In a phase 3 trial involving more than 15,000 participants, two doses of NVX-CoV2373, a recombinant SARS-CoV-2 nanoparticle vaccine, administered 21 days apart had a vaccine efficacy of 89.7%. ...Reactogenicity was generally mild and transient, and adverse events were infrequent and of low grade.
Update on Vaccines in Antenatal Care Galiza, Eva P; Khalil, Asma; Heath, Paul T
The Pediatric infectious disease journal,
2024-Feb-01, 2024-02-00, 20240201, Volume:
43, Issue:
2
Journal Article
The recombinant protein-based vaccine, NVX-CoV2373, demonstrated 89.7% efficacy against coronavirus disease 2019 (COVID-19) in a phase 3, randomized, observer-blinded, placebo-controlled trial in the ...United Kingdom. The protocol was amended to include a blinded crossover. Data to the end of the placebo-controlled phase are reported.
Adults aged 18-84 years received 2 doses of NVX-CoV2373 or placebo (1:1) and were monitored for virologically confirmed mild, moderate, or severe COVID-19 (onset from 7 days after second vaccination). Participants who developed immunoglobulin G (IgG) against nucleocapsid protein but did not show symptomatic COVID-19 were considered asymptomatic. Secondary outcomes included anti-spike (S) IgG responses, wild-type virus neutralization, and T-cell responses.
Of 15 185 participants, 13 989 remained in the per-protocol efficacy population (6989 NVX-CoV2373, 7000 placebo). At a maximum of 7.5 months (median, 4.5) postvaccination, there were 24 cases of COVID-19 among NVX-CoV2373 recipients and 134 cases among placebo recipients, a vaccine efficacy of 82.7% (95% confidence interval CI, 73.3%-88.8%). Vaccine efficacy was 100% (95% CI, 17.9%-100.0%) against severe disease and 76.3% (95% CI, 57.4%-86.8%) against asymptomatic disease. High anti-S and neutralization responses to vaccination were evident, together with S-protein-specific induction of interferon-γ secretion in peripheral blood T cells. Incidence of serious adverse events and adverse events of special interest were similar between groups.
A 2-dose regimen of NVX-CoV2373 conferred a high level of ongoing protection against asymptomatic, symptomatic, and severe COVID-19 through >6 months postvaccination. A gradual decrease of protection suggests that a booster may be indicated.
EudraCT, 2020-004123-16.
The omicron BA.1 bivalent booster is used globally. Previous open-label studies of the omicron BA.1 (Moderna mRNA-1273.214) booster showed superior neutralising antibody responses against omicron ...BA.1 and other variants compared with the original mRNA-1273 booster. We aimed to compare the safety and immunogenicity of omicron BA.1 monovalent and bivalent boosters with the original mRNA-1273 vaccine in a large, randomised controlled trial.
In this large, randomised, observer-blind, active-controlled, phase 3 trial in the UK (28 hospital and vaccination clinic sites), individuals aged 16 years or older who had previously received two injections of any authorised or approved COVID-19 vaccine, with or without an mRNA vaccine booster (third dose), were randomly allocated (1:1) using interactive response technology to receive 50 μg omicron BA.1 monovalent or bivalent vaccines or 50 μg mRNA-1273 administered as boosters via deltoid intramuscular injection. The primary outcomes were safety and immunogenicity at day 29, including prespecified non-inferiority and superiority of booster immune responses, based on the neutralising antibody geometric mean concentration (GMC) ratios of the monovalent and bivalent boosters compared with mRNA-1273. Safety was assessed in all participants who received first or second boosters, and primary immunogenicity outcomes were assessed in all participants who received the planned booster dose, had pre-booster and day 29 antibody data, had no major protocol deviations, and who were SARS-CoV-2-negative. The study is registered with EudraCT (2022-000063-51) and ClinicalTrials.gov (NCT05249829) and is ongoing.
Between Feb 16 and March 24, 2022, 724 participants were randomly allocated to receive omicron BA.1 monovalent (n=366) or mRNA-1273 (n=357), and between April 2 and June 17, 2022, 2824 participants were randomly allocated to receive omicron BA.1 bivalent (n=1418) or mRNA-1273 (n=1395) vaccines as second boosters. Median durations (months) between the most recent COVID-19 vaccine and study boosters were similar for omicron BA.1 monovalent (4·0 months IQR 3·6–4·7) and mRNA-1273 (4·1 3·5–4·7), and for the omicron BA.1 bivalent (5·5 4·8–6·2) and mRNA-1273 (5·4 4·8–6·2) boosters. The omicron BA.1 monovalent and bivalent boosters elicited superior neutralising GMCs against the omicron BA.1 variant compared with mRNA-1273, with GMC ratios of 1·68 (99% CI 1·45−1·95) and 1·53 (1·41−1·67) at day 29 post-booster doses in participants without previous SARS-CoV-2 infection. Both boosters induced non-inferior ancestral SARS-CoV-2 (Asp614Gly) immune responses with GMCs that were similar for the bivalent (2987·2 95% CI 2814·9–3169·9) versus mRNA-1273 (2911·3 2750·9–3081·0) and lower for the monovalent (2699·7 2431·3–2997·7 vs 3020·6 2776·5–3286·2) boosters, with respective GMC ratios of 1·05 (99% CI 0·96–1·15) and 0·82 (95% CI 0·74–0·91). Results were comparable regardless of previous SARS-CoV-2 infection status. Incidences of solicited adverse reactions with the omicron BA.1 monovalent (335 91·3% of 367 participants) and omicron BA.1 bivalent (1285 90·4% of 1421 participants) boosters were similar to those observed previously for mRNA-1273, with no new safety concerns identified and no occurrences of fatal adverse events.
Omicron-containing booster vaccines generated superior immunogenicity against omicron BA.1 and comparable immunogenicity against the original strain with no new safety concerns. It remains important to continuously monitor the immune responses and real-world vaccine effectiveness as divergent SARS-CoV-2 variants emerge.
Moderna.
•91% of Trusts had a written guideline for viral bronchiolitis.•Most infants with viral bronchiolitis are not managed optimally in hospital.•Many Trusts cohort infants with viral bronchiolitis, ...irrespective of viral testing.•Future NICE guideline updates should include advice on virus testing.
Viral bronchiolitis is the leading cause of hospitalisation in infants less than a year old. The United Kingdom (UK) National Institute for Health and Care Excellence (NICE) published a guideline for the management of viral bronchiolitis in June 2015.
This study aimed to prospectively survey the management of viral bronchiolitis in hospital Trusts in the UK to provide a baseline of practice prior to the publication of the 2015 NICE bronchiolitis guideline against which future practice can be assessed.
An electronic, structured questionnaire was sent to hospital paediatricians in the UK prior to the publication of the NICE bronchiolitis guideline via the Royal College of Paediatrics and Child Health e-portfolio system to assess the quality of Trust’s viral bronchiolitis management guidelines.
Paediatricians from 111 (65% of all) UK Trusts completed an electronic questionnaire. 91% of Trusts had a bronchiolitis guideline. Overall only 18% of Trusts would be fully compliant with the NICE guideline. Between 43–100% of Trusts would be compliant with different sections of the guideline. There was variation in hospital admission criteria with respect to the need for supplemental oxygen (oxygen saturations <88% to <95%). ‘Unnecessary’ medications (especially bronchodilators, nebulised hypertonic saline and antibiotics) and investigations (chest x-ray and blood gas) were regularly advised. 72% of Trusts advised respiratory virus testing in all hospitalised infants and 64% created bronchiolitis bays to cohort infants.
There was wide variation in the management of infants with bronchiolitis in Trusts. Most bronchiolitic infants are not managed optimally in hospitals. Future guidelines should include advice on virus testing and isolation/cohorting.
Pertussis Galiza, Eva P; Calvert, Anna; Drysdale, Simon B ...
Medicine (Abingdon. 1995, UK ed.),
December 2021, 2021-12-00, Volume:
49, Issue:
12
Journal Article
Peer reviewed
Pertussis is an infectious disease of the respiratory tract caused by the Gram-negative bacterium Bordetella pertussis. Pertussis vaccines have led to a significant reduction in the incidence and ...severity of pertussis in infants worldwide. Despite this decrease in incidence, pertussis remains one of the principal causes of vaccine-preventable death; the World Health Organization reported an estimated 24.1 million cases and 160,700 paediatric deaths in 2014. Pertussis infection can occur at any age. In the last 20 years, there has been an increase in the number of adolescent and adult cases reported in high-income countries, including those with high vaccination coverage. These cases represent a potential source of infection for unimmunized infants, who typically have a more severe course with higher mortality. Pertussis infection in previously immunized adults, elderly individuals or young infants frequently presents with atypical symptoms and can easily be overlooked as a diagnosis. This review provides a summary of Bordetella pertussis and discusses diagnostic tests, treatment and prevention.
ObjectiveTo 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.DesignWe 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.ResultsPost-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.ConclusionsApproximately 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.
To investigate the symptoms of SARS-CoV-2 infection, their dynamics and their discriminatory power for the disease using longitudinally, prospectively collected information reported at the time of ...their occurrence. We have analysed data from a large phase 3 clinical UK COVID-19 vaccine trial. The alpha variant was the predominant strain. Participants were assessed for SARS-CoV-2 infection via nasal/throat PCR at recruitment, vaccination appointments, and when symptomatic. Statistical techniques were implemented to infer estimates representative of the UK population, accounting for multiple symptomatic episodes associated with one individual. An optimal diagnostic model for SARS-CoV-2 infection was derived. The 4-month prevalence of SARS-CoV-2 was 2.1%; increasing to 19.4% (16.0%–22.7%) in participants reporting loss of appetite and 31.9% (27.1%–36.8%) in those with anosmia/ageusia. The model identified anosmia and/or ageusia, fever, congestion, and cough to be significantly associated with SARS-CoV-2 infection. Symptoms’ dynamics were vastly different in the two groups; after a slow start peaking later and lasting longer in PCR+ participants, whilst exhibiting a consistent decline in PCR- participants, with, on average, fewer than 3 days of symptoms reported. Anosmia/ageusia peaked late in confirmed SARS-CoV-2 infection (day 12), indicating a low discrimination power for early disease diagnosis.
Bacterial meningitis remains a major cause of morbidity and mortality in young infants. Understanding the epidemiology and burden of disease is important.
Prospective, enhanced, national ...population-based active surveillance was undertaken to determine the incidence, etiology, and outcome of bacterial meningitis in infants aged <90 days in the United Kingdom and Ireland.
During July 2010-July 2011, 364 cases were identified (annual incidence, 0.38/1000 live births; 95% confidence interval CI, .35-.42). In England and Wales, the incidence of confirmed neonatal bacterial meningitis was 0.21 (n = 167; 95% CI, .18-.25). A total of 302 bacteria were isolated in 298 (82%) of the cases. The pathogens responsible varied by route of admission, gestation at birth, and age at infection. Group B Streptococcus (GBS) (150/302 50%; incidence, 0.16/1000 live births; 95% CI, .13-.18) and Escherichia coli (41/302 14%; incidence, 0.04/1000; 95% CI, .03-.06) were responsible for approximately two-thirds of identified bacteria. Pneumococcal (28/302 9%) and meningococcal (23/302 8%) meningitis were rare in the first month, whereas Listeria meningitis was seen only in the first month of life (11/302 4%). In hospitalized preterm infants, the etiology of both early- and late-onset meningitis was more varied. Overall case fatality was 8% (25/329) and was higher for pneumococcal meningitis (5/26 19%) than GBS meningitis (7/135 5%; P = .04) and for preterm (15/90 17%) compared with term (10/235 4%; P = .0002) infants.
The incidence of bacterial meningitis in young infants remains unchanged since the 1980s and is associated with significant case fatality. Prevention strategies and guidelines to improve the early management of cases should be prioritized.
Improving the outcome of neonatal meningitis Galiza, Eva P; Heath, Paul T
Current opinion in infectious diseases,
2009-June, 2009-Jun, 2009-06-00, 20090601, Volume:
22, Issue:
3
Journal Article
Peer reviewed
PURPOSE OF REVIEWNeonatal meningitis is an important cause of mortality and morbidity worldwide, and although mortality has declined in developed countries over the last two decades, improvement in ...morbidity has been less evident. This review focuses on recent advances in the management of neonatal meningitis and its implications for improved outcomes.
RECENT FINDINGSRecent surveillance studies of neonatal meningitis have provided important information regarding the pathogens causing meningitis, their antibiotic-susceptibility profiles and their outcomes. Data supporting the importance of early recognition of the signs of neonatal meningitis, the early diagnosis of the causative pathogen, early and aggressive fluid therapy and supportive care and on the effect of adjunctive therapies on outcome measures are all largely theoretical or derived from paediatric and adult sepsis studies.
SUMMARYThere is likely to be considerable scope for improving the outcome from neonatal meningitis but more studies are required to define key interventions and to demonstrate their effectiveness.
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