Invasive Pneumococcal Disease in UK Children <1 Year of Age in the Post-13-Valent Pneumococcal Conjugate Vaccine Era: What Are the Risks Now?

BACKGROUND: Invasive pneumococcal disease (IPD) has declined significantly since the introduction of pneumococcal conjugate vaccines (PCVs). It is not known whether certain infant populations remain at higher risk of IPD in countries with established 13-valent PCV (PCV13) programs. We aimed to describe the epidemiology, clinical characteristics, serotype distribution, and outcomes of IPD in infants, and to estimate the relative risk of PCV13-type, non-PCV13-type, and overall IPD in premature infants compared to term infants during a 4-year period after the PCV13 program was established. METHODS: This was a prospective, enhanced national surveillance of laboratory-confirmed IPD in England in infants aged <1 year diagnosed during 2013-2016. RESULTS: There were 517 cases of IPD (incidence: 19/100000 infants). Incidence was significantly higher in premature infants compared with those born at term (49/100000 vs 17/100000; incidence rate ratio [IRR], 2.87; P < .001), with infants born before 28 weeks' gestation having the highest incidence (150/100000; IRR, 8.8; P < .001). Of the 454 IPD cases with serotyped isolates, most were caused by non-PCV13 serotypes (369 cases, 71.4%), with 85 cases (16.4%) due to PCV13 serotypes. There were 31 deaths (case fatality rate [CFR], 6.2% [95% confidence interval, 4.3%-8.6%]). Premature infants did not have a higher CFR than term infants (P = .62). CONCLUSIONS: IPD incidence in infants remains lower than rates reported prior to PCV7 introduction in England. The risk of IPD remains significantly higher in premature infants compared to infants born at term, for both PCV13 and non-PCV13 serotypes. Any changes to the infant PCV13 immunization schedule may disproportionally affect premature infants.

Rapid Spread of Pneumococcal Nonvaccine Serotype 7C Previously Associated with Vaccine Serotype 19F, England and Wales.

We observed a sudden and rapid increase in rare invasive pneumococcal disease serotype 7C, from an annual average of 3 cases during 2000-01 through 2015-16 to 29 cases in 2016-17. The increase was caused almost entirely by clonal expansion of sequence type 177, previously associated with vaccine serotype 19F.

Characteristics associated with COVID-19 vaccine uptake among adults aged 50 years and above in England (8 December 2020-17 May 2021): a population-level observational study.

OBJECTIVE: To determine characteristics associated with COVID-19 vaccine coverage among individuals aged 50 years and above in England since the beginning of the programme. DESIGN: Observational cross-sectional study assessed by logistic regression and mean prevalence margins. SETTING: COVID-19 vaccinations delivered in England from 8 December 2020 to 17 May 2021. PARTICIPANTS: 30 624 257/61 967 781 (49.4%) and 17 360 045/61 967 781 (28.1%) individuals in England were recorded as vaccinated in the National Immunisation Management System with a first dose and a second dose of a COVID-19 vaccine, respectively. INTERVENTIONS: Vaccination status with COVID-19 vaccinations. MAIN OUTCOME MEASURES: Proportion, adjusted ORs and mean prevalence margins for individuals not vaccinated with dose 1 among those aged 50-69 years and dose 1 and 2 among those aged 70 years and above. RESULTS: Of individuals aged 50 years and above, black/African/Caribbean ethnic group was the least likely of all ethnic groups to be vaccinated with dose 1 of the COVID-19 vaccine. However, of those aged 70 years and above, the odds of not having dose 2 was 5.53 (95% CI 5.42 to 5.63) and 5.36 (95% CI 5.29 to 5.43) greater among Pakistani and black/African/Caribbean compared with white British ethnicity, respectively. The odds of not receiving dose 2 was 1.18 (95% CI 1.16 to 1.20) higher among individuals who lived in a care home compared with those who did not. This was the opposite to that observed for dose 1, where the odds of being unvaccinated was significantly higher among those not living in a care home (0.89 (95% CI 0.87 to 0.91)). CONCLUSIONS: We found that there are characteristics associated with low COVID-19 vaccine coverage. Inequalities, such as ethnicity are a major contributor to suboptimal coverage and tailored interventions are required to improve coverage and protect the population from SARS-CoV-2.

Pneumococcal-related Hemolytic Uremic Syndrome in the United Kingdom: National Surveillance, 2006-2016.

BACKGROUND: children <5 years of age since the introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) in 2006 and its replacement with the 13-valent pneumococcal conjugate vaccine (PCV13) in 2010 in the United Kingdom. METHODS: Public Health England conducts enhanced national surveillance of invasive pneumococcal disease in England. Confirmed invasive pneumococcal disease cases diagnosed between September 1, 2006, and March 31, 2016, with hemolytic uremic syndrome reported as a complication were included in the analysis. RESULTS: There were 54 cases of pHUS during the surveillance period, with a median age of 17 months. The incidence of pHUS was 0.25/100,000 during the PCV7 period and 0.08/100,000 during the PCV13 period (incidence rate ratio: 0.31; 95% confidence interval: 0.16-0.57; P < 0.0001). Twelve children (22%) had an underlying comorbidity before disease onset. Overall, 31 (57%) presented with lower respiratory tract infection, 14 (25%) with meningitis, 8 (15%) with bacteremia and 1 (2%) with septic arthritis. An empyema was reported in 26/31 children (84%) with lower respiratory tract infection and cerebral abscess in 5/14 children (36%) with meningitis. The main responsible serotypes were 19A (n = 20), 3 (n = 6), 7F (n = 5) and 33F (n = 4). Eight children (15%) died, including 6 with meningitis. CONCLUSIONS: pHUS continues to be associated with significant morbidity and mortality. The incidence of pHUS was significantly lower after PCV13 replaced PCV7 in the childhood immunization program. Currently, most cases are due to non-PCV13 serotypes.

Characteristics of Children With Invasive Pneumococcal Disease After the Introduction of the 13-valent Pneumococcal Conjugate Vaccine in England and Wales, 2010-2016.

BACKGROUND: In England and Wales, replacement of childhood 7-valent pneumococcal conjugate vaccine (PCV7) with a 13-valent vaccine (PCV13) in 2010 was associated with a significant reduction in PCV13-serotype invasive pneumococcal disease (IPD), with a small increase in IPD due to non-vaccine serotypes. Here, we describe the clinical presentation, comorbidity prevalence, serotype distribution and outcomes of childhood IPD during the first 6 years after PCV13 introduction. METHODS: Public Health England conducts enhanced IPD surveillance in England and Wales, with detailed information requested from general practitioners for all cases in children <5 years of age. Invasive isolates are routinely serotyped at the Public Health England reference laboratory. RESULTS: From April 2010 to March 2016, 1280 IPD episodes were confirmed in 1255 children 3-59 months of age; 84.3% (1059/1255) isolates were serotyped. Clinical presentation with meningitis was most prevalent in 3- to 11-month olds (45.8%, 209/456) and lower respiratory tract infection in 24- to 59-month olds (46.7%, 133/285). Overall, 259 (20.6%) children had 292 comorbidities, particularly immunosuppression (31.6%, 92/292). Twenty-one children (1.8%) had recurrent IPD. The case fatality rate was 5.1% (64/1255; 95% confidence interval [CI]: 3.9%-6.5%) and independently associated with meningitis (aOR 3.53; 95% CI: 1.62-7.70) and presence of comorbidity (aOR, 2.41; 95% CI: 1.25-4.64). In 2015/2016, PCV13 serotypes were responsible for 10.8% (25/232) of serotyped cases; the most prevalent non-PCV13 serotypes were 12F (18%), 10A (12%), 23B (10%), 33F (10%), 15B/C (10%) and 8 (8%). CONCLUSIONS: Most childhood IPD cases are now due to non-PCV13 serotypes. A higher proportion of children with IPD have underlying comorbidity, but, reassuringly, the risk of recurrent IPD or death remains low.