Equity of the Meningitis B vaccination programme in England, 2016-2018.

In England, the Meningitis B (MenB) vaccine is scheduled at eight and 16 weeks with a booster dose at one year of age and protects children against invasive bacterial meningococcal disease caused by Neisseria meningitidis serogroup B. Coverage of the second dose of MenB vaccine at 12 months was >92% in 2017/18, but this may mask inequalities in coverage in particular population groups. MenB vaccination records for children aged six, 12 and 18 months of age from December 2016 to May 2018 were routinely extracted from GP patient management systems every month in England via a web-based platform for national monitoring of vaccine coverage. We determined the association between ethnicity, deprivation and area of residence, vaccine coverage and drop-out rates (between dose one and dose two), using binomial regression. After adjusting for other factors, ethnic groups with lowest dose one coverage (Black or Black British-Caribbean, White-Any other White background, White-Irish) also had lowest dose two coverage, but in addition, these ethnic groups also had the largest drop-out rates between dose one and dose two. The drop-out rate for Black or Black British-Caribbean children was 5.7 percentage points higher than for White-British children. Vaccine coverage decreased with increasing deprivation quintile, and this was most marked for the booster coverage (6.2 percentage points lower in the most deprived compared to least deprived quintile, p < 0.001). To achieve high coverage for completed courses across all ethnic groups and deprivation quintiles both high initiation rates and a reduction in drop-out rates for ethnic groups with lowest coverage is necessary. A qualitative approach to better understand reasons behind lower coverage and higher drop-out rates in the most underserved ethnic groups is required to develop tailored approaches addressing these inequalities.

Early impact of the coronavirus disease (COVID-19) pandemic and physical distancing measures on routine childhood vaccinations in England, January to April 2020.

Using electronic health records, we assessed the early impact of coronavirus disease (COVID-19) on routine childhood vaccination in England by 26 April 2020. Measles-mumps-rubella vaccination counts fell from February 2020, and in the 3 weeks after introduction of physical distancing measures were 19.8% lower (95% confidence interval: -20.7 to -18.9) than the same period in 2019, before improving in mid-April. A gradual decline in hexavalent vaccination counts throughout 2020 was not accentuated by physical distancing.

The changing epidemiology of diphtheria in the United Kingdom, 2009 to 2017.

BackgroundDiphtheria is a potentially fatal disease caused by toxigenic strains of Corynebacterium diphtheriae, C. ulcerans or C. pseudotuberculosis.AimOur objective was to review the epidemiology of diphtheria in the United Kingdom (UK) and the impact of recent changes in public health management and surveillance.MethodsPutative human toxigenic diphtheria isolates in the UK are sent for species confirmation and toxigenicity testing to the National Reference Laboratory. Clinical, epidemiological and microbiological information for toxigenic cases between 2009 and 2017 are described in this population-based prospective surveillance study.ResultsThere were 33 toxigenic cases of diphtheria aged 4 to 82 years. Causative species were C. diphtheriae (n = 18) and C. ulcerans (n = 15). Most C. diphtheriae cases were cutaneous (14/18) while more than half of C. ulcerans cases had respiratory presentations (8/15). Two thirds (23/33) of cases were inadequately immunised. Two cases with C. ulcerans infections died, both inadequately immunised. The major risk factor for C. diphtheriae aquisition was travel to an endemic area and for C. ulcerans, contact with a companion animal. Most confirmed C. diphtheriae or C. ulcerans isolates (441/507; 87%) submitted for toxigenicity testing were non-toxigenic, however, toxin positivity rates were higher (15/23) for C. ulcerans than C. diphtheriae (18/469). Ten non-toxigenic toxin gene-bearing (NTTB) C. diphtheriae were also detected.ConclusionDiphtheria is a rare disease in the UK. In the last decade, milder cutaneous C. diphtheriae cases have become more frequent. Incomplete vaccination status was strongly associated with the risk of hospitalisation and death.

Inequalities in childhood vaccination timing and completion in London.

The UK primary vaccination course includes vaccination against diphtheria, tetanus, pertussis, polio and Haemophilus influenzae type b (DTaP/IPV/Hib) and is scheduled at ages four, 8 and 12 weeks, followed by a 'preschool booster' at age three years four months. Vaccine coverage is generally measured at age one, two and five years. In addition to high coverage, vaccination should be timely to maximise population protection. Vaccination histories for 315,381 children born March 2001 to April 2010 were extracted from Child Health Information Systems in nine London health service areas and grouped into first and fifth birthday cohorts. We assessed timeliness of receipt of DTaP/IPV/Hib and drop-out rates by ethnicity, deprivation and area. Most children received their first, second and third doses on time at two, three, and four months. Among children completing by one year and after adjusting for deprivation and health area, compared with White-British children, Somali and Bangladeshi children were less likely to have received three doses of DTaP/IPV/Hib by six months of age (-11% and -5% respectively). Differences in timeliness by deprivation and health area existed, but were smaller. Compared with White-British children, children of Polish, Somali and Caribbean ethnicities were less likely to return for preschool booster, with a drop-out rate at least 7% higher in these groups. Within the fifth birthday cohort, only 2.3% of children who were completely unvaccinated (575/25,095) at age one year were fully vaccinated by age five. Higher proportions of partially vaccinated (one or two doses) children at age one year went on to be fully vaccinated by age five ((836/3213) 26.0% and (3565/6076) 58.7% respectively). These inequalities suggest that tailored approaches may be required to target specific groups with regards to improving vaccine uptake.

Extracting general practice data for timely vaccine coverage estimates: The England experience.

In England, primary care providers use standardised coding systems to record health events such as vaccination as well as patient characteristics. This information can be automatically extracted to estimate coverage for vaccine programmes delivered through primary care, in the general population as well as in specific geographical, ethnic, age or clinical groups. This system provides timely vaccine coverage estimates as well as the flexibility to extract tailored data in order to directly inform a continuously evolving national vaccine programme. It is however limited by the quality and completeness of clinical coding in primary care. A centralised, individual-level register would however improve data quality, completeness and reliability and remains the gold standard.

Sociodemographic predictors of variation in coverage of the national shingles vaccination programme in England, 2014/15.

INTRODUCTION: In September 2013, England introduced a shingles vaccination programme to reduce incidence and severity of shingles in the elderly. This study aims to assess variation in vaccine coverage with regards to selected sociodemographic factors to inform activities for improving equity of the programme. METHODS: Eligible 70year-olds were identified from a national vaccine coverage dataset in 2014/15 that includes 95% of GPs in England. NHS England Local Team (LT) and index of multiple deprivation (IMD) scores were assigned to patients based on GP-postcode. Vaccine coverage (%) with 95% confidence intervals (CIs), were calculated overall and by LT, ethnicity and IMD, using binomial regression. RESULTS: Of 502,058 eligible adults, 178,808 (35.6%) had ethnicity recorded. Crude vaccine coverage was 59.5% (95%CI: 59.3-59.7). Coverage was lowest in London (49.6% coverage, 95%CI: 49.0-50.2), and compared to this coverage was significantly higher in all other LTs (+6.3 to +10.4, p<0.001) after adjusting for ethnicity and IMD. Coverage decreased with increasing deprivation and was 8.2% lower in the most deprived (95%CI: 7.3-9.1) compared with the least deprived IMD quintile (64.1% coverage, 95%CI: 63.6-64.6), after adjustment for ethnicity and LT. Compared with White-British (60.7% coverage, 95%CI: 60.5-61.0), other ethnic groups had between 4.0% (Indian) and 21.8% (Mixed: White and Black African) lower coverage. After adjusting for IMD and LT, significantly lower coverage by ethnicity persisted in all groups, except in Mixed: Other, Indian and Bangladeshi compared with White-British. CONCLUSIONS: After taking geography and deprivation into account, shingles vaccine coverage varied by ethnicity. White-British, Indian and Bangladeshi groups had highest coverage; Mixed: White and Black African, and Black-other ethnicities had the lowest. Patients' ethnicity and IMD are predictors of coverage which contribute to, but do not wholly account for, geographical variation coverage. Interventions to address service-related, sociodemographic and ethnic inequalities in shingles vaccine coverage are required.

Effectiveness and impact of a reduced infant schedule of 4CMenB vaccine against group B meningococcal disease in England: a national observational cohort study.

BACKGROUND: In September, 2015, the UK became the first country to introduce the multicomponent group B meningococcal (MenB) vaccine (4CMenB, Bexsero) into a publicly funded national immunisation programme. A reduced two-dose priming schedule was offered to infants at 2 months and 4 months, alongside an opportunistic catch-up for 3 month and 4 month olds. 4CMenB was predicted to protect against 73-88% of MenB strains. We aimed to assess the effectiveness and impact of 4CMenB in vaccine-eligible infants in England. METHODS: Public Health England (PHE) undertakes enhanced surveillance of meningococcal disease through a combination of clinical, public health, and laboratory reporting. Laboratory-confirmed cases of meningococcal disease are followed up with PHE local health protection teams, general practitioners, and hospital clinicians to collect demographic data, vaccination history, clinical presentation, and outcome. For cases diagnosed between Sept 1, 2015, and June 30, 2016, vaccine effectiveness was assessed using the screening method. Impact was assessed by comparing numbers of cases of MenB in vaccine-eligible children to equivalent cohorts in the previous 4 years and to cases in vaccine-ineligible children. FINDINGS: Coverage of 4CMenB in infants eligible for routine vaccination was high, achieving 95·5% for one dose and 88·6% for two doses by 6 months of age. Two-dose vaccine effectiveness was 82·9% (95% CI 24·1-95·2) against all MenB cases, equivalent to a vaccine effectiveness of 94·2% against the highest predicted MenB strain coverage of 88%. Compared with the prevaccine period, there was a 50% incidence rate ratio (IRR) reduction in MenB cases in the vaccine-eligible cohort (37 cases vs average 74 cases; IRR 0·50 [95% CI 0·36-0·71]; p=0·0001), irrespective of the infants' vaccination status or predicted MenB strain coverage. Similar reductions were observed even after adjustment for disease trends in vaccine-eligible and vaccine-ineligible children. INTERPRETATION: The two-dose 4CMenB priming schedule was highly effective in preventing MenB disease in infants. Cases in vaccine-eligible infants halved in the first 10 months of the programme. While ongoing national surveillance will continue to monitor the longer-term impact of the programme, these findings represent a step forward in the battle against meningococcal disease and will help reassure that the vaccine protects against this deadly infection. FUNDING: Public Health England.

Childhood vaccination coverage by ethnicity within London between 2006/2007 and 2010/2011.

OBJECTIVES: To assess childhood vaccination coverage at first, second and fifth birthdays by ethnicity in London between 2006/2007 and 2010/2011 and identify factors relating to lower coverage. DESIGN: Data concerning receipt of diphtheria-containing vaccines were extracted from child health information systems (CHISs) and sent to the Health Protection Agency. SETTING: Nine London Primary Care Trusts (PCTs). PARTICIPANTS: Records for 315 381 children born April 2001-March 2010. MAIN OUTCOME MEASURES: Receipt of a full primary course of diphtheria-containing vaccines at first and second birthdays, and a primary course and preschool booster at fifth birthday. RESULTS: Consistently good vaccine coverage of the primary course (>88% at first birthday, >89% at second birthday) was achieved across the five largest ethnic groups. Coverage of the preschool booster at fifth birthday was >65% across the five largest ethnic groups. Lowest coverage was observed in smaller ethnic groups. Deprivation was not a strong indicator of coverage overall, and for most ethnic groups there was no relationship between deprivation and coverage. Coverage was significantly lower in children not assigned to a general practitioner practice in the CHIS. CONCLUSIONS: Smaller, less well-established ethnic groups within a PCT may require specific targeting to ensure children are fully immunised and to improve record keeping. Unregistered children need particular attention and may be missed by current scheduling processes in London. In order to monitor the impact of the current National Health Service (NHS) reorganisation on inequalities in access to healthcare data on country of birth, in addition to ethnicity, should be available for analysis.

Infections with spore-forming bacteria in persons who inject drugs, 2000-2009.

Since 2000 in the United Kingdom, infections caused by spore-forming bacteria have been associated with increasing illness and death among persons who inject drugs (PWID). To assess temporal and geographic trends in these illnesses (botulism, tetanus, Clostridium novyi infection, and anthrax), we compared rates across England and Scotland for 2000-2009. Overall, 295 infections were reported: 1.45 per 1,000 PWID in England and 4.01 per 1,000 PWID in Scotland. The higher rate in Scotland was mainly attributable to C. novyi infection and anthrax; rates of botulism and tetanus were comparable in both countries. The temporal and geographic clustering of cases of C. novyi and anthrax into outbreaks suggests possible contamination of specific heroin batches; in contrast, the more sporadic nature of tetanus and botulism cases suggests that these spores might more commonly exist in the drug supply or local environment although at varying levels. PWID should be advised about treatment programs, injecting hygiene, risks, and vaccinations.

Immunity to tetanus and diphtheria in the UK in 2009.

INTRODUCTION: This study aimed to estimate the immunity of the UK population to tetanus and diphtheria, including the potential impact of new glycoconjugatate vaccines, and the addition of diphtheria to the school leaver booster in 1994. METHODS: Residual sera (n=2697) collected in England in 2009/10 were selected from 18 age groups and tested for tetanus and diphtheria antibody. Results were standardised by testing a panel of sera (n=150) to enable comparison with a previously (1996) published serosurvey. Data were then standardised to the UK population. RESULTS: In 2009, 83% of the UK population were protected (≥0.1 IU/mL) against tetanus compared to 76% in 1996 (p=0.079), and 75% had at least basic protection against diphtheria (≥0.01 IU/mL) in 2009 compared to 60% in 1996 (p<0.001). Higher antibody levels were observed in those aged 1-3 years in 2009 compared to 1996 for both tetanus and diphtheria. Higher diphtheria immunity was observed in those aged 16-34 years in 2009 compared to 1996 (geometric mean concentration [GMC] 0.15 IU/mL vs. 0.03 IU/mL, p<0.001). Age groups with the largest proportion of susceptible individuals to both tetanus and diphtheria in 2009 were <1 year old (>29% susceptible), 45-69 years (>20% susceptible) and 70+ years (>32% susceptible). Low immunity was observed in those aged 10-11 years (>19% susceptible), between the scheduled preschool and school leaver booster administration. DISCUSSION: The current schedule appears to induce protective levels; increases in the proportions protected/GMCs were observed for the ages receiving vaccinations according to UK policy. Glycoconjugate vaccines appear to have increased immunity, in particular for diphtheria, in preschool age groups. Diphtheria immunity in teenagers and young adults has increased as a result of the addition of diphtheria to the school leaver booster. However, currently older adults remain susceptible, without any further opportunities for immunisations planned according to the present schedule.

Diphtheria in the postepidemic period, Europe, 2000-2009.

Diphtheria incidence has decreased in Europe since its resurgence in the 1990s, but circulation continues in some countries in eastern Europe, and sporadic cases have been reported elsewhere. Surveillance data from Diphtheria Surveillance Network countries and the World Health Organization European Region for 2000-2009 were analyzed. Latvia reported the highest annual incidence in Europe each year, but the Russian Federation and Ukraine accounted for 83% of all cases. Over the past 10 years, diphtheria incidence has decreased by >95% across the region. Although most deaths occurred in disease-endemic countries, case-fatality rates were highest in countries to which diphtheria is not endemic, where unfamiliarity can lead to delays in diagnosis and treatment. In western Europe, toxigenic Corynebacterium ulcerans has increasingly been identified as the etiologic agent. Reduction in diphtheria incidence over the past 10 years is encouraging, but maintaining high vaccination coverage is essential to prevent indigenous C. ulcerans and reemergence of C. diphtheriae.

The contribution of single antigen measles, mumps and rubella vaccines to immunity to these infections in England and Wales.

OBJECTIVE: To obtain information on the use of single antigen measles, mumps and rubella vaccines to improve estimates of population immunity and help predict outbreaks. DESIGN: We requested information from providers of single antigen vaccines and from the Medicine and Healthcare products Regulatory Agency on requests for importation of single antigen measles and mumps vaccines. SETTING: England and Wales. MAIN OUTCOME MEASURES: Number of doses of single measles, mumps and rubella vaccine, by age of child (in months), year given and area of residence, and number of children who have received all three single vaccinations. RESULTS: Of 27 providers identified, 13 held single site clinics: nine were individual general practitioners and five held clinics at multiple sites. Data were received from 9/27 (33%) providers operating 40/74 (54%) clinic sites. We received information on 60 768 vaccinations administered by single vaccine providers and 269 917 doses requested for importation. For children born in 2001/2002, the minimum estimates for the proportion who received single measles vaccine are 1.7% in 2001 and 2.1% in 2002, with a reasonable maximum estimate of 5.6% over the 2 years. For single mumps vaccine, the minimum estimates are 0.3% in 2001 and 0.02% in 2002, with a maximum estimate of 4.0%. CONCLUSION: The contribution of single vaccines to immunity is small in comparison to that of the combined measles, mumps and rubella vaccine (MMR). For recent birth cohorts this contribution could increase routine coverage for measles-containing vaccines by around 2%, still below the level of immunity required to sustain elimination.

Vaccine effectiveness estimates, 2004-2005 mumps outbreak, England.

The United Kingdom and United States have recently experienced large outbreaks of mumps, which raises concerns about vaccine effectiveness. The effectiveness of the mumps component of the measles, mumps, rubella (MMR) vaccine was estimated using the screening method. In England from January 2004 through March 2005, 312 cases of mumps were reported in children eligible to have received 2 doses of MMR vaccine. Of these children, 52 (16.7%) had received 1 dose of MMR vaccine, and 97 (31.1%) had received 2 doses. Vaccine effectiveness was 88% (95% confidence interval [CI] 83%-91%) for 1 dose and 95% (95% CI 93%-96%) for 2 doses. The effectiveness of 1 dose declined from 96% (95% CI 81%-99%) in 2-year-olds to 66% (95% CI 30%-83%) in 11- to 12-year-olds, and the effectiveness of 2 doses declined from 99% (95% CI 97%-99.5%) in 5- to 6-year-olds to 86% (95% CI 74%-93%) in 11- to 12-year-olds (p<0.001 for 1 or 2 doses). Waning immunity may contribute to mumps outbreaks in older vaccinated populations.

The effectiveness of the mumps component of the MMR vaccine: a case control study.

In 1998/1999, an outbreak of mumps occurred among children of a religious community in North East London. A case control study was conducted to assess the effectiveness of the mumps component of the MMR vaccine. One hundred and sixty-one cases of mumps were identified and 192 controls were selected. Fifty-one percent of cases and 77% of controls had a history at least one MMR vaccination. The observed effectiveness of any MMR vaccination adjusted for age, sex and general practice was 69% (95% CI: 41-84%). This is consistent with the results of other observational studies of mumps containing vaccines, but lower than the immunogenicity of mumps vaccines reported by clinical trials. This discrepancy is because observational studies tend to underestimate vaccine effectiveness, and because immunogenicity is not necessarily an accurate biological marker of vaccine effectiveness. Two doses of vaccine were more effective (88% (95% CI: 62-96%)) than a single dose (64% (95% CI: 40-78%)). The current two-dose vaccination programme remains the best method for controlling mumps infection in the community.

Genetic diversity of mumps virus in oral fluid specimens: application to mumps epidemiological study.

Three hundred nine mumps virus (MuV) strains detected in the United Kingdom during 1995-2002 were characterized by partial sequencing of the small hydrophobic gene and were shown to belong to at least 6 different genotypes. A strain representing a new genotype was isolated from a seminal fluid specimen. Identical strains belonging to genotypes G and C were found to circulate for up to 3 years. One genotype H strain reappeared after an absence of 4 years. Distinct lineages (G1-G7) within genotype G were recognizable in the present study, and this level of characterization proved to be very useful for tracking MuV importations and subsequent transmission. We propose, here, a preliminary standardization of international nomenclature for genetic characterization of MuV strains, to facilitate future molecular epidemiological studies of mumps. Oral fluid (OF) specimens (n=1441) were used to detect both anti-MuV IgM and MuV genome, and the results indicate that OF specimens can be used successfully for diagnosis and have the potential to play a valuable role in diagnosis and surveillance of mumps.