis (IAP) given to women who are GBS positive at prenatal screening or women with risk factors for EOD. Although successfully implemented, IAP has not fully eradicated EOD, and incidence rates of late-onset disease remain unchanged. Furthermore, antibiotic resistance may result from widespread antibiotic use. New prophylactic strategies are therefore of critical importance. A vaccine active against GBS, administered during pregnancy and combined with targeted IAP, could overcome these problems and reduce the mortality and morbidity associated with invasive diseases.

Keywords:

• early-onset disease
• Group B Streptococcus
• intrapartum antibiotic prophylaxis
• late-onset disease
• newborn infant
• pregnancy
• prevention
• sepsis
• vaccine

Financial & competing interests disclosure

I Margarit and D Maione are employed by GSK. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Key issues

• Group B Streptococcus (GBS) is the leading cause of serious bacterial infections in infants younger than 3 months.

• Intrapartum antibiotic prophylaxis has dramatically reduced the incidence of early-onset infections but has had no notable effects on late-onset infections.

• Widespread use of antibiotics is a major concern in many countries because of the increasing resistances of pathogens.

• Although GBS remains uniformly susceptible to penicillin, the minimum inhibitory concentrations have increased in some regions. A high proportion of isolates is currently resistant to erythromycin and clindamycin, therefore, their routine use for intrapartum antibiotic prophylaxis is not recommended.

• Although expensive, intrapartum real-time PCR-based tests might be more accurate for identifying women actually colonized at delivery and enable targeted treatment. Currently, however, no randomized clinical trial has compared antenatal screening and PCR-based tests at delivery for preventing early-onset disease.

• Late-onset infections remain an important cause of bacterial meningitis in the first 2 months of life. In about half of cases, meningitis may result in visual or hearing loss, motor or cognitive impairment or learning disabilities.

• The prevention of infections in newborns and infants has recently focused on the administration of vaccines during pregnancy. Improved outcome has been demonstrated by maternal immunization with influenza and tetanus, diphtheria and pertussis vaccines.

• A capsular polysaccharide protein conjugate vaccine (CPS-CRM197) is under clinical testing; it elicits capsular polysaccharides-specific IgG that could protect the baby from early- and late-onset infections by placental transfer.

• A vaccine should ideally be effective against 10 serotypes of GBS. Highly conserved protein structures (so-called ‘pili’) have been recently identified in all GBS capsular types. The development of a vaccine against these common proteins would be able to provide wide coverage against individual serotypes.

• Vaccines could be an effective strategy for resource-poor countries, where universal prenatal screening and large-scale intrapartum antibiotic prophylaxis are not feasible.

Notes