Community seroprevalence of SARS-CoV-2 in children and adolescents in England, 2019-2021.

OBJECTIVE: To understand community seroprevalence of SARS-CoV-2 in children and adolescents. This is vital to understanding the susceptibility of this cohort to COVID-19 and to inform public health policy for disease control such as immunisation. DESIGN: We conducted a community-based cross-sectional seroprevalence study in participants aged 0-18 years old recruiting from seven regions in England between October 2019 and June 2021 and collecting extensive demographic and symptom data. Serum samples were tested for antibodies against SARS-CoV-2 spike and nucleocapsid proteins using Roche assays processed at UK Health Security Agency laboratories. Prevalence estimates were calculated for six time periods and were standardised by age group, ethnicity and National Health Service region. RESULTS: Post-first wave (June-August 2020), the (anti-spike IgG) adjusted seroprevalence was 5.2%, varying from 0.9% (participants 10-14 years old) to 9.5% (participants 5-9 years old). By April-June 2021, this had increased to 19.9%, varying from 13.9% (participants 0-4 years old) to 32.7% (participants 15-18 years old). Minority ethnic groups had higher risk of SARS-CoV-2 seropositivity than white participants (OR 1.4, 95% CI 1.0 to 2.0), after adjusting for sex, age, region, time period, deprivation and urban/rural geography. In children <10 years, there were no symptoms or symptom clusters that reliably predicted seropositivity. Overall, 48% of seropositive participants with complete questionnaire data recalled no symptoms between February 2020 and their study visit. CONCLUSIONS: Approximately one-third of participants aged 15-18 years old had evidence of antibodies against SARS-CoV-2 prior to the introduction of widespread vaccination. These data demonstrate that ethnic background is independently associated with risk of SARS-CoV-2 infection in children. TRIAL REGISTRATION NUMBER: NCT04061382.

Success of 4CMenB in preventing meningococcal disease: evidence from real-world experience.

Meningococcal disease remains one of the most feared infectious diseases worldwide because of its sudden onset, rapid progression and high case fatality rates, while survivors are often left with severe long-term sequelae. Young children have the highest incidence of invasive meningococcal disease (IMD), and nearly all cases in the UK, as in most of Europe and many other industrialised countries, are due to group B meningococci (MenB). The licensure of a broad-coverage, recombinant protein-based MenB vaccine (4CMenB) in 2013 was, therefore, heralded a major breakthrough in the fight against IMD. This vaccine was, however, licensed on immunogenicity and reactogenicity studies only, raising uncertainties about field effectiveness, long-term safety and antibody persistence. In 2015, the UK became the first country to implement 4CMenB into the national infant immunisation schedule and, since then, several countries have followed suit. Seven years after licensure, a wealth of real-world data has emerged to confirm 4CMenB effectiveness, along with large-scale safety data, duration of protection in different age groups, successful strategies to reduce vaccine reactogenicity, impact on carriage in adolescents and the potential for 4CMenB to protect against other meningococcal serogroups and against gonorrhoea. A number of questions, however, remain unanswered, including the investigation and management of vaccine-associated fever in infants, as well as disease severity and assessment of breakthrough cases in immunised children. Increasing use of 4CMenB will provide answers in due course. We now have vaccines against all the major serogroups causing IMD worldwide. Next-generation and combination vaccines against multiple serogroups look very promising.

Vaccine-derived rotavirus strains in infants in England.

OBJECTIVE: To describe infants with acute gastroenteritis symptoms in primary and secondary care who have the Rotarix vaccine-derived G1P[8] rotavirus strain identified in their stools. DESIGN: This is a prospective national surveillance conducted by Public Health England (PHE). Rotavirus-positive samples from vaccine-eligible children are routinely submitted to PHE for confirmation, and general practitioners are requested to complete a surveillance questionnaire for all cases. The modified Vesikari Score was used to assess severity of gastroenteritis. SETTING: England, July 2013-September 2016. RESULTS: 2637 rotavirus strains were genotyped and 215 (8%) identified as the Rotarix vaccine-derived G1P[8] strain. There were no Rotarix vaccine-derived G1P[8] strains detected in unimmunised infants. Rotarix vaccine-derived G1P[8] strains clustered around the time of rotavirus vaccination and were responsible for 82% (107 of 130) of rotavirus-positive samples in 2-month-old infants and 68% (36 of 53) in 3-month-old infants. However, 13 samples were obtained more than 7 weeks after the last vaccination date; 10 of these specimens were from six children who were subsequently diagnosed with severe combined immunodeficiency (SCID). Diarrhoea was the single most common presenting symptom (83.0%) in infants with Rotarix vaccine-derived G1P[8] strains, who were less likely to present with fever, vomiting, dehydration or severe gastroenteritis than infants with wild-type rotavirus infection. CONCLUSIONS: Rotavirus identified in stools of infants around the time of their routine immunisations is most likely the Rotarix vaccine-derived G1P[8] strain. Infants with undiagnosed SCID at the time of rotavirus immunisation may experience prolonged gastroenteritis symptoms. Most infants with vaccine strains in their stools more than 7 weeks after immunisation had SCID.

Two centuries of immunisation in the UK (part 1).

The impact of immunisation is best understood through a historical lens, since so many of the diseases which placed a burden on our population have been eliminated or controlled through immunisation. The United Kingdom (UK) National Health Service (NHS), which celebrated its 70th birthday in 2018, is responsible for delivering the highly successful universal national immunisation programme. However, the first vaccines used in the UK were not part of a centrally coordinated programme until the 1960s. Resources that summarise the first 200 years of immunisation in the UK are not readily accessible. Here we provide a two part chronological insight into the history of the UK immunisation programme from primary sources. In Part I, we highlight the importance of wartime conditions, unprecedented vaccine development, and the polio outbreaks in the in driving developments in immunisation and discuss subsequent changes in the use of the original vaccines of the immunisation programme, namely, diphtheria, tetanus, pertussis, and polio. In Part 2, we discuss the formation of the Joint Committee on Vaccination and Immunisation and its role, working with public health agencies and advising the UK Governments on vaccine policy, to bring a comprehensive programme to defend the health of the population against serious infectious diseases, highlighting the importance of programme organisation and leadership.

Two centuries of immunisation in the UK (part II).

The centrally coordinated response that controlled the polio epidemics of the 1950s through immunisation led to the development of a national immunisation strategy in the UK and the formation of the Joint Committee on Vaccination and Immunisation (JCVI) in 1963, which oversees the immunisation programme and advises the UK Department of Health on new vaccine introductions. As a result of technological advances in vaccine development and scientific advances in immunology and microbiology over the 56 years since then, and the formation of a comprehensive public health surveillance system for vaccine-preventable disease, the National Health Service immunisation programme now covers 18 serious diseases of childhood, with an astonishing impact on child health. Here we consider the formation of the JCVI and the development of the national immunisation programme and review the introduction of vaccines over the past half century to defend public health.

COVID-19 in children: analysis of the first pandemic peak in England.

OBJECTIVES: To assess disease trends, testing practices, community surveillance, case-fatality and excess deaths in children as compared with adults during the first pandemic peak in England. SETTING: England. PARTICIPANTS: Children with COVID-19 between January and May 2020. MAIN OUTCOME MEASURES: Trends in confirmed COVID-19 cases, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positivity rates in children compared with adults; community prevalence of SARS-CoV-2 in children with acute respiratory infection (ARI) compared with adults, case-fatality rate in children with confirmed COVID-19 and excess childhood deaths compared with the previous 5 years. RESULTS: Children represented 1.1% (1,408/129,704) of SARS-CoV-2 positive cases between 16 January 2020 and 3 May 2020. In total, 540 305 people were tested for SARS-COV-2 and 129,704 (24.0%) were positive. In children aged <16 years, 35,200 tests were performed and 1408 (4.0%) were positive for SARS-CoV-2, compared to 19.1%-34.9% adults. Childhood cases increased from mid-March and peaked on 11 April before declining. Among 2,961 individuals presenting with ARI in primary care, 351 were children and 10 (2.8%) were positive compared with 9.3%-45.5% in adults. Eight children died and four (case-fatality rate, 0.3%; 95% CI 0.07% to 0.7%) were due to COVID-19. We found no evidence of excess mortality in children. CONCLUSIONS: Children accounted for a very small proportion of confirmed cases despite the large numbers of children tested. SARS-CoV-2 positivity was low even in children with ARI. Our findings provide further evidence against the role of children in infection and transmission of SARS-CoV-2.

PEPtalk2: results of a pilot randomised controlled trial to compare VZIG and aciclovir as postexposure prophylaxis (PEP) against chickenpox in children with cancer.

OBJECTIVE: To determine the likely rate of patient randomisation and to facilitate sample size calculation for a full-scale phase III trial of varicella zoster immunoglobulin (VZIG) and aciclovir as postexposure prophylaxis against chickenpox in children with cancer. DESIGN: Multicentre pilot randomised controlled trial of VZIG and oral aciclovir. SETTING: England, UK. PATIENTS: Children under 16 years of age with a diagnosis of cancer: currently or within 6 months of receiving cancer treatment and with negative varicella zoster virus (VZV) serostatus at diagnosis or within the last 3 months. INTERVENTIONS: Study participants who have a significant VZV exposure were randomised to receive PEP in the form of VZIG or aciclovir after the exposure. MAIN OUTCOME MEASURES: Number of patients registered and randomised within 12 months of the trial opening to recruitment and incidence of breakthrough varicella. RESULTS: The study opened in six sites over a 13-month period. 482 patients were screened for eligibility, 32 patients were registered and 3 patients were randomised following VZV exposure. All three were randomised to receive aciclovir and there were no cases of breakthrough varicella. CONCLUSIONS: Given the limited recruitment to the PEPtalk2 pilot, it is unlikely that the necessary sample size would be achievable using this strategy in a full-scale trial. The study identified factors that could be used to modify the design of a definitive trial but other options for defining the best means to protect such children against VZV should be explored. TRIAL REGISTRATION NUMBER: ISRCTN48257441, EudraCT number: 2013-001332-22, sponsor: University of Birmingham.