Stephanie J Schrag’s research while affiliated with Centers for Disease Control and Prevention and other places

Background Group B Streptococcus (GBS) is a major cause of neonatal sepsis. Outbreaks of GBS late-onset disease (LOD), defined as infection during the first 7–89 days of life, are uncommon. In September 2023, 4 GBS LOD cases were reported by a neonatal intensive care unit (NICU) to the Connecticut Department of Public Health (DPH). We investigated to characterize the outbreak and guide response. Methods We identified patients with invasive (i.e., GBS isolated from a sterile site) LOD hospitalized in the NICU through review of data from DPH’s Active Bacterial Core Surveillance Program during January 2019–April 2024. We distinguished outbreak cases through whole-genome sequencing (WGS) of associated bacterial isolates. Single nucleotide polymorphism (SNP) analysis with a cutoff of ≤12 SNPs defined a case as outbreak-related. We abstracted medical records to collect case data. We performed 3 on-site assessments of infection prevention and control (IPC) practices and policies. To monitor response effectiveness, we performed weekly GBS colonization screening (aural, oropharyngeal, rectal sites) of infants admitted to the NICU during December 2023–April 2024. We performed WGS on GBS isolates associated with each colonization. Results We identified 12 outbreak-related cases during January 2020–April 2024 based on WGS. Median case interval, time between illness onset, was 85 days but ranged from three days to 458 days; 3 outbreak-patients died. Chart abstraction and on-site assessments indicated the milk room as an area for potential transmission. Variability was noted in adherence to appropriate hand hygiene, personal protective equipment use, and environmental cleaning throughout the NICU. Screening identified 7 colonized infants; GBS isolates from 3 infants matched the outbreak, and 1 colonized infant developed LOD. We recommended addressing IPC gaps and continuing GBS colonization screening to monitor for ongoing transmission. Conclusion This investigation highlights the integration of WGS with classic epidemiology to distinguish outbreak-related cases with long intervals between identification. In LOD GBS outbreaks where IPC gaps appear to contribute to transmission, colonization screening and WGS can evaluate effectiveness of implementation of protocols to address IPC gaps. Disclosures Meghan Maloney, MPH, Pfizer Global R&D: Former employee, separated in 2009. I do have a retirement entitlement which I do not actively manage/no stock options. PGRD offers periodic buy outs

A standardized multiplex immunoassay (MIA) to quantify group B Streptococcus (GBS) anti-capsular polysaccharide (CPS) IgG serum concentrations was adopted by the Group B streptococcal Assay Standardization (GASTON) consortium as a standardized assay with the most immediate applications for facilitating the licensure of GBS vaccines. However, dried blood spot (DBS) samples offer advantages for immunological studies, including cost-effectiveness, ease of transport, and storage. To determine suitability of DBS as an alternative sample matrix to serum in multiplex immunoassays, a contrived GBS seropositive panel, including matched DBS and serum samples, was prepared using established methods. The calculated geometric mean titers of GBS anti-CPS IgG values by individual serotype were compared using a paired t-test to establish serum equivalency. Geometric mean values for the matched panel were assessed via Deming regression for precision, accuracy, and concordance correlation coefficient (CCC). The initial acceptance criterion was set at 0.95 for CCC. Two additional criteria based on confidence intervals of CCC, slope, and intercept were used to determine the necessity of a serotype-specific conversion factor. The paired t-test p-values were > 0.05 for serum equivalency. For sample matrix concordance, CCC values were > 0.95 and met correlation criteria for all serotypes. Conversion factors were applied to four serotypes (II, III, IV, and V) that did not meet the criteria for slope, intercept, or both. This demonstration of equivalency between DBS and serum supports the hypothesis that DBS is a suitable testing matrix from which to elucidate anti-CPS IgG concentrations in seroepidemiological and vaccine evaluation studies.

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.

Exposure to intrapartum antibiotic prophylaxis to reduce perinatal group B streptococcal disease was associated with increased childhood body mass index (BMI) persisting to age 10 years compared to no exposure (Δ BMI at 10 years: vaginal delivery 0.14 kg/m², caesarean 0.40 kg/m²).

Background: Descriptions of changes in invasive bacterial disease (IBD) epidemiology during the COVID-19 pandemic in the United States are limited. Methods: We investigated changes in the incidence of IBD due to Streptococcus pneumoniae, Haemophilus influenzae, group A Streptococcus (GAS), and group B Streptococcus (GBS). We defined the COVID-19 pandemic period as March 1-December 31, 2020. We compared observed IBD incidences during the pandemic to expected incidences, consistent with January 2014-February 2020 trends. We conducted secondary analysis of a healthcare database to assess changes in testing by blood and cerebrospinal fluid (CSF) culture during the pandemic. Results: Compared with expected incidences, the observed incidences of IBD due to S. pneumoniae, H. influenzae, GAS, and GBS were 58%, 60%, 28%, and 12% lower during the pandemic period of 2020, respectively. Declines from expected incidences corresponded closely with implementation of COVID-19-associated non-pharmaceutical-interventions (NPIs). Significant declines were observed across all age, race groups and surveillance sites for S pneumoniae and H influenzae. Blood and CSF culture testing rates during the pandemic were comparable to previous years. Conclusions: NPIs likely contributed to the decline in IBD incidence in the United States in 2020; observed declines were unlikely to be driven by reductions in testing.