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Objectives: Certain Group B Streptococcus (GBS) genotypes are associated with invasive disease in neonates. We conducted a comparative genomic analysis of GBS isolates from neonatal disease and maternal carriage in the Netherlands to determine distribution of genetic markers between the two host groups. Methods: Whole genome sequencing was used to characterise 685 neonatal invasive isolates (2006-2021) and 733 maternal carriage isolates (2017-2021) collected in the Netherlands. Results: Clonal complex (CC) 17 and serotype III were significantly more common in disease while carriage isolates were associated with serotypes II, IV, V as well as CC1. Previously reported CC17-A1 sub-lineage was dominant among disease isolates and significantly less common in carriage. The phiStag1 phage, previously associated with expansion of invasive CC17 isolates in the Netherlands, was more common among disease isolates compared to carriage isolates overall, however it was equally distributed between CC17 isolates from carriage and disease. Prevalence of antimicrobial resistance genes was overall lower in disease compared to carriage isolates, but increased significantly over time, mediated by rise in prevalence of a multidrug resistance element ICESag37 among disease isolates. Conclusion: There is a stable association between certain GBS genotypes and invasive disease, which suggests opportunities for developing more precise disease prevention strategies based on GBS targeted screening. In contrast, GBS mobile genetic elements appear less likely to be correlated with carriage or disease, and instead are associated with clonal expansion events across the GBS population. [ABSTRACT FROM AUTHOR]

Background Preterm birth and neonatal infections are both associated with mortality and long-term neurodevelopmental impairments (NDIs). We examined whether the effect of invasive group B Streptococcus disease (iGBS) on mortality and long-term NDI differs for preterm and term infants, and whether co-occurrence of iGBS and prematurity leads to worse outcome. Methods Nationwide cohort studies of children with a history of iGBS were conducted using Danish and Dutch medical databases. Comparison cohorts of children without iGBS were matched on birth year/month, sex, and gestational age. Effects of iGBS on all-cause mortality and NDI were analyzed using Cox proportional hazards and logistic regression. Effect modification by prematurity was evaluated on additive and multiplicative scales. Results We identified 487 preterm and 1642 term children with a history of iGBS and 21 172 matched comparators. Dutch preterm children exposed to iGBS had the highest mortality rate by 3 months of age (671/1000 [95% CI, 412–929/1000] person-years). Approximately 30% of this mortality rate could be due to the common effect of iGBS and prematurity. Preterm children with iGBS had the highest NDI risk (8.8% in Denmark, 9.0% in the Netherlands). Of this NDI risk 36% (Denmark) and 60% (the Netherlands) might be due to the combined effect of iGBS and prematurity. Conclusions Prematurity is associated with iGBS development. Our study shows that it also negatively impacts outcomes of children who survive iGBS. Preterm infants would benefit from additional approaches to prevent maternal GBS colonization, as this decreases risk of both preterm birth and iGBS. [ABSTRACT FROM AUTHOR]

Background Male infants have a higher incidence of invasive group B Streptococcus disease (iGBS) compared with female infants; however, data on sex differences in mortality and long-term outcomes after iGBS are lacking. We assessed whether a child's sex influences the effects of iGBS on mortality and risk of neurodevelopmental impairments (NDIs). Methods We used Danish and Dutch registry data to conduct a nationwide cohort study of infants with a history of iGBS. A comparison cohort, children without a history of iGBS, was randomly selected and matched on relevant factors. Effect modification by sex was assessed on additive and multiplicative scales. Results Our analyses included data from children with a history of iGBS in Denmark (period 1997 -2017; n = 1432) and the Netherlands (2000 -2017; n = 697) and from 21 172 children without iGBS. There was no clear evidence of between-sex heterogeneity in iGBS-associated mortality. Boys had a higher risk of NDI, with evidence for effect modification on additive scale at the age of 5 years for any NDI (relative excess risk due to interaction = 1.28; 95% confidence interval [CI], -0.53 to 3.09 in Denmark and 1.14; 95% CI, -5.13 to 7.41 in the Netherlands). A similar pattern was observed for moderate/severe NDI at age 5 years in Denmark and age 10 years in the Netherlands. Conclusion Boys are at higher risk of NDI ; our results suggest this is disproportionally increased in those who develop iGBS. Future studies should investigate mechanisms of this effect modification by sex. [ABSTRACT FROM AUTHOR]

Aim: The association between cranial ultrasound (CUS) or magnetic resonance imaging (MRI) lesions and neonatal Group B streptococcal (GBS) meningitis outcome has not been studied in detail.Methods: This retrospective study assessed CUS, cranial MRI and neurodevelopmental outcome in 50 neonates with GBS meningitis admitted to three neonatal intensive care units in the Netherlands between 1992 and 2014. Death, cognitive outcome and motor outcome below -1 SD were considered as adverse outcomes.Results: CUS was available in all and MRIs in 31 infants (62%) with 28 CUS (56%) and 27 MRIs (87%) being abnormal. MRI lesions were multifocal (n = 10, 37%), bilateral (n = 22; 82%) and extensive (n = 11; 41%). A total of 10 died in the neonatal period. Median age at assessment was 24 months. Among survivors, abnormal cognitive outcome and motor outcome were seen in 23 and 20 patients, respectively. Abnormal CUS [odds ratio (OR) 5.3, p = 0.017], extensive bilateral deep grey lesions (OR 6.7, p = 0.035) and white matter lesions (OR 14.0, p = 0.039) correlated with abnormal motor outcome. Extensive bilateral deep grey matter lesions correlated with abnormal cognitive outcome (OR 8.1, p = 0.029).Conclusion: Abnormal CUS and the most severely affected MRIs were associated with poor neurodevelopmental outcome in neonatal GBS meningitis. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: To describe prevalence of phenotypic and genotypic macrolide-resistance among GBS isolates in pregnant women and explore the possibility of clonal spread of resistant GBS isolates in a multicultural population. Study design: Antimicrobial resistance patterns of 107 GBS isolates obtained from asymptomatic pregnant women were determined using E-tests. Macrolide resistance genes mef(A), erm(TR) and erm(B) were determined with PCR and a subset of 39 isolates, including the 8 isolates harbouring macrolide resistance genes, was subjected to RAPD analysis to detect clonal spreading. Results: Resistance to erythromycin and clindamycin was found in 8% and 7%, respectively. Macrolide resistance genes mef(A), erm(TR) and erm(B) were found in 1, 2 and 5 isolates, respectively; only five of these eight isolates exhibited both genotypic as well as phenotypic resistance. One genotype occured in 36% of the subset. Conclusions: Earlier reports on prevalence of phenotypic resistance were confirmed. Among the susceptible isolates one clonal type of GBS was clearly predominant; one of the resistant isolates shared its genotype. When such clonal types acquire resistance traits in the future, GBS disease may become harder to control. [Copyright &y& Elsevier]

Abstract: Objective: This study was performed to determine the prevalence of GBS and to identify GBS colonisation risk factors in a multicultural population of pregnant women in The Netherlands. We calculated predictive values of cultures in pregnancy for intrapartum GBS carriage. Study design: From a total of 1702 women visiting several antenatal outpatient departments, rectovaginal swabs were collected at 35–37 weeks’ gestation. In 761 women swabs were repeated at time of delivery. Carriage of GBS late in third trimester and at time of delivery was analysed in relation to age, parity, ethnicity and socio-economic status. Results: Twenty-one percent was GBS carrier late in pregnancy. Compared to Europeans, African women were at a higher risk (29%, RR 1.4, CI 1.1–1.7) and Asian women were at lower risk (13%, RR 0.6, CI 0.4–0.8) for GBS carriage. No differences in colonisation were found between women with respect to age, parity or socio-economic background. Positive predictive value of GBS carriage at 35–37 weeks’ gestation for carriage at time of parturition was 79% and negative predictive value was 93%. Conclusions: It was not possible to identify a group of pregnant women at high risk for GBS colonisation. Predictive values of antenatal genital group B streptococci cultures at 35–37 weeks’ gestation for intrapartum GBS carriage are lower than previously reported. [Copyright &y& Elsevier]

Background: Male infants have a higher incidence of invasive group B Streptococcus disease (iGBS) compared with female infants; however, data on sex differences in mortality and long-term outcomes after iGBS are lacking. We assessed whether a child's sex influences the effects of iGBS on mortality and risk of neurodevelopmental impairments (NDIs)., Methods: We used Danish and Dutch registry data to conduct a nationwide cohort study of infants with a history of iGBS. A comparison cohort, children without a history of iGBS, was randomly selected and matched on relevant factors. Effect modification by sex was assessed on additive and multiplicative scales., Results: Our analyses included data from children with a history of iGBS in Denmark (period 1997 -2017; n = 1432) and the Netherlands (2000 -2017; n = 697) and from 21 172 children without iGBS. There was no clear evidence of between-sex heterogeneity in iGBS-associated mortality. Boys had a higher risk of NDI, with evidence for effect modification on additive scale at the age of 5 years for any NDI (relative excess risk due to interaction = 1.28; 95% confidence interval [CI], -0.53 to 3.09 in Denmark and 1.14; 95% CI, -5.13 to 7.41 in the Netherlands). A similar pattern was observed for moderate/severe NDI at age 5 years in Denmark and age 10 years in the Netherlands., Conclusion: Boys are at higher risk of NDI ; our results suggest this is disproportionally increased in those who develop iGBS. Future studies should investigate mechanisms of this effect modification by sex., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: Group B streptococcus (GBS) is a leading cause of sepsis, pneumonia and meningitis in infants, with long term neurodevelopmental sequelae. GBS may be associated with poor pregnancy outcomes, including spontaneous abortion, stillbirth and preterm birth. Intrapartum antibiotic prophylaxis (IAP) is currently the only way to prevent early-onset disease (presenting at 0 to 6 days of life), although it has no impact on the disease presenting over 6 days of life and its implementation is challenging in resource poor countries. A maternal vaccine against GBS could reduce all GBS manifestations as well as improve pregnancy outcomes, even in low-income countries. Main body: The term "PREPARE" designates an international project aimed at developing a maternal vaccination platform to test vaccines against neonatal GBS infections by maternal immunization. It is a non-profit, multi-center, interventional and experimental study (promoted by the St George University of London. [UK]) with the aim of developing a maternal vaccination platform, determining pregnancy outcomes, and defining the extent of GBS infections in children and mothers in Africa. PREPARE also aims to estimate the protective serocorrelates against the main GBS serotypes that cause diseases in Europe and Africa and to conduct two trials on candidate GBS vaccines. PREPARE consists of 6 work packages. In four European countries (Italy, UK, Netherlands, France) the recruitment of cases and controls will start in 2020 and will end in 2022. The Italian PREPARE network includes 41 centers. The Italian network aims to collect: GBS isolates from infants with invasive disease, maternal and neonatal sera (cases); cord sera and GBS strains from colonized mothers whose infants do not develop GBS infection (controls). Short conclusion: PREPARE will contribute information on protective serocorrelates against the main GBS serotypes that cause diseases in Europe and Africa. The vaccine that will be tested by the PREPARE study could be an effective strategy to prevent GBS disease. [ABSTRACT FROM AUTHOR]

Objectives: Streptococcus agalactiae (group B streptococcus, GBS) is an uncommon cause of bacterial meningitis in adults. We describe clinical characteristics, serotype distribution and outcome of adult GBS meningitis., Patients and Methods: Patients aged 16 years or older with GBS cultured in cerebrospinal fluid included in two prospective nationwide cohort studies performed in the Netherlands between 1998-2002 and 2006-2017 were evaluated., Results: We identified 33 patients with GBS meningitis with a median age of 58 years of whom 22 were male (67%). The mean annual incidence was .16 per 1.000.000 adults. Ten patients (30%) had an immunocompromised state, which was due to alcoholism in 6 (18%) and diabetes mellitus in 4 (12%). Eleven patients (33%) had a distant focus of infection of whom 4 had endocarditis (13%). Seven patients (21%) died and 6 (18%) survivors had sequelae causing disability, including reduced vision and blindness due to endophthalmitis (n = 2). Twenty patients (61%) made a full recovery. Most common bacterial serotypes were serotype III (41%) and Ia (25%). Serotype V was associated with increased mortality (3 of 4 [75%] serotype V died vs. 4 of 28 [14%] other serotypes, P = .025)., Conclusion: GBS is a rare cause of meningitis in adults that more frequently occurs in patients with underlying comorbidities. Patients should be carefully evaluated for distant foci of infection. GBS serotype V is associated with poor outcome., (Copyright © 2018 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)

Background: Animal models suggest that neuroprotective effects of therapeutic hypothermia (TH) after perinatal asphyxia are reduced in infants with early-onset sepsis., Objectives: To assess the outcome of infants with perinatal asphyxia, neonatal encephalopathy, and TH in the presence of early-onset sepsis., Methods: In a retrospective cohort of 1,084 infants with perinatal asphyxia and TH, the outcome of 42 infants (gestational age 36.1-42.6 weeks and birth weight 2,280-5,240 g) with proven sepsis (n = 14) and probable sepsis (n = 28) was analyzed. Death, cerebral palsy, or a delayed development at 2 years was considered an adverse outcome., Results: Sepsis was caused mostly by group B streptococci (n = 17), other Gram-positive bacteria (n = 5), and Candida albicans (n = 1). Of the 42 infants, 9 (21.4%) died, and 5 (11.9%) showed impairments on follow-up. The outcome is comparable to the previously reported outcome of infants with TH without early-onset sepsis., Conclusion: A good outcome was reported in the majority of infants with perinatal asphyxia, TH, and early-onset sepsis. Cooling should not be withheld from these infants., (© 2018 The Author(s) Published by S. Karger AG, Basel.)

Objective: To investigate whether vaginal Group B Streptococcus (GBS) colonisation or other baseline characteristics of women with preterm premature rupture of membranes (PPROM) can help in identifying subgroups of women who would benefit from immediate delivery., Design: Secondary analysis of the PPROMEXIL trials., Setting: Sixty hospitals in the Netherlands., Population: Women with PPROM between 34 and 37 weeks of gestation., Methods: Random assignment of 723 women to immediate delivery or expectant management., Main Outcome Measures: Early onset neonatal sepsis., Results: Vaginal GBS colonisation status was the only marker which was significantly associated with the benefit of immediate delivery (P for interaction: 0.04). GBS colonisation was observed in 14% of women. The risk of early onset neonatal sepsis in GBS-positive women was high (15.2%) when they were managed expectantly but this risk was reduced to 1.8% with immediate delivery. The early onset neonatal sepsis risk was much lower in neonates of GBS-negative women: 2.6% after expectant management and 2.9% with immediate delivery. We estimated that by inducing labour only in GBS-positive women, there would be a 10.4% increase in term delivery rate, while keeping neonatal sepsis and caesarean delivery rates comparable to a strategy of labour induction for all., Conclusions: Our post hoc findings suggest that women with PROM between 34 and 37 weeks might benefit from immediate delivery if they have GBS vaginal colonisation, while in GBS-negative women labour induction could be delayed until 37 weeks., (© 2014 Royal College of Obstetricians and Gynaecologists.)