{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T08:45:23Z","timestamp":1783413923842,"version":"3.54.6"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T00:00:00Z","timestamp":1764028800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100006823","name":"Boston Children's Hospital","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006823","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,5,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Group B Streptococcus (GBS) is a major cause of infant meningitis, often requiring intensive care. The molecular determinants of severe disease (meningitis\/Intensive Care Unit (ICU) admission) remain unclear. Although late-onset disease (LOD) and very late-onset disease (VLOD) appear clinically similar, their genomic distinctions are not well described.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We characterized invasive GBS isolates from 87 patients at Boston Children's Hospital over 15 years using whole-genome sequencing. Isolate diversity was compared with global samples. We assessed vaccine coverage, antimicrobial resistance, and the relationships between clinical features or pathogen virulence factors and disease severity or age of onset using regression models adjusted for population structure and multiple testing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Of the 87 patients, 44.3% required ICU care and 18.6% had meningitis. Five serotypes and six clonal complexes were identified, with hypervirulent clones CC17\/cpsIII and CC23\/cpsIa predominating. All isolates contained candidate polysaccharide conjugate and\/or protein vaccine targets and were susceptible to penicillin and vancomycin; 38% were erythromycin-resistant and 29% clindamycin-resistant. ICU admission correlated with specific hematologic abnormalities, but meningitis did not. No known virulence factors were associated with ICU admission or meningitis. LOD and VLOD isolates showed no major genomic differences, though the PI-2A1 pilus gene was more frequent in VLOD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Invasive GBS disease in infants frequently results in ICU admission and meningitis, yet no pathogen genomic features predicted these outcomes highlighting the likelihood of host response factors in determining outcomes. The similar clinical and genomic profiles of LOD and VLOD suggest their current classification may be arbitrary, with implications for surveillance and management.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/cid\/ciaf603","type":"journal-article","created":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T14:01:38Z","timestamp":1764079298000},"page":"860-867","source":"Crossref","is-referenced-by-count":1,"title":["A 15-year Single-center Analysis of Late-onset Group B\n                    <i>Streptococcus<\/i>\n                    Infection Correlating Clinical Severity With Pathogen Virulence Determinants"],"prefix":"10.1093","volume":"82","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1674-8801","authenticated-orcid":false,"given":"Carl","family":"Britto","sequence":"first","affiliation":[{"name":"Division of Critical Care, Department of Pediatrics, Boston Children's Hospital , Boston, Massachusetts ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L\u00e9a","family":"Cavalli","sequence":"additional","affiliation":[{"name":"Center for Communicable Disease Dynamics, Department of Epidemiology, Harvard T.H. Chan School of Public Health , Boston, Massachusetts ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madikay","family":"Senghore","sequence":"additional","affiliation":[{"name":"Department of Public Health and Epidemiology, College of Medicine and Health Sciences, Khalifa University , Abu Dhabi ,","place":["United Arab Emirates"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander J","family":"McAdam","sequence":"additional","affiliation":[{"name":"Infectious Diseases Diagnostic Laboratory, Department of Laboratory Medicine, Boston Children's Hospital , Boston, Massachusetts ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William P","family":"Hanage","sequence":"additional","affiliation":[{"name":"Center for Communicable Disease Dynamics, Department of Epidemiology, Harvard T.H. Chan School of Public Health , Boston, Massachusetts ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying-Jie","family":"Lu","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Boston Children's Hospital and Harvard Medical School , Boston, Massachusetts ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Malley","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Boston Children's Hospital and Harvard Medical School , Boston, Massachusetts ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,11,25]]},"reference":[{"key":"2026052019244414800_ciaf603-B1","doi-asserted-by":"crossref","first-page":"437","DOI":"10.3389\/fmicb.2018.00437","article-title":"Group B streptococcal colonization, molecular characteristics, and epidemiology","volume":"9","author":"Shabayek","year":"2018","journal-title":"Front Microbiol"},{"key":"2026052019244414800_ciaf603-B2","author":"World Health Organization"},{"key":"2026052019244414800_ciaf603-B3","author":"Center for Disease Control"},{"key":"2026052019244414800_ciaf603-B4","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.1093\/cid\/ciaa151","article-title":"Multistate, population-based distributions of candidate vaccine targets, clonal complexes, and resistance features of invasive group B streptococci within the United States, 2015\u20132017","volume":"72","author":"McGee","year":"2021","journal-title":"Clin Infect Dis"},{"key":"2026052019244414800_ciaf603-B5","doi-asserted-by":"crossref","first-page":"2056","DOI":"10.1001\/jama.299.17.2056","article-title":"Epidemiology of invasive group B streptococcal disease in the United States, 1999-2005","volume":"299","author":"Phares","year":"2008","journal-title":"JAMA"},{"key":"2026052019244414800_ciaf603-B6","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1001\/jamapediatrics.2018.4826","article-title":"Epidemiology of invasive early-onset and late-onset group B streptococcal disease in the United States, 2006 to 2015: multistate laboratory and population-based surveillance","volume":"173","author":"Nanduri","year":"2019","journal-title":"JAMA Pediatr"},{"key":"2026052019244414800_ciaf603-B7","first-page":"20499361221142732","article-title":"Transmission of Group B Streptococcus in late-onset neonatal disease: a narrative review of current evidence","volume":"9","author":"Miselli","year":"2022","journal-title":"Ther Adv Infect Dis"},{"key":"2026052019244414800_ciaf603-B8","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1007\/s12519-014-0450-8","article-title":"Late and very late onset group B Streptococcus sepsis: one and the same?","volume":"10","author":"Cantey","year":"2014","journal-title":"World J Pediatr"},{"key":"2026052019244414800_ciaf603-B9","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1097\/INF.0000000000001345","article-title":"Epidemiology of late and very late onset group B streptococcal disease: fifteen-year experience from two Australian tertiary pediatric facilities","volume":"36","author":"Bartlett","year":"2017","journal-title":"Pediatr Infect Dis J"},{"key":"2026052019244414800_ciaf603-B10","doi-asserted-by":"crossref","first-page":"e32","DOI":"10.1016\/S2666-5247(20)30192-0","article-title":"Molecular epidemiology and mortality of group B streptococcal meningitis and infant sepsis in The Netherlands: a 30-year nationwide surveillance study","volume":"2","author":"van Kassel","year":"2021","journal-title":"Lancet Microbe"},{"key":"2026052019244414800_ciaf603-B11","doi-asserted-by":"crossref","first-page":"S14","DOI":"10.1093\/cid\/ciab793","article-title":"Short-and long-term outcomes of group B Streptococcus invasive disease in Mozambican children: results of a matched cohort and retrospective observational study and implications for future vaccine introduction","volume":"74","author":"Bramugy","year":"2022","journal-title":"Clin Infect Dis"},{"key":"2026052019244414800_ciaf603-B12","doi-asserted-by":"crossref","first-page":"101358","DOI":"10.1016\/j.eclinm.2022.101358","article-title":"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","volume":"47","author":"Paul","year":"2022","journal-title":"EClinicalMedicine"},{"key":"2026052019244414800_ciaf603-B13","doi-asserted-by":"crossref","first-page":"e01864-19","DOI":"10.1128\/JCM.01864-19","article-title":"The clinical and laboratory standards institute subcommittee on antimicrobial susceptibility testing: background, organization, functions, and processes","volume":"58","author":"Weinstein","year":"2020","journal-title":"J Clin Microbiol"},{"key":"2026052019244414800_ciaf603-B14","doi-asserted-by":"crossref","first-page":"4310","DOI":"10.1093\/bioinformatics\/bty539","article-title":"Pyseer: a comprehensive tool for microbial pangenome-wide association studies","volume":"34","author":"Lees","year":"2018","journal-title":"Bioinformatics"},{"key":"2026052019244414800_ciaf603-B15","volume-title":"R: a language and environment for statistical computing","author":"R Core Team","year":"2013"},{"key":"2026052019244414800_ciaf603-B16","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1542\/hpeds.2020-005512","article-title":"Determining normative values for cerebrospinal fluid profiles in infants","volume":"11","author":"Mukherjee","year":"2021","journal-title":"Hosp Pediatr"},{"key":"2026052019244414800_ciaf603-B17","doi-asserted-by":"crossref","first-page":"ofaa634","DOI":"10.1093\/ofid\/ofaa634","article-title":"Low but increasing prevalence of reduced beta-lactam susceptibility among invasive group B streptococcal isolates, US population-based surveillance, 1998\u20132018","volume":"8","author":"Kobayashi","year":"2021","journal-title":"Open Forum Infect Dis"},{"key":"2026052019244414800_ciaf603-B18","doi-asserted-by":"crossref","first-page":"e1388","DOI":"10.1542\/peds.2013-0426","article-title":"Synchronous recurrence of group B streptococcal late-onset sepsis in twins","volume":"133","author":"Elling","year":"2014","journal-title":"Pediatrics"},{"key":"2026052019244414800_ciaf603-B19","doi-asserted-by":"crossref","first-page":"4215","DOI":"10.1038\/s41467-022-31858-4","article-title":"Population genomics of Group B Streptococcus reveals the genetics of neonatal disease onset and meningeal invasion","volume":"13","author":"Chaguza","year":"2022","journal-title":"Nat Commun"},{"key":"2026052019244414800_ciaf603-B20","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/S1473-3099(20)30478-3","article-title":"Safety and immunogenicity of a novel hexavalent group B streptococcus conjugate vaccine in healthy, non-pregnant adults: a phase 1\/2, randomised, placebo-controlled, observer-blinded, dose-escalation trial","volume":"21","author":"Absalon","year":"2021","journal-title":"Lancet Infect Dis"},{"key":"2026052019244414800_ciaf603-B21","doi-asserted-by":"crossref","first-page":"106261","DOI":"10.1016\/j.isci.2023.106261","article-title":"Safety and immunogenicity of the group B streptococcus vaccine AlpN in a placebo-controlled double-blind phase 1 trial","volume":"26","author":"Gonzalez-Miro","year":"2023","journal-title":"iScience"},{"key":"2026052019244414800_ciaf603-B22","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1056\/NEJMoa2116045","article-title":"Potential for maternally administered vaccine for infant group B streptococcus","volume":"389","author":"Madhi","year":"2023","journal-title":"N Engl J Med"},{"key":"2026052019244414800_ciaf603-B23","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1001\/jamainternmed.2018.7269","article-title":"Epidemiology of invasive group B streptococcal infections among nonpregnant adults in the United States, 2008-2016","volume":"179","author":"Francois Watkins","year":"2019","journal-title":"JAMA Intern Med"},{"key":"2026052019244414800_ciaf603-B24","doi-asserted-by":"crossref","first-page":"6682","DOI":"10.1016\/j.vaccine.2020.08.052","article-title":"Systematic review of Group B Streptococcal capsular types, sequence types and surface proteins as potential vaccine candidates","volume":"38","author":"Bianchi-Jassir","year":"2020","journal-title":"Vaccine"},{"key":"2026052019244414800_ciaf603-B25","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1038\/ng.2625","article-title":"Population genomics of post-vaccine changes in pneumococcal epidemiology","volume":"45","author":"Croucher","year":"2013","journal-title":"Nat Genet"},{"key":"2026052019244414800_ciaf603-B26","doi-asserted-by":"crossref","first-page":"1745","DOI":"10.1093\/infdis\/jis605","article-title":"Capsular switching in group B Streptococcus CC17 hypervirulent clone: a future challenge for polysaccharide vaccine development","volume":"206","author":"Bellais","year":"2012","journal-title":"J Infect Dis"},{"key":"2026052019244414800_ciaf603-B27","doi-asserted-by":"crossref","first-page":"43","DOI":"10.3390\/pathogens11010043","article-title":"Immunogenic proteins of group B Streptococcus\u2014potential antigens in immunodiagnostic assay for GBS detection","volume":"11","author":"Dobrut","year":"2021","journal-title":"Pathogens"},{"key":"2026052019244414800_ciaf603-B28","first-page":"1","article-title":"Prevention of perinatal group B streptococcal disease: revised guidelines from CDC, 2010","volume":"59","author":"Verani","year":"2010","journal-title":"MMWR Recomm Rep"},{"key":"2026052019244414800_ciaf603-B29","doi-asserted-by":"crossref","first-page":"ofac514","DOI":"10.1093\/ofid\/ofac514","article-title":"Appropriate antibiotic use for Group B streptococcus prophylaxis among penicillin-allergic patients in academic and nonacademic hospitals","volume":"9","author":"Pineles","year":"2022","journal-title":"Open Forum Infect Dis"},{"key":"2026052019244414800_ciaf603-B30","doi-asserted-by":"crossref","first-page":"1957","DOI":"10.1093\/cid\/ciab575","article-title":"Patterns of antibiotic nonsusceptibility among invasive group A Streptococcus infections\u2014United States, 2006\u20132017","volume":"73","author":"Fay","year":"2021","journal-title":"Clin Infect Dis"},{"key":"2026052019244414800_ciaf603-B31","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1086\/595564","article-title":"Preventing bacterial infections with pilus-based vaccines: the group B streptococcus paradigm","volume":"199","author":"Margarit","year":"2009","journal-title":"J Infect Dis"},{"key":"2026052019244414800_ciaf603-B32","doi-asserted-by":"crossref","first-page":"4842","DOI":"10.1016\/j.vaccine.2010.04.042","article-title":"Re-emergence of the type 1 pilus among Streptococcus pneumoniae isolates in Massachusetts, USA","volume":"28","author":"Regev-Yochay","year":"2010","journal-title":"Vaccine"}],"container-title":["Clinical Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/cid\/advance-article-pdf\/doi\/10.1093\/cid\/ciaf603\/65493046\/ciaf603.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/cid\/article-pdf\/82\/5\/860\/65493046\/ciaf603.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/cid\/article-pdf\/82\/5\/860\/65493046\/ciaf603.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T23:24:59Z","timestamp":1779319499000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/cid\/article\/82\/5\/860\/8341628"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,25]]},"references-count":32,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2025,11,25]]},"published-print":{"date-parts":[[2026,5,20]]}},"URL":"https:\/\/doi.org\/10.1093\/cid\/ciaf603","relation":{},"ISSN":["1058-4838","1537-6591"],"issn-type":[{"value":"1058-4838","type":"print"},{"value":"1537-6591","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,5,15]]},"published":{"date-parts":[[2025,11,25]]}}}