Immunisation status of children and adolescents with a new diagnosis of inflammatory bowel disease

Background Patients with Inflammatory Bowel Disease (IBD) are at increased risk of serious infections, including vaccine preventable diseases. Current evidence suggests uptake of additional recommended special risk vaccinations is low. Identification of IBD patients prior to commencing immunosuppressive therapy allows for optimisation of vaccination, including timely administration of live-attenuated and additional recommended vaccines, such as influenza and pneumococcal vaccines. Methods Paediatric patients (0–18 years) seen at the tertiary Royal Children’s Hospital, Melbourne, Australia, with a recent diagnosis of IBD were referred by the Gastroenterology Unit to our Specialist Immunisation Clinic (SIC) for assessment and provision of routine and special risk vaccines. Data was collected via a standardised REDCap questionnaire completed in or post attendance at the SIC and included serology results where available. Results Sixty-nine paediatric patients were recruited to the study between 2014 and 2017. Median age at IBD diagnosis was 11.25 years (IQR 4.64 years), with median time between diagnosis and SIC review of 0.88 years (IQR 2.84 years). At initial review 84.1% (58/69) of patients were up to date with vaccines on the Australian National Immunisation Program (NIP) schedule. Of those who were tested, serological evidence of immunity was demonstrated in 38.3% (23/60) of patients for Hepatitis B, 66.7% (36/54) for measles, 51.9% (28/54) for rubella and 41.9% (26/62) for Varicella Zoster Virus. Prior to SIC review 47.8% (33/69) had additional vaccinations and 92.8% (64/69) had vaccinations administered in the 12 months following SIC assessment. The Pneumococcal conjugate vaccine (76.8%, 53/69) was the most commonly administered vaccine after SIC review, followed by influenza vaccine (69.6%, 48/69). Within 12 months of SIC review 43.5% (30/69) of patients had completed the schedule and were up-to-date as recommended by the SIC. Conclusions Children with IBD and other special risk groups can benefit from early referral to a SIC team to ensure optimal administration of routine and additionally recommended vaccines, especially live and additional special risk vaccines. The value of optimising immunisations could also be applied to other special risk groups, including adult IBD cohorts, particularly those commencing newer biologic immunosuppressive medications.

Real-world data on immune responses following heterologous prime-boost COVID-19 vaccination schedule with Pfizer and AstraZeneca vaccines in England

Background There are limited data on immune responses to heterologous COVID–19 immunisation schedules, especially following an extended ≥12–week interval between doses. Methods SARS–CoV–2 infection–naïve and previously–infected adults receiving ChAd–BNT (ChAdOx1 nCoV–19, AstraZeneca followed by BNT162b2, Pfizer–BioNTech) or BNT–ChAd as part of the UK national immunisation programme provided blood samples at 30 days and 12 weeks after their second dose. Geometric mean concentrations (GMC) of anti–SARS–CoV–2 spike (S-antibody) and nucleoprotein (N-antibody) IgG antibodies and geometric mean ratios (GMR) were compared with a contemporaneous cohort receiving homologous ChAd–ChAd or BNT–BNT. Results During March–October 2021, 75,827 individuals were identified as having received heterologous vaccination, 9,489 invited to participate, 1,836 responded (19.3%) and 656 were eligible. In previously–uninfected adults, S–antibody GMC at 30 days post–second dose were lowest for ChAd–ChAd (862 (95%CI, 694– 1069)) and significantly higher for ChAd–BNT (6233 (5522– 7035); GMR 6.29; (5.04– 7.85); p<0.001), BNT-ChAd (4776 (4066– 5610); GMR 4.55 (3.56– 5.81); p<0.001) and BNT–BNT (5377 (4596– 6289); GMR 5.66 (4.49– 7.15); p<0.001). By 12 weeks after dose two, S–antibody GMC had declined in all groups and remained significantly lower for ChAd–ChAd compared to ChAd–BNT (GMR 5.12 (3.79– 6.92); p<0.001), BNT–ChAd (GMR 4.1 (2.96– 5.69); p<0.001) and BNT–BNT (GMR 6.06 (4.32– 8.50); p<0.001). Previously infected adults had higher S–antibody GMC compared to infection–naïve adults at all time–points and with all vaccine schedules. Conclusions These real–world findings demonstrate heterologous schedules with adenoviral–vector and mRNA vaccines are highly immunogenic and may be recommended after a serious adverse reaction to one vaccine product, or to increase programmatic flexibility where vaccine supplies are constrained.

COVID-19 vaccination and Guillain-Barré syndrome: analyses using the National Immunoglobulin Database

Vaccination against viruses has rarely been associated with Guillain-Barré syndrome (GBS). An association with the COVID-19 vaccine is unknown. We performed a population-based study of National Health Service (NHS) data in England and a multicentre surveillance study from UK hospitals, to investigate the relationship between COVID-19 vaccination and GBS. Firstly, we present a retrospective analysis of every GBS patient in England in the National Immunoglobulin Database (NID) linked with their COVID-19 vaccination data. Cases of GBS identified in the National Immunoglobulin Database (NID) from 8 December 2021 to 8 July 2021 were linked to data from the National Immunisation Management System (NIMS) in England to identify exposure to a COVID-19 vaccine. For the NID/NIMS linked dataset, GBS cases temporally associated with vaccination within a 6-week risk window of any COVID-19 vaccine were identified. Secondly, we prospectively collected incident UK GBS cases from 1 January 2021 to 7 November 2021 in a separate UK multicentre surveillance database, regardless of vaccine exposure, with vaccine timings and GBS phenotypic data. For this multicentre UK surveillance dataset, we explored phenotypes of reported GBS cases to identify features of COVID-19 vaccine-associated GBS. 996 GBS cases were recorded in the NID from January to October 2021. A spike of GBS cases above the 2016-2020 average occurred in March-April 2021. In England, among all cases of GBS, 198 occurred within 6 weeks of the first-dose COVID-19 vaccination (0.618 cases per 100,000 vaccinations, 176 ChAdOx1 nCoV-19 (AstraZeneca), 21 tozinameran (Pfizer), 1 mRNA-1273 (Moderna)). The excess of GBS occurs with a peak at 24 days; first-doses of ChAdOx1 nCoV-19 accounted for the excess. No excess was seen for second-dose vaccination. The absolute number of excess GBS cases was between 98-140 cases for first-dose ChAdOx1 nCoV-19 vaccination from January-July 2021. First-dose tozinameran and second-dose of any vaccination showed no excess GBS risk. 121 patients were reported in the separate multicentre surveillance dataset with no phenotypic or demographic differences identified between vaccinated and non-vaccinated GBS cases. Data from the linked NID/NIMS dataset suggest that first-dose ChAdOx1 nCoV-19vaccination is associated with an excess GBS risk of 0.576 (95%CI 0.481-0.691) cases per 100,000 doses. However, further data reported from a multicentre surveillance dataset suggest that no specific clinical features, including facial weakness, are associated with vaccination-related GBS compared to non-vaccinated cases. The pathogenic cause of the ChAdOx1 nCoV-19specific first dose link warrants further study.

Serological responses to COVID-19 booster vaccine in England

Importance: There are limited data on immune responses after COVID-19 vaccine boosters in individuals receiving primary immunisation with BNT162b2 (Pfizer-BioNTech) or AZD1222 (AstraZeneca) Objective: To assess SARS-CoV-2 antibody responses before and after booster vaccination with BNT162b2 in adults receiving two BNT162b2 or AZD1222 vaccine doses at least 6 months previously, as part of the United Kingdom national immunisation schedule Design: Prospective, cohort study Setting: London, England Participants: 750 immunocompetent adults aged ≥50 years Interventions: A single dose of BNT162b2 administered at least six months after primary immunisation with two doses of BNT162b2 given <30 days apart (BNT162b2-control) or ≥30 days apart (BNT162b2-extended) compared to AZD1222 given ≥30 days apart (AZD1222-extended) Main Outcome and Measures: SARS-CoV-2 spike protein antibody geometric mean titres (GMTs) before and 2-4 weeks after booster Results: Of 750 participants, 626 provided serum samples for up to 38 weeks after their second vaccine dose. Antibody GMTs peaked at 2-4 weeks after the second dose, before declining by 68% at 36-38 weeks after dose 2 for BNT162b2-control participants, 85% at 24-29 weeks for BNT162b2-extended participants and 78% at 24-29 weeks for AZD1222-extended participants. Antibody GMTs was highest in BNT162b2-extended participants (942 [95%CI, 797-1113]) than AZD1222-extended (183 [124-268]) participants at 24-29 weeks or BNT162b2-control participants at 36-38 weeks (208; 95%CI, 150-289). At 2-4 weeks after booster, GMTs were significantly higher than after primary vaccination in all three groups: 18,104 (95%CI, 13,911-23,560; n=47) in BNT162b2-control (76.3-fold), 13,980 (11,902-16,421; n=118) in BNT162b2-extended (15.9-fold) and 10,799 (8,510-13,704; n=43) in AZD1222-extended (57.2-fold) participants. BNT162b2-control participants (median:262 days) had a longer interval between primary and booster doses than BNT162b2-extended or AZD1222-extended (both median:186 days) participants. Conclusions and Relevance: We observed rapid serological responses to boosting with BNT162b2, irrespective of vaccine type or schedule used for primary immunisation, with higher post-booster responses with longer interval between primary immunisation and boosting. Boosters will not only provide additional protection for those at highest risk of severe COVID-19 but also prevent infection and, therefore, interrupt transmission, thereby reducing infections rates in the population. Ongoing surveillance will be important for monitoring the duration of protection after the booster.

Using moral foundations in government communication to reduce vaccine hesitancy

Having a vaccine available does not necessarily imply that it will be used. Indeed, uptake rates for existing vaccines against infectious diseases have been fluctuating in recent years. Literature suggests that vaccine hesitancy may be grounded in deeply rooted intuitions or values, which can be modelled using Moral Foundations Theory (MFT). We examine the respective prominence of the MFT dimensions in government communication regarding childhood vaccinations and explore its effect on parents’ vaccine hesitancy. We measure the MFT dimension loading of the vaccination information brochures from the Dutch National Institute for Public Health and the Environment (RIVM) between 2011-2019 and connect this information with the electronic national immunisation register to investigate if the use of moral foundations in government communication has a measurable effect on vaccination uptake. We find the largest positive effect for the dimensions Authority/Subversion and Liberty/Oppression and suggestive evidence in favour of a small positive effect for Purity/Degradation. Conversely, Loyalty/Betrayal actually has a negative effect on vaccination rates. For the dimension Harm/Care, we find no significant effect. While Purity/Degradation and Harm/Care appear to be the two most frequently used moral foundations by RIVM, these dimensions have in fact no or only a minor effect on parents’ vaccine hesitancy. Reducing the use of these moral foundations may be the first step towards optimising government communication in this context. Instead, formulations activating the moral foundations Authority/Subversion and Liberty/Oppression appear to have positive effects on vaccination uptake.

Rotavirus Genotypes in Abuja, Nigeria

Introduction: Nigeria had planned to introduce the rotavirus vaccine in the National Immunisation Programme in 2014, but this has yet to be done. Nigeria has the continent's highest mortality due to diarrhoeal diseases with little information on specific, prevalent genotypes. Aim: The study's main objectives were to identify the predominant rotavirus genotypes and examine the effects of existing local vaccination programs on prevailing rotavirus genotypes and on preventing rotavirus diarrhoea. Methodology: A one-year prospective descriptive study of children under 5 with acute diarrhoea was conducted from June 2018 to May 2019. Children with acute diarrhoea attending Asokoro District Hospital, Abuja. Children without diarrhoea were also recruited as a control group. Rotavirus ELISA and RNA extraction were done with commercially available kits, and positive samples were subjected to RT-PCR and electrophoresis to determine VP7 (G) and VP4 (P) genotypes. Results: Rotavirus-ELISA was positive among 231 (17.8%) children with diarrhoea and 29 (2.2%) of controls, with November, December. The predominant VP7 genotypes was G1 (n=116, 50.2%) followed by G9 (n=66, 28.5%). Viral Protein, VP4 (P) was mostly P [8] (n=143, 74.8%) followed by P [4] (n=21, 10.9%). The predominant genotype combinations found were G1 P [8] (n=108, 46.7%), G9 P [8] (n=62, 26.8%), and G2 P [4] (n=18, 7.7%). Very few mixed infections were found in the study, 2 (0.8%). Among 94 unvaccinated children with rotavirus isolates that were genotyped, G1 P [8] (n=88, 49.4%) and G9 P [8] (n=43, 24.1%) were predominant. Among 32 vaccinated children, G1 P [8] (n=13, 40.2%) and G9 P [8] (n=9, 28.1%) were predominant. Conclusion: The emergence of new genotypes such as G 12 P [4] found in this study emphasize the need for continued prospective monitoring of rotavirus at the molecular level to detect new threats to vaccine programs in future.

Seroepidemiological Studies on Japanese Encephalitis: A Systematic Review

Background Japanese encephalitis (JE) is one of the major mosquito-borne infectious diseases in the Western Pacific region, accounting for 20-30% of mortality cases. The JE virus (JEV) seroprevalence fluctuations indicate that continuous research is important for prevention and control activities. By mapping JEV seroprevalence by age stratification, the population profile for immunity and susceptibility can be identified to aid in vaccination programme planning. Thus, the aim of this study is to determine the trend of age-specific JEV seroprevalence. Method Systematic search was conducted on all studies conducted on JEV seroprevalence between the years 2010 until 2019. The two search engines used were PubMed and Web of Science. Eligible criteria were set and articles were screened according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines. Three investigators cross-checked all articles assigned. Data were extracted into Excel sheet and results were tabulated in tables and graphs accordingly. Result Four studies from four countries (Taiwan, Sri Lanka, South Korea, India) met the eligibility criteria. The papers show an increasing trend of JEV seropositivity in all countries as their populations reach older age cohorts. Nonetheless, there were slight downtrend notches seen among young adults in Taiwan and India before increasing again after reaching more mature ages. South Korea has the highest seroprevalence rate (97.8% to 98.3%) among the compared countries; this is most likely because it was the earliest to introduce the JEV vaccine in 1967 which was later made mandatory in early 1980s, while India has the lowest seroprevalence rate (12.9% to 18.1%). Among the old-vaccination-naïve population, seropositivity is commonly derived from natural infection. Conclusion Decreases in reported JE cases are mainly due to immunisation. As JEV is expected to remain in nature and the zoonotic chains, the risk of infection will persist. Hence, it is important to apply JEV vaccination protocols in national immunisation programmes with priority given to those at the young childhood stages.

Vaccine Hesitancy and Administrative Burden in the Australian National Immunisation Program: An Analysis of Twitter Discourse

In Australia, the National Immunisation Program and its Standard Vaccination Schedule are administered by the Australian Government Department of Health. While the public vaccination program’s safety and worth are generally agreed upon by doctors and public health professionals, some continue to see vaccinations as a source of danger and harm. The burden of vaccination in order to receive public services aligns government and medical interests, but a less-than-trusting public may see conspiracy in such requirements, resulting in vaccine hesitancy. The media’s attention to the topic, and a tendency toward misinformation on the part of anti-government opinion leaders, necessitate additional exploration of the administrative burden of vaccinations in an increasingly complex policy environment, where public health benefits are weighed against individual freedom and belief. This paper examines vaccinations as a burden, with costs in compliance, learning, and psychological terms, using posts from the social networking site Twitter as a corpus for exploratory content analysis in the specific case of Australia and its requirements. It is worth considering whether the positive aspects messaged by public health professionals are successfully entering into the discourse on vaccinations.

Vaccine interchangeability: problems and prospects

Vaccines by different manufacturers are available for most of the vaccine-preventable infections covered by the National Immunisation Schedule of the Russian Federation. Determination of the possibility of replacing a vaccine in the case of routine or emergency vaccination still remains a challenging issue. The aim of the study was to substantiate the problem of vaccine interchangeability, outline specific challenges and ways of solving them, analyse criteria underlying evaluation of vaccine interchangeability in Russia, and international experience in this area. The procedure for determining the interchangeability of biological products, including vaccines, was established in the Decree of the Government of the Russian Federation of 5 September 2020, No. 1360 “On the procedure for determination of interchangeability of medicinal products for human use”. The paper analyses the applicability of the official criteria for interchangeability of biological products, including vaccines. It outlines the main problems of performing evaluation of vaccine interchangeability in accordance with the established criteria. It is concluded that the vaccine interchangeability criteria need to be clarified in order to allow for assessment of comparability of active substances, and comparison of efficacy, safety, and immunogenicity of vaccines, taking into account vaccination schedules for different age groups. The possibility of evaluating interchangeability based on the results of post-authorisation studies also needs clarification. It is also necessary to align patient information leaflets for interchangeable vaccines.