Virulence, phenotype and genotype characteristics of invasive group B Streptococcus isolates obtained from Swedish pregnant women and neonates.

Group B streptococci (GBS) are bacteria that can cause preterm birth and invasive neonatal disease. Heterogeneous expression of virulence factors enables GBS to exist as both commensal bacteria and to become highly invasive. A molecular epidemiological study comparing GBS bacterial traits, genotype and host characteristics may indicate whether it is possible to predict the risk of perinatal invasive GBS disease and more accurately target intrapartum antibiotic prophylaxis. A total of 229 invasive GBS isolates from Swedish pregnant women or neonates were assessed for virulence and phenotypic traits: hemolysis zone, hemolytic pigment (Granada agar), Streptococcus B Carrot Broth (SBCB) assay, CAMP factor, and hyaluronidase activity. Genes regulating hemolytic pigment synthesis (covR/covS, abx1, stk1, stp1) were sequenced. Of the virulence factors and phenotypes assessed, a Granada pigment or SBCB score ≥ 2 captured more than 90% of EOD isolates with excellent inter-rater reliability. High enzyme activity of hyaluronidase was observed in 16% (36/229) of the invasive GBS isolates and notably, in one case of stillbirth. Hyaluronidase activity was also significantly higher in GBS isolates obtained from pregnant/postpartum individuals versus the stillbirth or neonatal invasive isolates (p < 0.001). Sequencing analysis found that abx1 (g.T106I), stk1 (g.T211N), stp1 (g.K469R) and covS (g.V343M) variants were present significantly more often in the higher (Granada pigment score ≥ 2) versus lower pigmented isolates (p < 0.001, each variant). Among the 203 higher Granada pigment scoring isolates, 22 (10.8%) isolates had 3 of the four sequence variants and 10 (4.9%) had 2 of the four sequence variants. Although heterogeneity in GBS virulence factor expression was observed, the vast majority were more highly pigmented and contained several common sequence variants in genes regulating pigment synthesis. High activity of hyaluronidase may increase risk for stillbirth and invasive disease in pregnant or postpartum individuals. Our findings suggest that testing for GBS pigmentation and hyaluronidase may, albeit imperfectly, identify pregnant people at risk for invasive disease and represent a step towards a personalized medical approach for the administration of intrapartum antibiotic prophylaxis.

Group B streptococcus - a pathogen not restricted to neonates.

Objectives: This was a retropective study of invasive group B streptococcal (GBS) infections isolated from blood, cerebrospinal fluid (CSF), synovial fluid, peritoneal fluid, pleural fluid, pericardial fluid and corpus vitreum in a defined region in southwest Sweden over a 14-year period. Design: Information on all invasive GBS infections was obtained from all four bacteriological laboratories in the region, with data obtained from individual patient records. Results: GBS was isolated from normally sterile body fluids in 1244 samples (579 from females and 665 from males) from 1101 patients. Of these patients, 196 were neonates. The incidence in neonates (0-27 days) was 7.3 per 100 000 live births per year, but there was a significant decrease from 2012 when risk-factor-based intrapartum antibibiotic prophylaxis was implemented. The great majority of neonatal infections were very early-onset infections. The incidence rates in children (28 days to 17 years), adults (18-64 years) and elderly patients (≥ 65 years) were 1.3, 3.6, and 12.9 per 100 000 per year, respectively. The majority of children and adults had severe underlying diseases, but severe infections were also seen in individuals with no risk factors. Conclusions: GBS is an important pathogen in all age groups. Intrapartum antibiotic prophylaxis significantly decreases very early-onset infections.

Late-onset Neonatal Infections 1997 to 2017 Within a Cohort in Western Sweden-The Last 21 Years of a 43-Year Surveillance.

BACKGROUND: The objective of the study was to assess the epidemiology of late-onset (LO) neonatal invasive infections with surveillance covering 43 years, starting from 1975. METHODS: Observational epidemiologic, retrospective study including a cohort of infants born in western Sweden in 1997-2017, who had a positive blood and cerebral spinal fluid culture between 3 and 120 days of age. A comparison was made of the incidence between 1997-2007 and 2008-2017. Data on LO infections during 3-27 days of life were assessed from 1975. RESULTS: A total of 473 cases of LO infections were registered in 437 patients. The incidence increased from 2.0 to 3.1/1000 live births (LB) between 1997-2007 and 2008-2017 (P < 0.001). The increase in incidence was most pronounced among infants born <28 weeks gestation (from 255 to 398/1000 LB, P < 0.001). The most frequent pathogens were Staphylococcus aureus (25%), coagulase-negative staphylococci (17%), and Escherichia coli (13%). Infections due to group B Streptococci rose from 0.16/1000 LB to 0.33 (P = 0.03). During the whole surveillance period from 1975 to 2017, there were 579 cases between 3 and 27 days of life. Although the incidence increased in 2008-2017 to 1.9/1000 LB after first declining in 1997-2007, the case-fatality rate continued to decline from 27/284 (9.5%) between 1975 and 1996 to 6/182 (3.3%) in 2008 and 2017 (P = 0.01). CONCLUSIONS: The incidence of LO neonatal invasive infections increased during the study period (1997-2017), but the case-fatality rate remained lower than in the previous surveillance period (1975-1996). Further surveillance and interventions with focus on prevention is critical to counteract the increasing incidence among high-risk infants.

Relation between BCG vaccine scar and an interferon-gamma release assay in immigrant children with "positive" tuberculin skin test (≥10 mm).

BACKGROUND: Immigrants from countries with high incidence of tuberculosis (TB) are usually offered screening when they arrive to low incidence countries. The tuberculin skin test (TST) is often used. The interferon gamma release assays (IGRAs) are more specific and not affected by BCG vaccination. The aims of this study were 1. To see if there if there is a correlation between a positive IGRA (QFT) and presence of a BCG scar in children with TST ≥10 mm, 2. To compare the TST diameter with QFT result, 3. To see if chest X-ray can be omitted in QFT negative children despite TST ≥10 mm. METHODS: 762 healthy children/adolescents (median age 14 years) arriving to Gothenburg and surroundings with TST ≥10 mm were tested with QFT. RESULTS: A total of 163/492 (33 %) children with BCG scar had positive QFT, whereas 205/270 (76 %) without BCG scar had positive QFT (p < 0.0001). The median TST was 12 mm in QFT negative and 18 mm in QFT positive children (p < 0.0001) but with considerable overlap. Median TST was the same (12 mm) in QFT negative children with and without BCG scar. Among the QFT positive children 25/368 had chest X-ray changes compared to 2/393 among the QFT negative children (p < 0.0007). CONCLUSIONS: Previous BCG vaccination had an effect on the TST diameter so an IGRA is recommended to diagnose latent TB. Using only TST for screening of latent TB would lead to overdiagnosis. The TST diameter was larger in QFT positive than in QFT negative children but could not predict QFT in the individual patient. Chest X ray contributes little to the diagnosis of TB in QFT negative children but can not be omitted because of late seroconversion of QFT in some patients. TRIAL REGISTRATION: Not applicable.

Serotypes of group B streptococci in western Sweden and comparison with serotypes in two previous studies starting from 1988.

BACKGROUND: Group B Streptococci (GBS) are the most common neonatal pathogens and infect immunocompromised and elderly individuals. The species has 10 different serotypes. Serotypes have been studied in the south-west area of Sweden in 1988-1997 and 1998-2001. The aim of this study was to study serotypes in the same area from 2004 to 2009. METHODS: Invasive GBS isolates were collected prospectively from 2004 to 2009 in two counties in western Sweden with a population of 1.8 million, and were serotyped by latex agglutination. Clinical data were obtained from hospital records. During the study period 410 invasive GBS isolates from 398 patients were collected (multiple episodes ≥ 1 month apart). Clinical data were not available for two patients who are excluded. Four isolates were from stillborn neonates, 88 were from live born neonates and infants, and 318 from adults. RESULTS: Serotype III was the most common serotype (48%) in neonates and infants followed by serotypes Ia (18%) and V (16%). In adults serotype V (39%) dominated followed by serotypes III (20%) and Ib (14%). There was a significant increase of serotype V in comparison with the first study (1988-1997) but there were no significant changes in the serotype distribution between the present study and the second study (1998-2001). There were a few cases of serotype VI-IX, both in children and adults, not seen in the previous studies. Serotype V was more common among patients with arthritis than with any other manifestation. CONCLUSIONS: Changes in GBS serotypes occur over time in the same region, which must be considered when GBS vaccines are formulated.