Understanding the health system barriers and enablers to childhood MMR and HPV vaccination among disadvantaged, minority or underserved populations in middle- and high-income countries: a systematic review.

BACKGROUND: Child vaccinations are among the most effective public health interventions. However, wide gaps in child vaccination remain among different groups with uptake in most minorities or ethnic communities in Europe substantially lower compared to the general population. A systematic review was conducted to understand health system barriers and enablers to measles, mumps and rubella (MMR) and human papilloma virus (HPV) child vaccination among disadvantaged, minority populations in middle- and high-income countries. METHODS: We searched Medline, Cochrane, CINAHL, ProQuest and EMBASE for articles published from 2010 to 2021. Following title and abstract screening, full texts were assessed for relevance. Study quality was appraised using Critical Appraisal Skills Program checklists. Data extraction and analysis were performed. Health system barriers and enablers to vaccination were mapped to the World Health Organization health system building blocks. RESULTS: A total of 1658 search results were identified from five databases and 24 from reference lists. After removing duplicates, 1556 titles were screened and 496 were eligible. Eighty-six full texts were assessed for eligibility, 28 articles met all inclusion criteria. Factors that affected MMR and HPV vaccination among disadvantaged populations included service delivery (limited time, geographic distance, lack of culturally appropriate translated materials, difficulties navigating healthcare system), healthcare workforce (language and poor communication skills), financial costs and feelings of discrimination. CONCLUSION: Policymakers must consider health system barriers to vaccination faced by disadvantaged, minority populations while recognizing specific cultural contexts of each population. To ensure maximum policy impact, approaches to encourage vaccinations should be tailored to the unique population's needs. A one-size-fits-all approach is not effective.

Vaccination of Infants with Meningococcal Group B Vaccine (4CMenB) in England.

BACKGROUND: In September 2015, the United Kingdom introduced the multicomponent meningococcal group B vaccine (4CMenB, Bexsero) into its publicly funded national immunization program at a reduced two-dose priming schedule for infants, with a 12-month booster. METHODS: Using data from enhanced national surveillance of invasive meningococcal disease in England, we evaluated the effect of vaccination on the incidence of meningococcal group B disease during the first 3 years of the program. The effect of vaccination was assessed by comparing the observed incidence of disease with the expected incidence based on the incidence during the 4-year prevaccination period in equivalent cohorts and with the use of disease trends in cohorts of children younger than 5 years of age who were not eligible to receive the vaccine. Vaccine effectiveness was estimated with the use of the indirect screening method. RESULTS: 4CMenB uptake in England remained consistently high; data from the first 3 months of 2018 showed that 92.5% of children had completed the primary immunizations by their first birthday and 87.9% had received all three doses by 2 years. From September 2015 through August 2018, the incidence of meningococcal group B disease in England (average annual birth cohort, approximately 650,000 infants) was significantly lower in vaccine-eligible cohorts than the expected incidence (63 observed cases as compared with 253 expected cases; incidence rate ratio, 0.25; 95% confidence interval [CI], 0.19 to 0.36), with a 75% reduction in age groups that were fully eligible for vaccination. The adjusted vaccine effectiveness against meningococcal group B disease was 52.7% (95% CI, -33.5 to 83.2) with a two-dose priming schedule for infants and 59.1% (95% CI, -31.1 to 87.2) with a two-dose priming schedule plus a booster at 1 year). Over the 3-year period, there were 169 cases of meningococcal group B disease in the vaccine-eligible cohorts, and an estimated 277 cases (95% CI, 236 to 323) were prevented. CONCLUSIONS: The 4CMenB program was associated with continued positive effect against meningococcal group B disease in children in England, and protection after three doses of the vaccine was sustained for at least 2 years. (Funded by Public Health England.).

Associations between reported post-COVID-19 symptoms and subjective well-being, Israel, July 2021 - April 2022.

The impact of individual symptoms reported post-COVID-19 on subjective well-being (SWB) is unknown. We described associations between SWB and selected reported symptoms following SARS-CoV-2 infection. We analysed reported symptoms and subjective well being from 2295 participants (of which 576 reporting previous infection) in an ongoing longitudinal cohort study taking place in Israel. We estimated changes in SWB associated with reported selected symptoms at three follow-up time points (3-6, 6-12 and 12-18 months post infection) among participants reporting previous SARS-CoV-2 infection, adjusted for key demographic variables, using linear regression. Our results suggest that the biggest and most sustained changes in SWB stems from non-specific symptoms (fatigue -7.7 percentage points (pp), confusion/ lack of concentration -10.7 pp, and sleep disorders -11.5pp, P < 0.005), whereas the effect of system-specific symptoms, such as musculoskeletal symptoms (weakness in muscles and muscle pain) on SWB, are less profound and more transient. Taking a similar approach for other symptoms and following individuals over time to describe trends in SWB changes attributable to specific symptoms will help understand the post-acute phase of COVID-19 and how it should be defined and better managed. Post-acute COVID19 symptoms were associated with a significant decrease in subjective well being up to 18 months after initial infection.

Maternal and Cord Anti-SARS-CoV-2-Spike IgG following COVID-19 Vaccination versus Infection during Pregnancy: A Prospective Study, Israel October 2021-March 2022.

OBJECTIVE: Defining how pregnant women respond to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and vaccination is critical to optimize vaccination strategies that protect mother and infant at the epidemic. This study aimed to compare anti-SARS-CoV-2-spike immunoglobulin G (IgG) of vaccinated versus infected women and to determine the optimal timing of maternal vaccination during pregnancy at the time of epidemic. STUDY DESIGN: We collected maternal/cord blood at delivery (October 2021-March 2022) and measured anti-SARS-CoV-2-spike IgG geometric mean concentrations (IgG-GMCs) using a quantitative immunoassay. We compared groups according to timing and number of doses and correlated maternal and fetal IgG levels. We described the proportion of women with IgG levels above the 150 AU/mL positivity threshold according to the timing of infection/vaccination and performed a subanalysis for maternal IgG-GMC levels pre- and during the Omicron wave. RESULTS: We included 238 vaccinated women, 125 who received two doses and 113 three doses, and 48 unvaccinated infected women. All groups infected/vaccinated in the second or third trimester had an IgG-GMC above the positivity threshold. Third-trimester vaccination (second/third dose) resulted in higher maternal and cord-blood IgG-GMC compared to the second trimester (maternal-IgG: 102,32 vs. 4,325 AU/mL, p < 0.001; cord-IgG: 12,113 vs. 8,112 AU/mL, p < 0.001). Compared with infected-only women, a higher proportion of vaccinated women with ≥2 doses and their newborns had IgG levels above the positivity threshold at all time points. In vaccinated women, there were higher maternal IgG-GMC levels during the Omicron wave than pre-Omicron. CONCLUSION: At the time of epidemic, receiving an additional COVID-19 vaccine dose in the third trimester resulted in a higher IgG-GMC compared to the second trimester. Relatively higher levels of maternal and cord IgG-GMC were achieved following vaccination than infection. Women infected during or before the first trimester might benefit from an additional third-trimester dose to prevent peripartum infection and to passively immunize their newborn. The higher levels of maternal IgG-GMC in the Omicron period are suggestive of hybrid immunity. KEY POINTS: · Higher maternal anti-SARS-IgGs in vaccinated → infected.. · Higher cord anti-SARS-IgGs in vaccinated → infected.. · Third-trimester vaccine resulted in high-cord IgG levels..

Antibody-Mediated Immunogenicity Against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Following Priming, Boosting, and Hybrid Immunity: Insights From 11 Months of Follow-up of a Healthcare Worker Cohort in Israel, December 2020-October 2021.

BACKGROUND: We determined circulating anti-S severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin G (IgG) antibody titers in a vaccinated healthcare workers (HCWs) cohort from Northern Israel in the 11 months following primary vaccination according to age, ethnicity, and previous infection status. METHODS: All consenting HCWs were invited to have their IgG levels measured before vaccination and at 6 subsequent timepoints using a quantitative S1/S2 IgG assay. All HCWs with suspected coronavirus disease 2019 (COVID-19) were polymerase chain reaction (PCR) tested. We described trends in circulating IgG geometric mean concentration (GMC) by age, ethnicity, timing of boosting, and previous infection status and compared strata using Kruskall-Wallis tests. RESULTS: Among 985 vaccinated HCWs, IgG titers between 1 month post 2nd dose to pre-boosting gradually decreased in all age groups. Younger or previously infected individuals had higher initial post-vaccination IgG levels (P < .001 in both cases); differences substantially decreased or disappeared at 7-9 months, before boosting. The proportion of individuals infected prior to initiating vaccination and re-infected after dose 1 was comparable to the proportion of breakthrough infection post-dose 2 in those not previously infected (4.2 vs 4.7%). Pre-infection IgG levels in the 40 participants with breakthrough infection after dose 2 were similar to levels measured at the same timepoint in vaccinated HCWs who remained uninfected (P > .3). Post-dose3 IgG levels were more than 10-fold those 1 month post-dose 2. CONCLUSIONS: Immunity waned in all age groups and previously infected individuals, reversed by boosting. IgG titers decrease and reinfections in individuals with hybrid immunity (infection + vaccination) suggests they may also require further doses. Our study also highlights the difficulty in determining protective IgG levels.

First Real-world Evidence of Meningococcal Group B Vaccine, 4CMenB, Protection Against Meningococcal Group W Disease: Prospective Enhanced National Surveillance, England.

BACKGROUND: 4CMenB is a protein-based meningococcal B vaccine, but the vaccine antigens may be present on non-group B meningococci. In September 2015, the UK implemented 4CMenB into the national infant immunization program, alongside an emergency adolescent meningococcal ACWY (MenACWY) program to control a national outbreak of group W (MenW) disease caused by a hypervirulent strain belonging to the ST-11 clonal complex. The adolescent program aimed to provide direct protection for adolescents and indirect protection across the population. METHODS: Public Health England conducts meningococcal disease surveillance in England. MenW cases confirmed during 4 years before and 4 years after implementation of both vaccines were analyzed. Poisson models were constructed to estimate direct protection against MenW disease offered by the infant 4CMenB program along with the indirect impact of the adolescent MenACWY program in children eligible for 4CMenB but not MenACWY. RESULTS: Model estimates showed 69% (adjusted incidence rate ratio [aIRR], .31; 95% CI, .20-.67) and 52% (aIRR, .48; 95% CI, .28-.81) fewer MenW cases than predicted among age-cohorts that were fully- and partly-eligible for 4CMenB, respectively. There were 138 MenW cases in <5-year-olds. 4CMenB directly prevented 98 (95% CI, 34-201) cases, while the MenACWY program indirectly prevented an additional 114 (conservative) to 899 (extreme) cases over 4 years. Disease severity was similar in 4CMenB-immunized and unimmunized children. CONCLUSIONS: This is the first real-world evidence of direct protection afforded by 4CMenB against MenW:cc11 disease. 4CMenB has the potential to provide some protection against all meningococcal serogroups.

Impact of a nurse-led enhanced monitoring, management and contact tracing intervention for chronic hepatitis B in England, 2015-2017.

Around 200,000 people live with chronic hepatitis B in England. Despite national guidance on identification and management of cases and their close contacts, testing rates of close contacts is as low as 43% in high prevalence areas of London. Our study aimed to determine whether a nurse-led enhanced management and contact tracing of chronically infected individuals improved testing uptake, vaccination and onward referral of close contacts. The study was conducted across Greater Manchester and East of England regions between October 2015 and July 2017. All HBV chronically infected individuals registered with a GP and their close contacts were eligible for recruitment. The proportion of contacts who were tested, vaccinated and referred where appropriate were compared before and after the nurse-led intervention. Baseline and outcome information was collected using questionnaires. The intervention improved case referral rates by an additional 14% (from 86% (88/102 cases) to 99.7%; 648/650 cases). The proportion of contacts tested increased from 34% to 72%-94% with 18 new cases of HBV diagnosed. Amongst close contacts tested, vaccination rates of at least three doses increased from 77% (43/56) to 93% (452/491) during the study. Our study has shown that nurse-led enhanced management greatly improves identification, testing and vaccination of close contacts. The identification of new acute and chronic cases is likely to make the intervention cost effective and local health commissioners should consider providing a nurse-led service as part of hepatitis B care pathways.

SARS-CoV-2 immunogenicity in individuals infected before and after COVID-19 vaccination: Israel, January-March 2021.

Between December 2020 and March 2021, we measured anti-SARS-CoV-2 IgG titres among 725 Israeli hospital workers vaccinated against COVID-19. Infection post-dose 1 vaccination did not increase IgG titres, and individuals infected post-dose 1 had IgG levels comparable to never-infected individuals who received a single dose, lower than fully vaccinated, never-infected individuals. This suggests dose 2, currently not offered to those infected post-dose 1, may be required in these individuals. Larger studies should confirm whether individuals infected post-dose 1 need the second.

Health technology assessment applied to emergency preparedness: a new perspective.

Emergency preparedness is a continuous quality improvement process through which roles and responsibilities are defined to effectively anticipate, respond to, and recover from the impact of emergencies. This process results in documented plans that provide a backbone structure for developing the core capacities to address health threats. Nevertheless, several barriers can impair an effective preparedness planning, as it needs a 360° perspective to address each component according to the best evidence and practice. Preparedness planning shares common principles with health technology assessment (HTA) as both encompass a multidisciplinary and multistakeholder approach, follow an iterative cycle, adopt a 360° perspective on the impact of intervention measures, and conclude with decision-making support. Our "Perspective" illustrates how each HTA domain can address different component(s) of a preparedness plan that can indeed be seen as a container of multiple HTAs, which can then be used to populate the entire plan itself. This approach can allow one to overcome preparedness barriers, providing an independent, systematic, and robust tool to address the components and ensuring a comprehensive evaluation of their value in the mitigation of the impact of emergencies.

Impact of age, ethnicity, sex and prior infection status on immunogenicity following a single dose of the BNT162b2 mRNA COVID-19 vaccine: real-world evidence from healthcare workers, Israel, December 2020 to January 2021.

The BNT162b2 mRNA COVID-19 vaccine showed high efficacy in clinical trials but observational data from populations not included in trials are needed. We describe immunogenicity 21 days post-dose 1 among 514 Israeli healthcare workers by age, ethnicity, sex and prior COVID-19 infection. Immunogenicity was similar by ethnicity and sex but decreased with age. Those with prior infection had antibody titres one magnitude order higher than naïve individuals regardless of the presence of detectable IgG antibodies pre-vaccination.

The impact of social and physical distancing measures on COVID-19 activity in England: findings from a multi-tiered surveillance system.

BackgroundA multi-tiered surveillance system based on influenza surveillance was adopted in the United Kingdom in the early stages of the coronavirus disease (COVID-19) epidemic to monitor different stages of the disease. Mandatory social and physical distancing measures (SPDM) were introduced on 23 March 2020 to attempt to limit transmission.AimTo describe the impact of SPDM on COVID-19 activity as detected through the different surveillance systems.MethodsData from national population surveys, web-based indicators, syndromic surveillance, sentinel swabbing, respiratory outbreaks, secondary care admissions and mortality indicators from the start of the epidemic to week 18 2020 were used to identify the timing of peaks in surveillance indicators relative to the introduction of SPDM. This timing was compared with median time from symptom onset to different stages of illness and levels of care or interactions with healthcare services.ResultsThe impact of SPDM was detected within 1 week through population surveys, web search indicators and sentinel swabbing reported by onset date. There were detectable impacts on syndromic surveillance indicators for difficulty breathing, influenza-like illness and COVID-19 coding at 2, 7 and 12 days respectively, hospitalisations and critical care admissions (both 12 days), laboratory positivity (14 days), deaths (17 days) and nursing home outbreaks (4 weeks).ConclusionThe impact of SPDM on COVID-19 activity was detectable within 1 week through community surveillance indicators, highlighting their importance in early detection of changes in activity. Community swabbing surveillance may be increasingly important as a specific indicator, should circulation of seasonal respiratory viruses increase.

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.

HPV vaccination of gay, bisexual and other men who have sex with men in sexual health and HIV clinics in England: vaccination uptake and attendances during the pilot phase.

BACKGROUND: Human papillomavirus (HPV) vaccination for gay, bisexual and other men who have sex with men (GBMSM) aged up to 45 years attending sexual health clinics (SHC) and HIV clinics began in England as a pilot in June 2016, with national roll-out from April 2018. The recommended course is three doses of the quadrivalent HPV vaccine over one to 2 years. We present the methodology and results of monitoring vaccination uptake (initiation and completion), and attendance patterns, during the pilot phase. METHODS: Total numbers of eligible GBMSM receiving HPV vaccine doses were extracted from routine datasets from pilot start to end of March 2018. Numbers of attendances since January 2009 were extracted and tested for trends before and after introduction of HPV vaccination. RESULTS: Overall, first dose uptake was 49.1 % (23 619/48 095), with clinics with highest data completeness achieving close to 90% uptake during the pilot period. Refusals were very low (3.5%). There was no evidence of increases in the number of GBMSM attendances at pilot SHC. CONCLUSIONS: HPV vaccination has not caused important deviations to expected attendance patterns of GBMSM at SHC throughout the pilot phase. Overall, recorded initiation has been encouraging given known issues with data recording, as is current status of second and third dose completion. Attendances, vaccination initiation and completion will continue to be monitored alongside surveillance of anogenital warts diagnoses and of rectal HPV prevalence.

Triangulation of measles vaccination data in the United Kingdom of Great Britain and Northern Ireland.

OBJECTIVE: To illustrate how data triangulation involving routine data sources can optimize data usage and provide insights into vaccine programme effectiveness by considering measles vaccination and disease incidence data in England. METHODS: We obtained data on measles, mumps and rubella (MMR) vaccine coverage in birth cohorts from 1985 to 2016 from child health records and adjusted for under-ascertainment and catch-up campaigns. We assumed that the population had no natural immunity and that vaccine effectiveness was 95% for one dose and 99.75% for two doses. Vaccinations done outside the routine schedule and in people who entered England after the age of immunization were identified from primary care records. Measles susceptibility was defined as the percentage of individuals who were not immune despite all vaccination activities. We triangulated measles susceptibility and incidence data. FINDINGS: Median susceptibility was 4.6% (range: 1.2-9.2). Among cohorts eligible for two MMR vaccine doses, those born between 1998 and 2004 were most susceptible. Measles incidence was highest in these cohorts. Data from primary care and child health records were comparable for cohorts after 2000, suggesting that little supplementary vaccination took place. For cohorts before 2000, primary care data quality was insufficient for accurately estimating coverage. CONCLUSION: Triangulating routine data on measles vaccination coverage and disease surveillance provided new insights into population immunity and helped identify vulnerable groups, which was useful for prioritizing public health actions to close gaps in immunity. This approach could be applied in any country that routinely records vaccine coverage and disease incidence.

Implementation and evaluation of the human papillomavirus (HPV) vaccination pilot for men who have sex with men (MSM), England, April 2016 to March 2017.

BACKGROUND: Opportunistic human papillomavirus (HPV) vaccination for men who have sex with men (MSM) was piloted in sexual health clinics (SHC) in England between 2016 and 2018. AIM: to evaluate the pilot's first year (April 2016-March 2017) in terms of feasibility, acceptability, uptake, impact and equity and interpret the outcome in the context of wide HPV vaccination policy. METHODS: Attendance and uptake data from routine SHC surveillance datasets and a cross-sectional survey administered to individuals receiving the vaccine were analysed. RESULTS: Among 18,875 eligible MSM, 8,580 (45.5%) were recorded as having received one HPV vaccine dose, decreasing slightly with increasing age, and uptake was higher in rural than urban areas. Survey results suggested that of those receiving the first dose of HPV vaccine, 8% were new attendees and that among those, less than 11% attended just to receive the vaccine. Of those having their first HPV vaccination, 95% indicated they would like to receive the next vaccine doses at the same clinic and 85% of patients reported accessing other services when visiting SHC for the first dose of vaccine. CONCLUSION: An opportunistic HPV vaccination programme for MSM can be delivered in an acceptable and, as far as can be evaluated, equitable manner, without major disruption to SHC and HIV clinics.

Gene therapy clinical trials worldwide to 2017: An update.

To date, almost 2600 gene therapy clinical trials have been completed, are ongoing or have been approved worldwide. Our database brings together global information on gene therapy clinical activity from trial databases, official agency sources, published literature, conference presentations and posters kindly provided to us by individual investigators or trial sponsors. This review presents our analysis of clinical trials that, to the best of our knowledge, have been or are being performed worldwide. As of our November 2017 update, we have entries on 2597 trials undertaken in 38 countries. We have analysed the geographical distribution of trials, the disease indications (or other reasons) for trials, the proportions to which different vector types are used, and the genes that have been transferred. Details of the analyses presented, and our searchable database are available via The Journal of Gene Medicine Gene Therapy Clinical Trials Worldwide website at: http://www.wiley.co.uk/genmed/clinical. We also provide an overview of the progress being made in gene therapy clinical trials around the world, and discuss key trends since the previous review, namely the use of chimeric antigen receptor T cells for the treatment of cancer and advancements in genome editing technologies, which have the potential to transform the field moving forward.

Hepatitis A outbreak disproportionately affecting men who have sex with men (MSM) in the European Union and European Economic Area, June 2016 to May 2017.

Between 1 June 2016 and 31 May 2017, 17 European Union (EU) and European Economic Area countries reported 4,096 cases associated with a multi-country hepatitis A (HA) outbreak. Molecular analysis identified three co-circulating hepatitis A virus (HAV) strains of genotype IA: VRD_521_2016, V16-25801 and RIVM-HAV16-090. We categorised cases as confirmed, probable or possible, according to the EU outbreak case definitions. Confirmed cases were infected with one of the three outbreak strains. We investigated case characteristics and strain-specific risk factors for transmission. A total of 1,400 (34%) cases were confirmed; VRD_521_2016 and RIVM-HAV16-090 accounted for 92% of these. Among confirmed cases with available epidemiological data, 92% (361/393) were unvaccinated, 43% (83/195) travelled to Spain during the incubation period and 84% (565/676) identified as men who have sex with men (MSM). Results depict an HA outbreak of multiple HAV strains, within a cross-European population, that was particularly driven by transmission between non-immune MSM engaging in high-risk sexual behaviour. The most effective preventive measure to curb this outbreak is HAV vaccination of MSM, supplemented by primary prevention campaigns that target the MSM population and promote protective sexual behaviour.

Emergency Meningococcal ACWY Vaccination Program for Teenagers to Control Group W Meningococcal Disease, England, 2015-2016.

During the first 12 months of an emergency meningococcal ACWY vaccination program for teenagers in England, coverage among persons who left school in 2015, the first cohort to be vaccinated, was 36.6%. There were 69% fewer group W meningococcal cases than predicted by trend analysis and no cases in vaccinated teenagers.