Ajoke Sobanjo-ter Meulen

Estimates of the Burden of Group B Streptococcal Disease Worldwide for Pregnant Women, Stillbirths, and Children

Group B Streptococcus is an important cause of disease in pregnant women, stillbirth, and infants. These first estimates show the magnitude and the potential impact of maternal vaccination.

Maternal Colonization With Group B Streptococcus and Serotype Distribution Worldwide: Systematic Review and Meta-analyses

Abstract Background Maternal rectovaginal colonization with group B Streptococcus (GBS) is the most common pathway for GBS disease in mother, fetus, and newborn. This article, the second in a series estimating the burden of GBS, aims to determine the prevalence and serotype distribution of GBS colonizing pregnant women worldwide. Methods We conducted systematic literature reviews (PubMed/Medline, Embase, Latin American and Caribbean Health Sciences Literature [LILACS], World Health Organization Library Information System [WHOLIS], and Scopus), organized Chinese language searches, and sought unpublished data from investigator groups. We applied broad inclusion criteria to maximize data inputs, particularly from low- and middle-income contexts, and then applied new meta-analyses to adjust for studies with less-sensitive sampling and laboratory techniques. We undertook meta-analyses to derive pooled estimates of maternal GBS colonization prevalence at national and regional levels. Results The dataset regarding colonization included 390 articles, 85 countries, and a total of 299924 pregnant women. Our adjusted estimate for maternal GBS colonization worldwide was 18% (95% confidence interval [CI], 17%–19%), with regional variation (11%–35%), and lower prevalence in Southern Asia (12.5% [95% CI, 10%–15%]) and Eastern Asia (11% [95% CI, 10%–12%]). Bacterial serotypes I–V account for 98% of identified colonizing GBS isolates worldwide. Serotype III, associated with invasive disease, accounts for 25% (95% CI, 23%–28%), but is less frequent in some South American and Asian countries. Serotypes VI–IX are more common in Asia. Conclusions GBS colonizes pregnant women worldwide, but prevalence and serotype distribution vary, even after adjusting for laboratory methods. Lower GBS maternal colonization prevalence, with less serotype III, may help to explain lower GBS disease incidence in regions such as Asia. High prevalence worldwide, and more serotype data, are relevant to prevention efforts.

Infant Group B Streptococcal Disease Incidence and Serotypes Worldwide: Systematic Review and Meta-analyses

Abstract Background Group B Streptococcus (GBS) remains a leading cause of neonatal sepsis in high-income contexts, despite declines due to intrapartum antibiotic prophylaxis (IAP). Recent evidence suggests higher incidence in Africa, where IAP is rare. We investigated the global incidence of infant invasive GBS disease and the associated serotypes, updating previous estimates. Methods We conducted systematic literature reviews (PubMed/Medline, Embase, Latin American and Caribbean Health Sciences Literature [LILACS], World Health Organization Library Information System [WHOLIS], and Scopus) and sought unpublished data regarding invasive GBS disease in infants aged 0–89 days. We conducted random-effects meta-analyses of incidence, case fatality risk (CFR), and serotype prevalence. Results We identified 135 studies with data on incidence (n = 90), CFR (n = 64), or serotype (n = 45). The pooled incidence of invasive GBS disease in infants was 0.49 per 1000 live births (95% confidence interval [CI], .43–.56), and was highest in Africa (1.12) and lowest in Asia (0.30). Early-onset disease incidence was 0.41 (95% CI, .36–.47); late-onset disease incidence was 0.26 (95% CI, .21–.30). CFR was 8.4% (95% CI, 6.6%–10.2%). Serotype III (61.5%) dominated, with 97% of cases caused by serotypes Ia, Ib, II, III, and V. Conclusions The incidence of infant GBS disease remains high in some regions, particularly Africa. We likely underestimated incidence in some contexts, due to limitations in case ascertainment and specimen collection and processing. Burden in Asia requires further investigation.

WHO consultation on group B Streptococcus vaccine development: Report from a meeting held on 27-28 April 2016.

Globally, group B Streptococcus (GBS) remains a leading cause of sepsis and meningitis in infants in the first 90 days of life. Intrapartum antibiotic prophylaxis (IAP) for women at increased risk of transmitting GBS to their newborns has been effective in reducing part, but not all, of the GBS disease burden in many high income countries (HICs). In low- and middle-income countries (LMICs), IAP use is low. Immunization of pregnant women with a GBS vaccine represents an alternative strategy to protecting newborns and young infants, through transplacental antibody transfer and potentially by reducing new vaginal colonization. This vaccination strategy was first suggested in the 1970s and several potential GBS vaccines have completed phase I/II clinical trials. During the 2015 WHO Product Development for Vaccines Advisory Committee meeting, GBS was identified as a high priority for the development of a vaccine for maternal immunization because of the major public health burden posed by GBS in LMICs, and the high technical feasibility for successful development. Following this meeting, the first WHO technical consultation on GBS vaccines was held on the 27th and 28th of April 2016, to consider development pathways for such vaccines, focused on their potential role in reducing newborn and young infant deaths and possibly stillbirths in LMICs. Discussion topics included: (1) pathophysiology of disease; (2) current gaps in the knowledge of global disease burden and serotype distribution; (3) vaccine candidates under development; (4) design considerations for phase III trials; and (5) pathways to licensure, policy recommendations and use. Efforts to address gaps identified in each of these areas are needed to establish the public health need for, the development and deployment of, efficacious GBS vaccines. In particular, more work is required to understand the global disease burden of GBS-associated stillbirths, and to develop quality-assured standardized antibody assays to identify correlates of protection.

Group B Streptococcal Disease Worldwide for Pregnant Women, Stillbirths, and Children: Why, What, and How to Undertake Estimates?

Group B Streptococcus is associated with multiple adverse pregnancy outcomes, yet previous epidemiology and interventions have mainly focused on neonatal invasive disease in high-income settings. We describe the rationale and approach for the first worldwide estimates of all relevant outcomes.

Preterm Birth Associated With Group B Streptococcus Maternal Colonization Worldwide: Systematic Review and Meta-analyses

Complications of preterm birth are the leading cause of deaths in children aged <5 years. Group B Streptococcus may be a preventable and important contributor to this burden.

Stillbirth with Group B Streptococcus Disease Worldwide: Systematic Review and Meta-analyses

Group B Streptococcus (GBS) is associated with invasive disease in utero and stillbirth. We estimated that 1% of all stillbirths in developed countries and 4% in Africa were associated with GBS.

Path to impact: A report from the Bill and Melinda Gates Foundation convening on maternal immunization in resource-limited settings; Berlin - January 29-30, 2015.

Global initiatives such as the Millennium Development Goals have led to major improvements in the health of women and children, and significant reductions in childhood mortality. Worldwide, maternal mortality has decreased by 45% and under-five mortality has fallen by over 50% over the past two decades [1]. However, improvements have not been achieved evenly across all ages; since 1990, under-five mortality has declined by ∼5% annually, but the average decrease in neonatal mortality is only ∼3% per year. Against this background, the Bill and Melinda Gates Foundation (BMGF) convened a meeting in Berlin on January 29-30, 2015 of global health stakeholders, representing funders, academia, regulatory agencies, non-governmental organizations, vaccine manufacturers, and Ministries of Health from Africa and Asia. The topic of discussion was the potential of maternal immunization (MI) to achieve further improvements in under-five morbidity and mortality rates in children, and particularly neonates and young infants, through targeting infectious diseases that are not preventable by other interventions in these age groups. The meeting focused on effective and appropriately priced MI vaccines against influenza, pertussis, and tetanus, as well as against respiratory syncytial virus, and the group B Streptococcus, for which no licensed vaccines currently exist. The primary goals of the BMGF 2015 convening were to bring together the global stakeholders in vaccine development, policy and delivery together with the Maternal, Newborn and Child Health (MNCH) community, to get recognition that MI is a strategy shared between these groups and so encourage increased collaboration, and obtain alignment on the next steps toward achieving a significant health impact through implementation of a MI program.

Risk of Early-Onset Neonatal Group B Streptococcal Disease with Maternal Colonization Worldwide: Systematic Review and Meta-analyses

Abstract Background Early-onset group B streptococcal disease (EOGBS) occurs in neonates (days 0–6) born to pregnant women who are rectovaginally colonized with group B Streptococcus (GBS), but the risk of EOGBS from vertical transmission has not been systematically reviewed. This article, the seventh in a series on the burden of GBS disease, aims to estimate this risk and how it varies with coverage of intrapartum antibiotic prophylaxis (IAP), used to reduce the incidence of EOGBS. Methods We conducted systematic reviews (Pubmed/Medline, Embase, Latin American and Caribbean Health Sciences Literature (LILACS), World Health Organization Library Information System [WHOLIS], and Scopus) and sought unpublished data from investigator groups on maternal GBS colonization and neonatal outcomes. We included articles with ≥200 GBS colonized pregnant women that reported IAP coverage. We did meta-analyses to determine pooled estimates of risk of EOGBS, and examined the association in risk of EOGBS with IAP coverage. Results We identified 30 articles including 20328 GBS-colonized pregnant women for inclusion. The risk of EOGBS in settings without an IAP policy was 1.1% (95% confidence interval [CI], .6%–1.5%). As IAP increased, the risk of EOGBS decreased, with a linear association. Based on linear regression, the risk of EOGBS in settings with 80% IAP coverage was predicted to be 0.3% (95% CI, 0–.9). Conclusions The risk of EOGBS among GBS-colonized pregnant women, from this first systematic review, is consistent with previous estimates from single studies (1%–2%). Increasing IAP coverage was linearly associated with decreased risk of EOGBS disease.

Strengthening the Reporting of Observational Studies in Epidemiology for Newborn Infection (STROBE-NI): an extension of the STROBE statement for neonatal infection research.

Neonatal infections are estimated to account for a quarter of the 2·8 million annual neonatal deaths, as well as approximately 3% of all disability-adjusted life-years. Despite this burden, few data are available on incidence, aetiology, and outcomes, particularly regarding impairment. We aimed to develop guidelines for improved scientific reporting of observational neonatal infection studies, to increase comparability and to strengthen research in this area. This checklist, Strengthening the Reporting of Observational Studies in Epidemiology for Newborn Infection (STROBE- NI), is an extension of the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) statement. STROBE-NI was developed following systematic reviews of published literature (1996-2015), compilation of more than 130 potential reporting recommendations, and circulation of a survey to relevant professionals worldwide, eliciting responses from 147 professionals from 37 countries. An international consensus meeting of 18 participants (with expertise in infectious diseases, neonatology, microbiology, epidemiology, and statistics) identified priority recommendations for reporting, additional to the STROBE statement. Implementation of these STROBE-NI recommendations, and linked checklist, aims to improve scientific reporting of neonatal infection studies, increasing data utility and allowing meta-analyses and pathogen-specific burden estimates to inform global policy and new interventions, including maternal vaccines.