A new neonatal BCG vaccination pathway in England: a mixed methods evaluation of its implementation.

INTRODUCTION: The introduction of a national evaluation of newborn screening for Severe Combined Immunodeficiency (SCID) in England triggered a change to the selective Bacillus Calmette-Guerin (BCG) vaccination programme delivery pathway, as this live attenuated vaccine is contraindicated in infants with SCID. The neonatal BCG vaccination programme is a targeted programme for infants at increased risk of tuberculosis and used to be offered shortly after birth. Since September 2021 the BCG vaccine is given to eligible infants within 28 days of birth, when the SCID screening outcome is available. We explore the experiences of those implementing the new pathway, and how they made sense of, engaged with, and appraised the change. METHODS: A mixed-methods evaluation was conducted between October 2022 and February 2023. This involved national online surveys with BCG commissioners and providers and qualitative semi-structured interviews with commissioners, providers, and Child Health Information System stakeholders in two urban areas. Survey data was analysed using descriptive statistics and interview data was analysed thematically. The data was triangulated using Normalization Process Theory as a guiding framework. RESULTS: Survey respondents (n = 65) and qualitative interviewees (n = 16) revealed that making sense of the new pathway was an iterative process. Some expressed a desire for more direction on how to implement the new pathway. The perceived value of the change varied from positive, ambivalent, to concerned. Some felt well-prepared and that improvements to data capture, eligibility screening, and accountably brought by the change were valuable. Others were concerned about the feasibility of the 28-day target, reductions in vaccination coverage, increased resource burden, and the outcome of the SCID evaluation. New collaborations and communities of practice were required to facilitate the change. Three main challenges in implementing the pathway and meeting the 28-day vaccination target were identified: appointment non-attendance; appointment and data systems; and staffing and resourcing. Feedback mechanisms were informal and took place in tandem with implementation. CONCLUSION: The new NHS neonatal BCG service specification has created an effective structure for monitoring and managing the BCG vaccination programme, but further work is required to support delivery of the 28-day vaccination target and improve uptake rates.

Policy-making and implementation for newborn bloodspot screening in Europe: a comparison between EURORDIS principles and UK practice.

Newborn bloodspot screening (NBS) policy is a contentious area in Europe. Variation in the screening panels on offer, in the approach to evidence assessment and in the use of health economic modelling are some of the issues which are debated on the topic. In this paper we focus on a set of patient-driven principles for newborn screening published by EURORDIS and use these as a reference point for exploration and comparison with NBS policy development and screening practice in the UK. In doing so, we share UK practice; we note the UK is generally well aligned with many of the recommended principles, but we also discuss areas of controversy and challenges. Some of these, like 'actionability', will undoubtedly continue to be debated and may never reach consensus. For others, such as patient and public voice participation in newborn screening systems, there are opportunities to continue improving existing processes and developing new mechanisms for stakeholder participation. Screening bodies in other European countries should also compare their policy-making and implementation practices with the EURORDIS principles to stimulate further discussion on the challenges and opportunities of newborn screening and provide a cross-European baseline.

Study Design for an Evaluation of Newborn Screening for SCID in the UK.

Severe combined immunodeficiency is a rare inherited disorder, which, if untreated, invariably proves fatal in late infancy or early childhood. With treatment, the prognosis is much improved. Early treatment of the siblings of cases, before they become symptomatic, has shown considerable improvements in outcomes. Based on this and the development of a test that can be used on the whole population of neonates (measurement of T-cell receptor excision circles-TRECs), many countries have added it to their routine newborn bloodspot screening programmes. The UK National Screening Committee (UKNSC) has considered whether SCID should be added to the UK screening programme and concluded that it was likely to be cost effective, but that there were a number of uncertainties that should be resolved before a national roll-out could be recommended. These include some aspects of the test, such as: cost; the use of different assays and cut-off levels to reduce false positive rates, while maintaining sensitivity; the overall benefits of screening for disease outcome in patients with SCID and other identified disorders; the need for a separate pathway for premature babies; the acceptability of the screening programme to parents of babies who have normal and abnormal (both true and false positive) screening results. To achieve this, screening of two thirds of babies born in England over a two-year period has been planned, beginning in September 2021. The outcomes and costs of care of babies identified by the screening will be compared with those of babies identified with SCID in the rest of the UK. The effect of the screening programme on parents will form part of a separate research project.

Newborn screening for severe combined immunodeficiency-Coming to a region near you soon.

The most profound of primary immunodeficiencies, severe combined immunodeficiency (SCID), presents in infancy. Infants appear healthy at birth, but they are unable to clear pathogens, particularly viruses, and present with recurrent infection, progressive pnueumonitis and failure to thrive due to enteric viral infection, often associated with persistent vaccine-strain rotavirus. The administration of live vaccines is contraindicated in these infants, but most who are eligible receive bacillus Calmette-Guérin vaccination and the live rotavirus vaccine before the diagnosis of SCID is made, making treatment more complicated. Newborn infants with SCID can be screened using the newborn bloodspot to measure T lymphocyte receptor excision circles (TRECs), episomal DNA formed during T lymphocyte receptor development and very low or absent in SCID. Introduction of this programme in the United Kingdom will require the neonatal BCG vaccination programme to be altered, with vaccination at 28 days, once the SCID screening result is known. Although SCID newborn screening has been successfully introduced in other countries, the change in neonatal BCG vaccination requires the introduction of newborn screening to be carefully introduced. An evaluation of impact of screening on SCID diagnosis, treatment and outcomes, together with an evaluation of the technology used to detect TRECs, and the impact of screening and changes to the BCG programme on families will commence in six screening regions in England in September 2021 for 2 years - should the evaluation prove positive, it is likely that screening for this fatal disease will be introduced across the United Kingdom.

Fifteen-minute consultation: Vaccine-hesitant parents.

Vaccination is a proven, highly effective intervention to protect against potentially serious infectious diseases. UK vaccine uptake rates are high overall, but considerable variation exists within and between districts. The main reason for under vaccination is difficulty accessing vaccination services for practical or logistical reasons. While some parents decline specific vaccines, only a small minority decline them all. It is unsurprising that many parents have questions about vaccination, but most are easily addressed. This article provides practical guidance on how to engage effectively with parents with the ultimate aim of supporting informed vaccination decisions. The focus will be on conversations with parents whose concerns make them unsure whether to accept vaccination or who have previously delayed or declined vaccines. In view of recent outbreaks of measles, the example question concerns MMR (measles, mumps and rubella) vaccine. Although conversations with some parents, especially those who are determinedly anti-vaccine, can be uncomfortable, even challenging, it is important to offer all parents the opportunity to discuss their concerns. Even though advice may go unheeded or even be unwelcome, parents can change their minds about previous decisions. Health professionals and the National Health Service are trusted sources of advice about vaccinations and have a responsibility to ensure parents are appropriately informed.

The duration of protection of school-aged BCG vaccination in England: a population-based case-control study.

Background: Evidence of protection from childhood Bacillus Calmette-Guerin (BCG) against tuberculosis (TB) in adulthood, when most transmission occurs, is important for TB control and resource allocation. Methods: We conducted a population-based case-control study of protection by BCG given to children aged 12-13 years against tuberculosis occurring 10-29 years later. We recruited UK-born White subjects with tuberculosis and randomly sampled White community controls. Hazard ratios and 95% confidence intervals (CIs) were estimated using case-cohort Cox regression, adjusting for potential confounding factors, including socio-economic status, smoking, drug use, prison and homelessness. Vaccine effectiveness (VE = 1 - hazard ratio) was assessed at successive intervals more than 10 years following vaccination. Results: We obtained 677 cases and 1170 controls after a 65% response rate in both groups. Confounding by deprivation, education and lifestyle factors was slight 10-20 years after vaccination, and more evident after 20 years. VE 10-15 years after vaccination was 51% (95% CI 21, 69%) and 57% (CI 33, 72%) at 15-20 years. Subsequently, BCG protection appeared to wane; 20-25 years VE = 25% (CI -14%, 51%) and 25-29 years VE = 1% (CI -84%, 47%). Based on multiple imputation of missing data (in 17% subjects), VE estimated in the same intervals after vaccination were similar [56% (CI 33, 72%), 57% (CI 36, 71%), 25% (-10, 48%), 21% (-39, 55%)]. Conclusions: School-aged BCG vaccination offered moderate protection against tuberculosis for at least 20 years, which is longer than previously thought. This has implications for assessing the cost-effectiveness of BCG vaccination and when evaluating new TB vaccines.

Observational study to estimate the changes in the effectiveness of bacillus Calmette-Guérin (BCG) vaccination with time since vaccination for preventing tuberculosis in the UK.

BACKGROUND: Until recently, evidence that protection from the bacillus Calmette-Guérin (BCG) vaccination lasted beyond 10 years was limited. In the past few years, studies in Brazil and the USA (in Native Americans) have suggested that protection from BCG vaccination against tuberculosis (TB) in childhood can last for several decades. The UK's universal school-age BCG vaccination programme was stopped in 2005 and the programme of selective vaccination of high-risk (usually ethnic minority) infants was enhanced. OBJECTIVES: To assess the duration of protection of infant and school-age BCG vaccination against TB in the UK. METHODS: Two case-control studies of the duration of protection of BCG vaccination were conducted, the first on minority ethnic groups who were eligible for infant BCG vaccination 0-19 years earlier and the second on white subjects eligible for school-age BCG vaccination 10-29 years earlier. TB cases were selected from notifications to the UK national Enhanced Tuberculosis Surveillance system from 2003 to 2012. Population-based control subjects, frequency matched for age, were recruited. BCG vaccination status was established from BCG records, scar reading and BCG history. Information on potential confounders was collected using computer-assisted interviews. Vaccine effectiveness was estimated as a function of time since vaccination, using a case-cohort analysis based on Cox regression. RESULTS: In the infant BCG study, vaccination status was determined using vaccination records as recall was poor and concordance between records and scar reading was limited. A protective effect was seen up to 10 years following infant vaccination [< 5 years since vaccination: vaccine effectiveness (VE) 66%, 95% confidence interval (CI) 17% to 86%; 5-10 years since vaccination: VE 75%, 95% CI 43% to 89%], but there was weak evidence of an effect 10-15 years after vaccination (VE 36%, 95% CI negative to 77%; p = 0.396). The analyses of the protective effect of infant BCG vaccination were adjusted for confounders, including birth cohort and ethnicity. For school-aged BCG vaccination, VE was 51% (95% CI 21% to 69%) 10-15 years after vaccination and 57% (95% CI 33% to 72%) 15-20 years after vaccination, beyond which time protection appeared to wane. Ascertainment of vaccination status was based on self-reported history and scar reading. LIMITATIONS: The difficulty in examining vaccination sites in older women in the high-risk minority ethnic study population and the sparsity of vaccine record data in the later time periods precluded robust assessment of protection from infant BCG vaccination > 10 years after vaccination. CONCLUSIONS: Infant BCG vaccination in a population at high risk for TB was shown to provide protection for at least 10 years, whereas in the white population school-age vaccination was shown to provide protection for at least 20 years. This evidence may inform TB vaccination programmes (e.g. the timing of administration of improved TB vaccines, if they become available) and cost-effectiveness studies. Methods to deal with missing record data in the infant study could be explored, including the use of scar reading. FUNDING: The National Institute for Health Research Health Technology Assessment programme. During the conduct of the study, Jonathan Sterne, Ibrahim Abubakar and Laura C Rodrigues received other funding from NIHR; Ibrahim Abubakar and Laura C Rodrigues have also received funding from the Medical Research Council. Punam Mangtani received funding from the Biotechnology and Biological Sciences Research Council.

BCG vaccination in England since 2005: a survey of policy and practice.

OBJECTIVE: Assess the current BCG vaccination policies and delivery pathways for immunisation in Primary Care Trusts (PCTs) in England since the 2005 change in recommendations. DESIGN: A survey of key informants across PCTs using a standardised, structured questionnaire. SETTING: 152 PCTs in England. RESULTS: Complete questionnaires were returned from 127 (84%) PCTs. Sixteen (27%) PCTs reported universal infant vaccination and 111 (73%) had selective infant vaccination. Selective vaccination outside infancy was also reported from 94 (74%) PCTs. PCTs with selective infant policy most frequently vaccinated on postnatal wards (51/102, 50%), whereas PCTs with universal infant vaccination most frequently vaccinated in community clinics (9/13, 69%; p=0.011). To identify and flag up eligible infants in PCTs with targeted infant immunisation, those who mostly vaccinate on postnatal wards depend on midwives and maternity records, whereas those who vaccinate primarily in the community rely more often on various healthcare professionals. CONCLUSIONS: Targeted infant vaccination has been implemented in most PCTs across the UK. PCTs with selective infant vaccination provide BCG vaccine via a greater variety of healthcare professionals than those with universal infant vaccination policies. Data on vaccine coverage would help evaluate the effectiveness of delivery. Interruptions of delivery noted here emphasise the importance of not just an agreed, standardised, local pathway, but also a named person in charge.

Ethical aspects of the expansion of neonatal screening programme due to technological advances.

Many countries are considering the expansion of their newborn bloodspot screening programmes. Whereas some countries screen for very few conditions, others are planning to screen for dozens. While advances in technology may facilitate this expansion, they must not lead it at the expense of considerations of the possible harms of this expansion. This article reviews some of the potential disbenefits of this expansion and outlines the ethical issues that should be considered.

Pragmatic management of programmatic vaccination errors--lessons learnt from incidents in London.

Correct storage, handling and administration of vaccines are vital components of a successful immunisation programme. However, with the large number of different healthcare professionals now involved in delivering the vaccine programme on a daily basis, it is inevitable that programmatic errors will occur. Decisions as to how best to rectify these errors can be difficult however, as often they are unprecedented and there may be no hard evidence on which to base their management. These decisions must therefore be based on what is known and any available previous experience. They also often take place in an environment of concern about litigation and liability which puts pressure on health care workers to take a defensive or conservative approach. Management decisions may ultimately also have to be a pragmatic choice based on the individual situation and what is deemed to be the best way to minimise adverse reactions, ensure patients are adequately protected and maintain public confidence in the immunisation programme. Here, we describe our experiences of managing vaccine programmatic errors and some of the many factors that we had to consider.