Authors: Emelie E. C. Alsheim (1,2) , Naing T. Thet (1), Maisem Laabei (2), A. Toby A. Jenkins (1)
(1) Department of Chemistry, University of Bath, Bath, UK
(2) Department of Life Science, University of Bath, Bath, UK
Introduction: Streptococcus agalactiae, or Group B Streptococcus (GBS) causes the majority of all neonatal infections. Primary transmission occurs from a GBS positive mother during labour. Current guidelines recommend GBS testing during gestation week 35-37 (Manning et al., 2004). With GBS being a transient coloniser, this can lead to false test positives and negatives. We have developed a biosensor test using liposomes composed of lipids with known interactions to GBS virulence factors that could allow for point-of-care testing intrapartum (Figure 1).
Figure 1. Schematic of biosensor mode of action. Vaginal swab from mother, or neonatal swab taken either in the nose or pharynx is introduced into vesicle solution. After 45 minutes, GBS virulence factors have caused lysis of vesicles allowing for release of fluorescent 5(6)-carboxyfluorescein.
Objective: To determine the sensitivity and specificity of the test in healthy humans, ethical permission to use donated vaginal swabs was obtained from the Research Ethical Committee for Health (REACH) at the University of Bath (REACH No EP 22 072). Vaginal swabs were collected from anonymous healthy volunteers, over 18 years of age, not currently pregnant, physically able to swab themselves, and able to consent to the study. Previous data has shown specificity of our test to GBS in a laboratory setting (Alsheim et al., 2022).
Method: Vesicles are composed of several lipids, which form a lipid bilayer, encapsulating a self-quenching fluorescent dye (Young et al., 2020). When vesicles are in contact with GBS virulence factors, vesicles lyse, and a fluorescent signal is visibly seen. Anonymous donors were recruited at the University of Bath through advertising. Donors donated two lower vaginal swabs, one to be used on our test, and one which was processed using standard enriched medium culture (ECM) testing. The first swab was incubated at 46°C for 45min with our vesicle solution, afterwards the fluorescence intensity was determined (Figure 2). The second swab was processed using the ECM test which was used as a gold standard.
Results: A total of 51 individuals have to date (March, 2023) participated. GBS carriage rate was determined to be 15.7% using the ECM test. Biosensor test specificity and sensitivity is at 91.5% and 80% respectively, with an overall accuracy of 89.5% (Figure 3).
Figure 2: Biosensor fluorescence response for 51 participants in study. Green shows true GBS negative samples (using ECM) and red shows GBS positive samples (using ECM). Values over the lowest positive threshold is deemed GBS positive using the biosensor test, whilst samples under the highest negative threshold is deemed GBS negative using the biosensor test. Thresholds are set arbitrary.
Figure 3: Standards for Reporting of Diagnostic Accuracy (STARD) flow diagram.
Conclusion: This novel biosensor test shows potential to be used as a point-of-care test for detection of GBS. With accuracy as good as other current GBS test trialed currently but with the major advantage of being able to be used intrapartum at point-of-care with results in 45min (Gao et al., 2021). Further samples will be collected to enhance the understanding of the sensitivity and specificity.
Acknowledgement: This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie SKŁODOWSKA-CURIE grant agreement No 955664.
Authors: Mohid Malik (1), Dr Bayad Nozad (2), Professor Azeem Majeed (3)
(1) Faculty of Medicine, Imperial College London, London, UK
(2) Health Protection Team, UK Health Security Agency South West, Bristol, UK
(3)Department of Primary Care and Public Health, Imperial College London, London, UK
Background and Objective: Group B Streptococcus (GBS) infection is an important public health problem with serious health implications for both pregnant women and newborns. Screening for GBS is not routinely available in the UK, however, some NHS hospitals offer this to pregnant women who are identified as high-risk. This systematic review aims to investigate the cost-effectiveness and feasibility of providing universal screening for GBS to all pregnant women and to determine if it should be offered by the NHS.
Method: A mixed methods project was conducted. This included a systematic review of the current published literature from 2013. Electronic searches of multiple relevant databases were conducted, including Ovid, Embase, Cinahl, Global Health and Maternal and Child Health. Studies were included in the review if they met the inclusion/exclusion criteria. The authors then assessed the selected studies. Cost-effectiveness studies of universal GBS screening in pregnant women were included in comparison to no screening or risk-based screening alone. The included studies were assessed for their quality using the Cochrane Risk of Bias tool. Additionally, semi-structured interviews of healthcare professionals and stakeholder groups were conducted to identify additional barriers to universal screening implementation. These were conducted online using Microsoft Teams, recorded, transcribed, and analysed using a narrative approach.
Results: Of the 23 studies included in the review, 8 used decision-analytic models to evaluate cost-effectiveness, whilst 1 used a cost-utility model. Three reviews were included, alongside 2 randomised controlled trials, 3 comparative studies and 6 retrospective cohort studies. Universal screening for GBS in pregnant women was found to show cost-effectiveness compared to both no screening and screening only those identified as high-risk. The overall quality of the evidence was moderate to high. Narrative analysis of interview transcripts revealed patient compliance, result uncertainty and resource allocation as key barriers needed to overcome.
Conclusion: Universal screening for GBS in pregnant women can significantly reduce GBS disease incidence in newborns as well as maternal GBS infection rates. This systematic review highlights the feasibility of the NHS implementing universal GBS screening. Further research is needed to determine the most cost-effective approach and to assess the long-term effects of screening. Additional barriers, including negative stakeholder perspectives, must also be further explored. Ongoing studies, such as the GBS3 trial, will play an important role in future policy decision making.
Authors: Dorota Jamrozy (1), Guduru Gopal Rao (2), Theresa Feltwell (4), Theresa Lamagni (5), Priya Khanna (2), Androulla Efstratiou (5), Julian Parkhill (6), Stephen D. Bentley (1)
(1) Parasites and Microbes Programme, Wellcome Sanger Institute, Hinxton, UK
(2) Departments of Microbiology, Northwick Park Hospital, London North West University Healthcare NHS Trust, London, UK
(3) Faculty of Medicine, Imperial College, London, UK
(4) Cambridge Institute for Medical Research, School of Clinical Medicine, University of Cambridge, Cambridge, UK
(5) World Health Organization Collaborating Centre for Diphtheria and Streptococcal Infections, UK Health Security Agency, London, UK
(6) Department of Veterinary Medicine, University of Cambridge, Cambridge, UK
Introduction: Maternal immunization against Group B Streptococcus (GBS) has the potential to significantly reduce the burden of neonatal GBS infections. Population genetics of GBS from maternal carriage can offer key insights into vaccine target distribution.
Objective: To describe the population structure of GBS isolates from maternal carriage in London, in particular prevalence of vaccine targets and any association between these molecular markers and maternal ethnicity.
Method: GBS from maternal carriage was isolated from recto-vaginal swabs from pregnant women between March 2014 and December 2015 during a screening programme for the prevention of early-onset GBS infection in London North West University Healthcare NHS Trust, UK. A total of 656 isolates were randomly selected for sequencing. Following data QC, 535 isolates were selected for the analysis, which involved molecular typing and phylogenetic analyses.
Results: The isolates clustered into nine clonal complexes (CCs) but the majority (95%) belonged to five lineages: CC1 (26%), CC19 (26%), CC23 (21%), CC17 (13%) and CC8/10 (10%). Nine serotypes were identified, the most common were serotypes III (26%), V (21%), II (19%) and Ia (19%). Other serotypes (Ib, IV, VI, VII, IX) represented less than 10% of all isolates each. Intra-lineage serotype diversity was observed in all major CCs but was highest in CC1, which revealed nine serotypes. Nearly all isolates (99%) carried at least one of the four alpha family protein genes (alpha, alp1, alp23, rib). All isolates were susceptible to penicillin. We found 21% and 13% of isolates to be resistant to clarithromycin and clindamycin, respectively. Prevalence of macrolide-lincosamide-streptogramin B (MLSB) resistance genes was 22% and they were most common in CC19 (37%) and CC1 (28%), and isolates with serotypes V (38%) and IV (32%). We identified some associations between maternal ethnicity and GBS population structure. Serotype Ib was significantly less common among the South Asian compared to Black women (S. Asian: 3/142, Black: 15/135, p=0.019). There was also a significantly lower proportion of CC1 isolates among the White other (24/142) in comparison to Black (43/135) and S. Asian (44/142) women (p = 0.04). We found a significantly higher proportion of CC17 isolates among the White other compared to S. Asian women (White other: 32/142, S. Asian: 10/142, p = 0.004).
Conclusion: Our study showed high prevalence of GBS vaccine targets among isolates from pregnant women in London. However, the observed serotype diversity in CC1 and high prevalence of MLSB resistance genes in CC19 demonstrates presence of high-risk lineages, which might act as a reservoir of non-vaccine strains and antimicrobial resistance determinants.
Acknowledgments: This work was supported by the London North West Healthcare Charity. SDB is funded by the Wellcome Trust grant 098051. Thank you to all members of the Pathogen Informatics Team and the sequencing teams at the Wellcome Sanger Institute.
Authors: Dustin D. Flannery (1), Miren Dhudasia (1), Sagori Mukhopadhyay (1), Madeline Pfeifer (1), Paul Planet (1), Ravi Patel (2), Yun Wang (2), Suneet Chauhan (4), Sunbola Ashimi Ademola (4), Rachel Greenberg (3), Kristin Weimer (3), Kimberley Fisher (3), Bailey M. Alston (5), Palak Yogesh Patel (5), Kimberly M. Moss (5), Shanna Bolcen (5), Pete Maniatis (5), Li Deng (5), Wei Xing (5), Julia Rhodes (5), Stephanie Schrag (5), Karen M. Puopolo (1)
(1) Children’s Hospital of Philadelphia
(2) Emory University
(3) Duke University
(4) University of Texas Houston
(5) Centers for Disease Control and Prevention
Background: Maternal vaccines targeted to the 6 most common group B Streptococcus (GBS) serotypes (Ia-V) may help prevent GBS-associated morbidities including early- and late-onset neonatal infection, stillbirth, and preterm birth. Prior phase 1 and 2 vaccine trials suggest that persons lacking naturally-acquired antibodies require >1 dose for adequate response. Contemporary data on prevalence of serotype-specific maternal GBS antibodies are needed to develop an optimal vaccination strategy.
Objective: To estimate maternal prevalence of naturally-acquired, serotype-specific antibodies to GBS capsular polysaccharides and to assess placental antibody transfer.
Methods: Prospective observational study. Serum leftover from clinical testing at admission for delivery was collected from pregnant persons and newborns at five academic centers. Deidentified clinical data were abstracted from medical records. A standardized multiplex Luminex immunoassay (Gaston) was used to quantify IgG antibodies to GBS capsular polysaccharide serotypes Ia-V.
Results: Demographic and clinical characteristics of the 1096 included pregnant persons are shown in Table 1. Of these, 988 (90.2%) pregnant persons had no detectable antibodies to at least 1 serotype; 540 (49.3%) had no detectable antibodies to at least 3/6 serotypes; and 19 (1.7%) lacked antibodies to all 6 serotypes. Antibody prevalence was lowest for serotypes III (53.9%) and Ib (50.8%) (Table 2). Paired maternal and newborn sera were available for 348 dyads. Placental antibody transfer was detected for all serotypes, ranging from 82.5% of 171 mothers positive for serotype IV to 93.6% of 220 mothers positive for serotype Ia. Maternal and neonatal antibody concentrations and transfer ratios by gestational age at delivery are shown in Table 3. Placental antibody transfer was detected as early as 28 weeks’ gestation, and efficiency increased with increased gestational age at birth.
Conclusions: In a contemporary, multicenter cohort of pregnant persons, ~90% lacked antibodies to at least 1 of the 6 most common GBS serotypes that cause neonatal infection. Placental transfer of GBS antibodies was detectable in most pregnancies and as early as 28 weeks’ gestation. These findings suggest that the majority of pregnant persons would potentially benefit from a maternal GBS vaccine that could offer neonatal protection from infection. As nearly half of persons lacked antibodies to at least 3 of 6 common serotypes, a single-dose vaccination strategy may not be sufficient for optimal serotype coverage.
Footnote: 1All gestational age calculations include the four pairs available from births at <28 weeks’ gestation: two serotype II, one serotype IV and one serotype V. In only two cases (one serotype II: maternal IgG 6.45 mcg/mL, neonatal IgG 1.91 mcg/mL, transfer ratio 0.30; one serotype V: maternal IgG 0.15 mcg/mL, neonatal IgG 0.04 mcg/mL, transfer ratio 0.27). 2Maternal IgG geometric mean levels only include cases for which there was detectable infant IgG.
Authors: Malene Risager Lykke (1), Henrik Toft Sørensen (1), Joy Elisabeth Lawn (2), Erzsébet Horváth-Puhó (1)
(1) Department of Clinical Epidemiology, Aarhus University and Aarhus University Hospital, Aarhus, Denmark.
(2) Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London, United Kingdom.
Importance: It is unknown to which extend sex, prematurity, and maternal socioeconomic position (SEP) modifies the risk of epilepsy after neonatal Group B Streptococcus (GBS) disease.
Objective: To evaluate the risk of epilepsy among GBS affected infants in various sub-groups.
Design: This analysis investigated effect modification (EM) by sex, prematurity, and maternal SEP on the additive scale in a population-based matched cohort study from Denmark between 1997 and 2017 with follow-up until 31 December 2018. Linkage between Danish national registers were applied for data collection. SEP was defined by maternal education. Prematurity was defined as < 37 full weeks of gestation.
Setting: Population-based cohort study from Denmark.
Participants: Infants aged 0-89 days diagnosed with GBS sepsis or meningitis. A general population comparison cohort was randomly selected and matched by sex, the child’s year and month of birth, and gestational age.
Exposure: Hospital-diagnosed invasive GBS (sepsis or meningitis) during the first 89 days after birth.
Outcomes and measures: The outcome was epilepsy. EM by sex, prematurity, and maternal SEP was assessed by calculating the interaction contrast (IC) using incidence rates per 1000 person/years. An attributable proportion (AP) resembled the proportion of the combined effect due to the interaction.
Results: 1432 children were identified with invasive GBS diseases of which 44.7% were girls and 21.4% were born premature. The IC for boys versus girls at 5 years of follow-up was 0.85 (95% confidence interval [CI]: -2.48–4.19) and the AP 15.9%. Premature versus term born had an IC of 3.22 (95%CI: -1.85–8.29) and the AP for prematurity was 42.4%. Low versus high maternal education showed an IC of 2.52 (95%CI: -3.33–8.37), and an AP of low education of 47.7%.
Conclusion: Being a boy, born premature or having a mother with low education status modified epilepsy risk after neonatal GBS disease.
Proportion of the incidence rates per 1000 person-years attributable to group B Streptococcus alone, sex (boy vs girl), prematurity (preterm vs term), maternal education (medium vs low and high vs. low), and the interaction.
Authors: Bruna Alves da Silva Pimentel † (1), Pamella Silva Lannes-Costa †(1), Alice Slotfeldt Viana (2), Isabelle Rodrigues Fernandes (1), Lucas Lima de Oliveira (1), Kaian Santos Sousa (1), Bernadete Teixeira Ferreira-Carvalho (2) Prescilla Emy Nagao (1)
† Authors contributed equally to this work
(1) Laboratory of Molecular Biology and Physiology of Streptococci, Institute of Biology Roberto Alcantara Gomes, Rio de Janeiro State University (UERJ), Rio de Janeiro, Brazil.
(2) Department of Medical Microbiology, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Introduction: Streptococcus agalactiae (group B streptococci, GBS) is an opportunistic microorganism that colonizes the human gastrointestinal, oral, and rectovaginal tracts. S. agalactiae can ascend to the uterus in colonized pregnant women, cross the placental barrier and induces neonatal complications and/or death. Prevention of GBS infection in pregnancy is complex and influenced by factors such as pathogenicity, host, vaginal microbiome, and antibiotic resistance. Monitoring the mother and child in the maternity of origin is important, and may contribute to prophylactic therapy.
Aim: The aim of this study was to evaluate the clinical-epidemiological and pathogenic aspects of S. agalactiae isolated from pregnant women and newborns attended at the Carmela Dutra Maternity (Rio de Janeiro, RJ) were evaluated.
Results: A total of 214 bacterial strains (vaginal and rectal) from pregnant women between 34-37 weeks of gestation and 80 strains (belly button and external ear) from neonates born within 24-48 h were submitted to identification by multiplex PCR and MALD TOF techniques. Twenty-nine (29/214) and nineteen (19/80) bacterial strains were identified as S. agalactiae, respectively. Multiplex PCR demonstrated that capsular type Ia was predominant (42%), followed by types V (31%), III (13%), II (10%), VI (2%) and VII (2%). The comorbidities reported in pregnant women with higher incidence during childbirth were hypertension (35%) and diabetes mellitus (25%). Interesting, capsular type Ia was identified in S. agalactiae strains from pregnant women with hypertension, gestational diabetes, HPV infection, candidiasis, and eclampsia. Pregnant women aged 29 to 36 years (40%), followed by 21 to 28 years (25%) colonized by S. agalactiae were predominant. Brown (44%) and white mothers (31%) were prevalent in relation to black mothers (25%). The lmb and iag genes were detected in all S. agalactiae isolates, while the hvgA was detected only one S. agalactiae strain (G1919). The fbsA, fbsB and hylB genes were detected in 91,6%, 95,83%, and 70,83% of clinical isolates, respectively. S. agalactiae strains showed resistance to tetracycline (87,5.17%), cotrimoxazole (29,16%), and azithromycin and erythromycin (6.25%, each). Fifteen S. agalactiae strains presented resistance genes for tetM 93.34%, ermB 46.6% and mefA/E 13.33%. The ermA, linB and tetO genes did not show amplification. Multi-Locus Sequence Typing (MLST) analysis identified 5 clones (CC1, CC17, CC19, CC23 and CC452) and 11 sequence types (STs). Only the GBS1919 strain belonged to ST-17, being characterized as hypervirulent.
Conclusion: Our findings demonstrated the importance of clinical-epidemiological studies in pregnant women colonized by S. agalactiae, including newborns of these mothers who may develop invasive infections by colonization in the belly button and external ear during normal delivery, reinforcing the need for control measures S. agalactiae in Brazil.
Authors: Laura Maria Andrade Oliveira (1) , Natália Silva Costa (1) , Leandro Corrêa Simões (1) , Daniele Cristina Alvim (1) , Penélope Saldanha Marinho (2) , Sérgio Eduardo Longo Fracalanzza (1) , Lucia Martins Teixeira (1) , Uzma Basit Khan (3) , Dorota Jamrozy (3) , Stephen Bentley (3) , Tatiana Castro Abreu Pinto (1)
(1) Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil
(2) Faculdade de Medicina, Maternidade Escola, Universidade Federal do Rio de Janeiro, Rio de Janeiro 22240-000, Brazil
(3) Wellcome Sanger Institute, Hinxton, Cambridgeshire, United Kingdom
Introduction: Group B Streptococcus (GBS) is highlighted as a major agent of neonatal disease and it is also an important source of maternal infections. Estimates show GBS accounts for 91,000 infant deaths each year across the globe and a maternal vaccine is considered the ideal preventive measure to reduce GBS disease burden. The most promising vaccine candidates at clinical trials include a trivalent (Ia, Ib, III) and a hexavalent (Ia, Ib, II, III, IV, V) polysaccharide-protein conjugate schemes and a protein subunit approach targeting the N-terminal domains of Alpha-like proteins.
Methods: We evaluated GBS isolates from carriage (n=339) and cases of infections (n=36) in Brazil over a period of 44 years (1978-2021). Short-read whole genome sequencing was performed to predict sequence type (ST), serotype, antimicrobial resistance (AMR) genes, and surface protein genes.
Results: Carriage GBS (cGBS) belonged mostly to serotype Ia (46.6%), followed by serotypes II (18.6%), V (17.7%), III (8.8%), Ib (6.8%), and IX (1.8%). Seven clonal complexes (CCs) accounted for 96.2% of cGBS isolates, as follows: 23 (41%), 19 (16.5%), 1 (13%), 24 (11.8%), 103 (4.7%), 10 (4.7%), 17 (4.4%). A total of 79.4% of cGBS harbored tet genes (tetM=79.4%, tetO=2.9%, tetL=0.3%). Macrolide resistance genes were found in 27 (8%) isolates (ermA+ermB=2.4%; mefA+mrsD=5.6%). Nearly all cGBS (98.2%) harbored alpha protein family genes (rib=49.9%, alp1=11.8%, alp2/3=9.7%, alpha=26.8%); pili genes were found in 97.1% cGBS (PI-1=37.8%, PI-2a1=60.8%, PI-2a2=21.8%, PI-2b=10%), and serine-rich repeat glycoprotein determinants were harbored by 95.3% (srr1=90.9%, srr2=4.4%) isolates. Regarding GBS isolates from disease (dGBS), 36.1% belonged to serotype III, followed by serotypes Ia (25%), II (19.4%), V, (8.3%), IX (5.6%), Ib (5.6%). Most dGBS belonged to CC1 (30.6%), CC23 (27.8%), and CC17 (22.2%), although CC19 (11.1%) and CC130 (5.6%) were also found. A total of 80.6% of dGBS carried tet genes (tetM=63.9%, tetO=16.7%, tetL=2.8%), but macrolide resistance genes were not identified. As seen among cGBS, nearly all (97.2%) dGBS carried alpha protein family genes (rib=55.6%, alp1=22.2%, alpha=11%, alp2/3=8.3%), pili genes (PI-1=61%, PI-2a1=39%, PI-2a2=33%, PI-2b=22%), and serine-rich repeat glycoprotein determinants (srr1=75%, srr2=22%).
Conclusion: Our study contributes with unprecedented whole genome sequence-based data of a comprehensive GBS collection in Brazil, shedding light on the molecular epidemiology, AMR and virulence profiles of human GBS from a low-and-middle income country perspective and with potential to inform vaccine design.
Authors: Natalia Costa (1), André Rio-Tinto (1), Ana Elisa Almeida (1), Isabella Bittencourt (1), Danielle Alvim (1), Laura Oliveira (1), Sergio Fracalanzza (1), Lucia Teixeira (1), Penélope Marinho (2), Joffre Amim Jr (2), Stephen Taylor (3), Steve Thomas (3), Tatiana Pinto (1)
(1) Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro;
(2) Maternidade Escola, Universidade Federal do Rio de Janeiro
(3) Public Health England, United Kingdom
Background & objective: Group B Streptococcus (GBS) is a leading cause of perinatal infections. GBS can be found in genitourinary and gastrointestinal tract of up to 40% of pregnant women, being the main source for transmission to newborns. We have recently shown that after COVID-19 pandemic onset GBS colonization rates significantly decreased in our setting, dropping from 13.8% between Jan 2019-Mar 2020 to 5.3% between May 2020-Mar 2021 (Costa et al., 2022). Here we aimed to expand the analysis timeframe and determine GBS colonization rate among pregnant women attended at a maternity in Rio de Janeiro, Brazil considering scenarios before (Jan 2019-Mar 2020; 521), after pandemic onset (May 2020-Jun 2021; 360) and after introduction of COVID-19 vaccine and relaxation of non-pharmaceutical interventions (Jul 2021-Aug 2022; 436).
Method: Anovaginal samples (1317) were streaked onto chromogenic media and colonies were identified by MALDI-TOF MS. GBS strains had susceptibility profiles determined according to CLSI and serotypes determined by latex agglutination.
Results: Overall, GBS was detected in 10.3% of anovaginal samples. Although GBS colonization rate significantly decreased from before to after pandemic onset (13.8% before vs 5% after; p<0.0001), rates significantly increased again in the third period (5% vs 10.5%; p=0.004), when COVID-19 vaccines were introduced and non-pharmaceutical interventions were relaxed. Overall, all strains were susceptible to penicillin, vancomycin and levofloxacin, while 83.2%, 17.8% and 8.4% were non-susceptible to tetracycline, erythromycin and clindamycin respectively, and despite no difference (p>0.05) was detected between three scenarios, increasing trends of resistance to these antimicrobials were observed. In general, serotype Ia was most frequent (34.6%), followed by serotypes V (25.3%), II (15.9%), III (12.1%), Ib (5.6%), IV (0.9%), VIII (0.9%), and 4.7% non-typeable. Comparing the three different scenarios, serotype Ia significantly decreased in the third scenario (p=0.005), while serotype V increased during pandemic, being the most detected serotype in the third scenario.
Conclusions: These results indicate that fluctuations in GBS colonization rates coincided with pandemic-related events in our setting, suggesting that non-pharmaceutical interventions and changes in clinical practices due to pandemic may have also been impacting other infectious diseases.
Authors: Rebecca Moore (1), Jennifer Gaddy (1)
(1) Vanderbilt University Medical Center
Introduction: Streptococcus agalactiae (Group B Streptococcus, GBS) is an opportunistic bacterium that is commonly isolated from the female gastrointestinal and reproductive tracts. GBS colonization of the rectovaginal mucosa during pregnancy puts the infant at risk for preterm premature rupture of the membranes (PPROM, i.e., the water breaking), preterm birth, stillbirth, maternal sepsis, chorioamnionitis, severe invasive disease, or neonatal mortality. Shortly after birth, the neonate is exposed to human milk oligosaccharides (HMOs) which are present in high abundance in colostrum and have potent antimicrobial activities against GBS.
Objective: In order to better understand how HMOs can prevent GBS disease pathogenesis, placental macrophages (PMs) which are fetally-derived immune cells will be utilized to examine the immunomodulatory effects HMOs exert in response to GBS infection.
Methods: De-identified placental tissues from healthy, term, non-laboring C-sections were collected. The gestational membranes were removed and 12-mm sections were cultured ex vivo, followed by ex vivo isolation of placental macrophages from the villous core. Immunomodulatory activities of HMOs against PMs were assessed for phagocytosis, proinflammatory cytokine and chemokine production, anti-inflammatory molecule production, and extracellular trap production.
Results: In this work, we demonstrate that HMOs also have immunomodulatory activities against fetally-derived PMs including: enhancing GBS phagocytosis, repressing deployment of extracellular traps, inhibiting production of 16 proinflammatory cytokines and chemokines implicated in disease progression, and enhancing the production of epithelial growth factor and fractalkine, anti-inflammatory molecules.
Conclusions: We demonstrated that these antimicrobial milk sugars are able to combat GBS pathogenesis within fetally-derived PMs by enhancing bacterial phagocytosis and inhibiting release of extracellular traps. Additionally, HMOs repressed proinflammatory cytokine and chemokine production, while enhancing the production of two anti-inflammatory molecules, epithelial growth factor and fractalkine, a marker of causing a shift towards the tolerogenic M2 phenotype. With the knowledge that PMs are critical for GBS disease progression, we have shown that HMOs could be utilized as a potential therapeutic for managing inflammation.
Authors: Namrata Prasad (1,2), Arthur Reingold (3,4), Megan Barnes (5), Susan Petit (6), Monica M Farley (7), Lee H. Harrison (8), Ruth Lynfield (9), Jessica Houston (10), Bridget. J. Anderson (11), Ann Thomas (12), William Schaffner (13), Melissa L. Arvay (1), Stephanie J. Schrag (1)
(1) Division of Bacterial Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
(2) Epidemic Intelligence Service, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
(3) California Emerging Infections Program, Oakland, California United States
(4) Berkeley School of Public Health, University of California, Berkeley, California, United States
(5) Colorado Department of Public Health and the Environment, Denver, Colorado, United States
(6) Connecticut Department of Public Health, Hartford, Connecticut, United States
(7) Department of Medicine, Emory University School of Medicine and the Atlanta VAMC, Atlanta, Georgia, United States
(8) Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, United States
(9) Minnesota Department of Health, St. Paul, Minnesota, United States
(10) New Mexico Emerging Infections Program, New Mexico Department of Health, Santa Fe, New Mexico, United States
(11) New York State Department of Health, Albany, New York, United States
12 Public Health Division, Oregon Health Authority, Portland, Oregon, United States
13 Department of Health Policy, Vanderbilt University School of Medicine, Nashville, Tennessee, United States
Authors: Leandro Corrêa Simões (1), Laura Maria Andrade Oliveira (1), Natália Silva Costa (1), Ana Caroline Nunes Botelho (1), Sérgio Eduardo Longo Fracalanzza (1), Lucia Martins Teixeira (1), Tatiana de Castro Abreu Pinto (1)
Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Brazil
Background & Objective: Group B Streptococcus (GBS) population is composed by several lineages that can differ in virulence and antimicrobial resistance. The development of alternative cost-effective typing methods is desirable for GBS surveillance and disease control once traditional methods (e.g. WGS, MLST) are expensive and not easily accessible in LMIC. We assessed the potential of CRISPR1-RFLP as a typing method to discriminate human GBS isolates (anovaginal carriage: n=10, 59%; and disease: n=7, 41%) belonging to serotype III, recovered between 1991 and 2020 in Brazil.
Design: Carriage strains were all obtained from pregnant women, while the GBS strains from cases of infectious diseases were obtained from both adult patients (n=4) and neonates (n=3) and from various clinical sources, including: bloodstream (3/17; 18%), cerebrospinal fluid (3/17; 18%) and bone lesion secretion (1/17; 5%).
Method: CRISPR1 elements were identified by PCR, subjected to RFLP (DdeI enzyme), and fingerprinting profiles were analyzed with BioNumerics v7.6.3. Data regarding the clinical source and MLST profiles of the GBS isolates were included for comparative purposes.
Results: CRISPR1-RFLP grouped the GBS strains in 3 clusters considering the cutoff of 80% of similarity (Simpson’s Index of Diversity (SID) =0.912), and was more discriminatory than the MLST clustering (SID =0.750). Grouping was mostly driven by the Sequence Type (ST) of each GBS strain (Adjusted Wallace (AW) coefficient =0.556); however, isolates of the same clinical source tended to group together. Clusters were represented mostly by strains belonging to CC17 and CC23. ST17 represents a hypervirulent GBS lineage and is recognized as the main cause of GBS neonatal meningitis, while ST23 is associated with asymptomatic carriage and disease.
Conclusions: Data gathered here demonstrate the discriminatory power of CRISPR1-RFLP as an effective and cost-efficient GBS typing technique. In order to better evaluate its congruence with other established techniques (e.g. MLST) a larger number of strains should be analyzed. Still, CRISPR1-RFLP consists on an innovative and promising technique for analyzing the molecular epidemiology of GBS, with cost-effectiveness and potential for incorporation in LMIC settings, which tend to have limited access to more costly techniques.
Authors: Francesca Miselli (1,2), Luca Bedetti (1,2), Chiara Minotti (2), Riccardo Cuoghi Costantini (3), Maria Letizia Bacchi Reggiani (4), Caterina Tamburini (5), Chiara Cocconcelli (5), Caterina Vocale (6), Roberta Creti (7), Licia Lugli (2), Alberto Berardi (2)
(1) PhD Program in Clinical and Experimental Medicine, University of Modena and Reggio Emilia
(2) Neonatal Intensive Care Unit, University Hospital of Modena
(3) Department of Medical and Surgical Sciences for Mother, Child and Adult, University of Modena and Reggio Emilia
(4) Department of Specialistic, Diagnostic and Sperimental Medicine, S. Orsola Malpighi Univesity Hospidal, University of Bologna
(5) Pediatric Postgraduate School, University of Modena and Reggio Emilia Regional
(6) Reference Center for Microbiological Emergencies (CRREM), Unit of Microbiology, St Orsola Malpighi University Hospital
(7) Department of Infectious Diseases, Istituto Superiore di Sanità, Rome
Objective: To describe epidemiological changes of group B Streptococcus (GBS) early-onset sepsis (EOD) and late-onset sepsis (LOD) after widespread diffusion of intrapartum antibiotic prophylaxis (IAP).
Design: Prospective area-based surveillance (Emilia-Romagna, Northern Italy) for neonatal GBS sepsis, among live births (LBs) infants. A screening-based strategy for EOD prevention according to CDC guidelines has been in place since 2003.
Methods: To measure trends in EOD and LOD incidence, we divided the study period in four-year intervals (2003-2006, 2007-2010, 2011-2014, 2015-2018) and calculated incidence rates among full-term (gestational age 37 weeks’ gestation) and preterm (gestational age <37 weeks’ gestation) infants.
Results: During the study period, 605,485 LBs occurred (561,501 full-term infants and 43,984 preterm infants). Overall, the incidence of LOD (0.33 per 1,000 LBs, 95%CI 0.28-0.38) was higher than that of EOD (0.22 per 1,000 LBs 95%CI 0.19-0.27, p<0.001). From 2003 to 2018 we observed a trend towards a reduction in EOD incidence (p=0.07); when comparing the first period (2003-2006) to the last one (2015-2018), the incidence of EOD reduced from 0.29 to 0.14 per 1,000 LBs (p<0.01). By contrast, during the whole study period, the incidence of LOD remained stable.
When considering full-term infants, the incidence of EOD (0.19 per 1,000 LBs 95%CI 0.16-0.23) and LOD (0.23 per 1,000 LBs 95%CI 0.19-0.27) remained stable. Among preterm infants, the incidence of LOD (1.61 per 1,000 LBs 95%CI 1.26-2.04) was more than twice than that of EOD (0.70 per 1,000 LBs 95%CI 0.48-1.00) and steadily increased from 1.62 per 1,000 LBs in 2003-2006 to 2.88 per 1,000 LBs in 2015-2018 (p<0.01). Notably, in the last period (2015-2018), the incidence of LOD among preterm infants (2.88 per 1,000 LBs 95% CI 1.92-4.16) was almost ten-time fold higher than that of EOD (0.31 per 1,000 LBs 95% CI 0.06-0.90, p<0.001). GBS isolates remained universally susceptible to penicillin.
Conclusions: After a period of widespread IAP, we observed a reducing trend in EOD incidence, with no increase in GBS resistance to beta-lactams. However, not only the incidence of LOD remained unaffected, but it increased among preterm infants. In fact, IAP cannot eradicate GBS from the mother, who remains a potential source of infection for the newborn. As a result, LOD incidence is now almost ten-fold higher than EOD among preterm infants, requiring preventive strategies to be implemented. As the landscape of EOD and LOD epidemiology continues to evolve, ongoing surveillance of cases is required.
Authors: Chiara Minotti (1), Luca Bedetti (2), Francesca Miselli (2), Licia Lugli (1), Alberto Berardi (1)
(1) Neonatal Intensive Care Unit, University Hospital of Modena, University of Modena and Reggio-Emilia.
(2) PhD Program in Clinical and Experimental Medicine, University of Modena and Reggio-Emilia.
Background: Traditionally, intrapartum antibiotic prophylaxis (IAP) is considered most effective if administered at least 4 hours before delivery. Although according to international guidelines, a shorter duration of recommended IAP is considered less effective, exposure to 2 or more hours of antibiotics has been demonstrated to reduce maternal GBS vaginal colony counts and decrease the incidence of early-onset neonatal sepsis. The aim of this work is the systematic description of the available evidence, to date, on the efficacy of different patterns of IAP in preventing GBS vertical transmission and/or neonatal sepsis/early-onset disease.
Design: A systematic mini-review of the literature was led, according to the PRISMA guidelines.
Method: The Embase and MEDLINE databases were searched on 14th February 2023. Studies in all languages reporting evidence on the impact on GBS vertical transmission of patterns of IAP were included.
Results: Ten of 102 articles, published between 1998 and 2022, were eligible for inclusion, reporting data on more than 2900 mother-newborn dyads, including neonates born >/=34 weeks of gestational age, from mothers receiving different IAP patterns. The most represented study design was prospective (six studies), followed by retrospective and case-cohort (2 studies each). No RCTs were retrieved. Settings included tertiary care centers (half of the studies). Four studies (40%) concluded a direct correlation between the duration of IAP <= 4 h and neonatal illness and a decreased risk for any form of intrapartum antibiotic given more than 4 hours before delivery. Two studies (20%) reported a reduced vertical transmission of GBS when the time between the start of antibiotics and delivery is at least 2 hours. Last, four studies (40%) concluded that the rate of vertical transmission was independent of the duration of IAP before delivery. Three studies also provided pharmacokinetic data, stating that short durations of prophylaxis achieved levels significantly above the MIC, suggesting an advantage even in precipitous labors.
Conclusions: 60% of the retrieved studies either reported that IAP started at least 2 hours before delivery could be successful in reducing vertical transmission, or that vertical transmission was not influenced by the duration of maternal antibiotic prophylaxis. The identification of neonates exposed to less than 4 hours of antibiotics as at a higher risk for GBS sepsis may be not fully supported by pharmacokinetics data. Further studies are needed to confirm this hypothesis.
Authors:Georgina Constantinou (1), Susan Ayers (1), Eleanor J. Mitchell (2), Jane Daniels (2), Kate Walker (3), Eleanor Harrison (2) Kerry Barker-Williams (2)
(1) Centre for Maternal and Child Health Research, City, University of London
(2) Nottingham Clinical Trials Unit, University of Nottingham
(3) Population and Lifespan Unit, School of Medicine, University of Nottingham
Background & Objective: GBS3 is a large trial to determine the clinical and cost effectiveness of routine testing for Group B Strep. Considerations of the acceptability of routine testing to women and healthcare professionals is essential. This study aimed to: (i) determine the acceptability of the different methods of routine testing for GBS colonisation to pregnant women and Health Care Professionals; (ii) identify the barriers and facilitators to implementation of either routine testing strategy; and (iii) understand how individual and site-level context and process mechanisms influence the acceptability of testing.
Design: Interviews were conducted with 39 women and 25 health professionals via telephone or online video call using a semi-structured schedule examining the acceptability of routine GBS testing and individual and site-specific contexts that might impact this. Interviews were recorded and transcribed verbatim.
Methods: Participants were recruited from four NHS maternity units in the GBS3 trial. Research midwives at each site were responsible for recruiting women who met the inclusion criteria; up to 12 weeks postpartum, aged 16 years or older, and reasonably fluent in English. Registered healthcare professionals were eligible to take part if working in an NHS maternity or neonatal service in one of the four sites. Purposive sampling was used to identify specific groups of women including; place of birth, preterm birth, age and ethnicity. The data has been analysed using systematic thematic analysis and the framework method has been used to summarise the data.
Results: The findings provide information on women and healthcare professionals’ views on the acceptability of introducing routine testing for GBS, with the introduction of testing deemed acceptable by the majority of women and healthcare professionals, and many reciprocated views between groups. However, participants differed in their experiences of the barriers and facilitators surrounding testing with healthcare professionals noting the factors which influenced implementing testing at their hospital, and identifying the influence of site-specific context and process mechanisms on GBS testing.
Conclusions: GBS testing was well received by the majority of women interviewed, in addition to many of the healthcare professionals implementing the testing. However, both would like to be informed by the results of the trial surrounding the efficacy of testing. The barriers and facilitators identified allow for improvement of the training of midwives providing testing and those sites in their implementation phase to ensure improved care.
Authors: Abeba Mengist (1), Hemalatha Kannan (2), Alemseged Abdissa (3)
(1) Department of Medical Laboratory Science, school of medicine and College of Health Sciences, Debre Markos University.
(2) Department of Medical Laboratory Science and Pathology, College of Public Health and Medical Sciences, Jimma University, Jimma, Ethiopia.
(3) Armauer Hanssen Research Institute, Addis Ababa, Ethiopia
Background: Streptococcus agalactiae (group B Streptococcus, GBS) is the most frequent pathogen isolated from neonates with invasive bacterial disease and responsible for serious infections in newborns such as pneumonia, septicemia and meningitis. Infection is primarily acquired vertically from mothers colonized with GBS. However, the prevalence and antimicrobial susceptibility pattern of GBS among pregnant women in Ethiopia are less studied.
Methods: This cross-sectional study involved 126 pregnant women at 35-37 weeks of gestation attending the antenatal clinic at Jimma University Hospital. Anorectal and vaginal swabs were cultured on to Todd-Hewitt broth medium supplemented with Gentamicin and Nalidixic acid and subsequently sub-cultured on 5% sheep blood agar followed by identification of isolates based on colonial morphology, Gram stain, catalase reaction, hippurate hydrolysis and Christie, Atkins, Munch-Petersen (CAMP) test, and testing for their susceptibility to antimicrobial agents using the Kirby-Bauer method.
Results: The overall carriage rate of GBS was 19.0 % (24/126), and the rectal and vaginal carrier rates were 14.3% (18/126) and 10.4% (13/126), respectively. Concomitant vaginal and anorectal colonization was recorded in 29.2% (7/24) of the women who were culture positive. All GBS isolates were susceptible to penicillin G, ampicillin, and vancomycin, but a considerable proportion was resistant to clindamycin (3.2%), erythromycin (6.5%), ciprofloxacin (9.7%), ceftriaxone (9.7%), norfloxacin (12.9%), cotrimoxazole (29%), and tetracycline (45.2%).
Conclusions: This study reveals high carriage rate of GBS among pregnant women compared to some previous studies in Ethiopia. However, further epidemiological investigations should be done in different parts of the country in order to know the actual GBS colonization rate of pregnant women and to consider the possibility of implementing prophylactic treatment to prevent potential adverse maternal and neonatal outcomes. Future studies should be conducted to reveal serotype distributions of GBS in this community.