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Objectives: (1) To describe the epidemiology of neonatal group B streptococcal (GBS) disease over five years (1997–2001) in the Netherlands, stratified for proven and probable sepsis and for very early (<12 h), late early (12 h – <7 days) and late (7–90 days) onset sepsis. (2) To evaluate the effect of the introduction in January 1999 of guidelines for prevention of early onset GBS disease based on risk factors. Methods: Data on cases were collected in collaboration with the Dutch Paediatric Surveillance Unit and corrected for under-reporting by the capture-recapture technique. Results: Total incidence of proven very early onset, late early onset and late onset GBS sepsis was 0.32, 0.11 and 0.14 per 1000 live births, respectively, and of probable very early onset, late early onset and late onset GBS sepsis was 1.10, 0.18 and 0.02 per 1000 live births, respectively. Maternal risk factors were absent in 46% of the proven early onset cases. Considerably more infants with proven GBS sepsis were boys. 64% of the infants with proven very early onset GBS sepsis were first borns compared with 47% in the general population. After the introduction of guidelines the incidence of proven early onset sepsis decreased considerably from 0.54 per 1000 live births in 1997–8 to 0.36 per 1000 live births in 1999–2001. However, there was no decrease in the incidence of meningitis and the case fatality rate in the first week of life. The incidence of late onset sepsis also remained unchanged. Conclusion: After the introduction prevention guidelines based on risk factors there has been a limited decrease in the incidence of proven early onset GBS sepsis in the Netherlands. This study therefore recommends changing the Dutch GBS prevention guidelines.

Objectives: To quantify long term impairment after neonatal meningitis. Design: Longitudinal case-control study over 9–10 years. Subjects and methods: A total of 111 children who had suffered neonatal meningitis were seen and compared with 113 matched controls from their birth hospital and 49 controls from general practices. Assessments included the WISC IIIUK , movement assessment battery for children (mABC), audiometry, vision testing, and social and medical data. Statistical analysis was by multiple regression, analysis of variance, and χ2 tests. Results: Some 10.8% of cases had a severe and 9% a moderate overall outcome compared with 0% and 1.8% for the hospital controls. The mean intelligence quotient (IQ) of the cases (88.8) was significantly less than that of the hospital controls (99.4) or the GP controls (99.6) . The mABC score was significantly worse for the cases (7.08) than the hospital (5) or GP (4) controls. Some 3.6% of cases had sensorineural hearing loss, 2.7% had persisting hydrocephalus; no controls did. Some 5.4% of cases and 1.7% of hospital controls had treatment for seizures. Conclusions: Severe neurodisability and milder motor and psychometric impairment result from neonatal meningitis. Both clinical follow up and comprehensive developmental assessment are needed after this disease.

► Group B streptococcal type III capsular polysaccharide (CPSIII) is an important Ag. ► We compared a panel of different mAbs to CPSIII using multiple immunoassays. ► MAbs showed unique patterns of fine specificity and host-reactivity. ► These studies raise caution in developing CPSIII-based vaccines. Group B streptococcus (GBS) is a major cause of neonatal sepsis and meningitis. Despite aggressive campaigns using antenatal prophylactic antibiotic therapy, infections continue. Developing an effective maternal vaccine is a public health priority. Antibody (Ab) to the capsular polysaccharide (CPS) is considered the dominant “protective” immune mediator. Here we study the fine specificity and potential host reactivity of a panel of well-characterized murine monoclonal Abs against the type III CPS by examining the binding of the Abs to intact and neuraminidase-digested GBS, purified CPS, synthetic carbohydrate structures, and cells. The results showed marked differences in the fine specificity among these mAbs to a single carbohydrate structure. Cross-reactions with synthetic GD3 and GT3 carbohydrates, representing structures found on surfaces of neural and developing cells, were demonstrated using carbohydrate array technology. The anti-CPSIII mAbs did not react with cells expressing GD3 and GT3, nor did mAbs specific for the host carbohydrates cross-react with GBS, raising questions about the physiological relevance of this cross-reaction. But in the process of these investigations, we serendipitously demonstrated cross-reactions of some anti-CPSIII mAbs with antigens, likely carbohydrates, found on human leukocytes. These studies suggest caution in the development of a maternal vaccine to prevent infection by this important human pathogen.

Preterm birth and infectious diseases are the most common causes of neonatal and early childhood deaths worldwide. The rates of preterm birth have increased over recent decades and account for 11% of all births worldwide. Preterm infants are at significant risk of severe infection in early life and throughout childhood. Bacteraemia, inflammation, or both during the neonatal period in preterm infants is associated with adverse outcomes, including death, chronic lung disease, and neurodevelopmental impairment. Recent studies suggest that bacteraemia could trigger cerebral injury even without penetration of viable bacteria into the CNS. Here we review available evidence that supports the concept of a strong association between bacteraemia, inflammation, and cerebral injury in preterm infants, with an emphasis on the underlying biological mechanisms, clinical correlates, and translational opportunities.

Background. Late-onset sepsis is a major problem in neonatology, but the habitat of the pathogens before bloodstream invasion occurs is not well established. Methods. We examined prospectively collected stools from premature infants with sepsis to find pathogens that subsequently invaded their bloodstreams, and sought the same organisms in stools of infants without sepsis. Culture-based techniques were used to isolate stool bacteria that provisionally matched the bloodstream organisms, which were then genome sequenced to confirm or refute commonality. Results. Of 11 children with late-onset neonatal bloodstream infections, 7 produced at least 1 stool that contained group B Streptococcus (GBS), Serratia marcescens, or Escherichia coli before their sepsis episode with provisionally matching organisms. Of 96 overlap comparison subjects without sepsis temporally associated with these cases, 4 were colonized with provisionally matching GBS or S. marcescens. Of 175 comparisons of stools from randomly selected infants without sepsis, 1 contained a GBS (this infant had also served as an overlap comparison subject and both specimens contained provisionally matching GBS). Genome sequencing confirmed common origin of provisionally matching fecal and blood isolates. The invasive E. coli were present in all presepticemic stools since birth, but gut colonization with GBS and S. marcescens occurred closer to time of bloodstream infection. Conclusions. The neonatal gut harbors sepsis-causing pathogens, but such organisms are not inevitable members of the normal microbiota. Surveillance microbiology, decolonization, and augmented hygiene might prevent dissemination of invasive bacteria between and within premature infants.

A highly conserved fragment adjacent to the cfb gene encoding the CAMP factor is the target of PCR-based molecular diagnostic systems for the identification of S. agalactiae (group B streptococci (GBS)). Six PCR-negative, culture-positive GBS strains were whole genome sequenced to assess why they escaped molecular diagnostics. GBS strains did not constitute a clonal cluster and presented variably sized chromosomal deletions (from 7 to 33 kb) which always included the cfb gene, a finding never described before. GBS strains that escape molecular diagnostics are considered rare; however, they can cause false-negative results using molecular diagnostics alone, affecting medical decisions.

Background We describe the serotype distribution of Streptococcus agalactiae (GBS) carriage isolates from women in labor and among GBS isolates causing invasive infections during the same period to see if the distribution of carriage serotypes reflects the GBS serotypes causing invasive diseases including early-onset disease (EOGBS). Methods Data on invasive isolates from 2019 including serotype, erythromycin and clindamycin susceptibility was retrieved from the Danish national reference laboratory, Statens Serum Institut. Carriage isolates were collected from women with risk factors for EOGBS enrolled at delivery at the maternity ward at a Danish University Hospital, first half of 2019. Results Among carriage isolates, the dominant serotype was IX (21 %) followed by serotype III (19 %). The resistance to erythromycin and clindamycin was 21 and 26 %, respectively. Among invasive GBS isolates, no case of EOGBS with serotype IX was detected but the distribution of serotypes were otherwise similar to the GBS carrier strains. The corresponding resistance to erythromycin and clindamycin was 23  and 15 %, respectively. Penicillin resistance was not detected among carriage nor invasive isolates. Conclusions The distribution of serotypes among carriage and invasive GBS reflects the assumption that EOGBS occur following transmission of GBS from mother to newborn, with the exception of serotype IX.

Introduction Group B Streptococci (GBS) colonize almost one third of human gastrointestinal and genitourinary tracts, particularly in females. The aim of this study is to evaluate the epidemiology, microbiological characteristics, and clinical outcomes of invasive GBS disease in Qatar from all age groups. Methods A retrospective study was conducted on patients with confirmed GBS blood stream infections during the period between January 2015 and March 2019. Microbiological identification was performed using automated BD PhoenixTM system, while additional antimicrobial susceptibility tests were performed using E test and disc diffusion methods. Result During the four years period, the incidence steadily rose from 1.48 to 2.09 cases per 100.000 population. Out of 196 confirmed cases of invasive GBS infections, the majority were females (63.7%, 125/196) of which 44.8% were pregnant and 53.6% were colonized. Three distinct affected age groups were identified: children ≤ 4 years of age (35.7%), young adults 25–34 (20.9%) and the elderly ≥ 65 year (17.4%). Presenting symptoms were mild with fever in 53% of cases while 89% of cases had Pitt bacteraemia score of ≤ 2. Isolates were universally sensitive to penicillin, ceftriaxone, and vancomycin at 100% but with significant resistance to erythromycin (49%) and clindamycin (28.6%) while 16.8% had inducible clindamycin resistance. Clinical outcomes showed cure rate of 87.25% with complications in (8.76%) and 4% mortality. Conclusion There is a rising trend of Group B Streptococcal blood stream infections in Qatar with significantly high clindamycin and erythromycin resistance rates. Universal susceptibility rates were demonstrated for penicillin, ceftriaxone, and vancomycin.

Background The emergence of Streptococcus agalactiae infections in patients with bacteremia is increasing. It is crucial to investigate the epidemiology, molecular characteristics, biofilm status, and virulence analysis of Streptococcus agalactiae in these patients. Methods In this cross-sectional study, 61 S. agalactiae isolated from blood infection were subjected to characterization through antimicrobial susceptibility tests, biofilm formation, multilocus sequence typing (MLST), and PCR analysis for detecting resistance ( tet and erm family) and virulence genes (alp2/3 , alp4 , bca , bac , eps , rib , lmb , cylE , and pilus island genes). Results Overall, 32.7% of the isolates demonstrated an inducible clindamycin resistance phenotype. The results showed that 49.2, 24.6, and 8.2% of confirmed Streptococcus agalactiae strains were classified as strong, intermediate, and weak biofilm-forming strains, respectively. tet (M) (57.1%) was recovered most, followed by tet (M)  + tet (L) (14.3%), tet (S) +  tet (K) (10.7%), tet (M) +  tet (K) (8.9%), tet (M) +  tet (K) +  tet (O) (5.4%), and tet (S) +  tet (L) +  tet (O) (3.6%). Three virulence gene profiles of cylE , lmb , bca , rib (24.6%; 15/61), cylE , lmb , rib , alp3 (19.7%; 12/61), and cylE , lmb , bac , rib (16.4%; 10/61) were detected in approximately two-thirds of the isolates. MLST revealed that the 61 isolates belonged to six clonal complexes, including CC1 (49.2%), followed by CC12 (18%), CC19 (13.1%), CC22 (9.8%), CC17 (6.6%), and CC283 (3.3%), and 11 different sequence types (STs), including ST1 (24.6%), ST7 (14.8%), ST918 (13.1%), ST2118 (9.8%), ST19 (9.8%), ST48 (6.6%), ST1372 (4.9%), ST22 (4.9%), ST40 (4.9%), ST734 (3.3%), and ST283 (3.3%). Remarkably, all CC1 and CC12 isolates, three-fourths of CC19, and half of CC22 were confirmed as biofilm producers. Conversely, CC17 and CC28 isolates were found to be nonproducers. The occurrence of strong biofilm formation was limited to specific CCs, namely CC1 (34.4%), CC12 (8.2%), CC19 (3.3%), and CC22 (3.3%). Conclusion The high prevalence of CC1 and CC12 clones among S. agalactiae strains reflects the emergence of these lineages as successful clones in Iran, which is a serious concern and poses a potential threat to patients.

Timely and accurate detection of Group B Streptococcus (GBS) carriage in pregnant women allows for targeted peripartum prophylaxis. Replacing culture-based screening by molecular biology assays enables faster results obtention, better targeted antibiotic prophylaxis, and reduces the laboratory workload. Here, we present a comparative analysis between a Loop Mediated Isothermal Amplification assay (HiberGene GBS kit) and culture (gold-standard). The HiberGene GBS kit showed a sensitivity of 97.9% and a specificity of 96.8% compared with culture. The limit of detection was estimated at 10 3  cfu/ml and results were obtained within 30 min. HiberGene GBS assay can be used for peripartum GBS screening and targeted antibiotic prophylaxis provided sample processing can be swiftly performed around the clock.