Immunogenicity and safety of 13-valent pneumococcal conjugate vaccine (PCV13) formulated with 2-phenoxyethanol in multidose vials given with routine vaccination in healthy infants: An open-label randomized controlled trial.

BACKGROUND: This open-label randomized controlled trial in infants compared safety, tolerability, and immunogenicity of the 13-valent pneumococcal conjugate vaccine (PCV13) formulated with the preservative 2-phenoxyethanol (2-PE) in a multidose vial (MDV) to the current PCV13 without 2-PE in a single-dose syringe (SDS). METHODS: Gambian infants were randomized 1:1 to receive PCV13 as either MDV or SDS at ages 2, 3, and 4months. Serotype-specific antipneumococcal antibody responses and opsonophagocytic activity ([OPA]; subset) were measured at age 5months. Noninferiority was declared if the lower bound of the 97.5% CI for the difference (MDV-SDS) in proportions of subjects achieving IgG concentrations ≥0.35μg/mL (primary endpoint) was greater than -10%. IgG geometric mean concentrations (GMCs) were noninferior if the lower limit of the two-sided 97.5% CI of the geometric mean ratio (MDV vs SDS) was greater than 0.5. Reactogenicity and other adverse events were collected. RESULTS: 500 participants were randomized and vaccinated; 489 (MDV: n=245; SDS: n=244) completed the trial. Noninferiority of MDV was demonstrated for all serotypes as measured by percentage of subjects achieving antibody responses above ≥0.35μg/mL. IgG GMCs (coprimary endpoint) also demonstrated noninferiority of MDV; OPA results supported these findings. Safety and tolerability were comparable between groups. CONCLUSIONS: PCV13 in MDV was safe and immunogenic when administered according to the routine schedule to infants. MDV was noninferior to SDS for all 13 pneumococcal serotypes. Comparable immunogenicity and safety profiles of PCV13 MDV and SDS suggest PCV13 MDV can help optimize vaccination in resource-limited settings. ClinicalTrials.gov NCT01964716 https://clinicaltrials.gov/ct2/show/NCT01964716

Attendance and vaccination at immunization clinics in rural Gambia before and during the COVID-19 pandemic.

INTRODUCTION: The COVID-19 pandemic has affected the delivery of essential health services, such as routine immunization. We assessed the impact of the pandemic on the uptake of routine immunization in rural Gambia. METHODS: We collected real-time vaccine administration data in the Basse and Fuladu West Health & Demographic Surveillance Systems from September 01, 2019, to December 31, 2020. We assessed the monthly number of Expanded Program on Immunization (EPI) clinic attendances and vaccines administered, comparing data during the baseline period (September 01, 2019-March 31, 2020), COVID-19 interruption period (April 01-June 30, 2020), initial recovery period (Jul 01-September 30, 2020) and the late recovery period (October 01-December 31, 2020). RESULTS: Compared to the baseline period, there was an overall average monthly decline of 13.4% in EPI attendance and 38.3% reduction in average monthly immunizations during the interruption period. This decrease was particularly noticeable for Bacille Calmette-Guérin (BCG) (47.2%), birth dose hepatitis B (Hep B) (46.9%), 1st dose pentavalent (Penta1) (43.1%), 1st dose pneumococcal conjugate vaccine (PCV1) (42.4%), and measles vaccines (15.5%). Comparing the late recovery to baseline period, average monthly EPI attendance was 5.3% higher, with 1.9% increase in average monthly immunizations. Monthly immunizations for BCG were 3.0% greater, 2.5% greater for Hep B, 22.7% greater for oral polio vaccine (OPV1), 2.0% less for Penta1, 19.2% less for Penta2, and 2.6% less for PCV1. CONCLUSION: The reduced EPI attendance during the pandemic interruption period lasted only 3 months. Significant recovery in EPI attendance occurred during the late recovery period, while rates of monthly immunization returned to pre-pandemic levels for most antigens. EPI programmes should implement strategies to deliver missed antigens when infants do present to EPI clinics, aware that missed doses may be age dependent

Microbiological Methods Used in the Enterics for Global Health <i>Shigella</i> Surveillance Study

Funder: UKRI; DOI: https://doi.org/10.13039/100014013Abstract Background Shigella is a major cause of diarrhea in young children worldwide. Multiple vaccines targeting Shigella are in development, and phase 3 clinical trials are imminent to determine efficacy against shigellosis. Methods The Enterics for Global Health (EFGH) Shigella surveillance study is designed to determine the incidence of medically attended shigellosis in 6- to 35-month-old children in 7 resource-limited settings. Here, we describe the microbiological methods used to isolate and identify Shigella. We developed a standardized laboratory protocol for isolation and identification of Shigella by culture. This protocol was implemented across all 7 sites, ensuring consistency and comparability of results. Secondary objectives of the study are to determine the antibiotic resistance profiles of Shigella, compare isolation of Shigella from rectal swabs versus whole stool, and compare isolation of Shigella following transport of rectal swabs in Cary-Blair versus a modified buffered glycerol saline transport medium. Conclusions Data generated from EFGH using culture methods described herein can potentially be used for microbiological endpoints in future phase 3 clinical trials to evaluate vaccines against shigellosis and for other clinical and public health studies focused on these organisms. </jats:sec

Microbiological Methods Used in the Enterics for Global Health Shigella Surveillance Study.

Funder: UKRI; DOI: https://doi.org/10.13039/100014013BACKGROUND: Shigella is a major cause of diarrhea in young children worldwide. Multiple vaccines targeting Shigella are in development, and phase 3 clinical trials are imminent to determine efficacy against shigellosis. METHODS: The Enterics for Global Health (EFGH) Shigella surveillance study is designed to determine the incidence of medically attended shigellosis in 6- to 35-month-old children in 7 resource-limited settings. Here, we describe the microbiological methods used to isolate and identify Shigella. We developed a standardized laboratory protocol for isolation and identification of Shigella by culture. This protocol was implemented across all 7 sites, ensuring consistency and comparability of results. Secondary objectives of the study are to determine the antibiotic resistance profiles of Shigella, compare isolation of Shigella from rectal swabs versus whole stool, and compare isolation of Shigella following transport of rectal swabs in Cary-Blair versus a modified buffered glycerol saline transport medium. CONCLUSIONS: Data generated from EFGH using culture methods described herein can potentially be used for microbiological endpoints in future phase 3 clinical trials to evaluate vaccines against shigellosis and for other clinical and public health studies focused on these organisms