Invasive Group B Streptococcus Disease Research Articles

Burden of Invasive Group B Streptococcus Infection Among Omani Infants Less Than 90 Days Old: A Multicenter Study.

Group B Streptococcus (GBS) infection is the leading cause of neonatal morbidity and mortality worldwide. This study aims to investigate the incidence of invasive GBS disease among infants less than 90 days old in Oman and to describe their risk factors, clinical presentations and clinical outcomes. We retrospectively collected the data of less than 90-day-old Omani infants with culture-positive GBS from sterile samples. This study was conducted in 3 tertiary hospitals in Oman from 2009 to 2018. Over 10 years, we identified 92 cases of culture-confirmed invasive GBS infection from 178,285 live births in the 3 hospitals, giving an overall incidence of 0.53 per 1000 live births [95% confidence interval (CI): 0.4-0.7)]. Of those, 59 (64.1%) had early-onset neonatal GBS disease and 33 (35.9%) had late-onset neonatal GBS disease. The incidence of invasive GBS disease was significantly higher in the last 5 years from 2014 to 2018 (0.69 per 1000 live births, 95% CI: 0.5-0.9) compared to the previous years from 2009 to 2013 (0.36 per 1000 live births, 95% CI: 0.2‒0.5), (P = 0.004). Infants with late-onset neonatal GBS disease had a higher risk of meningitis compared to infants with early-onset neonatal GBS disease (30.3% vs. 10.2%, P = 0.021). The mortality rate was 13.5%. The incidence of invasive GBS disease in Oman is similar to what was reported worldwide, however, the burden of the disease in terms of mortality is high. In addition, a significant increase in the annual incidence of invasive GBS disease in Omani infants was found over the study period.

Interlaboratory comparison of a multiplex immunoassay that measures human serum IgG antibodies against six-group B streptococcus polysaccharides

ABSTRACT Measurement of IgG antibodies against group B streptococcus (GBS) capsular polysaccharide (CPS) by use of a standardized and internationally accepted multiplex immunoassay is important for the evaluation of candidate maternal GBS vaccines in order to compare results across studies. A standardized assay is also required if serocorrelates of protection against invasive GBS disease are to be established in infant sera for the six predominant GBS serotypes since it would permit the comparison of results across the six serotypes. We undertook an interlaboratory study across five laboratories that used standardized assay reagents and protocols with a panel of 44 human sera to measure IgG antibodies against GBS CPS serotypes Ia, Ib, II, III, IV, and V. The within-laboratory intermediate precision, which included factors like the lot of coated beads, laboratory analyst, and day, was generally below 20% relative standard deviation (RSD) for all six serotypes, across all five laboratories. The cross-laboratory reproducibility was < 25% RSD for all six serotypes, which demonstrated the consistency of results across the different laboratories. Additionally, anti-CPS IgG concentrations for the 44-member human serum panel were established. The results of this study showed assay robustness and that the resultant anti-CPS IgG concentrations were reproducible across laboratories for the six GBS CPS serotypes when the standardized assay was used.

Incidence of invasive infections with Group B streptococcus in adults in Norway 1996-2019: a nationwide registry-based case-control study.

Group B streptococcus (GBS) colonizes the gastrointestinal and vaginal mucosa in healthy adults, but has also become an increasing cause of invasive infection. The aims of this study were to describe the incidence and factors associated with the occurrence of invasive GBS disease in adults in Norway. We performed a nationwide retrospective case-control study of invasive GBS infections during 1996-2019, with two control groups; invasive Group A streptococcal disease (GAS) to control for changes in surveillance and diagnostics, and a second representing the general population. A total of 3710 GBS episodes were identified. The age-standardized incidence rate increased steadily from 1.10 (95% CI 0.80-1.50) in 1996 to 6.70 (95% CI 5.90-7.50) per 100,000 person-years in 2019. The incidence rate had an average annual increase of 6.44% (95% CI 5.12-7.78). Incidence rates of GAS varied considerably, and there was no evidence of a consistent change over the study period. GBS incidence was highest among adults > 60years of age. Cardiovascular disease, cancer, and diabetes were the most common comorbid conditions. There was a shift in the distribution of capsular serotypes from three dominant types to more equal distribution among the six most common serotypes. The incidence of invasive GBS disease in adults increased significantly from 1996 to 2019. The increasing age of the population with accompanying underlying comorbid conditions might contribute to the increasing burden of invasive GBS disease. Interestingly, type 1 diabetes was also associated with the occurrence of invasive GBS disease.

Gestational diabetes augments group B Streptococcus infection by disrupting maternal immunity and the vaginal microbiota

Group B Streptococcus (GBS) is a pervasive perinatal pathogen, yet factors driving GBS dissemination in utero are poorly defined. Gestational diabetes mellitus (GDM), a complication marked by dysregulated immunity and maternal microbial dysbiosis, increases risk for GBS perinatal disease. Using a murine GDM model of GBS colonization and perinatal transmission, we find that GDM mice display greater GBS in utero dissemination and subsequently worse neonatal outcomes. Dual-RNA sequencing reveals differential GBS adaptation to the GDM reproductive tract, including a putative glycosyltransferase (yfhO), and altered host responses. GDM immune disruptions include reduced uterine natural killer cell activation, impaired recruitment to placentae, and altered maternofetal cytokines. Lastly, we observe distinct vaginal microbial taxa associated with GDM status and GBS invasive disease status. Here, we show a model of GBS dissemination in GDM hosts that recapitulates several clinical aspects and identifies multiple host and bacterial drivers of GBS perinatal disease.

Adherence to universal screening for group B Streptococcus in pregnancy and prevalence of colonised pregnancies in Caserta province, Italy.

Group B Streptococcus (Streptococcus agalactiae; GBS) infection is a significant contributor to neonatal morbidity and mortality. In the early 1970s, the neonatal mortality rate for infants with invasive GBS disease was 55%. With the adoption of the first medical community guidelines to prevent GBS infection in the 1990s, the mortality rate decreased to approximately 5%. The main obstetric procedure for preventing vertical transmission of GBS infection involves universal screening of pregnant women using a vaginal-rectal swab (VRS) to identify those eligible for intrapartum antibiotic prophylaxis (IAP). The study analyzes the adherence of screening and the trend of GBS infection in pregnancy in the province of Caserta, Italy. Data were obtained from pregnant women who gave birth in a first level birthing center in 2022 from birth assistance certificate (CEDAP), obstetric and neonatal record. Postnatal evaluation collected through computer-assisted telephone interviews. 567 women delivered at our center during the study period. The average coverage of GBS testing in pregnancy was 99.2% (562), and the proportion of GBS colonised women was 12.6% (71) according with the national average, which is about 10-20%. The spread of positive cases appears to fluctuate among the various groups of pregnant women studied, indicating no significant statistical variance among presence of a partner, among women who have given birth multiple times, among Italian nationals, or across different ages, but a significant statistical excess is evident among mothers with less education. In 93% (66) of GBS carrier mothers, intrapartum antibiotic prophylaxis (IAP) was administered correctly, regardless of the type of delivery performed. Despite the successful integration of GBS screening, a significant gap remains between the ideal scenario and the actual implementation of IAP. At the three-month assessment, no child required hospitalization, consistent with the relatively low incidence of invasive GBS infection. Nevertheless, for those who are not eligible to VRS screening, such as preterm birth, or IAP, as in precipitous birth, the identification of biomarkers enabling early recognition of invasive GBS disease remains essential. Additionally, the emergence of vaccines administered during gestation, conferring passive immunity to newborns represents a promising possible new direction. Therefore, to ensure the practical application of GBS screening and actual IAP by healthcare providers, periodic audits and regular monitoring should be encouraged.

Group B Streptococcal Disease in Infants in Japan.

This review describes the epidemiology of group B Streptococcus (GBS) infection in infants in Japan and discusses unresolved issues and future perspectives. Guidelines for the prevention of vertical transmission in Japan were implemented in 2008. The incidence of early-onset disease in Japan has remained stable at approximately 0.10/1000 livebirths or less, which is lower than in Europe and North America. The incidence of late-onset disease is also low, but has increased over the last decade, with an estimated 0.29/1000 livebirths in 2020. National surveillance studies in 2011-2015 and 2016-2020 reported case fatality rates of 4.5% and 6.5% for early-onset disease and 4.4% and 3.0% for late-onset disease, respectively. Sequelae of neurodevelopmental impairments were considerably associated with infants who developed meningitis. Predominant neonatal invasive strains have remained in the following order of serotypes: III, Ia, Ib and V, for the past 30 years. Conversely, the predominant serotypes of maternal colonization strains markedly changed from serotypes VI and VIII around 2000 to serotypes Ia, Ib, III and V over the last decade. Recurrence rates among infants < 1-year-old were estimated to be 2.8%-3.7%, and preterm birth and antenatal maternal GBS colonization were risk factors for recurrence. Several unresolved issues remain. First, the exact disease burden remains unclear because Japan does not have a nationwide system to register all infants affected by invasive GBS disease, and even population-based surveys are limited to up to 10 of the 47 prefectures. Others include low adherence to prevention guidelines of vertical transmission and the development of strategies based on Japanese epidemiological evidence rather than the Center for Disease Control and Prevention guidelines. The effectiveness of introducing maternal vaccines in Japan, where the disease incidence is low, needs to be carefully verified.

Immune responses against group B Streptococcus monovalent and pentavalent capsular polysaccharide tetanus toxoid conjugate vaccines in Balb/c mice

Immunization of pregnant women with Group B Streptococcus (GBS) capsular polysaccharide (CPS) conjugate vaccine (CV) could protect young infants against invasive GBS disease. We evaluated the immunogenicity of investigational five GBS monovalent (serotypes Ia, Ib, II, III, and V) CPS-tetanus toxoid (TT)-CV with adjuvant and GBS pentavalent CPS-TT-CV with adjuvant (GBS5-CV-adj) and without adjuvant (GBS5-CV-no-adj), in Balb/c mice. Aluminum phosphate was the adjuvant in the formulations, where included. The homotypic immunoglobulin G (IgG) geometric mean concentration (GMC) and opsonophagocytic activity (OPA) geometric mean titer (GMT) did not differ after the third dose of the GBS5-CV-adj vaccine compared with the monovalent counterparts for all five serotypes. The GBS5-CV-adj induced higher post-vaccination serotype-specific IgG GMCs and OPA GMTs compared to GBS5-CV-no_adj. The GBS5-CV with and without adjuvant should be considered for further development as a potential vaccine for pregnant women to protect their infants against invasive GBS disease.

Stillbirths and Neonatal Deaths Caused by Group B Streptococcus in Africa and South Asia Identified Through Child Health and Mortality Prevention Surveillance (CHAMPS).

Invasive Group B Streptococcus (GBS) is a common cause of early-onset neonatal sepsis and is also associated with stillbirth. This study aimed to determine the proportion of stillborn infants and infants who died between 0 and 90 days attributable to GBS using postmortem minimally invasive tissue sampling (MITS) in 7 low- and middle-income countries (LMICs) participating in Child Health and Mortality Prevention Surveillance (CHAMPS). Deaths that occurred between December 2016 and December 2021 were investigated with MITS, including culture for bacteria of blood and cerebrospinal fluid (CSF), multipathogen polymerase chain reaction on blood, CSF, and lung tissue and histopathology of lung, liver, and brain. Data collection included clinical record review and verbal autopsy. Expert panels reviewed all information and assigned causes of death. We evaluated 2966 deaths, including stillborn infants (n = 1322), infants who died during first day of life (0 to <24 hours, n = 597), early neonatal deaths (END) (1 day to <7 days; END; n = 593), and deaths from 7 to 90 days (n = 454). Group B Streptococcus was determined to be in the causal pathway of death for 2.7% of infants (79 of 2, 966; range, 0.3% in Sierra Leone to 7.2% in South Africa), including 2.3% (31 of 1322) of stillbirths, 4.7% (28 of 597) 0 to <24 hours, 1.9% (11 of 593) END, and 2.0% (9 of 454) of deaths from 7 to 90 days of age. Among deaths attributed to GBS with birth weight data available, 61.9% (39 of 63) of decedents weighed <2500 grams at birth. Group B Streptococcus sepsis was the postmortem diagnosis for 100% (31 of 31) of stillbirths. For deaths <90 days, postmortem diagnoses included GBS sepsis (83.3%, 40 of 48), GBS meningitis (4.2%, 2 of 48), and GBS pneumonia (2.1%, 1 of 48). Our study reveals significant heterogeneity in the contribution of invasive GBS disease to infant mortality across different countries, emphasizing the need for tailored prevention strategies. Moreover, our findings highlight the substantial impact of GBS on stillbirths, shedding light on a previously underestimated aspect in LMICs.

Early-onset group B streptococcal disease in African countries and maternal vaccination strategies.

Invasive group B streptococcal (GBS) disease is the commonest perinatally-acquired bacterial infection in newborns; the burden is higher in African countries where intrapartum antibiotic prophylaxis strategies are not feasible. In sub-Saharan Africa, almost one in four newborns with GBS early-onset disease will demise, and one in ten survivors have moderate or severe neurodevelopmental impairment. A maternal GBS vaccine to prevent invasive GBS disease in infancy is a pragmatic and cost-effective preventative strategy for Africa. Hexavalent polysaccharide protein conjugate and Alpha family surface protein vaccines are undergoing phase II clinical trials. Vaccine licensure may be facilitated by demonstrating safety and immunological correlates/thresholds suggestive of protection against invasive GBS disease. This will then be followed by phase IV effectiveness studies to assess the burden of GBS vaccine preventable disease, including the effect on all-cause neonatal infections, neonatal deaths and stillbirths.

Geographical, Temporal and Host-Species Distribution of Potentially Human-Pathogenic Group B Streptococcus in Aquaculture Species in Southeast Asia.

Group B Streptococcus (GBS) is a major pathogen of humans and aquatic species. Fish have recently been recognized as the source of severe invasive foodborne GBS disease, caused by sequence type (ST) 283, in otherwise healthy adults in Southeast Asia. Thailand and Vietnam are among the major aquaculture producers in Southeast Asia, with GBS disease reported in fish as well as frogs in both countries. Still, the distribution of potentially human-pathogenic GBS in aquaculture species is poorly known. Using 35 GBS isolates from aquatic species in Thailand collected from 2007 to 2019 and 43 isolates from tilapia collected in Vietnam in 2018 and 2019, we have demonstrated that the temporal, geographical, and host-species distribution of GBS ST283 is broader than previously known, whereas the distribution of ST7 and the poikilothermic lineage of GBS are geographically restricted. The gene encoding the human GBS virulence factor C5a peptidase, scpB, was detected in aquatic ST283 from Thailand but not in ST283 from Vietnam or in ST7 from either country, mirroring current reports of GBS strains associated with human sepsis. The observed distribution of strains and virulence genes is likely to reflect a combination of spill-over, host adaptation through the gain and loss of mobile genetic elements, and current biosecurity practices. The plastic nature of the GBS genome and its importance as a human, aquatic, and potentially foodborne pathogen suggests that active surveillance of GBS presence and its evolution in aquaculture systems may be justified.

Association of infant Rib and Alp1 surface protein N-terminal domain immunoglobulin G and invasive Group B Streptococcal disease in young infants.

Vaccine development for Group B Streptococcus (GBS), a common cause of invasive disease in early-infancy and adverse pregnancy outcomes, include exploring widely-expressed GBS surface proteins as vaccine epitopes. We investigated the association between natural infant serum IgG against the RibN and Alp1N domains and risk of invasive GBS disease caused by isolates expressing these proteins. We analyzed maternal and infant serum samples from GBS disease cases and infants born to GBS-colonized women controls. Bayesian modelling was used to calculate the GBS homotypic IgG concentration associated with risk reduction of invasive disease in the infant. PCR-based typing of 85 GBS invasive isolates showed 46 and 24 possessing the gene for Rib and Alp1, respectively. These were matched to 46 and 36 infant controls whose mothers were colonized with GBS expressing Rib and Alp1, respectively. RibN IgG geometric mean concentrations (GMC) were lower in cases than controls among infants (0.01; 95%CI: 0.01-0.02 vs 0.04; 95%CI: 0.03-0.06; p<0.001), no significant difference was found between maternal RibN IgG GMC in cases compared to controls. Alp1N IgG GMC was also lower in infant cases (0.02; 95%CI: 0.01-0.03) than controls (0.05; 95%CI: 0.04-0.07; p<0.001); albeit not so in mothers. An infant IgG threshold≥0.428 and≥0.112µg/mL was associated with 90% risk reduction of invasive GBS disease due to Rib and Alp1 expressing strains, respectively. Lower serum RibN and Alp1N IgG GMC were evident in infants with invasive GBS disease compared with controls born to women colonized with GBS expressing the homotypic protein. These data support the evaluation of Alp family proteins as potential vaccine candidates against invasive GBS disease.

Using Dried Blood Spots for a Sero-Surveillance Study of Maternally Derived Antibody against Group B Streptococcus.

Vaccination during pregnancy could protect women and their infants from invasive Group B Streptococcus (GBS) disease. To understand if neonatal dried blood spots (DBS) can be used to determine the amount of maternally derived antibody that protects infants against invasive GBS disease, a retrospective case-control study was conducted in England between 1 April 2014 and 30 April 2015. The DBS of cases with invasive GBS disease (n = 61) were matched with healthy controls (n = 125). The haematocrit, DBS storage temperature, freeze-thaw cycle, and paired serum/DBS studies were set up to optimise the antibody assessment. The samples were analysed using a multiplex immunoassay, and the results were assessed using parametric and nonparametric tests. Antibody concentrations were stable at haematocrits of up to 50% but declined at 75%. DBS storage at room temperature was stable for three months compared with storage from collection at -20 °C and rapidly degraded thereafter. Total IgG levels measured in DBS and paired serum showed a good correlation (r2 = 0.99). However, due to suboptimal storage conditions, no difference was found in the GBS IgG levels between DBS samples from cases and controls. We have demonstrated a proof of concept that assays utilising DBS for assessing GBS serotype-specific antibodies in infants is viable. This method could be used to facilitate future large sero-correlate studies, but DBS samples must be stored at -20 °C for long term preservation of antibody.

2134. A Phase 2 Study to Evaluate the Safety, Tolerability, and Immunogenicity of a Booster Dose of a Group B Streptococcus 6-Valent Polysaccharide Conjugate Vaccine (GBS6)

Abstract Background Group B streptococcus (GBS) is a leading cause of invasive bacterial infections in young infants and pregnant women. Pfizer is developing a hexavalent GBS vaccine (GBS6) as a maternal vaccine to prevent invasive GBS disease due to the 6 most prevalent serotypes in young infants. We previously reported Phase 1 safety and immunogenicity data for GBS6. There is precedent for repeat doses of vaccines to augment or sustain circulating antibodies available for placental transfer with each pregnancy; thus, data to inform GBS6 booster strategies were required. Methods This was a Phase 2 open-label extension study to evaluate the safety and immunogenicity of a booster dose of GBS6 (20 μg capsular polysaccharide (CPS)/serotype/dose) with or without AlPO4, given ∼2 years after primary vaccination in 151 healthy nonpregnant adults. Sera taken before and 1-month postbooster were assessed for anti-CPS IgG using a direct Luminex immunoassay. Participants recorded solicited local and systemic events for 14 days after vaccination and unsolicited safety events through 6 months after vaccination. Immunogenicity time points from the Phase 1 study are referred to as primary dose. Results Immunogenicity results For all serotypes, serotype-specific IgG geometric mean concentrations (GMCs) remained elevated compared to baseline at the prebooster time point and were higher 1-month postbooster than 1 month post primary. The 1-month postbooster IgG GMCs were 10- to 59-fold higher than at the prebooster time point. There were similar responses between the 2 formulations. Safety and tolerability results The most frequently reported local reaction was mild to moderate pain at the injection site. Greater pain was associated with AlPO4 formulation. The most frequently reported systemic events were mild to moderate headache and fatigue. The frequency of adverse events was low. Figure 1Antibody Response Line Plot of IgG GMCs by Vaccine Group - All SerotypesFigure 2.Reverse Cumulative Distribution Curves (RCDCs) for IgG 1 Month After Primary and Booster Vaccination, by Vaccine Group – All SerotypesFigure 3.IgG Geometric Mean Fold Rises (GMFRs) at 1 Month Postbooster Vaccination Conclusion A booster dose of GBS6 given ∼2 years after a primary dose to healthy nonpregnant adults was safe and elicited robust immune responses that were also consistently higher than after primary dose. This study suggests that repeat vaccination with GBS6 may confer additional benefit in pregnant women in subsequent pregnancies. Disclosures Babalwa Jongihlati, MD, MBA, Pfizer: Stocks/Bonds Judith Absalon, MD, MPH, Pfizer: Stocks/Bonds Samantha Munson, MPH, MBA, Pfizer: Stocks/Bonds Yasmin Sanchez-Pearson, PhD, Pfizer: Stocks/Bonds Raphael Simon, PhD, Pfizer: Stocks/Bonds Natalie Silmon de Monerri, PhD, Pfizer: Stocks/Bonds David Radley, MS, Pfizer: Employee|Pfizer: Stocks/Bonds Emily A. Gomme, Ph.D., Pfizer: Stocks/Bonds Michelle Gaylord, PhD, Pfizer: Stocks/Bonds William C. Gruber, MD, Pfizer, Inc.: Salary|Pfizer, Inc.: Stocks/Bonds Kathrin U. Jansen, PhD, Pfizer: Stocks/Bonds Daniel A. Scott, MD, Pfizer: Employee|Pfizer: Stocks/Bonds Annaliesa S. Anderson, PhD, Pfizer: Stocks/Bonds.

Microbiological and clinical characteristics of invasive Group B Streptococcal blood stream infections in children and adults from Qatar

IntroductionGroup 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.MethodsA 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.ResultDuring 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.ConclusionThere 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.

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.

Population genomics of Group B Streptococcus reveals the genetics of neonatal disease onset and meningeal invasion

Group B Streptococcus (GBS), or Streptococcus agalactiae, is a pathogen that causes preterm births, stillbirths, and acute invasive neonatal disease burden and mortality. Here, we investigate bacterial genetic signatures associated with disease onset time and meningeal tissue infection in acute invasive neonatal GBS disease. We carry out a genome-wide association study (GWAS) of 1,338 GBS isolates from newborns with acute invasive disease; the isolates had been collected annually, for 30 years, through a national bacterial surveillance program in the Netherlands. After controlling for the population structure, we identify genetic variation within noncoding and coding regions, particularly the capsule biosynthesis locus, statistically associated with neonatal GBS disease onset time and meningeal invasion. Our findings highlight the impact of integrating microbial population genomics and clinical pathogen surveillance, and demonstrate the effect of GBS genetics on disease pathogenesis in neonates and infants.

Group B streptococcal bacteraemia: changing trends in a tropical region of Australia

Group B streptococcus (GBS) is a recognised perinatal and neonatal pathogen. There are reports of increasing GBS sepsis globally outside this demographic. North Queensland is part of tropical Australia, with a relatively high proportion of Indigenous Australians. To analyse the epidemiology of GBS bacteraemia and explore associated risk factors. This was a 10-year retrospective review of GBS bacteraemia in a tertiary facility in North Queensland, between 2010 and February 2020. Data variables collected included: demographics, risk factors, clinical source and outcomes. Multivariable logistic regression was performed to examine the association of indigenous status and other relevant clinical factors with mortality from GBS bacteraemia at 3 months. Of the 164 total cases, 123 were not pregnancy related. The annual rate of GBS bacteraemia for the indigenous population was 12.48 per 100 000 and 4.84 per 100 000 for the non-indigenous population. Indigenous patients were more likely to have diabetes and chronic kidney disease compared with the non-indigenous patients. Males (adjusted odds ratio (AOR) = 4.34; 95% CI 1.14-16.56; P = 0.031) and immunosuppressed patients (AOR = 11.49; 95% CI 2.73-48.42; P < 0.001) were more likely to experience mortality at 3 months from GBS bacteraemia even after adjusting for other risk factors respectively. GBS bacteraemia is deviating from being primarily a neonatal disease. While the indigenous population of North Queensland are disproportionately affected, the demographics affected differ. GBS appears to target the older non-indigenous patients with greater comorbidities. In the non-indigenous population, invasive GBS disease is an emerging issue. Three-month mortality appears to be increased in males and the immunosuppressed.

Variation of invasive neonatal GBS disease across the regions

Group B streptococcus (GBS) emerged in the 1960s as the leading cause of neonatal disease in the USA,1 and yet the reason for its emergence is unknown. Possible reasons are past underdiagnosis or a change in the population structure of GBS.2 Intrapartum antibiotic prophylaxis (IAP) was recommended as the prevention strategy for early-onset invasive GBS (EOGBS),3 and was adopted by various high-income countries. As a result, a substantial decline in the incidence of neonatal disease was observed.

Neurodevelopmental and growth outcomes after invasive Group B Streptococcus in early infancy: A multi-country matched cohort study in South Africa, Mozambique, India, Kenya, and Argentina

SummaryBackgroundData are limited regarding long-term consequences of invasive GBS (iGBS) disease in early infancy, especially from low- and middle-income countries (LMIC) where most cases occur. We aimed to estimate risk of neurodevelopmental impairment (NDI) in children with a history of iGBS disease.MethodsA multi-country matched cohort study was undertaken in South Africa, India, Mozambique, Kenya, and Argentina from October 2019 to April 2021. The exposure of interest was defined as a history of iGBS disease (sepsis or meningitis) before 90 days of age, amongst children now aged 1·5–18 years. Age and sex-matched, children without history of GBS were also recruited. Age-appropriate, culturally-adapted assessments were used to define NDI across multiple domains (cognitive, motor, hearing, vision, emotional-behaviour, growth). Pooled NDI risk was meta-analysed across sites. Association of iGBS exposure and NDI outcome was estimated using modified Poisson regression with robust variance estimator.FindingsAmongst 138 iGBS survivors and 390 non-iGBS children, 38·1% (95% confidence interval [CI]: 30·0% – 46·6%) of iGBS children had any NDI, compared to 21·7% (95% CI: 17·7% - 26·0%) of non- iGBS children, with notable between-site heterogeneity. Risk of moderate/severe NDI was 15·0% (95% CI: 3·4% - 30·8%) among GBS-meningitis, 5·6% (95% CI: 1·5% - 13·7%) for GBS-sepsis survivors. The adjusted risk ratio (aRR) for moderate/severe NDI among iGBS survivors was 1.27 (95% CI: 0.65, 2.45), when compared to non-GBS children. Mild impairment was more frequent in iGBS (27.6% (95% CI: 20.3 – 35.5%)) compared to non-GBS children (12.9% (95% CI: 9.7% - 16.4%)). The risk of emotional-behavioural problems was similar irrespective of iGBS exposure (aRR=0.98 (95% CI: 0.55, 1.77)).InterpretationOur findings suggest that iGBS disease is on average associated with a higher risk of moderate/severe NDI, however substantial variation in risk was observed between sites and data are consistent with a wide range of values. Our study underlines the importance of long-term follow-up for at-risk neonates and more feasible, standardised assessments to facilitate diagnosis in research and clinical practice.FundingThis work was supported by a grant (INV-009018) from the Bill & Melinda Gates Foundation to the London School of Hygiene &Tropical Medicine.

Group B streptococcus infection during pregnancy and infancy: estimates of regional and global burden

SummaryBackgroundGroup B streptococcus (GBS) colonisation during pregnancy can lead to invasive GBS disease (iGBS) in infants, including meningitis or sepsis, with a high mortality risk. Other outcomes include stillbirths, maternal infections, and prematurity. There are data gaps, notably regarding neurodevelopmental impairment (NDI), especially after iGBS sepsis, which have limited previous global estimates. In this study, we aimed to address this gap using newly available multicountry datasets.MethodsWe collated and meta-analysed summary data, primarily identified in a series of systematic reviews published in 2017 but also from recent studies on NDI and stillbirths, using Bayesian hierarchical models, and estimated the burden for 183 countries in 2020 regarding: maternal GBS colonisation, iGBS cases and deaths in infants younger than 3 months, children surviving iGBS affected by NDI, and maternal iGBS cases. We analysed the proportion of stillbirths with GBS and applied this to the UN-estimated stillbirth risk per country. Excess preterm births associated with maternal GBS colonisation were calculated using meta-analysis and national preterm birth rates.FindingsData from the seven systematic reviews, published in 2017, that informed the previous burden estimation (a total of 515 data points) were combined with new data (17 data points) from large multicountry studies on neurodevelopmental impairment (two studies) and stillbirths (one study). A posterior median of 19·7 million (95% posterior interval 17·9–21·9) pregnant women were estimated to have rectovaginal colonisation with GBS in 2020. 231 800 (114 100–455 000) early-onset and 162 200 (70 200–394 400) late-onset infant iGBS cases were estimated to have occurred. In an analysis assuming a higher case fatality rate in the absence of a skilled birth attendant, 91 900 (44 800–187 800) iGBS infant deaths were estimated; in an analysis without this assumption, 58 300 (26 500–125 800) infant deaths from iGBS were estimated. 37 100 children who recovered from iGBS (14 600–96 200) were predicted to develop moderate or severe NDI. 40 500 (21 500–66 200) maternal iGBS cases and 46 200 (20 300–111 300) GBS stillbirths were predicted in 2020. GBS colonisation was also estimated to be potentially associated with considerable numbers of preterm births.InterpretationOur analysis provides a comprehensive assessment of the pregnancy-related GBS burden. The Bayesian approach enabled coherent propagation of uncertainty, which is considerable, notably regarding GBS-associated preterm births. Our findings on both the acute and long-term consequences of iGBS have public health implications for understanding the value of investment in maternal GBS immunisation and other preventive strategies.FundingBill & Melinda Gates Foundation.