Population structure of group B streptococcus from a low-incidence region for invasive neonatal disease

The population structure of group B streptococcus (GBS) from a low-incidence region for invasive neonatal disease (Israel) was investigated using multilocus genotype data. The strain collection consisted of isolates from maternal carriage (n=104) and invasive neonatal disease (n=50), resolving into 46 sequence types. The most prevalent sequence types were ST-1 (17·5 %), ST-19 (10·4 %), ST-17 (9·7 %), ST-22 (8·4 %) and ST-23 (6·5 %). Serotype III was the most common, accounting for 29·2 % of the isolates. None of the serotypes was significantly associated with invasive neonatal disease. burst analysis resolved the 46 sequence types into seven lineages (clonal complexes), from which only lineage ST-17, expressing serotype III only, was significantly associated with invasive neonatal disease. Lineage ST-22 expressed mainly serotype II, and was significantly associated with carriage. The distribution of the various sequence types and lineages, and the association of lineage ST-17 with invasive disease, are consistent with the results of analyses from a global GBS isolate collection. These findings could imply that the global variation in disease incidence is independent of the circulating GBS populations, and may be more affected by other risk factors for invasive GBS disease, or by different prevention strategies.

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Estimation of country-level incidence of early-onset invasive Group B Streptococcus disease in infants using Bayesian methods

PLoS Computational Biology ◽

10.1371/journal.pcbi.1009001 ◽

2021 ◽

Vol 17 (6) ◽

pp. e1009001

Author(s):

Bronner P. Gonçalves ◽

Simon R. Procter ◽

Sam Clifford ◽

Artemis Koukounari ◽

Proma Paul ◽

...

Keyword(s):

Early Onset ◽

Disease Incidence ◽

Group B Streptococcus ◽

Epidemiological Data ◽

Epidemiological Studies ◽

Invasive Disease ◽

Country Level ◽

Detection Assay ◽

Group B ◽

Country Specific

Neonatal invasive disease caused by Group B Streptococcus (GBS) is responsible for much acute mortality and long-term morbidity. To guide development of better prevention strategies, including maternal vaccines that protect neonates against GBS, it is necessary to estimate the burden of this condition globally and in different regions. Here, we present a Bayesian model that estimates country-specific invasive GBS (iGBS) disease incidence in children aged 0 to 6 days. The model combines different types of epidemiological data, each of which has its own limitations: GBS colonization prevalence in pregnant women, risk of iGBS disease in children born to GBS-colonized mothers and direct estimates of iGBS disease incidence where available. In our analysis, we present country-specific maternal GBS colonization prevalence after adjustment for GBS detection assay used in epidemiological studies. We then integrate these results with other epidemiological data and estimate country-level incidence of iGBS disease including in countries with no studies that directly estimate incidence. We are able to simultaneously estimate two key epidemiological quantities: the country-specific incidence of early-onset iGBS disease, and the risk of iGBS disease in babies born to GBS-colonized women. Overall, we believe our method will contribute to a more comprehensive quantification of the global burden of this disease, inform cost-effectiveness assessments of potential maternal GBS vaccines and identify key areas where data are necessary.

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Temporal population structure of invasive Group BStreptococcusduring a period of rising disease incidence shows expansion of a CC17 clone

10.1101/447037 ◽

2018 ◽

Cited By ~ 2

Author(s):

Dorota Jamrozy ◽

Marcus C de Goffau ◽

Merijn W Bijlsma ◽

Diederik van de Beek ◽

Taco W. Kuijpers ◽

...

Keyword(s):

Population Structure ◽

The Netherlands ◽

Genome Sequencing ◽

Late Onset ◽

Disease Incidence ◽

Invasive Disease ◽

Whole Genome ◽

Adhesion Protein ◽

Group B

AbstractGroup BStreptococcus(GBS) is a major cause of neonatal invasive disease worldwide. In the Netherlands, the incidence of the disease increased, despite the introduction of prevention guidelines in 1999. This was accompanied by changes in pathogen genotype distribution, with a significant increase in the prevalence of isolates belonging to clonal complex (CC) 17. To better understand the mechanisms of temporal changes in the epidemiology of GBS genotypes that correlated with the rise in disease incidence, we applied whole genome sequencing (WGS) to study a national collection of invasive GBS isolates. A total of 1345 isolates from patients aged 0 – 89 days and collected between 1987 and 2016 in the Netherlands were sequenced and characterised. The GBS population contained 5 major lineages representing CC17 (39%), CC19 (25%), CC23 (18%), CC10 (9%), and CC1 (7%). There was a significant rise in the prevalence of isolates representing CC17 and CC23 among cases of early-and late-onset disease, due to expansion of discrete sub-lineages. The most prominent was shown by a CC17 sub-lineage, identified here as CC17-1A, which experienced a major clonal expansion at the end of the 1990s. The CC17-1A expansion correlated with the emergence of a novel phage carrying a gene encoding a putative adhesion protein, named here StrP. The first occurrence of this phage (designated phiStag1) within the collection in 1997, was followed by multiple, independent acquisitions by CC17 and parallel clonal expansions of CC17-1A and another cluster, CC17-1B. The CC17-1A clone was identified in external datasets, and represents a globally distributed invasive sub-lineage of CC17. Our work describes how a sudden change in the epidemiology of specific GBS sub-lineages, in particular CC17-1A, correlates with the rise in the disease incidence, and indicates a putative key role of a novel phage in driving the expansion of this CC17 clone.Author summaryGroup BStreptococcus(GBS) is a commensal organism of the gastrointestinal and genitourinary tracts. However, it is also an opportunistic pathogen and a major cause of neonatal invasive disease, which can be classified into early-onset (0 – 6 days of life) or late-onset (7 – 89 days of life). Current disease prevention strategy involves intrapartum antibiotic prophylaxis (IAP), which aims to prevent the transmission of GBS from mother to baby during labour. Many developed countries adapted national IAP guidelines. In the Netherlands, these were introduced in 1999. However, the incidence of GBS disease increased after IAP introduction. In this study we applied whole genome sequencing to characterise a nationwide collection of invasive GBS from cases of neonatal disease that occurred between 1987 and 2016. Analysis of GBS population structure involving phylogenetic partitioning of individual lineages revealed that the rise in disease incidence involved the expansion of specific clusters from two major GBS lineages, CC17 and CC23. Our study provides new insights into the recent evolution of the ‘hypervirulent’ CC17 and describes a rapid expansion of a discrete, pre-existing sub-lineage that occurred after acquisition of a novel phage carrying a putative adhesion protein gene, underscoring the major role of CC17 in neonatal diseases.

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Molecular characteristics of group B Streptococcus isolates from infants in southern mainland China

BMC Infectious Diseases ◽

10.1186/s12879-019-4434-0 ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 2

Author(s):

Juan Li ◽

Wenjing Ji ◽

Kankan Gao ◽

Haijian Zhou ◽

Lihua Zhang ◽

...

Keyword(s):

Late Onset ◽

Group B Streptococcus ◽

Mainland China ◽

Invasive Disease ◽

Molecular Characteristics ◽

Antibiotic Resistant ◽

Invasive Group ◽

Group B ◽

And Control ◽

Sequence Types

Abstract Background Invasive group B Streptococcus (GBS) disease in Chinese infants has gradually gained attention in recent years, but the molecular epidemiology of the pathogen is still not well known. Methods This multicenter study retrospectively investigated distribution of capsular serotypes, sequence types (STs), and hypervirulent GBS adhesin gene (hvgA) in clinical GBS isolates that caused invasive disease in infants aged < 3 months of age in southern mainland China between January 2013 and June 2016. Genes for antibiotic resistance to tetracycline, erythromycin, and clindamycin were also examined. Results From a total of 93 GBS isolates taken from 34 early-onset disease (EOD, 0–6 days after birth) and 59 late-onset disease (LOD, 7–89 days after birth) cases, four serotypes were identified: serotypes III (79.6%), Ib (12.9%), Ia (4.3%), and V (3.2%). Serotype III accounted for 73.5% of EOD and 83.1% of LOD and was responsible for 75.5% of cases involving meningitis. Fifteen STs were found, with the majority being ST17 (61.3%), ST12 (7.5%), ST19 (7.5%), and others (23.7%). 96.8% of STs belonged to only five clonal complexes (CCs): CC17 (64.5%), CC10 (12.9%), CC19 (9.7%), CC23 (6.5%), and CC1 (3.2%). The hvgA gene was detected in 66.7% of GBS isolates and 95% of CC17 isolates, all of which were serotype III except one serotype Ib/CC17 isolate. A large proportion of GBS isolates were found to be resistant to tetracycline (93.5%), clindamycin (65.5%), and erythromycin (60.2%). Genes of tetO (74.7%) and tetM (46.0%) were found in tetracycline resistant isolates, linB (24.6%) in clindamycin resistant isolates, and ermB (87.5%) and mefA (3.6%) in erythromycin resistant isolates. Conclusion Our results reveal higher prevalence of serotype III, ST17, CC17, hvgA expressing, and antibiotic resistant GBS isolates than previously reported in southern mainland China. This study provides guidance for appropriate measures of prevention and control to be taken in the future.

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Genomic and phenotypic characterisation of invasive neonatal and colonising group B Streptococcus isolates from Slovenia, 2001–2018

BMC Infectious Diseases ◽

10.1186/s12879-020-05599-y ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Tina Perme ◽

Daniel Golparian ◽

Maja Bombek Ihan ◽

Andrej Rojnik ◽

Miha Lučovnik ◽

...

Keyword(s):

Pregnant Women ◽

Virulence Factors ◽

Late Onset ◽

Group B Streptococcus ◽

Genomic Diversity ◽

Neonatal Disease ◽

Phenotypic Characterisation ◽

High Prevalence ◽

Group B ◽

The Impact

Abstract Background Group B Streptococcus (GBS) is the leading cause of invasive neonatal disease in the industrialized world. We aimed to genomically and phenotypically characterise invasive GBS isolates in Slovenia from 2001 to 2018 and contemporary colonising GBS isolates from screening cultures in 2018. Methods GBS isolates from 101 patients (invasive isolates) and 70 pregnant women (colonising isolates) were analysed. Basic clinical characteristics of the patients were collected from medical records. Antimicrobial susceptibility and phenotypic capsular serotype were determined. Whole-genome sequencing was performed to assign multilocus sequence types (STs), clonal complexes (CCs), pathogenicity/virulence factors, including capsular genotypes, and genome-based phylogeny. Results Among invasive neonatal disease patients, 42.6% (n = 43) were females, 41.5% (n = 39/94) were from preterm deliveries (< 37 weeks gestation), and 41.6% (n = 42) had early-onset disease (EOD). All isolates were susceptible to benzylpenicillin with low minimum inhibitory concentrations (MICs; ≤0.125 mg/L). Overall, 7 serotypes were identified (Ia, Ib, II-V and VIII); serotype III being the most prevalent (59.6%). Twenty-eight MLST STs were detected that clustered into 6 CCs. CC-17 was the most common CC overall (53.2%), as well as among invasive (67.3%) and non-invasive (32.9%) isolates (p < 0.001). CC-17 was more common among patients with late-onset disease (LOD) (81.4%) compared to EOD (47.6%) (p < 0.001). The prevalence of other CCs was 12.9% (CC-23), 11.1% (CC-12), 10.5% (CC-1), 8.2% (CC-19), and 1.8% (CC-498). Of all isolates, 2.3% were singletons. Conclusions A high prevalence of hypervirulent CC-17 isolates, with low genomic diversity and characteristic profile of pathogenicity/virulence factors, was detected among invasive neonatal and colonising GBS isolates from pregnant women in Slovenia. This is the first genomic characterisation of GBS isolates in Slovenia and provides valuable microbiological and genomic baseline data regarding the invasive and colonising GBS population nationally. Continuous genomic surveillance of GBS infections is crucial to analyse the impact of IND prevention strategies on the population structure of GBS locally, nationally, and internationally.

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Approach to the Febrile Patient with No Obvious Focus of Infection

Pediatrics in Review ◽

10.1542/pir.5.10.305 ◽

1984 ◽

Vol 5 (10) ◽

pp. 305-315

Author(s):

Sarah S. Long

Keyword(s):

Antimicrobial Agents ◽

Group B Streptococcus ◽

Invasive Disease ◽

Chemotherapeutic Agents ◽

The Body ◽

Therapeutic Modalities ◽

Body Of Knowledge ◽

Age Related ◽

Focus Of Infection ◽

Group B

The summary in Table 1 could be used as a mental checklist for the pediatrician who examines a child with fever. Whether the pediatrician opts to "keep the rules" or appropriately decides to "break the rules," knowledge of the guidelines will help him to focus his approach and to adopt attitudes of caution in certain circumstances. The body of knowledge of infectious agents chemotherapeutic agents has burgeoned over the past 40 years; the rules have changed very little. Thus, the rules might also serve as standards against which "new discoveries" that dictate departure from an established mode of clinical practice would have to be weighed. The adage, "Name the bug before you choose a drug," is especially germaine to pediatrics. Potential pathogens or "bugs" continually change as the patient's age, exposure, and immunity change. The serious diseases they cause mandate that initial treatment be given with the best "drugs." The age-related causes of bacterial meningitis presented in Table 2 could serve as a primer for age-related causes of other invasive disease as well. For bone, joint, and soft tissue infection as well as for septicemia without a focus the age line for group B Streptococcus and H influenzae would be extended upward and S aureus would be added for all ages. Although the relative importance of each pathogen for each clinical entity might vary, therapeutic considerations would be appropriately served by a schema such as this. Unfortunately, the susceptibility of pathogens to antimicrobial agents will continue to change. Fortunately, new and potentially better therapeutic agents will continue to be discovered or invented. When new problems of antibiotic resistance emerge or when superior therapeutic modalities are proved, the pediatrician must be knowledgeable of such events and be prepared for change.

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Fatal, Fulminant and Invasive Non-Typeable Haemophilus influenzae Infection in a Preterm Infant: A Re-Emerging Cause of Neonatal Sepsis

Tropical Medicine and Infectious Disease ◽

10.3390/tropicalmed5010030 ◽

2020 ◽

Vol 5 (1) ◽

pp. 30 ◽

Cited By ~ 2

Author(s):

Sudipta Roy Chowdhury ◽

Srabani Bharadwaj ◽

Suresh Chandran

Keyword(s):

Haemophilus Influenzae ◽

Preterm Infant ◽

Neonatal Sepsis ◽

Group B Streptococcus ◽

Invasive Disease ◽

Preventative Measures ◽

Increased Risk ◽

Extremely Preterm ◽

Serotype B ◽

Group B

Early-onset neonatal sepsis (EOS) is a major cause of neonatal death and long-term neurodevelopmental disabilities among survivors. The common pathogens causing EOS are group B streptococcus (GBS) and Escherichia coli. Haemophilus influenzae (H. influenzae) is a Gram-negative coccobacillus that can cause severe invasive disease and can be divided into either typeable or non-typeable strains. H. influenzae serotype b (Hib) is the most virulent and the major cause of bacterial meningitis in young children prior to routine immunization against Hib. Hib infection rates have dramatically reduced since then. However, a number of studies have reported an increasing incidence of non-typeable H. influenzae (NTHi) sepsis in neonates worldwide and concluded that pregnant women may have an increased risk to invasive NTHi disease with poor pregnancy outcomes. We present a case of fulminant neonatal sepsis caused by NTHi in an extremely preterm infant and discuss potential preventative measures to reduce its re-emergence.

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Group B Streptococcus (Streptococcus agalactiae)

10.1093/med/9780190604813.003.0019 ◽

2018 ◽

Author(s):

Kirsty Le Doare ◽

Christine E. Jones ◽

Paul T. Heath

Keyword(s):

Early Onset ◽

Late Onset ◽

Group B Streptococcus ◽

Significant Risk ◽

Neonatal Infection ◽

Significant Risk Factor ◽

Invasive Disease ◽

Neurodevelopmental Outcomes ◽

Intrapartum Antibiotic ◽

Group B

Group B Streptococcus (GBS) is a leading cause of early neonatal infection and neonatal mortality, with long-term adverse neurodevelopmental outcomes in up to 50% of survivors of GBS meningitis. GBS has a likely underappreciated role in causing preterm birth and stillbirth. GBS colonizes the vagina and gastrointestinal tract of the pregnant woman, and transmission to the infant occurs during or just before delivery. Although the majority of these infants do not develop invasive disease, maternal colonization is a prerequisite for early onset disease (0–6 days of life, most commonly associated with sepsis and respiratory distress) and a significant risk factor for late onset disease (7–89 days of life, most commonly associated with sepsis and meningitis). The introduction of intrapartum antibiotic prophylaxis has resulted in significant declines in the incidence of early onset disease but provides no protection against late onset disease.

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The Italian arm of the PREPARE study: an international project to evaluate and license a maternal vaccine against group B streptococcus

Italian Journal of Pediatrics ◽

10.1186/s13052-020-00923-3 ◽

2020 ◽

Vol 46 (1) ◽

Author(s):

Alberto Berardi ◽

◽

Tiziana Cassetti ◽

Roberta Creti ◽

Caterina Vocale ◽

...

Keyword(s):

Low Income ◽

Pregnancy Outcomes ◽

Group B Streptococcus ◽

Invasive Disease ◽

Low Income Countries ◽

International Project ◽

Main Body ◽

Non Profit ◽

Maternal Vaccination ◽

Group B

Abstract 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.

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Serotype Distribution, Population Structure, and Antimicrobial Resistance of Group B Streptococcus Strains Recovered from Colonized Pregnant Women

Journal of Clinical Microbiology ◽

10.1128/jcm.01615-16 ◽

2016 ◽

Vol 55 (2) ◽

pp. 412-422 ◽

Cited By ~ 36

Author(s):

Sarah Teatero ◽

Patricia Ferrieri ◽

Irene Martin ◽

Walter Demczuk ◽

Allison McGeer ◽

...

Keyword(s):

Population Structure ◽

Pregnant Women ◽

Antimicrobial Agents ◽

Vaccine Development ◽

Group B Streptococcus ◽

Tetracycline Resistance ◽

The United States ◽

High Rate ◽

Content Type ◽

Group B

ABSTRACTUsing serotyping, multilocus sequence typing, and whole-genome sequencing (WGS) of selected strains, we studied the population structure of 102 group BStreptococcus(GBS) isolates prospectively sampled in 2014 from vaginal/rectal swabs of healthy pregnant women in metropolitan Toronto, Canada. We also determined the susceptibilities of each of the colonizing isolates to penicillin, erythromycin, clindamycin, tetracycline, and other antimicrobial agents. Overall, we observed a high rate of tetracycline resistance (89%) among colonizing GBS isolates. We found resistance to erythromycin in 36% of the strains, and 33% were constitutively or inducibly resistant to clindamycin. The most frequently identified serotypes were III (25%), Ia (23%), and V (19%). Serotype IV accounted for 6% of the colonizing isolates, a rate consistent with that observed among patients with invasive GBS infections in metropolitan Toronto. The majority of serotype IV isolates belonged to sequence type (ST)459, a tetracycline-, erythromycin-, and clindamycin-resistant ST first identified in Minnesota, which is considered to be the main driver of serotype IV GBS expansion in North America. WGS revealed that ST459 isolates from Canada are clonally related to colonizing and invasive ST459 organisms circulating in regions of the United States. We also used WGS to study recombination in selected colonizing strains from metropolitan Toronto, which revealed multiple episodes of capsular switching. Present and future circulating GBS organisms and their genetic diversity may influence GBS vaccine development.

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