The Pediatric Infectious Disease Journal • Volume 34, Number 5, May 2015
Edwards et al
RELEVANCE OF AGE AT DIAGNOSIS TO PREVENTION OF LATE-ONSET GROUP B STREPTOCOCCAL DISEASE BY MATERNAL IMMUNIZATION Morven S. Edwards, MD,* Marcia A. Rench, BSN,* and Carol J. Baker, MD*†‡ Abstract: Among 248 infants with late-onset group B streptococcal (GBS) disease from 1993 to 2012, approximately two thirds (63%) had a gestation of at least 35 weeks and 72% of these became ill within 6 weeks of life (median 27 days), suggesting that third trimester maternal GBS immunization could substantially reduce the late-onset GBS disease burden in the United States. Key Words: group B Streptococcus, late-onset sepsis, vaccine, maternal immunization Accepted for publication November 17, 2014. From the *Section of Infectious Disease, Department of Pediatrics, and †Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas; and ‡Center for Vaccine Awareness and Research, Texas Children’s Hospital, Houston, Texas. This work was funded in part by donations from families of infants afflicted with late-onset GBS disease. M.S.E. serves as a consultant to Novartis Vaccines. C.J.B. serves as a consultant and advisory board member for Novartis Vaccines as well as for Pfizer Inc. Marcia Rench has no conflicts. Address for correspondence: Morven S. Edwards, MD, Section of Infectious Disease, Department of Pediatrics, Baylor College of Medicine, 1102 Bates Street, Suite 1120, Houston, Texas 77030. E-mail: [email protected]. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. DOI: 10.1097/INF.0000000000000640
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he incidence of late-onset group B streptococcal (GBS) disease in the United States in 2013 was 0.25 per 1000 live births, or approximately 1000 cases.1 Late-onset cases are not reduced under current prevention strategies and, when associated with meningitis, often result in death or permanent disability.2 Third trimester maternal immunization with a glycoconjugate vaccine composed of the 5 common GBS capsular types (Ia, Ib, II, III and V) could potentially prevent over 85% of GBS invasive infection in infancy.3 Maternal immunization to prevent late-onset disease will require that infants passively acquire maternally derived GBS-specific antibodies at a concentration sufficient to sustain protective levels through their age of susceptibility. Transplacental transport of maternal IgG begins at about 17 weeks gestation, but the bulk is actively transferred to the fetus after 33 weeks gestation. Approximately one half of infants with late-onset GBS disease in the United States are born at less than 37 weeks of gestation. Limited data are available that stratify late-onset GBS disease according to both the infant’s gestational age and the day of life at onset of the infection. Our objective was to stratify late-onset GBS cases by gestational age at birth and age at onset of infection to inform estimates of potential effectiveness of a GBS glycoconjugate vaccine administered to pregnant women during the third trimester to prevent late-onset GBS disease.
METHODS Study Population Infants age 7–89 days admitted to Texas Children’s Hospital or Ben Taub General Hospital, Houston, from January, 1993 to December, 2012 with late onset GBS disease comprised the study population. Late-onset disease was defined as isolation of GBS from a blood or cerebrospinal fluid (CSF) culture. Data regarding maternal ethnicity, gestation at delivery, infant birth weight and age
538 | www.pidj.com
at onset of infection were collected from hospital records. Infants with more than 1 pathogen isolated from a blood culture were excluded from the analysis as were those for whom gestational age was not available. Infants were stratified by gestational age into 4 groups: those born at term (≥37 weeks), near term (35 0/7 to 36 6/7 weeks), preterm (33 0/7 to 34 6/7 weeks) and very preterm (
Edwards et al
RELEVANCE OF AGE AT DIAGNOSIS TO PREVENTION OF LATE-ONSET GROUP B STREPTOCOCCAL DISEASE BY MATERNAL IMMUNIZATION Morven S. Edwards, MD,* Marcia A. Rench, BSN,* and Carol J. Baker, MD*†‡ Abstract: Among 248 infants with late-onset group B streptococcal (GBS) disease from 1993 to 2012, approximately two thirds (63%) had a gestation of at least 35 weeks and 72% of these became ill within 6 weeks of life (median 27 days), suggesting that third trimester maternal GBS immunization could substantially reduce the late-onset GBS disease burden in the United States. Key Words: group B Streptococcus, late-onset sepsis, vaccine, maternal immunization Accepted for publication November 17, 2014. From the *Section of Infectious Disease, Department of Pediatrics, and †Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas; and ‡Center for Vaccine Awareness and Research, Texas Children’s Hospital, Houston, Texas. This work was funded in part by donations from families of infants afflicted with late-onset GBS disease. M.S.E. serves as a consultant to Novartis Vaccines. C.J.B. serves as a consultant and advisory board member for Novartis Vaccines as well as for Pfizer Inc. Marcia Rench has no conflicts. Address for correspondence: Morven S. Edwards, MD, Section of Infectious Disease, Department of Pediatrics, Baylor College of Medicine, 1102 Bates Street, Suite 1120, Houston, Texas 77030. E-mail: [email protected]. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. DOI: 10.1097/INF.0000000000000640
T
he incidence of late-onset group B streptococcal (GBS) disease in the United States in 2013 was 0.25 per 1000 live births, or approximately 1000 cases.1 Late-onset cases are not reduced under current prevention strategies and, when associated with meningitis, often result in death or permanent disability.2 Third trimester maternal immunization with a glycoconjugate vaccine composed of the 5 common GBS capsular types (Ia, Ib, II, III and V) could potentially prevent over 85% of GBS invasive infection in infancy.3 Maternal immunization to prevent late-onset disease will require that infants passively acquire maternally derived GBS-specific antibodies at a concentration sufficient to sustain protective levels through their age of susceptibility. Transplacental transport of maternal IgG begins at about 17 weeks gestation, but the bulk is actively transferred to the fetus after 33 weeks gestation. Approximately one half of infants with late-onset GBS disease in the United States are born at less than 37 weeks of gestation. Limited data are available that stratify late-onset GBS disease according to both the infant’s gestational age and the day of life at onset of the infection. Our objective was to stratify late-onset GBS cases by gestational age at birth and age at onset of infection to inform estimates of potential effectiveness of a GBS glycoconjugate vaccine administered to pregnant women during the third trimester to prevent late-onset GBS disease.
METHODS Study Population Infants age 7–89 days admitted to Texas Children’s Hospital or Ben Taub General Hospital, Houston, from January, 1993 to December, 2012 with late onset GBS disease comprised the study population. Late-onset disease was defined as isolation of GBS from a blood or cerebrospinal fluid (CSF) culture. Data regarding maternal ethnicity, gestation at delivery, infant birth weight and age
538 | www.pidj.com
at onset of infection were collected from hospital records. Infants with more than 1 pathogen isolated from a blood culture were excluded from the analysis as were those for whom gestational age was not available. Infants were stratified by gestational age into 4 groups: those born at term (≥37 weeks), near term (35 0/7 to 36 6/7 weeks), preterm (33 0/7 to 34 6/7 weeks) and very preterm (
