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Maternal antibody at delivery protects neonates from early onset group B streptococcal disease.

ABSTRACT: Further reduction in the group B streptococcal (GBS) disease burden in neonates in the United States awaits an additional prevention strategy, such as maternal immunization.We performed a prospective, multicenter, case-control study of 33 mothers delivering neonates with early onset GBS infection (cases), and 99 age- and ethnicity-matched mothers colonized with the same capsular polysaccharide (CPS) types delivering healthy neonates (controls). Relative risk and absolute risk were calculated for early onset disease associated with concentrations of type Ia, III, or V CPS-specific antibody in maternal serum.For GBS types Ia and III, maternal CPS-specific antibody concentrations of ? 0.5 µg/mL were associated with a relative risk of approximately 0.1 (95% confidence intervals [CIs], .01-.74 and 0-.72, respectively; P = .02 for each), corresponding to a 90% risk reduction (by logistic regression). For type V, the relative risk was 0.3 (95% CI, .01-3.1), corresponding to a 70% risk reduction. By Bayesian modeling, the risk of early onset disease would decrease by 70% if maternal CPS-specific antibody concentrations for these 3 GBS types were ? 1 µg/mL.Maternal CPS-specific antibody serum concentrations of ? 1 ?g/mL at the time of delivery appear to protect most neonates from early onset GBS type Ia and III disease.

SUBMITTER: Baker CJ

PROVIDER: S-EPMC3923540 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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Maternal antibody at delivery protects neonates from early onset group B streptococcal disease.

Baker Carol J CJ Carey Vincent J VJ Rench Marcia A MA Edwards Morven S MS Hillier Sharon L SL Kasper Dennis L DL Platt Richard R

The Journal of infectious diseases 20131016 5

<h4>Background</h4>Further reduction in the group B streptococcal (GBS) disease burden in neonates in the United States awaits an additional prevention strategy, such as maternal immunization.<h4>Methods</h4>We performed a prospective, multicenter, case-control study of 33 mothers delivering neonates with early onset GBS infection (cases), and 99 age- and ethnicity-matched mothers colonized with the same capsular polysaccharide (CPS) types delivering healthy neonates (controls). Relative risk an ...[more]

PMID: 24133184

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Project description:ImportanceInvasive disease owing to group B Streptococcus (GBS) remains an important cause of illness and death among infants younger than 90 days in the United States, despite declines in early-onset disease (EOD; with onset at 0-6 days of life) that are attributed to intrapartum antibiotic prophylaxis (IAP). Maternal vaccines to prevent infant GBS disease are currently under development.ObjectiveTo describe incidence rates, case characteristics, antimicrobial resistance, and serotype distribution of EOD and late-onset disease (LOD; with onset at 7-89 days of life) in the United States from 2006 to 2015 to inform IAP guidelines and vaccine development.Design, setting, and participantsThis study used active population-based and laboratory-based surveillance for invasive GBS disease conducted through Active Bacterial Core surveillance in selected counties of 10 states across the United States. Residents of Active Bacterial Core surveillance areas who were younger than 90 days and had invasive GBS disease in 2006 to 2015 were included. Data were analyzed from December 2017 to April 2018.ExposuresGroup B Streptococcus isolated from a normally sterile site.Main outcomes and measuresEarly-onset disease and LOD incidence rates and associated GBS serotypes and antimicrobial resistance.ResultsThe Active Bacterial Core surveillance program identified 1277 cases of EOD and 1387 cases of LOD. From 2006 to 2015, EOD incidence declined significantly from 0.37 to 0.23 per 1000 live births (P < .001), and LOD rates remained stable (mean, 0.31 per 1000 live births). Among the mothers of 1277 infants with EOD, 617 (48.3%) had no indications for IAP and did not receive it, and 278 (21.8%) failed to receive IAP despite having indications. Serotype data were available for 1743 of 1897 patients (91.3%) from 7 sites that collect GBS isolates. Among patients with EOD, serotypes Ia (242 [27.3%]) and III (242 [27.3%]) were most common. Among patients with LOD, serotype III was most common (481 [56.2%]), and this increased from 2006 to 2015 from 0.12 to 0.20 cases per 1000 live births (P < .001). Serotype IV caused 53 cases (6.2%) of EOD and LOD combined. The 6 most common serotypes (Ia, Ib, II, III, IV, and V) caused 881 EOD cases (99.3%) and 853 LOD cases (99.7%). No β-lactam resistance was identified; 359 isolates (20.8%) tested showed constitutive clindamycin resistance. In 2015, an estimated 840 EOD cases and 1265 LOD cases occurred nationally.Conclusions and relevanceThe rates of LOD among US infants are now higher than EOD rates. Combined with addressing IAP implementation gaps, an effective vaccine covering the most common serotypes might further reduce EOD rates and help prevent LOD, for which there is no current public health intervention.

Project description:BACKGROUND:Early-onset group B streptococcal (EOGBS) disease (including sepsis, meningitis, and pneumonia) causes significant morbidity and mortality in newborn infants worldwide. Antibiotic prophylaxis can prevent vertical streptococcal transmission, yet no uniform criteria exist to identify eligible women for prophylaxis. Some guidelines recommend universal GBS screening to pregnant women in their third trimester (screening-based protocol), whereas others employ risk-based protocols. OBJECTIVES:To compare the effectiveness of screening-based versus risk-based protocols in preventing EOGBS disease. SEARCH STRATEGY:Key words for the database searches included GBS, Streptococcus agalactiae, pregnancy, screening, culture-based, risk-based. SELECTION CRITERIA:Studies were included if they investigated EOGBS disease incidence in newborn infants and compared screening or risk-based protocols with each other or with controls. DATA COLLECTION AND ANALYSIS:Risk ratios (RR) and 95% confidence intervals (CI) were determined using Mantel-Haenszel analyses with random effects. MAIN RESULTS:Seventeen eligible studies were included. In this meta-analysis, screening was associated with a reduced risk for EOGBS disease compared either with risk-based protocols (ten studies, RR 0.43, 95% CI 0.32-0.56) or with no policy (four studies, RR 0.31, 95% CI 0.11-0.84). Meta-analysis could not demonstrate a significant effect of risk-based protocols versus no policy (seven studies, RR 0.86, 95% CI 0.61-1.20). In studies reporting on the use of antibiotics, screening was not associated with higher antibiotic administration rates (31 versus 29%). CONCLUSIONS:Screening-based protocols were associated with lower incidences of EOGBS disease compared with risk-based protocols, while not clearly overexposing women to antibiotics. This information is of relevance for future policymaking. TWEETABLE ABSTRACT:Meta-analysis: general screening is associated with lower rates of early-onset group B strep. neonatal sepsis compared with risk-based protocols.

Project description:Group B Streptococcus (GBS) is a major opportunistic pathogen in certain adult populations, including pregnant women, and remains a leading etiologic agent of newborn disease. During pregnancy, GBS asymptomatically colonizes the vaginal tract of 20-30% of healthy women, but can be transmitted to the neonate in utero or during birth resulting in neonatal pneumonia, sepsis, meningitis, and subsequently 10-15% mortality regardless of antibiotic treatment. While various GBS virulence factors have been implicated in vaginal colonization and invasive disease, the regulation of many of these factors remains unclear. Recently, CRISPR-associated protein-9 (Cas9), an endonuclease known for its role in CRISPR/Cas immunity, has also been observed to modulate virulence in a number of bacterial pathogens. However, the role of Cas9 in GBS colonization and disease pathogenesis has not been well-studied. We performed allelic replacement of cas9 in GBS human clinical isolates of the hypervirulent sequence-type 17 strain lineage to generate isogenic Δcas9 mutants. Compared to parental strains, Δcas9 mutants were attenuated in murine models of hematogenous meningitis and vaginal colonization and exhibited significantly decreased invasion of human brain endothelium and adherence to vaginal epithelium. To determine if Cas9 alters transcription in GBS, we performed RNA-Seq analysis and found that 353 genes (>17% of the GBS genome) were differentially expressed between the parental WT and Δcas9 mutant strain. Significantly dysregulated genes included those encoding predicted virulence factors, metabolic factors, two-component systems (TCS), and factors important for cell wall formation. These findings were confirmed by qRT-PCR and suggest that Cas9 may regulate a significant portion of the GBS genome. We studied one of the TCS regulators, CiaR, that was significantly downregulated in the Δcas9 mutant strain. RNA-Seq analysis of the WT and ΔciaR strains demonstrated that almost all CiaR-regulated genes were also significantly regulated by Cas9, suggesting that Cas9 may modulate GBS gene expression through other regulators. Further we show that CiaR contributes to GBS vaginal colonization and persistence. Altogether, these data highlight the potential complexity and importance of the non-canonical function of Cas9 in GBS colonization and disease.

Dataset Information

Maternal antibody at delivery protects neonates from early onset group B streptococcal disease.

Publications

Maternal antibody at delivery protects neonates from early onset group B streptococcal disease.

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