OBJECTIVE: To assess the relationship between the Childhood Opportunity Index (COI), a comprehensive measurement of social determinants of health (SDOH), and specific COI domains on patient-specific outcomes following congenital cardiac surgery in the metropolitan region of Atlanta, Georgia. STUDY DESIGN: In this retrospective chart review, we included patients who underwent an index operation for congenital heart disease (CHD) between 2010 and 2020 in a single pediatric health care system. Patients' addresses were geocoded and mapped to census tracts. Descriptive statistics, univariable analysis, and multivariable regression models were employed to assess associations between variables and outcomes. RESULTS: Of the 7460 index surgeries, 3798 (51%) met eligibility criteria. Presence of an adverse outcome, defined as either mortality or one of several other major post-operative morbidities, was significantly associated with COI in the univariable model (p=0.008), but not the multivariable regression model (p=0.39). Postoperative hospital length of stay (PHLOS) was significantly associated with COI (p<0.001) in univariable and multivariable regression models. There was no significant association between COI and readmission within 30 days of hospital discharge in univariable (p<0.094) and multivariable (p=0.49) models. CONCLUSION: COI is associated with PHLOS but not all outcomes in patients after congenital heart surgery. By understanding the role of COI in outcomes related to cardiac surgery, targeted interventions can be developed to improve health equity.

Cases of disease in fully vaccinated persons, referred to as vaccine breakthrough cases, may weaken public confidence in vaccines. Breakthrough cases are expected even with highly effective vaccines. As vaccination coverage increases, breakthrough cases will account for increasing proportions of all cases. In 1985, Orenstein and colleagues proposed the use of a simple, rapid screening method for field investigations of measles outbreaks.1 Applicable to other vaccine-preventable diseases, the screening method was designed to rapidly determine whether vaccines are performing as expected and whether further investigation is warranted. With effective vaccines, the proportion of cases among vaccinated individuals will be lower than the proportion of the general population that is vaccinated.

Is it feasible to eradicate measles and rubella globally? In response to a request from the 70th World Health Assembly in 2017, a group of experts concluded in 2020 that global eradication was technically feasible with sustained high coverage of two doses of measles- and rubella-containing vaccine, but the more realistic course was to accelerate regional progress towards measles and rubella elimination.1 Advances have been hard-fought and occasionally reversed in the six WHO regions that have established measles elimination goals and the four regions with rubella elimination goals. Measles and rubella have been verified as eliminated in 81 and 93 countries, respectively, as of 2020.2, 3

BACKGROUND: We conducted a systematic review to assess whether measles humoral immunity wanes in previously infected or vaccinated populations in measles elimination settings. METHODS: After screening 16,822 citations, we identified nine articles from populations exposed to wild-type measles and 16 articles from vaccinated populations that met our inclusion criteria. RESULTS: Using linear regression, we found that geometric mean titers (GMTs) decreased significantly in individuals who received two doses of measles-containing vaccine (MCV) by 121.8 mIU/mL (95% CI -212.4, -31.1) per year since vaccination over one to five years, 53.7 mIU/mL (95% CI -95.3, -12.2) five to ten years, 33.2 mIU/mL (95% CI -62.6, -3.9) ten to 15 years, and 24.1 mIU/mL (95% CI -51.5,3.3) 15 to 20 years since vaccination. Decreases in GMT over time were not significant after one dose of MCV or after infection. Decreases in the proportion of seropositive individuals over time were not significant after one or two doses of MCV, or after infection. CONCLUSIONS: Measles antibody waning in vaccinated populations should be considered in planning for measles elimination.

PURPOSE: To examine the association between state laws protecting lesbian, gay, bisexual, transgender, and queer/questioning (LGBTQ) students and school districts' recommendations or requirements for establishing gay-straight alliances (GSAs) in schools. Beginning in fall 2013, 19 state education agencies (SEAs) engaged in HIV/STI and pregnancy prevention activities in "priority" school districts. SEAs provided support to priority districts to require or recommend GSAs in their schools. METHODS: This study used semi-annually collected program evaluation data and state law data from the Gay, Lesbian, and Straight Education Network. We assessed whether increases in the percentage of priority districts recommending or requiring schools to provide GSAs varied by the presence of nondiscrimination or enumerated antibullying laws with a difference-in-difference design. RESULTS: States with nondiscrimination laws began with more priority districts recommending or requiring schools to provide GSAs (52.5%) compared to states without laws (47.5%). We found a significant interaction (p < .01) between increases in the percentage of priority districts recommending or requiring a GSA and having a state nondiscrimination law. Across the first 3 years of program implementation, there was a 30% increase (p < .01) in priority districts recommending or requiring schools to provide GSAs in states with nondiscrimination laws, compared to a 12% increase (p < .01) in states without laws. There was no significant interaction between states with enumerated antibullying laws and districts recommending or requiring a GSA. DISCUSSION: State LGBTQ nondiscrimination laws for students may facilitate school district support of GSAs, which may decrease health risks among LGBTQ youth.

The global measles vaccination program has been extraordinarily successful in reducing measles-related disease and deaths worldwide. Eradication of measles is feasible because of several key attributes, including humans as the only reservoir for the virus, broad access to diagnostic tools that can rapidly detect measles-infectious persons, and availability of highly safe and effective measles-containing vaccines (MCVs). All 6 World Health Organization (WHO) regions have established measles elimination goals. Globally, during 2000-2018, measles incidence decreased by 66% (from 145 to 49 cases per million population) and deaths decreased by 73% (from 535 600 to 142 300), drastically reducing global disease burden. Routine immunization with MCV has been the cornerstone for the control and prevention of measles. Two doses of MCV are 97% effective in preventing measles, qualifying MCV as one of the most effective vaccines ever developed. Mild adverse events occur in <20% of recipients and serious adverse events are extremely rare. The economic benefits of measles vaccination are highlighted by an overall return on investment of 58 times the cost of the vaccine, supply chains, and vaccination. Because measles is one of the most contagious human diseases, maintenance of high (≥95%) 2-dose MCV coverage is crucial for controlling the spread of measles and successfully reaching measles elimination; however, the plateauing of global MCV coverage for nearly a decade and the global measles resurgence during 2018-2019 demonstrate that much work remains. Global commitments to increase community access to and demand for immunizations, strengthen national and regional partnerships for building public health infrastructure, and implement innovations that can overcome access barriers and enhance vaccine confidence, are essential to achieve a world free of measles.

Phase 3 randomized-controlled trials have provided promising results of COVID-19 vaccine efficacy, ranging from 50 to 95% against symptomatic disease as the primary endpoints, resulting in emergency use authorization/listing for several vaccines. However, given the short duration of follow-up during the clinical trials, strict eligibility criteria, emerging variants of concern, and the changing epidemiology of the pandemic, many questions still remain unanswered regarding vaccine performance. Post-introduction vaccine effectiveness evaluations can help us to understand the vaccine's effect on reducing infection and disease when used in real-world conditions. They can also address important questions that were either not studied or were incompletely studied in the trials and that will inform evolving vaccine policy, including assessment of the duration of effectiveness; effectiveness in key subpopulations, such as the very old or immunocompromised; against severe disease and death due to COVID-19; against emerging SARS-CoV-2 variants of concern; and with different vaccination schedules, such as number of doses and varying dosing intervals. WHO convened an expert panel to develop interim best practice guidance for COVID-19 vaccine effectiveness evaluations. We present a summary of the interim guidance, including discussion of different study designs, priority outcomes to evaluate, potential biases, existing surveillance platforms that can be used, and recommendations for reporting results.

Global gains in vaccination coverage during the early 21st century have been threatened by the emergence of antivaccination groups that have questioned the effectiveness of vaccines to generate public distrust of vaccines and immunisation programmes. This manuscript summarises six key topics that have been at the centre of global discussions on vaccine safety during the early 21st century: thiomersal in multi-dose non-live vaccines, aluminium adjuvants used with several non-live vaccines, autism and auto-immune conditions as possible consequences of vaccination, a risk of immune overload with increasing numbers of vaccinations, and detrimental non-specific effects (NSEs) of vaccination. For each topic, we describe the hypothesis behind the public concern, the evidence reviewed by the WHO's Global Advisory Committee for Vaccine Safety (GACVS) during 1999-2019, and any significant new data that has emerged since GACVS conclusions were made. Although the scientific evidence on these issues overwhelmingly supports the safety of vaccines, communication messages to caregivers and providers need to condense and convey scientific information in an appropriate way to address concerns contributing to vaccine distrust. In addition, there is need for further studies specifically designed to address both positive and negative NSE of vaccination. The role of GACVS will be increasingly important in evaluating the evidence and engaging the global community in promoting and assuring the safety of vaccines in the decades to come as we move into an era in which we use new vaccination platforms, antigens and formulations.

While morbidity and mortality associated with measles and rubella (MR) have dramatically decreased, there are still >100000 estimated deaths due to measles and an estimated 100000 infants born with congenital rubella syndrome annually. Given highly effective MR vaccines, the primary barrier to global elimination of these diseases is low vaccination coverage, especially among the most underserved populations in resource-limited settings. In contrast to conventional MR vaccination by hypodermic injection, microneedle patches are being developed to enable MR vaccination by minimally trained personnel. Simplified supply chain, reduced need for cold chain storage, elimination of vaccine reconstitution, no sharps waste, reduced vaccine wastage, and reduced total system cost of vaccination are advantages of this approach. Preclinical work to develop a MR vaccine patch has proceeded through successful immunization studies in rodents and non-human primates. On-going programs seek to make MR vaccine patches available to support MR elimination efforts around the world.

The licensure and recommendation processes for vaccines are complex. In the United States, vaccines are licensed for the civilian and military populations on the basis of review of Biologics License Applications submitted to the Food and Drug Administration (FDA) by vaccine manufacturers. For FDA-licensed vaccines, the product label includes indications, contraindications, and precautions for each vaccine. Package inserts do not include recommendations for vaccine use from the Advisory Committee on Immunization Practices (ACIP). The ACIP is chartered as a federal advisory committee to provide expert external advice and guidance to the director of the Centers for Disease Control and Prevention on the use of vaccines and related agents for control of vaccine preventable diseases in the civilian and military populations of the United States. As an external advisory committee to the Centers for Disease Control and Prevention, the ACIP has no regulatory authority but the committee does have responsibility for approving vaccines to be covered under the Vaccines for Children program. To implement ACIP vaccine recommendations in the public and private sectors, a collaboration of federal, state, and local governments as well as private organizations dealing with public health, vaccine supply, vaccine administration, vaccine finance, outcomes monitoring, public perception, and public trust and support must work together. Issues including vaccine misinformation, declining community immunity (herd protection), and need for risk communication add stress to this complex and fragile system. This study describes the functions of and interactions between FDA and ACIP.

BACKGROUND: Many studies assume that the serologic correlate of protection from measles disease is 120 mIU/mL. We systematically reviewed the literature to examine the evidence supporting this correlate of protection. METHODS: We searched peer-reviewed and gray literature for articles reporting a measles correlate of protection. We excluded studies focusing on special populations, infants aged <9 months, and those using animal models or nonstandard vaccines or administration routes. We extracted and synthesized data from full-text articles that met inclusion criteria. RESULTS: We screened 14 778 articles and included 5 studies in our review. The studies reported either preexposure antibody concentrations of individuals along with a description of symptoms postexposure, or the proportion of measles cases that had preexposure antibody concentrations above a threshold of immunity specified by the authors. Some studies also described secondary antibody responses upon exposure. The variation in laboratory methods between studies made comparisons difficult. Some of the studies that assumed 120 mIU/mL as a correlate of protection identified symptomatic individuals with preexposure titers exceeding this threshold. CONCLUSIONS: Our findings underscore the scant data upon which the commonly used 120 mIU/mL measles threshold of protection is based, suggesting that further work is required to characterize the measles immunity threshold.

INTRODUCTION: Limited evidence is available about the effectiveness of strategies to remind caregivers when to bring children back for future vaccinations in low- and middle-income country settings. We evaluated the effectiveness of two reminder strategies based on home-based vaccination records (HBR) in Indonesia. METHODS: In this cluster-randomized controlled trial involving 3616 children <1year of age, 90 health facilities were randomly assigned to either a control group or one of two intervention groups: (1) HBR-only group, where healthcare workers provided an HBR to any child without an HBR during a vaccination visit and instructed the caregiver to keep it at home between visits, or (2) HBR+sticker group, where, in addition to HBR provision, healthcare workers placed vaccination appointment reminder stickers on the HBR. The primary outcome was receipt of the third dose of diphtheria-tetanus-pertussis-containing vaccine (DTPcv3) within 7months and the secondary outcome was receipt of a timely DTPcv3 dose. RESULTS: Control group DTPcv3 coverage was 81%. In intention-to-treat analysis, neither intervention group had significantly different DTPcv3 coverage compared with the control group (RR=0.94, 95% confidence interval [CI] 0.87; 1.02 for HBR-only group; RR=0.97, 95% CI 0.90; 1.04 for HBR+sticker group) by study end. However, children in the HBR+sticker group were 50% more likely to have received a DTPcv3 vaccination (RR=1.46, 95% CI 1.02, 2.09) within 60days of DTPcv1 vaccination, compared with children in the control group; children in the HBR-only group were not more likely to have done so (RR=1.05, 95% CI 0.71, 1.55). DISCUSSION: Reminder stickers had an immediate effect on coverage by improving the proportion of children who received a timely DTPcv3 dose but no effect on the proportion who received DTPcv3 after 7months. Coupling reminder stickers with strategies to address other reasons why children do not return for vaccination visits should be further explored.

In the past decade, multiple mumps outbreaks have occurred in the United States, primarily in close-contact, high-density settings such as colleges, with a high attack rate among young adults, many of whom had the recommended 2 doses of mumps-measles-rubella (MMR) vaccine. Waning humoral immunity and the circulation of divergent wild-type mumps strains have been proposed as contributing factors to mumps resurgence. Blood samples from 71 healthy 18- to 23-year-old college students living in a non-outbreak area were assayed for antibodies and memory B cells (MBCs) to mumps, measles, and rubella. Seroprevalence rates of mumps, measles, and rubella determined by IgG enzyme-linked immunosorbent assay (ELISA) were 93, 93, and 100%, respectively. The index standard ratio indicated that the concentration of IgG was significantly lower for mumps than rubella. High IgG avidity to mumps Enders strain was detected in sera of 59/71 participants who had sufficient IgG levels. The frequency of circulating mumps-specific MBCs was 5 to 10 times lower than measles and rubella, and 10% of the participants had no detectable MBCs to mumps. Geometric mean neutralizing antibody titers (GMTs) by plaque reduction neutralization to the predominant circulating wild-type mumps strain (genotype G) were 6-fold lower than the GMTs against the Jeryl Lynn vaccine strain (genotype A). The majority of the participants (80%) received their second MMR vaccine >/=10 years prior to study participation. Additional efforts are needed to fully characterize B and T cell immune responses to mumps vaccine and to develop strategies to improve the quality and durability of vaccine-induced immunity.

BACKGROUND: The pace of global progress must increase if the Global Vaccine Action Plan (GVAP) goals are to be achieved by 2020. We administered a two-phase survey to key immunization stakeholders to assess the utility and application of GVAP, including how it has impacted country immunization programs, and to find ways to strengthen the next 10-year plan. METHODS: For the Phase I survey, an online questionnaire was sent to global immunization stakeholders in summer 2017. The Phase II survey was sent to regional and national immunization stakeholders in summer 2018, including WHO Regional Advisors on Immunization, Expanded Programme on Immunization managers, and WHO and UNICEF country representatives from 20 countries. Countries were selected based on improvements (10) versus decreases (10) in DTP3 coverage from 2010 to 2016. RESULTS: Global immunization stakeholders (n=38) cite global progress in improving vaccine delivery (88%) and engaging civil society organizations as advocates for vaccines (83%). Among regional and national immunization stakeholders (n=58), 70% indicated reaching mobile and underserved populations with vaccination activities as a major challenge. The top ranked activities for helping country programs achieve progress toward GVAP goals include improved monitoring of vaccination coverage and upgrading disease surveillance systems. Most respondents (96%) indicated GVAP as useful for determining immunization priorities and 95% were supportive of a post-2020 GVAP strategy. CONCLUSIONS: Immunization stakeholders see GVAP as a useful tool, and there is cause for excitement as the global immunization community looks toward the next decade of vaccines. The next 10-year plan should attempt to increase political will, align immunization activities with other health system agendas, and address important issues like reaching mobile/migrant populations and improving data reporting systems.

INTRODUCTION: Public health focuses on a range of evidence-based approaches for addressing chronic conditions, from individual-level clinical interventions to broader changes in policies and environments that protect people's health and make healthy living easier. This study examined the potential long-term impact of clinical and community interventions as they were implemented by Community Transformation Grant (CTG) program awardees. METHODS: We used the Prevention Impacts Simulation Model, a system dynamics model of cardiovascular disease prevention, to simulate the potential 10-year and 25-year impact of clinical and community interventions implemented by 32 communities receiving a CTG program award, assuming that program interventions were sustained during these periods. RESULTS: Sustained clinical interventions implemented by CTG awardees could potentially avert more than 36,000 premature deaths and $3.2 billion in discounted direct medical costs (2017 US dollars) over 10 years and 109,000 premature deaths and $8.1 billion in discounted medical costs over 25 years. Sustained community interventions could avert more than 24,000 premature deaths and $3.4 billion in discounted direct medical costs over 10 years and 88,000 premature deaths and $9.1 billion in discounted direct medical costs over 25 years. CTG clinical activities had cost-effectiveness of $302,000 per death averted at the 10-year mark and $188,000 per death averted at the 25-year mark. Community interventions had cost-effectiveness of $169,000 and $57,000 per death averted at the 10- and 25-year marks, respectively. CONCLUSION: Clinical interventions have the potential to avert more premature deaths than community interventions. However, community interventions, if sustained over the long term, have better cost-effectiveness.

In 2010, the Centers for Disease Control and Prevention (CDC) funded communities to implement policy, systems, and environmental (PSE) changes under the Communities Putting Prevention to Work (CPPW) program to make it easier for people to make healthier choices to prevent chronic disease. Twenty-one of 50 funded communities implemented interventions intended to reduce tobacco use. To examine the potential cost-effectiveness of tobacco control changes implemented under CPPW from a healthcare system perspective, we compared program cost estimates with estimates of potential impacts. We used an existing simulation model, the Prevention Impacts Simulation Model (PRISM), to estimate the potential cumulative impact of CPPW tobacco interventions on deaths and medical costs averted through 2020. We collected data on the costs to implement CPPW tobacco interventions from 2010 to 2013. We adjusted all costs to 2010 dollars. CPPW tobacco interventions cost $130.5 million across all communities, with an average community cost of $6.2 million. We found $735 million in potentially averted medical costs cumulatively from 2010 through 2020 because of the CPPW-supported interventions. If the CPPW tobacco control PSE changes are sustained through 2020 without additional funding after 2013, we find that medical costs averted will likely exceed program costs by $604 million. Our results suggest that the medical costs averted through 2020 may more than offset the initial investment in CPPW tobacco control interventions, implying that such interventions may be cost saving, especially over the long term.

BACKGROUND: Parents' attitudes and beliefs in vaccination are important to understand for shaping vaccine acceptance and demand interventions. Little research has focused on developing a validated scale to measure parents' attitudes towards vaccinations in low and middle-income countries; Ghana provided an opportunity develop a caregiver vaccination attitudes scale (CVAS) validated against childhood vaccine compliance. METHODS: We conducted a cluster survey of 373 households with children aged 12-35months of age from Northern Region, Ghana. Caregivers responded to 22 vaccination behavior and belief survey items and provided the child's vaccination status. In exploratory factor analysis (EFA) to assess CVAS content validity, we used parallel analysis to guide the number of factors to extract and principal axis factor analysis for factor extraction. Reliability of the scale was assessed using McDonald's Omega coefficient. Criterion validity of scale and subscales was assessed against receipt of vaccinations by 12months of age and vaccination delay, using number of days undervaccinated. RESULTS: EFA of CVAS responses resulted in removing 11 of 22 survey items due to loadings <0.30 and development of a 5-factor structure with subscales for Vaccine-Preventable Disease (VPD) Awareness, Vaccine Benefits, Past Behavior, Vaccine Efficacy and Safety, and Trust. The 5 factors accounted for 69% of the common variance and omega coefficients were >0.73 for all subscales. Validity analysis indicated that for every unit increase in the parent's scale score, the odds of the child being vaccinated decreased by 0.58 (95% confidence interval [CI]: 0.37, 0.68) and the number of days under-vaccinated increased by 86 (95%CI: 28, 143). The final 3-factor scale included Vaccine Benefits, Past Behavior, and Vaccine Efficacy and Safety. DISCUSSION: The final CVAS included three factors associated with vaccine compliance in Ghana, although several survey items suggested for use in vaccine acceptance scales were dropped. Replicating this study in several country settings will provide additional evidence to assist in refining a tool for use in routine vaccine acceptance and demand surveillance efforts.

Background: As a risk-mitigation strategy to minimize paralytic polio following withdrawal of Sabin type 2 from the oral poliovirus vaccine in April 2016, a single full dose or 2 fractional doses of inactivated poliovirus vaccine (IPV) are recommended. However, limited knowledge exists on long-term persistence of immune memory following 1- or 2-dose IPV schedules. Methods: We examined induction and maintenance of immune memory following single- vs 2-dose IPV schedules, either full-dose intramuscular or fractional-dose intradermal, in rhesus macaques. Humoral responses, bone marrow-homing antibody-secreting plasma cells, and blood-circulating/lymph node-homing memory B cells were examined longitudinally. Results: A single dose of IPV, either full or fractional, induced binding antibodies and memory B cells in all vaccinated macaques, despite failing to induce neutralizing antibodies (NT Abs) in many of them. However, these memory B cells declined rapidly, reaching below detection in the systemic circulation by 5 months; although a low frequency of memory B cells was detectable in draining lymph nodes of some, but not all, animals. By contrast, a 2-dose vaccination schedule, either full or fractional, efficiently induced NT Abs in all animals along with bone marrow-homing plasma cells and memory B cells. These memory B cells persisted in the systemic circulation for up to 16 months, the maximum duration tested after the second dose of vaccination. Conclusions: Two doses of IPV, regardless of whether fractional or full, are more effective than a single dose for inducing long-lasting memory B cells.

Objectives The Advisory Committee on Immunization Practices (ACIP) and the American College of Obstetricians and Gynecologists (ACOG) recommend that pregnant women receive the Tdap vaccine during every pregnancy. The objectives of this paper are to evaluate disparities in Tdap vaccination among pregnant women in the U.S., and to assess whether race/ethnicity and other characteristics are associated with factors that inform pregnant women's decisions about Tdap vaccination. Methods We conducted a nationwide cross-sectional web-based survey of pregnant women in the U.S. during June-July 2014. The primary outcome was self-reported vaccination status with Tdap during pregnancy, categorized as vaccinated, unvaccinated with intent to be vaccinated during the current pregnancy, and unvaccinated with no intent to be vaccinated during the current pregnancy. Secondary outcomes included factors that influenced women's decisions about vaccination and information needs. We used multivariable logistic regression models to estimate odds ratios for associations between race/ethnicity and the outcomes. Results Among pregnant women who completed the survey, 41% (95% CI 36-45%) reported that they had received Tdap during the current pregnancy. Among those women in the third trimester at the time of survey, 52% (95% CI 43-60%) had received Tdap during the current pregnancy. Hispanic women had higher Tdap vaccination than white women and black women (53%, p < 0.05, compared with 38 and 36%, respectively). In logistic regression models adjusting for maternal age, geographic region, education, and income, Hispanic women were more likely to have been vaccinated with Tdap compared with white women (aOR 2.29, 95% CI 1.20-4.37). Higher income and residing in the western U.S. were also independently associated with Tdap vaccination during pregnancy. Twenty-six percent of surveyed women had not been vaccinated with Tdap yet but intended to receive the vaccine during the current pregnancy; this proportion did not differ significantly by race/ethnicity. The most common factor that influenced women to get vaccinated was a health care provider (HCP) recommendation. The most common reason for not getting vaccinated was a concern about safety of the vaccine. Conclusions This study found that some disparities exist in Tdap vaccination among pregnant women in the U.S., and HCPs have an important role in providing information and recommendations about the maternal Tdap recommendation to pregnant women so they can make informed vaccination decisions.

All World Health Organization (WHO) Regions have goals to interrupt endemic measles circulation on or before 2020. This is a worthy, feasible (already achieved in the Region of the Americas) but formidable challenge, given the unique contagiousness of the measles virus, which demands homogeneous population immunity over 92% in most settings. High population immunity is necessary to ensure that the effective reproduction number is driven below 1, a pre-requisite for achieving and sustaining elimination. | | To provide guidance for verifying measles elimination, the WHO has published a framework that details evidence across five domains required to substantiate an individual country’s or Region’s claim to have interrupted endemic measles virus transmission. These evidence domains are: (1) a careful description of measles epidemiology over an extended period; (2) indicators of the quality of epidemiological and laboratory surveillance; (3) laboratory evidence of the absence of an endemic or, following importation, a sustained transmission measles genotype; (4) confirmation of immunisation program sustainability; and (5) measures of robust population immunity by birth cohort [1]. The accurate determination of population immunity is constrained by the inadequate quality of routinely available administrative data in many settings i.e., recording of vaccine doses administered either during the routine immunisation programme or by supplementary immunisation activities (SIAs) as the numerator, while the denominator is estimated from census data after considering births, deaths, and migration. Although vaccine coverage data appears an efficient means for estimating immunity, the quality of coverage data and routinely reported measles case data is extraordinarily variable globally and this seriously compromises the construction of credible immunity profiles across all age groups, at different spatial scales, and in population sub-groups. Disproportionate delivery of vaccine often occurs during non-selective SIAs with individuals who are already immune from prior vaccination being more readily accessible to the health system. They are thus more commonly revaccinated than persons never previously vaccinated, and this further complicates coverage determination and, by extrapolation, immunity estimation. Use of incomplete or inaccurate surveillance data is a major hurdle to calculating population immunity derived from wild virus infection [2].

Limited data are available on the costs of evidence-based community-wide prevention programs. The objective of this study was to estimate the per-person costs of strategies that support policy, systems, and environmental changes implemented under the Community Transformation Grants (CTG) program. We collected cost data from 29 CTG awardees and estimated program costs as spending on labor; consultants; materials, travel, and services; overhead activities; partners; and the value of in-kind contributions. We estimated costs per person reached for 20 strategies. We assessed how per-person costs varied with the number of people reached. Data were collected in 2012-2015, and the analysis was conducted in 2015-2016. Two of the tobacco-free living strategies cost less than $1.20 per person and reached over 6 million people each. Four of the healthy eating strategies cost less than $1.00 per person, and one of them reached over 6.5 million people. One of the active living strategies cost $2.20 per person and reached over 7 million people. Three of the clinical and community preventive services strategies cost less than $2.30 per person, and one of them reached almost 2 million people. Across all 20 strategies combined, an increase of 10,000 people in the number of people reached was associated with a $0.22 reduction in the per-person cost. Results demonstrate that interventions, such as tobacco-free indoor policies, which have been shown to improve health outcomes have relatively low per-person costs and are able to reach a large number of people.

Lyerly et al refer to historical aspects of the rubella vaccination program as “a cautionary tale about caution” concerning Zika vaccine research.1 The US rubella vaccination program has been a tale of appropriate caution and a remarkable success in rubella and congenital rubella syndrome (CRS) elimination2. We concur with the authors' assertion that safety studies in pregnant women are important and could have overcome the initial reluctance to give rubella vaccine to women of childbearing age (WCBA). However, points within the article warrant comment.

INTRODUCTION: In 1988, an estimated 350,000 children were paralyzed by polio and 125 countries reported polio cases, the World Health Assembly passed a resolution to achieve polio eradication by 2000, and the Global Polio Eradication Initiative (GPEI) was established as a partnership focused on eradication. Today, following eradication efforts, polio cases have decreased >99% and eradication of all three types of wild polioviruses is approaching. However, since polio resources substantially support disease surveillance and other health programs, losing polio assets could reverse progress toward achieving Global Vaccine Action Plan goals. Areas covered: As the end of polio approaches and GPEI funds and capacity decrease, we document knowledge, experience, and lessons learned from 30 years of polio eradication. Expert commentary: Transitioning polio assets to measles and rubella (MR) elimination efforts would accelerate progress toward global vaccination coverage and equity. MR elimination feasibility and benefits have long been established. Focusing efforts on MR elimination after achieving polio eradication would make a permanent impact on reducing child mortality but should be done through a 'diagonal approach' of using measles disease transmission to identify areas possibly susceptible to other vaccine-preventable diseases and to strengthen the overall immunization and health systems to achieve disease-specific goals.

BACKGROUND: Vaccination requirements for kindergarten entry vary by state, but all states require 2 doses of measles containing vaccine (MCV) at kindergarten entry. OBJECTIVE: To assess (i) national MCV vaccination coverage for children who had attended kindergarten; (ii) the extent to which undervaccination after kindergarten entry is attributable to parents' requests for an exemption; (iii) the extent to which undervaccinated children had missed opportunities to be administered missing vaccine doses among children whose parent did not request an exemption; and (iv) the vaccination coverage gap between the "highest achievable" MCV coverage and actual MCV coverage among children who had attended kindergarten. METHODS: A national survey of 1465 parents of 5-7year-old children was conducted during October 2013 through March 2014. Vaccination coverage estimates are based provider-reported vaccination histories. Children have a "missed opportunity" for MCV if they were not up-to-date and if there were dates on which other vaccines were administered but not MCV. The "highest achievable" MCV vaccination coverage rate is 100% minus the sum of the percentages of (i) undervaccinated children with parents who requested an exemption; and (ii) undervaccinated children with parents who did not request an exemption and whose vaccination statuses were assessed during a kindergarten grace period or period when they were provisionally enrolled in kindergarten. RESULTS: Among all children undervaccinated for MCV, 2.7% were attributable to having a parent who requested an exemption. Among children who were undervaccinated for MCV and whose parent did not request an exemption, 41.6% had a missed opportunity for MCV. The highest achievable MCV coverage was 98.6%, actual MCV coverage was 90.9%, and the kindergarten vaccination gap was 7.7%. CONCLUSION: Vaccination coverage may be increased by schools fully implementing state kindergarten vaccination laws, and by providers assessing children's vaccination status at every clinic visit, and administering missed vaccine doses.

Macartney et al1 report in this issue of JAMA Pediatrics on the safety of using combination measles-mumps-rubella-varicella (MMRV) vaccine as the second dose of measles-mumps-rubella (MMR) vaccine and sole dose of varicella vaccine in Australia, and the effect of this policy on national vaccine coverage. They found that there was no increase in febrile seizures when MMRV is administered in the second year of life approximately 6 months after a first dose of MMR and that on-time vaccination increased with use of MMRV. Are these findings an indication that the timing and use of combination MMRV vaccine should be reconsidered for the United States? | In the United States, since measles vaccine was first recommended in 1963, the measles vaccination schedule changed as knowledge of measles immunity increased and the epidemiology of measles evolved. An analysis of measles outbreaks occurring from 1985 to 1986 showed that outbreaks in which preschoolers predominated were largely related to failure to receive any doses of vaccine. In contrast, in outbreaks that affected primarily school-aged children, the major problem was 1-dose vaccine failure.2,3 In 1989, because of measles outbreaks among school-aged children, the US Advisory Committee on Immunization Practices (ACIP) recommended 2 doses, with the first dose at age 15 months and the second dose at age 4 through 6 years, before school entry. Because of the success of the measles vaccination program in achieving and maintaining high1-dose MMR vaccine coverage in preschool-aged children and high 2-dose MMR vaccine coverage in school-aged children, measles was verified as eliminated from the United States in 2000.4

BACKGROUND: More than 99% of poliovirus infections are non-paralytic and therefore, not detected by acute flaccid paralysis (AFP) surveillance. Environmental surveillance (ES) can detect circulating polioviruses from sewage without relying on clinical presentation. With extensive ES and continued circulation of polioviruses, Pakistan presents a unique opportunity to quantify the impact of ES as a supplement to AFP surveillance on overall completeness and timeliness of poliovirus detection. METHODS: Genetic, geographic and temporal data were obtained for all wild poliovirus (WPV) isolates detected in Pakistan from January 2011 through December 2013. We used viral genetics to assess gaps in AFP surveillance and ES as measured by detection of 'orphan viruses' (≥1.5% different in VP1 capsid nucleotide sequence). We compared preceding detection of closely related circulating isolates (≥99% identity) detected by AFP surveillance or ES to determine which surveillance system first detected circulation before the presentation of each polio case. FINDINGS: A total of 1,127 WPV isolates were detected by AFP surveillance and ES in Pakistan from 2011-2013. AFP surveillance and ES combined exhibited fewer gaps (i.e., % orphan viruses) in detection than AFP surveillance alone (3.3% vs. 7.7%, respectively). ES detected circulation before AFP surveillance in nearly 60% of polio cases (200 of 346). For polio cases reported from provinces conducting ES, ES detected circulation nearly four months sooner on average (117.6 days) than did AFP surveillance. INTERPRETATION: Our findings suggest ES in Pakistan is providing earlier, more sensitive detection of wild polioviruses than AFP surveillance alone. Overall, targeted ES through strategic selection of sites has important implications in the eradication endgame strategy.

In the past 200years, vaccines have had unmistakable impacts on public health including declines in morbidity and mortality, most markedly in economically-developed countries. Highly engineered vaccines including vaccines for conditions other than infectious diseases are expected to dominate future vaccine development. We examine immunization vaccine policy as a driver of vaccine innovation and development. The pathways to recommendation for use of licensed vaccines in the US, UK, Canada and Australia have been similar, including: expert review of disease epidemiology, disease burden and severity; vaccine immunogenicity, efficacy and safety; programmatic feasibility; public demand; and increasingly cost-effectiveness. Other attributes particularly important in development of future vaccines are likely to include: duration of immunity for improved vaccines such as pertussis; a greater emphasis on optimizing community protection rather than direct protection only; programmatic implementation, feasibility, improvements (as in the case of development of a universal influenza vaccine); public concerns/confidence/fears related to outbreak pathogens like Ebola and Zika virus; and major societal burden for combating hard to treat diseases like HIV and antimicrobial resistant pathogens. Driving innovation and production of future vaccines faces enormous economic hurdles as available approaches, technologies and regulatory pathways become more complex. As such, cost-mitigating strategies and focused, aligned efforts (by governments, private organizations, and private-public partnerships) will likely be needed to continue to spur major advances in vaccine technologies and development.

BACKGROUND: Pertussis remains a cause of morbidity and mortality among young infants. There are limited data on the pertussis disease burden in this age group from low- and lower-middle-income countries, including in South Asia. METHODS: We conducted an active community-based surveillance study from February 2015 to April 2016 among 2 cohorts of young infants in 4 low-income settlements in Karachi, Pakistan. Infants were enrolled either at birth (closed cohort) or at ages up to 10 weeks (open cohort) and followed until 18 weeks of age. Nasopharyngeal swab specimens were obtained from infants who met a standardized syndromic case definition and tested for Bordetella pertussis using real-time polymerase chain reaction. We determined the incidence of pertussis using a protocol-defined case definition, as well as the US Centers for Disease Control and Prevention (CDC) definitions for confirmed and probable pertussis. RESULTS: Of 2021 infants enrolled into the study, 8 infants met the protocol-defined pertussis case definition, for an incidence of 3.96 (95% confidence interval [CI], 1.84-7.50) cases per 1000 infants. Seven of the pertussis cases met the CDC pertussis case definition (5 confirmed, 2 probable), for incidences of CDC-defined confirmed pertussis of 2.47 (95% CI, .90-5.48) cases per 1000 infants, and probable pertussis of 0.99 (95% CI, .17-3.27) cases per 1000 infants. Three of the pertussis cases were severe according to the Modified Preziosi Scale score. CONCLUSIONS: In one of the first prospective surveillance studies of infant pertussis in a developing country, we identified a moderate burden of pertussis disease in early infancy in Pakistan.

OBJECTIVE: For medically treated asthma, we estimated prevalence, medical and absenteeism costs, and projected medical costs from 2015 to 2020 for the entire population and separately for children in the 50 US states and District of Columbia (DC) using the most recently available data. METHODS: We used multiple data sources, including the Medical Expenditure Panel Survey, U.S. Census Bureau, Kaiser Family Foundation, Medical Statistical Information System, and Current Population Survey. We used a two-part regression model to estimate annual medical costs of asthma and a negative binomial model to estimate annual school and work days missed due to asthma. RESULTS: Per capita medical costs of asthma ranged from $1,860 (Mississippi) to $2,514 (Michigan). Total medical costs of asthma ranged from $60.7 million (Wyoming) to $3.4 billion (California). Medicaid costs ranged from $4.1 million (Wyoming) to $566.8 million (California), Medicare from $5.9 million (DC) to $446.6 million (California), and costs paid by private insurers ranged from $27.2 million (DC) to $1.4 billion (California). Total annual school and work days lost due to asthma ranged from 22.4 thousand (Wyoming) to 1.5 million days (California) and absenteeism costs ranged from $4.4 million (Wyoming) to $345 million (California). Projected increase in medical costs from 2015 to 2020 ranged from 9% (DC) to 34% (Arizona). CONCLUSION: Medical and absenteeism costs of asthma represent a significant economic burden for states and these costs are expected to rise. Our study results emphasize the urgency for strategies to strengthen state level efforts to prevent and control asthma attacks.

OBJECTIVE: Understanding the current status of parents' vaccine decision making is crucial to inform public policy. We sought to assess changes in vaccine decisions among parents of young children. METHODS: We conducted a web-based national poll of parents of children <7years in 2012 and 2014. Participants reported vaccine decisions for their youngest child. We calculated survey-weighted population estimates of overall immunizations decisions, and delay/refusal rates for specific vaccines. RESULTS: In 2012, 89.2% (95% CI, 87.3-90.8%) reported accepting or planning to accept all recommended non-influenza childhood vaccines, 5.5% (4.5-6.6%) reported intentionally delaying one or more, and 5.4% (4.1-6.9%) reported refusing one or more vaccines. In 2014, the acceptance, delay, and refusal rates were 90.8% (89.3-92.1%), 5.6% (4.6-6.9%), and 3.6% (2.8-4.5%), respectively. Between 2012 and 2014, intentional vaccine refusal decreased slightly among parents of older children (2-6years) but not younger children (0-1years). The proportion of parents working to catch up on all vaccines increased while those refusing some but not all vaccines decreased. The South experienced a significant increase in estimated acceptance (90.1-94.1%) and a significant decrease in intentional ongoing refusal (5.0-2.1%). Vaccine delay increased in the Northeast (3.2-8.8%). CONCLUSIONS: Nationally, acceptance and ongoing intentional delay of recommended non-influenza childhood vaccines were stable. These findings suggest that more effort is warranted to counter persistent vaccine hesitancy, particularly at the local level. Longitudinal monitoring of immunization attitudes is also warranted to evaluate temporal shifts over time and geographically.