In Elimination Settings, Measles Antibodies Wane After Vaccination but Not After Infection: A Systematic Review and Meta-Analysis.

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 9 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 2 doses of measles-containing vaccine (MCV) by 121.8 mIU/mL (95% confidence interval [CI], -212.4 to -31.1) per year since vaccination over 1 to 5 years, 53.7 mIU/mL (95% CI, -95.3 to -12.2) 5 to 10 years, 33.2 mIU/mL (95% CI, -62.6 to -3.9), 10 to 15 years, and 24.1 mIU/mL (95% CI, -51.5 to 3.3) 15 to 20 years since vaccination. Decreases in GMT over time were not significant after 1 dose of MCV or after infection. Decreases in the proportion of seropositive individuals over time were not significant after 1 or 2 doses of MCV or after infection. CONCLUSIONS: Measles antibody waning in vaccinated populations should be considered in planning for measles elimination.

MomsTalkShots, tailored educational app, improves vaccine attitudes: a randomized controlled trial.

BACKGROUND: Many pregnant women and parents have concerns about vaccines. This analysis examined the impact of MomsTalkShots, an individually tailored educational application, on vaccine attitudes of pregnant women and mothers. METHODS: MomsTalkShots was the patient-level component of a multi-level intervention to improve maternal and infant vaccine uptake that also included provider- and practice-level interventions. The impact of these interventions was studied using a two-by-two factorial design, randomizing at both the patient- and the practice-level. Study staff recruited pregnant women from a diverse set of prenatal care practices in Colorado and Georgia between June 2017 and July 2018. All participants (n = 2087) received a baseline survey of maternal and infant vaccine intentions and attitudes, and two follow-up surveys at least 1 month and 1 year after their infant's birth, respectively. Half of participants (n = 1041) were randomly assigned to receive educational videos through MomsTalkShots, algorithmically tailored to their vaccine intentions, attitudes, and demographics. Since the practice/provider intervention did not appear impactful, this analysis focused on MomsTalkShots regardless of the practice/provider intervention. RESULTS: By 1 month post-birth, MomsTalkShots increased perceived risk of maternal influenza disease (61% among MomsTalkShots recipients vs 55% among controls; Odds Ratio: 1.61, 95% Confidence Interval: 1.23-2.09), confidence in influenza vaccine efficacy (73% vs 63%; OR: 1.97, 95%CI: 1.47-2.65), and perceived vaccine knowledge (55% vs 48%; OR: 1.39, 95%CI: 1.13-1.72). Among those intending not to vaccinate at baseline, MomsTalkShots increased perceived risk of maternal influenza disease (38% vs 32%; OR: 2.07, 95%CI: 1.15-3.71) and confidence in influenza vaccine efficacy (44% vs 28%; OR: 2.62, 95%CI: 1.46-4.69). By 1 year post-birth, MomsTalkShots increased perceived vaccine knowledge (62% vs 50%; OR: 1.74, 95%CI: 1.36-2.24) and trust in vaccine information from obstetricians and pediatricians (64% vs 55%; OR: 1.53, 95%CI: 1.17-2.00). Among those uncertain about vaccinating at baseline, MomsTalkShots increased perceived vaccine knowledge (47% vs 12%; OR: 6.89, 95%CI: 1.52-31.25) and reduced infant vaccine safety concerns (71% vs 91%; OR: 0.24, 95%CI: 0.06-0.98). CONCLUSIONS: MomsTalkShots improved pregnant women's and mothers' knowledge and perceptions of maternal and infant vaccines and the diseases they prevent, and offers a scalable tool to address vaccine hesitancy. TRIAL REGISTRATION: Registered at Clinicaltrials.gov on 13/09/2016 (registration number: NCT02898688).

Decreased humoral immunity to mumps in young adults immunized with MMR vaccine in childhood.

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.

Use of Random Domain Intercept Technology to Track COVID-19 Vaccination Rates in Real Time Across the United States: Survey Study.

BACKGROUND: Accurate and timely COVID-19 vaccination coverage data are vital for informing targeted, effective messaging and outreach and identifying barriers to equitable health service access. However, gathering vaccination rate data is challenging, and efforts often result in information that is either limited in scope (eg, limited to administrative data) or delayed (impeding the ability to rapidly respond). The evaluation of innovative technologies and approaches that can assist in addressing these limitations globally are needed. OBJECTIVE: The objective of this survey study was to assess the validity of Random Domain Intercept Technology (RDIT; RIWI Corp) for tracking self-reported vaccination rates in real time at the US national and state levels. RDIT-a form of online intercept sampling-has the potential to address the limitations of current vaccination tracking systems by allowing for the measurement of additional data (eg, attitudinal data) and real-time, rapid data collection anywhere there is web access. METHODS: We used RDIT from June 30 to July 26, 2021, to reach a broad sample of US adult (aged ≥18 years) web users and asked questions related to COVID-19 vaccination. Self-reported vaccination status was used as the focus of this validation exercise. National- and state-level RDIT-based vaccination rates were compared to Centers for Disease Control and Prevention (CDC)-reported national and state vaccination rates. Johns Hopkins University's and Emory University's institutional review boards designated this project as public health practice to inform message development (not human subjects research). RESULTS: By using RDIT, 63,853 adult web users reported their vaccination status (6.2% of the entire 1,026,850 American web-using population that was exposed to the survey). At the national level, the RDIT-based estimate of adult COVID-19 vaccine coverage was slightly higher (44,524/63,853, 69.7%; 95% CI 69.4%-70.1%) than the CDC-reported estimate (67.9%) on July 15, 2021 (ie, midway through data collection; t63,852=10.06; P<.001). The RDIT-based and CDC-reported state-level estimates were strongly and positively correlated (r=0.90; P<.001). RDIT-based estimates were within 5 percentage points of the CDC's estimates for 29 states. CONCLUSIONS: This broad-reaching, real-time data stream may provide unique advantages for tracking the use of a range of vaccines and for the timely evaluation of vaccination interventions. Moreover, RDIT could be harnessed to rapidly assess demographic, attitudinal, and behavioral constructs that are not available in administrative data, which could allow for deeper insights into the real-time predictors of vaccine uptake-enabling targeted and timely interventions.

An Exploratory Study of an Online Vaccine Education Program in Middle-School Students to Promote Vaccine Acceptance.

Background: While vaccines have reduced the incidence of vaccine-preventable diseases, vaccine hesitancy threatens the re-emergence of childhood infectious diseases. Purpose: This randomized controlled study evaluated an online vaccine education program to advance vaccine acceptance among middle-school students. Methodology: Study participants were randomly assigned to an intervention group who viewed the VEP videos or to a comparison group who viewed a science-based video unrelated to vaccines. Results: Knowledge scores improved in both groups and more favorable shifts in vaccine-related beliefs and attitudes occurred in the intervention than in the comparison group. Conclusions: This program can be feasibly delivered via an online platform to middle school students, resulting in shifts in vaccine-related knowledge, beliefs and attitudes. Implications: Delivering evidence-based content to instruct about vaccine effectiveness and safety is an area in which school nurses have demonstrated an important role as a resource for patient education to promote vaccine advocacy.

The Importance of Advancing Severe Acute Respiratory Syndrome Coronavirus 2 Vaccines in Children.

While the role of children in the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains to be defined, children likely play an important role based on our knowledge of other respiratory viruses. Children are more likely to be asymptomatic or have milder symptoms and less likely to present for healthcare and be tested for SARS-CoV-2. Thus, our current estimates are likely under-representative of the true burden of SARS-CoV-2 in children. Given the potential direct benefit of a SARS-CoV-2 vaccine in children and the substantial indirect benefit through community protection, or "herd immunity," we argue that planning and implementation of SARS-CoV-2 vaccines should include children. Furthermore, community protection occurred after widespread implementation of prior childhood vaccines against Streptococcus pneumoniae, rubella, and rotavirus. We detail considerations for vaccine clinical trials, potential barriers to the implementation of widespread vaccination and argue why children would be an ideal target population for vaccination.

Elimination of cervical cancer: Lessons learned from polio and earlier eradication programs.

This paper reviews definitions of control, elimination, and eradication and considers lessons learned from prior and current elimination/eradication efforts that might inform the current effort to eliminate cervical cancer. This task is complicated by the varying definitions of elimination extant. Lessons for cervical cancer elimination notably include the necessity for political will/champions; the need for a specific target with a time span; the need for program efforts to be guided by surveillance of disease and death (not just coverage); the need for accountability, monitoring, and evaluation at all levels; and the need for ongoing research. Although achieving the goal of elimination will be difficult, success will mean the prevention of millions of deaths due to cervical cancer.

A Dynamic Model for Evaluation of the Bias of Influenza Vaccine Effectiveness Estimates From Observational Studies.

Given that influenza vaccination is now widely recommended in the United States, observational studies based on patients with acute respiratory illness (ARI) remain as the only option to estimate influenza vaccine effectiveness (VE). We developed a dynamic probability model to evaluate bias of VE estimates from passive surveillance cohort, test-negative, and traditional case-control studies. The model includes 2 covariates (health status and health awareness) that might affect the probabilities of vaccination, developing ARI, and seeking medical care. Our results suggest that test-negative studies produce unbiased estimates of VE against medically attended influenza when: 1) Vaccination does not affect the probability of noninfluenza ARI; and 2) health status has the same effect on the probability of influenza and noninfluenza ARIs. The same estimate might be severely biased (i.e., estimated VE - true VE ≥ 0.20) for estimating VE against symptomatic influenza if the vaccine affects the probability of seeking care against influenza ARI. VE estimates from test-negative studies might also be severely biased for both outcomes of interest when vaccination affects the probability of noninfluenza ARI, but estimates from passive surveillance cohort studies are unbiased in this case. Finally, VE estimates from traditional case-control studies suffer from bias regardless of the source of bias.

The Many Faces of Emerging and Reemerging Infectious Disease.

The emergence of disease threats can take many forms, from the adaptation of a traditionally zoonotic pathogen for efficient spread in humans, to the development of antibiotic resistance in well-known pathogens, to the creation of new niches for established disease through social and societal changes. In this commentary, the authors explore these various facets of disease emergence through the lens of the papers included in this issue of Epidemiologic Reviews. The authors explore multiple aspects of emergence and the ways in which emergent pathogens can be controlled with the limited tools available. In doing so, they put the papers in this issue in the context of the broader research agenda around understanding and combatting emergent pathogens.

Disparities in Tdap Vaccination and Vaccine Information Needs Among Pregnant Women in the United States.

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.

The Salzburg Statement on Vaccination Acceptance.

Immunization represents one of the greatest public health achievements. Vaccines save lives, make communities more productive and strengthen health systems. They are critical to attaining the UN Sustainable Development Goals. Vaccination also represents value for investment in public health. It is undisputedly one of the most cost-effective ways of avoiding disease, each year preventing 2-3 million deaths globally. We the concerned scientists, public health professionals, physicians, and child health advocates issue this Salzburg Statement along with the International Working Group on Vaccination and Public Health Solutions, proclaiming our unwavering commitment to universal childhood vaccination, and our pledge to support the development, testing, implementation, and evaluation of new, effective, and fact-based communication programs. Our goal is to explain vaccinations to parents or caregivers, answer their questions, address their concerns, and maintain public confidence in the personal, family and community protection that childhood vaccines provide. Every effort will also be made to communicate the dangers associated with these childhood illnesses to parents and communities since this information seems to have been lost in the present-day narrative. While vaccine misinformation has led to serious declines in community vaccination rates that require immediate attention, in other communities, particularly in low-income countries, issues such as lack of access. and unstable supply of vaccines need to be addressed.

Protecting the Community Through Child Vaccination.

The direct impact of vaccines on children is well described, but the major public health impact of indirect protection provided to the community by vaccines is underappreciated. Community protection occurs when vaccinated persons block the chain of transmission, protecting undervaccinated or unvaccinated susceptible community members by preventing exposure and limiting the spread of the pathogen through the community. Substantial declines in disease incidence have occurred shortly after implementing new childhood vaccines, including declines among vaccine-ineligible children, adolescents, and adults. Protection of susceptible community members depends on maintaining high vaccination rates. Improved recognition of community protection will strengthen childhood vaccination strategies that will protect our communities into the future.

A comparison of the test-negative and the traditional case-control study designs for estimation of influenza vaccine effectiveness under nonrandom vaccination.

BACKGROUND: As annual influenza vaccination is recommended for all U.S. persons aged 6 months or older, it is unethical to conduct randomized clinical trials to estimate influenza vaccine effectiveness (VE). Observational studies are being increasingly used to estimate VE. We developed a probability model for comparing the bias and the precision of VE estimates from two case-control designs: the traditional case-control (TCC) design and the test-negative (TN) design. In both study designs, acute respiratory illness (ARI) patients seeking medical care testing positive for influenza infection are considered cases. In the TN design, ARI patients seeking medical care who test negative serve as controls, while in the TCC design, controls are randomly selected individuals from the community who did not contract an ARI. METHODS: Our model assigns each study participant a covariate corresponding to the person's health status. The probabilities of vaccination and of contracting influenza and non-influenza ARI depend on health status. Hence, our model allows non-random vaccination and confounding. In addition, the probability of seeking care for ARI may depend on vaccination and health status. We consider two outcomes of interest: symptomatic influenza (SI) and medically-attended influenza (MAI). RESULTS: If vaccination does not affect the probability of non-influenza ARI, then VE estimates from TN studies usually have smaller bias than estimates from TCC studies. We also found that if vaccinated influenza ARI patients are less likely to seek medical care than unvaccinated patients because the vaccine reduces symptoms' severity, then estimates of VE from both types of studies may be severely biased when the outcome of interest is SI. The bias is not present when the outcome of interest is MAI. CONCLUSIONS: The TN design produces valid estimates of VE if (a) vaccination does not affect the probabilities of non-influenza ARI and of seeking care against influenza ARI, and (b) the confounding effects resulting from non-random vaccination are similar for influenza and non-influenza ARI. Since the bias of VE estimates depends on the outcome against which the vaccine is supposed to protect, it is important to specify the outcome of interest when evaluating the bias.

Impact of Gender-Specific Human Papillomavirus Vaccine Recommendations on Uptake of Other Adolescent Vaccines: Analysis of the NIS-Teen (2008-2012).

In the United States, human papillomavirus vaccination was routinely recommended for adolescent females in 2006 and provisionally recommended for adolescent males in 2009. We evaluated the hypothesis that gender-specific human papillomavirus vaccination recommendations would impact gender-specific uptake of other vaccines using National Immunization Survey-Teen public use data sets (2008-2012). Female adolescents had higher coverage than males of at least 1 other adolescent vaccine in 2008 (3.0% higher) and 2009 (4.3% higher). Gender differences abated in 2010, 2011, and 2012 (0.2%, 0.9%, and 0.4%, respectively). To evaluate unintended consequences of gender-based recommendations, countries with female-only human papillomavirus vaccination recommendations should evaluate gender-specific uptake of other adolescent vaccines.

Impact of Statins on Influenza Vaccine Effectiveness Against Medically Attended Acute Respiratory Illness.

BACKGROUND: Statins have antiinflammatory effects that may impact vaccine-induced immune responses. We investigated the impact of statin therapy on influenza vaccine effectiveness (VE) against medically attended acute respiratory illness (MAARI). METHODS: We conducted a retrospective cohort study over nine influenza seasons using research databases of a large managed care organization in the United States. Influenza vaccination and statin prescription statuses of cohort members and MAARI cases were ascertained on a per-season basis. Incidence rate ratios (IRRs) of MAARI were estimated using Poisson regression and stratified by statin use. Using a ratio of ratios approach, we compared IRRs from periods during to IRRs from periods before influenza circulation and then used relative IRRs to compute VE. RESULTS: After adjustment for multiple prespecified covariates, the influenza VE against MAARI was lower among statin users than nonusers during periods of local (14.1% vs 22.9%; mean difference, 11.4%; 95% confidence interval [CI], -1.7% to 26.1%) and widespread (12.6% vs 26.2%; mean difference, 18.4%; 95% CI, 2.9%-36.2%) influenza circulation. CONCLUSIONS: In this study, statin therapy was associated with reduced influenza VE against MAARI. Since many cases of MAARI are not caused by influenza, studies of the impact of statins on influenza VE against laboratory-confirmed influenza are needed.

Protective Effect of Contemporary Pertussis Vaccines: A Systematic Review and Meta-analysis.

BACKGROUND: Acellular pertussis (aP) and whole-cell (wP) pertussis vaccines are presumed to have similar short-term (<3 years after completion of the primary series) efficacy. However, vaccine effect varies between individual pertussis vaccine formulations, and many originally studied formulations are now unavailable. An updated analysis of the short-term protective effect of pertussis vaccines limited to formulations currently on the market in developed countries is needed. METHODS: We conducted a systematic review and meta-analysis of published studies that evaluated pertussis vaccine efficacy or effectiveness within 3 years after completion (>3 doses) of a primary series of a currently available aP or wP vaccine formulation. The primary outcome was based on the World Health Organization (WHO) clinical case definitions for pertussis. Study quality was assessed using the approach developed by the Child Health Epidemiology Research Group. We determined overall effect sizes using random-effects meta-analyses, stratified by vaccine (aP or wP) and study (efficacy or effectiveness) type. RESULTS: Meta-analysis of 2 aP vaccine efficacy studies (assessing the 3-component GlaxoSmithKline and 5-component Sanofi-Pasteur formulations) yielded an overall aP vaccine efficacy of 84% (95% confidence interval [CI], 81%-87%). Meta-analysis of 3 wP vaccine effectiveness studies (assessing the Behringwerke, Pasteur/Mérieux, and SmithKline Beecham formulations) yielded an overall wP vaccine effectiveness of 94% (95% CI, 88%-97%) (bothI(2)= 0%). CONCLUSIONS: Although all contemporary aP and wP formulations protect against pertussis disease, in this meta-analysis the point estimate for short-term protective effect against WHO-defined pertussis in young children was lower for currently available aP vaccines than wP vaccines.