ReviewPreventing the broad spectrum of perinatal morbidity and mortality through group B streptococcal vaccination
Highlights
► GBS contributes substantially to maternal pregnancy-associated morbidity. ► GBS contributes substantially to neonatal morbidity and mortality. ► GBS immunization during pregnancy will reduce peripartum morbidity and rates of prematurity and stillbirth. ► GBS immunization during pregnancy will reduce deaths and improve long-term outcomes in neonates and young infants.
Introduction
Infections caused by group B Streptococcus (GBS) contribute substantially to morbidity and mortality among pregnant women and their infants [1]. The U.S. Centers for Disease Control and Prevention's (CDC) Active Bacterial Core Surveillance report estimated the total disease burden from invasive GBS disease as 24,700 people in 2010 with an estimated incidence of 8.0 cases per 100,000 population [2]. Approximately 20% of cases and 6% of the estimated GBS 1650 annual deaths occurred among adults of childbearing age. Infants accounted for approximately 2070 annual cases.
Prevention of GBS infections in pregnant women and their infants through maternal immunization has been a vision for decades and now is an attainable goal. Susceptibility to invasive GBS neonatal infection correlates with low concentrations of GBS capsular polysaccharide (CPS)-specific antibodies in serum [3], [4]. Investigational GBS CPS–protein conjugate vaccines have been well-tolerated and immunogenic in healthy adults, including pregnant women [5], [6], [7], [8], [9], [10]. Recently, a manufacturer's interest in GBS glycoconjugate vaccine development has increased and candidate vaccines capable of inducing in women strong, durable protective immunity against GBS are in clinical testing [11]. A phase 1 study enrolled 320 healthy, non-pregnant Belgian women in a placebo-controlled, dose-ranging trial of a trivalent GBS vaccine containing GBS types Ia, Ib and III conjugated to CRM197 and found the vaccine well-tolerated and immunogenic [12]. A phase 3 efficacy trial in pregnant women is in the planning stages. Maternal immunization offers the potential to prevent GBS infection in the maternal–neonatal dyad by active protection in mothers and passively, through placental transfer of antibodies, in their infants. In addition, GBS vaccines can be administered to prevent disease in resource-limited settings where prenatal screening and intrapartum antibiotic prophylaxis is generally not feasible.
Our two-fold objective is to summarize the pregnancy-related and infant-associated conditions caused by or potentially attributable to GBS and to project the potential impact of GBS glycoconjugate immunization during pregnancy upon the broad spectrum of perinatal GBS disease morbidity and mortality. We propose that widespread implementation of immunization during pregnancy with a multivalent GBS vaccine will reduce substantially the global burden of maternal and neonatal GBS-related morbidity and mortality and will also result in a reduction in prematurity and stillbirths.
Section snippets
Incidence and scope of maternal infection
The incidence of invasive GBS disease in pregnant women and girls, as determined by the U.S. CDC Active Bacterial Core surveillance network in 1993, before implementation of consensus guidelines for the prevention of perinatal GBS disease, was 0.29 per 1000 live births [13]. The case definition employed required isolation of GBS from a normally sterile site, such as blood or cerebrospinal fluid, and did not include cases identified by isolation of GBS from amniotic fluid, placenta or urine
Incidence of invasive GBS in infancy
In an attempt to estimate the global burden of GBS disease in infants younger than three months of age, a systematic review and meta-analysis by region was conducted for the years 2000–2011 [38]. The mean incidence of invasive GBS disease in infants 0–89 days of age was 0.53 per 1000 live births (95% CI, 0.44–0.62) and the mean case fatality rate was 9.6% (95% CI, 7.5–11.8). The incidence of early-onset disease (0.43 per 1000 live births, 95% CI 0.37–0.49) and case fatality (12.1%, CI 6.2–18.3)
GBS glycoconjugate vaccines
Candidate glycoconjugate vaccines incorporating each of the five major capsular polysaccharides of GBS have been evaluated in phase 1 and 2 trials and found to be safe and immunogenic [5], [6], [7], [8], [9], [10], [12]. When vaccine was administered during the third trimester of pregnancy, placental transfer of antibodies to type III capsular polysaccharide in concentrations sufficient to protect neonates and young infants from invasive GBS infection was demonstrated [7]. Adults responding to
Conclusion
In conclusion, a glycoconjugate vaccine incorporating GBS types Ia, Ib, II, III and V can potentially prevent at least 85% of invasive GBS disease in neonates and young infants globally. A GBS vaccination program to immunize women during pregnancy has the potential to reduce the incidence of maternal invasive GBS infection by up to 88% and to prevent 1–2% of premature births and 5–10% of stillbirths related to infection.
Acknowledgments
We gratefully acknowledge Carol J. Baker, M.D. for reviewing the manuscript and for her helpful comments and Robin D. Schroeder for assistance in preparation of the manuscript.
Conflict of interest statement: Dr. Edwards is a consultant to and receives research funding from Novartis Vaccines & Diagnostics. Dr. Gonik is a consultant to Novartis Vaccines & Diagnostics.
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