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Group B Streptococcus (GBS) is a pathobiont that can ascend to the placenta and cause adverse pregnancy outcomes, in part through production of the toxin β‐hemolysin/cytolysin (β‐h/c). Innate immune cells have been implicated in the response to GBS infection, but the impact of β‐h/c on their response is poorly defined. We show that GBS modulates innate immune cell states by subversion of host inflammation through β‐h/c, allowing worse outcomes. We used an ascending mouse model of GBS infection to measure placental cell state changes over time following infection with a β‐h/c‐deficient and isogenic wild type GBS strain. Transcriptomic analysis suggests that β‐h/c‐producing GBS elicit a worse phenotype through suppression of host inflammatory signaling in placental macrophages and neutrophils, and comparison of human placental macrophages infected with the same strains recapitulates these results. Our findings have implications for identification of new targets in GBS disease to support host defense against pathogenic challenge. Synopsis Analyses of placental responses in an ascending infection model show that mice infected with a Group B Streptococcus (GBS) toxin knockout strain show a milder tissue‐level phenotype but their innate immune cells exhibit more inflammation than wild type GBS‐infected counterparts. Comparison of infection with β‐h/c knockout (KO) and wild type (WT) GBS in an ascending model of infection reveals more severe tissue‐level phenotype over time in the WT‐infected group. Transcriptomic analysis reveals a large shift in innate immune cell expression in response to infection. Despite the milder tissue‐level phenotype, β‐h/c KO GBS elicited a more inflammatory phenotype in innate immune cells. Infection of human placental macrophages with the same two strains recapitulated these results on the transcript and protein level and highlighted expression of immunomodulatory genes in β‐h/c KO GBS‐infected cells. Graphical Abstract Analyses of placental responses in an ascending infection model show that mice infected with a Group B Streptococcus (GBS) toxin knockout strain show a milder tissue‐level phenotype but their innate immune cells exhibit more inflammation than WT GBS‐infected counterparts.

Background Group B Streptococcus (GBS) infection is a leading cause of neonatal morbidity. Maternal rectovaginal GBS colonization is a primary risk factor for early onset neonatal GBS infection. In Belgium, pregnant women are screened and, if positive or at risk of transmission, offered intrapartum antibiotic prophylaxis (IAP). We aimed to provide the first comprehensive overview of Belgian data and identify possible risk factors of maternal GBS colonization and neonatal infection. Methods We calculated proportions of maternal screening, colonization and incidence of all neonatal GBS infections and identified their risk factors using log binomial regression from national registries’ data between 2012–2021. Results Of all women, 90.2% were screened and of them, 18.5% were GBS colonized. These proportions were stable over time. Risk factors for maternal GBS colonization included Sub-Saharan (aRR = 1.45, [1.41–1.48]) and North-African origin (aRR = 1.31, [1.28–1.34]) and 5 + parity (aRR = 1.21, [1.18–1.25]). Neonatal GBS sepsis incidence showed a gradually decreasing trend in two individual data sources. Flanders’ overall neonatal GBS sepsis estimates were around 0.49 cases per 1000 livebirths. Risk factors for neonatal GBS infection included preterm birth (aRR=3-27, depending on level of prematurity) and very low birthweight (aRR=3.13, [1.32-7.44]). Babies of colonized women were at higher risk without (aRR=7.21, [4.84-10.75]) than with IAP (aRR=4.40, [3.31-5.85]) compared to non-colonized women. Conclusions The maternal colonization rate and the neonatal GBS sepsis incidence in Belgium is comparable to European data. We identified already known risk factors and effectiveness of IAP. Mothers at risk for GBS colonization and premature/low birth weight deliveries could benefit most from additional maternal vaccination strategy.

•IAP for pregnant women colonized with group B streptococcus (GBS) has reduced neonatal GBS disease.•GBS nonetheless remains a leading cause of neonatal sepsis, with 1000 late-onset cases annually.•Maternal GBS vaccine could be an attractive alternative to IAP if the vaccine is about 90% effective.•Maternal vaccine as an adjunct to IAP is an expensive strategy, costing $115,400-$358,900 per QALY.•Coverage, typically low for maternal vaccines, is key to the vaccine’s impact on GBS disease. In the U.S., intrapartum antibiotic prophylaxis (IAP) for pregnant women colonized with group B streptococcus (GBS) has reduced GBS disease in the first week of life (early-onset/EOGBS). Nonetheless, GBS remains a leading cause of neonatal sepsis, including 1000 late-onset (LOGBS) cases annually. A maternal vaccine under development could prevent EOGBS and LOGBS. Using a decision-analytic model, we compared the public health impact, costs, and cost-effectiveness of five strategies to prevent GBS disease in infants: (1) no prevention; (2) currently recommended screening/IAP; (3) maternal GBS immunization; (4) maternal immunization with IAP when indicated for unimmunized women; (5) maternal immunization plus screening/IAP for all women. We modeled a pentavalent vaccine covering serotypes 1a, 1b, II, III, and V, which cause almost all GBS disease. In the base case, screening/IAP alone prevents 46% of EOGBS compared to no prevention, at a cost of $70,275 per quality-adjusted life-year (QALY) from a healthcare and $51,249/QALY from a societal perspective (2013 US$). At coverage rates typical of maternal vaccines in the U.S., a pentavalent vaccine alone would not prevent as much disease as screening/IAP until its efficacy approached 90%, but would cost less per QALY. At vaccine efficacy of ≥70%, maternal immunization together with IAP for unimmunized women would prevent more disease than screening/IAP, at a similar cost/QALY. GBS maternal immunization, with IAP as indicated for unvaccinated women, could be an attractive alternative to screening/IAP if a pentavalent vaccine is sufficiently effective. Coverage, typically low for maternal vaccines, is key to the vaccine’s public health impact.

•Group B Streptococcus (GBS) causes considerable disease burden in the Netherlands.•Maternal immunization would be cost-effective at €58 per dose (€20,000/QALY).•Trivalent vaccine would gain 186 QALYs and prevent ~€3.1 million health care costs.•Expanding vaccine serotype coverage would have limited additional benefit.•Discontinuation of intrapartum antibiotic prophylaxis (IAP) would save costs. Neonatal invasive Group B Streptococcus (GBS) infection causes considerable disease burden in the Netherlands. Intrapartum antibiotic prophylaxis (IAP) prevents early-onset disease (EOD), but has no effect on late-onset disease (LOD). A potential maternal GBS vaccine could prevent both EOD and LOD by conferring immunity in neonates. Explore under which circumstances maternal vaccination against GBS would be cost-effective as an addition to, or replacement for the current risk factor-based IAP prevention strategy in the Netherlands. We assessed the maximum cost-effective price per dose of a trivalent (serotypes Ia, Ib, and III) and hexavalent (additional serotypes II, IV, and V) GBS vaccine in addition to, or as a replacement for IAP. To project the prevented costs and disease burden, a decision tree model was developed to reflect neonatal GBS disease and long-term health outcomes among a cohort based on 169,836 live births in the Netherlands in 2017. Under base-case conditions, maternal immunization with a trivalent vaccine would gain 186 QALYs and prevent more than €3.1 million in health care costs when implemented in addition to IAP. Immunization implemented as a replacement for IAP would gain 88 QALYs compared to the current prevention strategy, prevent €1.5 million in health care costs, and avoid potentially ~ 30,000 IAP administrations. The base-case results correspond to a maximum price of €58 per dose (vaccine + administration costs; using a threshold of €20,000/QALY). Expanding the serotype coverage to a hexavalent vaccine would only have a limited additional impact on the cost-effectiveness in the Netherlands. A maternal GBS vaccine could be cost-effective when implemented in addition to the current risk factor-based IAP prevention strategy in the Netherlands. Discontinuation of IAP would save costs and prevent antibiotic use, however, is projected to lead to a lower health gain compared to vaccination in addition to IAP.

GBS (group B streptococcus) is an opportunistic pathogen that can colonize healthy individuals but presents significant challenges in clinical obstetrics and gynecology, as it can cause miscarriage, preterm birth, and invasive infections in newborns. To develop specific and personalized preventative strategies, a better understanding of the epidemiological characteristics and pathogenic features of GBS is essential. We conducted a comprehensive strain-level genomic analysis of GBS, examining serotype and genotype distributions, as well as the composition and correlations of virulence genes using the blastn-short mode of the BLAST program(v2.10.0+), mlstsoftware (https://github.com/tseemann/mlst), Snippy (v4.6.0), FastTree (v2.1.11) and iTOL. The coding sequence region of virulence factors was annotated by Prodigal (v2.6.3) and Glimmer(v3.02b). We further identified host protein interacting with Srr2 by mass spectrometry analysis. While certain genotypes showed strong serotype consistency, there was no significant association between overall serotypes and genotypes. However, the composition of virulence genes was more closely related to the phylogeny of GBS, among which simultaneous presence of Srr2 and HygA exhibit significant association with hypervirulence. Tubulin emerged as the most distinct and abundant hit. The specific interaction of Tubulin with Srr2-BR, rather than Srr1-BR, was further confirmed by immunoblotting. Considering the impact of cytoskeleton rearrangement on GBS pathogenesis, this observation offers a plausible explanation for the hypervirulence triggered by Srr2. Collectively, our findings indicate that in the future clinical practice, virulence gene detection should be given more attention to achieve precise GBS surveillance and disease prevention.

or Group B (GBS) causes serious infections in neonates with a particularly high burden of disease in Africa. Maternal vaginal colonization is the primary source of neonatal transmission. Molecular surveillance of the maternal GBS population is crucial for informing maternal vaccine development and monitoring of the global circulation of GBS clones. The current study analyzes the structure and diversity of the clustered regularly interspaced palindromic repeat (CRISPR)-associated (Cas) system and phage content in colonizing GBS isolates collected from healthy pregnant women from Ismailia, Egypt. The isolates were characterized by whole-genome sequencing within the global JUNO project. CRISPR arrays and phages were detected in a vast majority of GBS isolates. A strong congruence was observed between multilocus sequence typing (MLST), CRISPR profile, and phage content. Region-specific sequence types (STs) observed only in Africa were distinguishable from other lineages. CRISPR typing is a promising low-cost tool for investigating the population structure of GBS clones, particularly in middle- and low-income countries.

•Maternal GBS vaccination could prevent many neonatal deaths in low-income sub-Saharan Africa.•Immunization during pregnancy could cut GBS deaths by 30%-55% in typical sub-Saharan settings.•To show the full cost of vaccination, cost/dose includes vaccine price and delivery cost.•Maternal GBS vaccine is cost-effective at $2 to more than $20/dose, depending on efficacy and disease incidence.•A maternal GBS vaccine would be cost-effective in low-income sub-Saharan Africa. A maternal group B streptococcal (GBS) vaccine could prevent neonatal sepsis and meningitis. Its cost-effectiveness in low-income sub-Saharan Africa, a high burden region, is unknown. We used a decision tree model, with Markov nodes to project infants’ lifetimes, to compare maternal immunization delivered through routine antenatal care with no immunization. 37 countries were clustered on the basis of economic and health resources and past public health performance. Vaccine efficacy for covered serotypes was ranged from 50% to 90%. The model projected EOGBS (early-onset) and LOGBS (late-onset) cases and deaths, disability-adjusted life years (DALYs), healthcare costs (2014 US$), and cost-effectiveness for a representative country in each of the four clusters: Guinea-Bissau, Uganda, Nigeria, and Ghana. Maximum vaccination costs/dose were estimated to meet two cost-effectiveness benchmarks, 0.5 GDP and GDP per capita/DALY, for ranges of disease incidence (reported and adjusted for under-reporting) and vaccine efficacy. At coverage equal to the proportion of pregnant women with≥4 antenatal visits (ANC4) and serotype-specific vaccine efficacy of 70%, maternal GBS immunization would prevent one-third of GBS cases and deaths in Uganda and Nigeria, where ANC4 is 50%, 42–43% in Guinea-Bissau (ANC4=65%), and 55–57% in Ghana (ANC4=87%). At a vaccination cost of $7/dose, maternal immunization would cost $320-$350/DALY averted in Guinea-Bissau, Nigeria, and Ghana, less than half these countries’ GDP per capita. In Uganda, which has the lowest case fatality ratios, the cost would be $573/DALY. If the vaccine prevents a small proportion of stillbirths, it would be even more cost-effective. Vaccination cost/dose, disease incidence, and case fatality were key drivers of cost/DALY in sensitivity analyses. Maternal GBS immunization could be a cost-effective intervention in low-income sub-Saharan Africa, with cost-effectiveness ratios similar to other recently introduced vaccines. The vaccination cost at which introduction is cost-effective depends on disease incidence and vaccine efficacy. Clinical Trial registry name and registration number: Not applicable.

It is estimated that about 11–35% of pregnant women are colonized with Group B streptococcus. Intrapartum antibiotic prophylaxis (IAP) is the primary intervention to decrease the risk of infecting babies born to GBS colonized mothers. A total of 5,996 pregnant women, who received the Taiwanese universal GBS screening program from 2012 to 2020, were included in this study that investigated GBS colonization, antimicrobial resistance rates and their neonatal incidence of invasive GBS infection. The average GBS colonization rate was 18.5%. Older age groups had higher colonization rates than younger age groups. Compared to Taiwanese, immigrant women from Indonesia had a greater positive rate. GBS isolated from Vietnamese women had significant greater resistance to clindamycin relative to Taiwanese women. Rates of resistance to erythromycin increase from 35.5% to 45.5% over the 9 years of measurements. The incidence of invasive GBS disease was about 0.6/1,000 (4/6,204) live births during the study. Although relatively low incidence of invasive GBS diseases was observed after implementation of IAP, the colonization of GBS remains high and antimicrobial resistance of GBS is increasing. An effective GBS vaccine holds promise to be a solution for these issues.

In the last two decades, group B streptococcus (GBS) infection has established itself as a major cause of perinatal morbidity and mortality. The purpose of this study is to identify if the electively induced labor with oxytocin in women with positive cultures of Streptococcus agalactiae, namely the group B streptococcus (GBS), helps the mother and fetus and decreases the risk associated with perinatal transmission of GBS compared with the spontaneous labor. Results associated with induction of labor with oxytocin compared with spontaneous labor in pregnant women who have GBS - positive cervical cultures, are also used to determine whether induction of labor decreases the risk of complications from GBS infection.

Background Group B Streptococcus (GBS) infection is the leading cause of septicemia, meningitis, and pneumonia in neonates. Aberrant gut colonization in early life may predispose children to various diseases in adulthood. However, the associations between gut microbial changes and GBS colonization is still unclear. Results The composition and diversity of meconium microbiota in GBS group were similar to that of healthy controls. However, we identified several specific taxa that were differentially abundant between the two groups (linear discriminant analysis (LDA) effect size (LEfSe): p  < 0.05, LDA > 2.0). Particularly, the relative abundance of Lactobacillus paracasei was significantly reduced, indicating a role in GBS colonization. Conclusions Our study presented a series of bacterial species colonized by GBS, thus providing novel evidence in support of initial intestinal microbiota dysbiosis in the neonates with mother’s GBS colonization.