Persistence of group B Streptococcus vaginal colonization and prevalence of hypervirulent CC-17 clone correlate with the country of birth: a prospective 3-month follow-up cohort study.

To identify factors associated with vaginal colonization and persistence by group B Streptococcus (GBS) and by the hypervirulent neonatal CC-17 clone in late pregnancy and after delivery, a multicentre prospective observational cohort with 3-month follow-up was established in two university hospitals, Paris area, France. Pregnant women were recruited when antenatal screening for GBS vaginal colonization at 34-38 weeks of gestational age was positive. Vaginal samples were analysed by conventional culture methods at antenatal screening, delivery, and 21 and 60 days following delivery. Identification of the hypervirulent neonatal GBS CC-17 was performed. Colonization was defined as persistent when all vaginal samples were positive for GBS. A total of 754 women were included. GBS vaginal colonization was persistent in 63% of the cases (95% CI 59%-67%). Persistent colonization was more likely in women born in Sub-Saharan Africa compared with women born in France (OR = 1.88, 95% CI 1.05-3.52), and GBS CC-17 was overrepresented in women born in Sub-Saharan Africa (OR = 2.09, 95% CI 1.20-3.57). Women born in Sub-Saharan Africa are at higher risk for GBS vaginal persistence than women born in France. This observation correlates with an increased prevalence of the hypervirulent GBS CC-17 in the former group, which likely reflect variations linked to ethnicity and vaginal community-state types and might account for the increased susceptibility of black neonates to GBS infections.

Risk Factors for Infant Colonization by Hypervirulent CC17 Group B Streptococcus: Toward the Understanding of Late-onset Disease.

BACKGROUND: In infants, the mode of acquisition of CC17 group B Streptococcus (GBS), the hypervirulent clone responsible for late-onset disease (LOD), remains elusive. METHODS: In a prospective multicenter study in France, we evaluated GBS colonization in mother-baby pairs with 2 months of follow-up between 2012 and 2015. Criteria included positivity for GBS colonization at antenatal screening or at delivery. Maternal vaginal samples and infant oral cavity and stool samples were analyzed at delivery, 21 ± 7 days (D21), and 60 ± 7 days (D60) post-delivery. RESULTS: A total of 890 mother-baby pairs were analyzed. GBS colonized 7%, 21%, and 23% of the infants at birth, D21, and D60, respectively, of which 10%, 11%, and 13% were identified as CC17 GBS. Concordance between maternal and infant GBS type was 96%. At D21, the main risk factors for infant colonization by GBS were simultaneous maternal colonization of the vagina (odds ratio [OR], 4.50; 95% confidence interval [CI], 1.69-15.61) and breast milk (OR, 7.93; 95% CI, 3.81-17.14). Importantly, 38% (95% CI, 23%-56%) of infants colonized by CC17 GBS appeared colonized for the first time at D60 vs 18% (95% CI, 14%-24%; P < .049) of infants colonized by non-CC17 GBS. Multivariate analysis showed a higher risk for de novo infant colonization by CC17 at D60 than by other GBS (OR, 2.45; 95% CI, 1.02-5.88). CONCLUSIONS: The high incidence of CC17 GBS in LOD is likely due to an enhanced post-delivery mother-to-infant transmission.

Clinical and Laboratory Features of Group B Streptococcus Meningitis in Infants and Newborns: Study of 848 Cases in France, 2001-2014.

Background: Group B Streptococcus (GBS) disease is the leading cause of neonatal bacterial meningitis despite women receiving an intravenous antibiotic prophylaxis during labor. We aimed to describe GBS meningitis in children <1 year old in France. Methods: Clinical and biological data of GBS meningitis gathered by the Association Clinique et Thérapeutique Infantile du Val de Marne (ACTIV) were analyzed. The cases were classified by age: 0-6 days old (early-onset disease [EOD]), newborns and infants 7-89 days old (late-onset disease [LOD]: LOD1, 7-26 days; LOD2, 27-89 days), and infants aged 3 months to 1 year (infant disease). Results: Among 848 GBS meningitis cases from 2001 to 2014, the incidence of EOD decreased by 63.3% (95% confidence interval [CI], 43.9%-80.1%]; P < .001) and that of LOD increased by 58.1% (95% CI, 39.1%-75.5%); P < .001) (52.9% and 64.3% for LOD1 and LOD2, respectively). The mean gestational age (GA) decreased significantly for EOD, LOD1, LOD2, and infant disease cases (38.7, 38.6, 37.3, and 34 weeks, respectively). Serotype III accounted for 83.9% of cases, with no significant difference among the 4 groups or by GA. The frequency of GBS belonging to the clonal complex 17 did not differ among the 4 groups. Case mortality was 11.4%. Conclusions: In the era of intravenous antibiotic prophylaxis, we found decreased incidence of early-onset GBS meningitis but, unexpectedly, increased incidence of LOD. These data underline the interest in the development of effective GBS vaccines for pregnant women.

Characterization of Streptococcus pyogenes isolates responsible for adult meningitis in France from 2003 to 2013.

Sixty-three cases of Streptococcus pyogenes meningitis in adults were studied. Three predominant emm types were associated with meningitis: emm1 (44%), emm3 (11%), and emm6 (11%). Streptococcal toxic shock syndrome and mortality rates were 40% and 38%, respectively.

Whole-Genome Comparison Uncovers Genomic Mutations between Group B Streptococci Sampled from Infected Newborns and Their Mothers.

UNLABELLED: Streptococcus agalactiae (group B Streptococcus or GBS), a commensal of the human gut and genitourinary tract, is a leading cause of neonatal infections, in which vertical transmission from mother to child remains the most frequent route of contamination. Here, we investigated whether the progression of GBS from carriage to disease is associated with genomic adaptation. Whole-genome comparison of 47 GBS samples from 19 mother-child pairs uncovered 21 single nucleotide polymorphisms (SNPs) and seven insertions/deletions. Of the SNPs detected, 16 appear to have been fixed in the population sampled whereas five mutations were found to be polymorphic. In the infant strains, 14 mutations were detected, including two independently fixed variants affecting the covRS locus, which is known to encode a major regulatory system of virulence. A one-nucleotide insertion was also identified in the promoter region of the highly immunogenic surface protein Rib gene. Gene expression analysis after incubation in human blood showed that these mutations influenced the expression of virulence-associated genes. Additional identification of three mutated strains in the mothers' milk raised the possibility of the newborns also being a source of contamination for their mothers. Overall, our work showed that GBS strains in carriage and disease scenarios might undergo adaptive changes following colonization. The types and locations of the mutations found, together with the experimental results showing their phenotypic impact, suggest that those in a context of infection were positively selected during the transition of GBS from commensal to pathogen, contributing to an increased capacity to cause disease. IMPORTANCE: Group B Streptococcus (GBS) is a major pathogen responsible for neonatal infections. Considering that its colonization of healthy adults is mostly asymptomatic, the mechanisms behind its switch from a commensal to an invasive state are largely unknown. In this work, we compared the genomic profile of GBS samples causing infections in newborns with that of the GBS colonizing their mothers. Multiple mutations were detected, namely, within key virulence factors, including the response regulator CovR and surface protein Rib, potentially affecting the pathogenesis of GBS. Their overall impact was supported by differences in the expression of virulence-associated genes in human blood. Our results suggest that during GBS's progression to disease, particular variants are positively selected, contributing to the ability of this bacterium to infect its host.

Comparative evaluation of 5 different selective media for Group B Streptococcus screening in pregnant women.

We compared the performances and the cost-effectiveness of 5 selective media for Group B Streptococcus (GBS) screening in vaginal samples from pregnant women. The usefulness of these media is unquestionable for GBS screening; the choice will depend largely on the laboratory organization.

Molecular characterization of Streptococcus agalactiae isolates harboring small erm(T)-carrying plasmids.

Among 1,827 group B Streptococcus (GBS) strains collected between 2006 and 2013 by the French National Reference Center for Streptococci, 490 (26.8%) strains were erythromycin resistant. The erm(T) resistance gene was found in six strains belonging to capsular polysaccharides Ia, III, and V and was carried by the same mobilizable plasmid, which could be efficiently transferred by mobilization to GBS and Enterococcus faecalis recipients, thus promoting a broad dissemination of erm(T).

[Maternal and perinatal infections to Streptococcus agalactiae]. / Infections materno-fœtales à Streptococcus agalactiae.

Streptococcus agalactiae (Group B Streptococcus, GBS) is a Gram-positive encapsulated bacterium, found in the digestive and vaginal tracts of 20-30% healthy individuals. It is the leading cause of neonatal invasive infections (septicaemia and meningitis). Two GBS-associated syndromes have been recognized in neonates, the early-onset disease (EOD) and the late-onset disease (LOD), which occur in the first week of life (age 0-6 days) and after (age 7 days-3 months), respectively. Since the establishment of early antibiotic prophylaxis there has been a decrease in the incidence of EOD. However, LOD incidence remains stable. Epidemiological studies revealed a strong association between LOD and a single capsular serotype III ST-17 clone. This ST-17 clone, referred to as the "hypervirulent" clone, possesses specific virulence factors that could account for its increased virulence and neonatal tropism. Conjugate vaccines directed against several capsular serotypes are being developed to prevent invasive disease. However, hypervirulent strains having made a switch to a capsular serotype not covered by such vaccines are emerging, reinforcing the need to identify new candidate vaccines.

Group A Streptococcus endometritis following medical abortion.

Medical abortion is not recognized as a high-risk factor for invasive pelvic infection. Here, we report two cases of group A Streptococcus (GAS; Streptococcus pyogenes) endometritis following medical abortions with a protocol of oral mifepristone and misoprostol.