Changes in vaccination administration in Japan.

This paper reviews the administration related to vaccination in Japan after the enactment of the Immunization Act in 1948, under which vaccination was implemented mandatory for the public. To enhance the effectiveness of vaccination activities, the government implemented group vaccination, which is convenient for vaccinating recipients all at once. In 1976, Japan established the relief system for health damage after vaccination. While some projects, such as the mass administration of live oral polio vaccine in 1961, achieved excellent results, incidents leading to health damage occurred, such as the diphtheria toxoid immunization incident (1948) and frequent occurrence of aseptic meningitis owing to the measles, mumps, and rubella vaccine (1989). In December 1992, the Tokyo High Court sentenced that the onset of health damage after vaccination could be attributed to the negligence of the national government. In the revision of the Immunization Act in 1994, the "mandatory vaccination" enforced until then was changed to "recommended vaccination." The Act was also changed to recommend "individual vaccination" in principle, which is performed after primary care physicians investigate the physical condition of individual recipients and carefully conduct preliminary examination. For approximately 20 years from the 1990s, a vaccine gap existed between Japan and other countries. From around 2010, efforts have been made to bridge this gap and establish the global standard in vaccination.

Assessing the relationship between operationally defined zero-dose communities and access to selected primary healthcare services for children and pregnant women in emergency settings.

In this study the authors examine the relationship between "zero-dose" communities and access to healthcare services. This was done by first ensuring the first dose of the Diphtheria Tetanus and Pertussis vaccine was a better measure of zero-dose communities than the measles-containing vaccine. Once ensured, it was used to examine the association with access to primary healthcare services for children and pregnant women in the Democratic Republic of Congo, Afghanistan, and Bangladesh. These services were divided into: a) unscheduled healthcare services such as birth assistance as well as seeking care and treatment for diarrheal diseases and cough/fever episodes and b) other scheduled health services such as antenatal care visits and vitamin A supplementation. Using recent Demographic Health Survey data (2014: Democratic Republic of Congo, 2015: Afghanistan, 2018: Bangladesh), data was analyzed via Chi Squared analysis or Fischer's Exact Test. If significant, a linear regression analysis was performed to examine if the association was linear. While the linear relationship observed between children who had received the first dose of the Diphtheria Tetanus and Pertussis vaccine (the reverse to zero-dose communities) and coverage of other vaccines was expected, the results of the regression analysis depicted an unexpected split in behavior. For scheduled and birth assistance health services, a linear relationship was generally observed. For unscheduled services associated with illness treatments, this was not the case. While it does not appear that the first dose of the Diphtheria Tetanus and Pertussis vaccine can be used to predict (at least in a linear manner) access to some primary (particularly illness treatment) healthcare services in emergency/ humanitarian settings, it can serve as an indirect measure of health services not associated with the treatment of childhood infections such as antenatal care, skilled birth assistance, and to a lesser degree even vitamin A supplementation.

[Quality analysis of a combined domestic vaccine for the prevention of measles, rubella and mumps].

INTRODUCTION: The need to maintain a high level of vaccination coverage against measles, rubella and mumps in conditions of an increased risk of outbreaks of infections due to violations of vaccination tactics associated with the pandemic of coronavirus infection and due to the unfavorable epidemic situation in neighboring countries determines the advisability of using a combined vaccine for the simultaneous prevention of these three socially significant infections. THE AIM OF THE STUDY: to analyze the quality of commercial series of a new domestic combined cultured live vaccine against measles, rubella and mumps (MRM) throughout the entire time of its manufacturing according to all specification indicators in regulatory documentation (RD). MATERIALS AND METHODS: The object of the study was the combined cultured live vaccine against measles, rubella and mumps. The analysis of the quality of the drug was carried out according to 86 consolidated production protocols of manufactured series, as well as according to the results of control of these series in the Testing Center for Quality Expertise of the Federal State Budgetary Institution NCESMP of the Ministry of Health of the Russian Federation. RESULTS: It is shown that the quality of the combined drug for the prevention of measles, rubella and mumps corresponds to the RD in all studied indicators. The drug does not contain an antibiotic. Bovine serum albumin, which is a technological impurity, is detected in quantities more than 5 times lower than the established norm. A comparison of the specific activity of the viral components of new combined domestic vaccine and the components of the bivalent vaccine against measles and mumps produced by the company in 20192021 showed that the spread of the activity values of the viral components in the new drug and in the series of mumps-measles vaccine was minimal, which allowed us to make a conclusion about the stability of the production technology. CONCLUSION: The quality of the new domestic combined vaccine for the prevention of measles, rubella and mumps meets WHO requirements. The results of the conducted studies indicate the stability of production and the standard quality of the drug. The use of a combined vaccine against three significant infections will ensure the necessary level of vaccination coverage in the population. Information about the results of studies can help reduce the number of vaccination refusal.

Recombinant measles virus encoding the spike protein of SARS-CoV-2 efficiently induces Th1 responses and neutralizing antibodies that block SARS-CoV-2 variants.

Owing to the rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants, the development of effective and safe vaccines has become a priority. The measles virus (MeV) vaccine is an attractive vaccine platform as it has been administered to children for more than 40 years in over 100 countries. In this study, we developed a recombinant MeV expressing the full-length SARS-CoV-2 spike protein (rMeV-S) and tested its efficacy using mouse and hamster models. In hCD46Tg mice, two-dose rMeV-S vaccination induced higher Th1 secretion and humoral responses than one-dose vaccination. Interestingly, neutralizing antibodies induced by one-dose and two-dose rMeV-S immunization effectively blocked the entry of the α, ß, γ, and δ variants of SARS-CoV-2. Furthermore, two-dose rMeV-S immunization provided complete protection against SARS-CoV-2 in the hamster model. These results suggest the potential of rMeV-S as a vaccine candidate for targeting SARS-CoV-2 and its variants.

Amid Ohio Measles Outbreak, New Global Report Warns of Decreased Vaccination During COVID-19 Pandemic.

This Medical News article discusses an annual report on measles from the World Health Organization and the US Centers for Disease Control and Prevention.

Decline in reported measles cases in Italy in the COVID-19 era, January 2020 - July 2022: The need to prevent a resurgence upon lifting non-pharmaceutical pandemic measures.

From January 2020 to July 2022, 120 measles cases were reported to the Italian national surveillance system, of which 105 had symptom onset in 2020, nine in 2021 and six in the first seven months of 2022. This represents a sharp decline compared to the time period immediately preceding the COVID-19 pandemic, most likely due to the non-pharmaceutical interventions implemented to prevent SARS-CoV2 transmission. Of 105 cases reported in 2020, 103 acquired the infection before a national lockdown was instituted on 9 March 2020. Overall, one quarter of cases reported at least one complication. As non-pharmaceutical pandemic measures are being eased worldwide, and considering measles seasonality, infectiousness, and its potential severity, it is important that countries ensure high vaccination coverage and close immunity gaps, to avoid risk of future outbreaks.

Added value of the measles-rubella supplementary immunization activity in reaching unvaccinated and under-vaccinated children, a cross-sectional study in five Indian districts, 2018-20.

INTRODUCTION: Supplementary immunization activities (SIAs) aim to interrupt measles transmission by reaching susceptible children, including children who have not received the recommended two routine doses of MCV before the SIA. However, both strategies may miss the same children if vaccine doses are highly correlated. How well SIAs reach children missed by routine immunization is a key metric in assessing the added value of SIAs. METHODS: Children aged 9 months to younger than 5 years were enrolled in cross-sectional household serosurveys conducted in five districts in India following the 2017-2019 measles-rubella (MR) SIA. History of measles containing vaccine (MCV) through routine services or SIA was obtained from documents and verbal recall. Receipt of a first or second MCV dose during the SIA was categorized as "added value" of the SIA in reaching un- and under-vaccinated children. RESULTS: A total of 1,675 children were enrolled in these post-SIA surveys. The percentage of children receiving a 1st or 2nd dose through the SIA ranged from 12.8% in Thiruvananthapuram District to 48.6% in Dibrugarh District. Although the number of zero-dose children prior to the SIA was small in most sites, the proportion reached by the SIA ranged from 45.8% in Thiruvananthapuram District to 94.9% in Dibrugarh District. Fewer than 7% of children remained measles zero-dose after the MR SIA (range: 1.1-6.4%) compared to up to 28% before the SIA (range: 7.3-28.1%). DISCUSSION: We demonstrated the MR SIA provided considerable added value in terms of measles vaccination coverage, although there was variability across districts due to differences in routine and SIA coverage, and which children were reached by the SIA. Metrics evaluating the added value of an SIA can help to inform the design of vaccination strategies to better reach zero-dose or undervaccinated children.

Implications of COVID-19 and "super floods" for routine vaccination in Pakistan: The reemergence of vaccine preventable-diseases such as polio and measles.

With multiple waves and variants, the coronavirus disease 2019 (COVID-19) pandemic has affected routine vaccination programs globally. Its impact is also visible in Pakistan as routine health services continue to be disrupted. Consequently, thousands of children have emerged as vulnerable in the face of vaccine-preventable diseases (VPDs), which have already started causing outbreaks in the country. Infections with polio and measles have been significantly reported, especially during the last few years. This reemergence of both diseases is posing great challenges for the country at local, national, and global levels. These impacts are being multiplied by the 2022 flooding - called "super floods" - in the country. Hence, relevant stakeholders, such as the Pakistani government and the World Health Organization (WHO), need to revisit the entire vaccination program to address and resolve issues occurring at the management or local levels. It is highly important to pay attention to the context that provides a fertile ground to negatively affect vaccine uptake.

Progress Toward Regional Measles Elimination - Worldwide, 2000-2021.

All six World Health Organization (WHO) regions have committed to eliminating measles.* The Immunization Agenda 2021-2030 (IA2030)† aims to achieve the regional targets as a core indicator of impact and positions measles as the tracer of a health system's ability to deliver essential childhood vaccines. IA2030 highlights the importance of ensuring rigorous measles surveillance systems to document immunity gaps and achieve 95% coverage with 2 timely doses of measles-containing vaccine (MCV) among children. This report describes progress toward measles elimination during 2000-2021 and updates a previous report (1). During 2000-2021, estimated global coverage with a first MCV dose (MCV1) increased from 72% to a peak of 86% in 2019, but decreased during the COVID-19 pandemic to 83% in 2020 and to 81% in 2021, the lowest MCV1 coverage recorded since 2008. All countries conducted measles surveillance, but only 47 (35%) of 135 countries reporting discarded cases§ achieved the sensitivity indicator target of two or more discarded cases per 100,000 population in 2021, indicating surveillance system underperformance in certain countries. Annual reported measles incidence decreased 88% during 2000-2016, from 145 to 18 cases per 1 million population, then rebounded to 120 in 2019 during a global resurgence (2), before declining to 21 in 2020 and to 17 in 2021. Large and disruptive outbreaks were reported in 22 countries. During 2000-2021, the annual number of estimated measles deaths decreased 83%, from 761,000 to 128,000; an estimated 56 million measles deaths were averted by vaccination. To regain progress and achieve regional measles elimination targets during and after the COVID-19 pandemic, accelerating targeted efforts is necessary to reach all children with 2 MCV doses while implementing robust surveillance and identifying and closing immunity gaps to prevent cases and outbreaks.

Association between the side effect induced by COVID-19 vaccines and the immune regulatory gene polymorphism.

People often worry about the side effects after vaccination, reducing the willingness to vaccinate. Thus, we tried to find out the risk of single nucleotide polymorphism (SNP) vaccines to improve the willingness and confidence in vaccination. Allergic and inflammatory reactions are the common vaccine side effects caused by immune system overreaction. In addition, a previous study showed significantly higher frequency of febrile reactions to measles vaccines in American Indians than in Caucasian children, indicating that the side effects varied in accordance with genetic polymorphisms in individuals. Thus, SNPs of immune regulatory genes, cytotoxic T-lymphocyte-associated protein 4 (CTLA4), CD28, tumor necrosis factor ligand superfamily member 4 (TNFSF4) and programmed cell death protein 1 (PDCD1) were included in this study to analyze their association with vaccine side effects. Moreover, 61 healthy participants were asked on the number of doses they received, the brand of the vaccine, and the side effects they suffered. We found that several SNPs were associated with side effects after the first or second dose of mRNA or adenoviral vector vaccines. Furthermore, these SNPs were associated with several autoimmune diseases and cancer types; thus, they played an important role in immune regulation. Moreover, rs3181096 and rs3181098 of CD28, rs733618 and rs3087243 of CTLA, and rs1234314 of TNFSF4 were associated with mild vaccine side effects induced by mRNA and adenoviral vector vaccines, which would play a potential role in vaccine-induced immune responses and may further lead to fatal side effects. These results could serve as a basis for investigating the mechanism of vaccine side effects. Furthermore, it was hoped that these results would address public concerns about the side effects of the COVID-19 vaccination. In clinical application, a rapid screening test can be performed to assess the risk of vaccine side effects before vaccination and provide immediate treatment.

Can high COVID-19 vaccination rates in adults help protect unvaccinated children? Evidence from a unique mass vaccination campaign, Schwaz/Austria, March 2021.

BackgroundAfter an outbreak of the SARS-CoV-2 Beta variant in the district of Schwaz/Austria, vaccination with Comirnaty vaccine (BNT162b2 mRNA, BioNTech-Pfizer) had been offered to all adult inhabitants (≥ 16 years) in March 2021. This made Schwaz one of the most vaccinated regions in Europe at that time (70% of the adult population took up the offer). In contrast, all other Austrian districts remained with low vaccine coverage.AimWe studied whether this rapid mass vaccination campaign provided indirect protection to unvaccinated individuals such as children (< 16 years) living in the same district.MethodsTo study the effect of the campaign we used two complementary approaches. We compared infection rates among the population of children (< 16 years) in Schwaz with (i) the child population from similar districts (using the synthetic control method), and (ii) with the child population from municipalities along the border of Schwaz not included in the campaign (using an event study approach).ResultsBefore the campaign, we observed very similar infection spread across the cohort of children in Schwaz and the control regions. After the campaign, we found a significant reduction of new cases among children of -64.5% (95%-CI: -82.0 to -30.2%) relative to adjacent border municipalities (using the event study model). Employing the synthetic control method, we observed a significant reduction of -42.8% in the same cohort.ConclusionOur results constitute novel evidence of an indirect protection effect from a group of vaccinated individuals to an unvaccinated group.

Routine Vaccination Coverage - Worldwide, 2021.

In 2020, the World Health Assembly endorsed the Immunization Agenda 2030, an ambitious global immunization strategy to reduce morbidity and mortality from vaccine-preventable diseases (1). This report updates a 2020 report (2) with global, regional,* and national vaccination coverage estimates and trends through 2021. Global estimates of coverage with 3 doses of diphtheria-tetanus-pertussis-containing vaccine (DTPcv3) decreased from an average of 86% during 2015-2019 to 83% in 2020 and 81% in 2021. Worldwide in 2021, 25.0 million infants (19% of the target population) were not vaccinated with DTPcv3, 2.1 million more than in 2020 and 5.9 million more than in 2019. In 2021, the number of infants who did not receive any DTPcv dose by age 12 months (18.2 million) was 37% higher than in 2019 (13.3 million). Coverage with the first dose of measles-containing vaccine (MCV1) decreased from an average of 85% during 2015-2019 to 84% in 2020 and 81% in 2021. These are the lowest coverage levels for DTPcv3 and MCV1 since 2008. ​Global coverage estimates were also lower in 2021 than in 2020 and 2019 for bacillus Calmette-Guérin vaccine (BCG) as well as for the completed series of Haemophilus influenzae type b vaccine (Hib), hepatitis B vaccine (HepB), polio vaccine (Pol), and rubella-containing vaccine (RCV). The COVID-19 pandemic has resulted in disruptions to routine immunization services worldwide. Full recovery to immunization programs will require context-specific strategies to address immunization gaps by catching up missed children, prioritizing essential health services, and strengthening immunization programs to prevent outbreaks (3).

The impact of the COVID-19 pandemic on vaccine coverage in Kilifi, Kenya: A retrospective cohort study.

The COVID-19 pandemic caused unprecedented disruption in health service delivery, globally. This study sought to provide evidence on the impact of the pandemic on vaccine coverage in Kilifi County, Kenya. We conducted a vaccine coverage survey between April and June 2021 within the Kilifi Health and Demographic Surveillance System (KHDSS). Simple random sampling was used to identify 1500 children aged 6 weeks-59 months. Participants were grouped into three retrospective cohorts based on when they became age-eligible for vaccination: before the pandemic, during the first year, or during the second year of the pandemic. Survival analysis with Cox regression was used to evaluate the association between the time-period at which participants became age-eligible for vaccination and the rate of vaccination within a month of age-eligibility for the third dose of pentavalent vaccine (Pentavalent-3) and within three months of age-eligibility for the first dose of Measles vaccine (MCV-1). A total of 1,341 participants were included in the survey. Compared to the pre-COVID-19 baseline period, the rate of vaccination within a month of age-eligibility for Pentavalent-3 was not significantly different in the first year of the pandemic (adjusted hazard ratio [aHR] 1.03, 95 % confidence interval [CI] 0.90-1.18) and was significantly higher during the second year of the pandemic (aHR 1.33, 95 % CI 1.07-1.65). The rate of vaccination with MCV-1 within three months of age-eligibility was not significantly different among those age-eligible for vaccination during the first year of the pandemic (aHR 1.04, 95 % CI 0.88-1.21) and was 35 % higher during the second year of the pandemic (95 % CI 1.11-1.64), compared to those age-eligible pre-COVID-19. After adjusting for known determinants of vaccination, the COVID-19 pandemic did not adversely affect the rate of vaccination within the KHDSS.

Correlating IgG Levels with Neutralising Antibody Levels to Indicate Clinical Protection in Healthcare Workers at Risk during a Measles Outbreak.

The rapid transmission of measles poses a great challenge for measles elimination. Thus, rapid testing is required to screen the health status in the population during measles outbreaks. A pseudotype-based virus neutralisation assay was used to measure neutralising antibody titres in serum samples collected from healthcare workers in Sheffield during the measles outbreak in 2016. Vesicular stomatitis virus (VSV) pseudotypes bearing the haemagglutinin and fusion glycoproteins of measles virus (MeV) and carrying a luciferase marker gene were prepared; the neutralising antibody titre was defined as the dilution resulting in 90% reduction in luciferase activity. Spearman's correlation coefficients between IgG titres and neutralising antibody levels ranged from 0.40 to 0.55 (p < 0.05) or from 0.71 to 0.79 (p < 0.0001) when the IgG titres were obtained using different testing kits. In addition, the currently used vaccine was observed to cross-neutralise most circulating MeV genotypes. However, the percentage of individuals being "well-protected" was lower than 95%, the target rate of vaccination coverage to eliminate measles. These results demonstrate that the level of clinical protection against measles in individuals could be inferred by IgG titre, as long as a precise correlation has been established between IgG testing and neutralisation assay; moreover, maintaining a high vaccination coverage rate is still necessary for measles elimination.

Measles incidence in South Africa: a six-year review, 2015-2020.

In 2012 the World Health Organization (WHO) aimed to eliminate measles in five regions by 2020. This retrospective descriptive study reviewed measles surveillance data in South Africa for the period 2015-2020 to document the epidemiology of measles and the progress made towards meeting the 2020 measles elimination goal.A total of 22,578 specimens were tested over the period 2015-2020 yielding 401 (1.8%) confirmed measles cases, 321 (1.4%) compatible and 21,856 (96.8%) discarded cases. The most affected age group was 0-4 year olds. At the provincial level, South Africa achieved adequate surveillance, defined as more than two cases of febrile rash notified annually per 100 000 popoulation, except for KwaZulu-Natal and Limpopo in 2020, probably due to COVID-19 lockdown restrictions. Of confirmed cases, only 26% were vaccinated, 3% were too young to receive vaccines, 5% were not vaccinated, and 65% had unknown vaccination status. Measles vaccine effectiveness amongst 1-4 year olds was 80%. Using the standard case definition, South Africa achieved the measles elimination target of less than one case per one million nationally in years 2015, 2016 and 2020. The years 2017 to 2019 had incidence rates exceeding one per million nationally. Using a narrow case definition, that excluded positive rubella cases, improved the indicators with only the year 2017 having an incidence rate of more than one per million.South Africa displays intermittent measles outbreaks approximately six-yearly interspersed by inter-epidemic periods in which the country meets measles elimination targets. Intense effort is needed to increase the vaccine coverage to avoid periodic outbreaks. Enhanced molecular testing of each case will be required as measles incidence declines regionally.

Creation of a Global Vaccine Risk Index.

The World Health Organization has identified vaccine hesitancy as one of its top ten global health threats for 2019. Efforts are underway to define the factors responsible for reductions in vaccine confidence. However, as global measles cases accelerated beginning in 2018, it became evident that additional factors were promoting measles re-emergence, including war, political and socio-economic collapse, shifting poverty, and vulnerability to weather events and climate change. Accordingly, we propose a Global Vaccine Risk Index (VRI) to consider these variables as a more comprehensive means to identify vulnerable nations where we might expect measles and other vaccine-preventable diseases to emerge or re-emerge. In Sub-Saharan African and Middle Eastern nations, conflict and political instability predominated as the basis for high vaccine risk scores, whereas in Southeast Asian countries, the major reasons included climate variability, current levels of measles vaccination coverage, and economic and educational disparities. In Europe, low vaccine confidence and refugee movements predominated, while in the Americas, economic disparities and vaccine confidence were important. The VRI may serve as a useful indicator and predictor for international agencies committed to childhood immunizations and might find relevance for accelerating future COVID19 vaccination programs.