Documenting the Full Value of Vaccination: A Systematic Review of Value Frameworks.

OBJECTIVES: Economic evaluations of vaccination may not fully account for nonhealth patient impacts on families, communities, and society (ie, broader value elements). Omission of broader value elements may reflect a lack of established measurement methodology, lack of agreement over which value elements to include in economic evaluations, and a lack of consensus on whether the value elements included should vary by vaccination type or condition. We conducted a systematic review of value frameworks to identify broader value elements and measurement guidance that may be useful for capturing the full value of vaccination. METHODS: We searched Ovid MEDLINE, PubMed, Embase, and the gray literature to identify value frameworks for all health interventions, and we extracted information on each framework's context, value elements, and any available guidance on how these elements should be measured. We used descriptive statistics to analyze and compare the prevalence of broader value elements in vaccination value frameworks and other healthcare-related value frameworks. RESULTS: Our search identified 62 value frameworks that met inclusion criteria, 9 of which were vaccination specific. Although vaccination frameworks included several broader value elements, such as reduced transmissibility and public health benefits, the elements were represented inconsistently across the frameworks. Vaccination frameworks omitted several value elements included in nonvaccination-specific frameworks, including dosing and administration complexity and affordability. In addition, guidance for measuring broader value elements was underdeveloped. CONCLUSIONS: Future efforts should further evaluate inclusion of broader value elements in economic evaluations of vaccination and develop standards for their subsequent measurement.

Forecasting the 2014 West African Ebola Outbreak.

In 2014-2015, a large Ebola outbreak afflicted Liberia, Guinea, and Sierra Leone. We performed a systematic review of 26 manuscripts, published between 2014 and April 2015, that forecasted the West African Ebola outbreak while it was occurring, and we derived implications for how results could be interpreted by policymakers. Forecasted case counts varied widely. An important determinant of forecast accuracy for case counts was how far into the future predictions were made. Generally, forecasts for less than 2 months into the future tended to be more accurate than those made for more than 10 weeks into the future. The exceptions were parsimonious statistical models in which the decay of the rate of spread of the pathogen among susceptible individuals was dealt with explicitly. The most important lessons for policymakers regarding future outbreaks, when using similar modeling results, are: 1) uncertainty of forecasts will be greater in the beginning of the outbreak; 2) when data are limited, forecasts produced by models designed to inform specific decisions should be used complementarily for robust decision-making (e.g., 2 statistical models produced the most reliable case-counts forecasts for the studied Ebola outbreak but did not enable understanding of interventions' impact, whereas several compartmental models could estimate interventions' impact but required unavailable data); and 3) timely collection of essential data is necessary for optimal model use.

The PanVax Tool to Improve Pandemic Influenza Emergency Vaccination Program Readiness and Partnership.

Objectives. To show how the Centers for Disease Control and Prevention's Pandemic Vaccine Campaign Planning Tool (PanVax Tool) can help state and local public health emergency planners demonstrate and quantify how partnerships with community vaccine providers can improve their overall pandemic vaccination program readiness.Methods. The PanVax Tool helps planners compare different strategies to vaccinate their jurisdiction's population in a severe pandemic by allowing users to customize the underlying model inputs in real time, including their jurisdiction's size, community vaccine provider types, and how they allocate vaccine to these providers. In this report, we used a case study with hypothetical data to illustrate how jurisdictions can utilize the PanVax Tool for preparedness planning.Results. By using the tool, planners are able to understand the impact of engaging with different vaccine providers in a vaccination campaign.Conclusions. The PanVax Tool is a useful tool to help demonstrate the impact of community vaccine provider partnerships on pandemic vaccination readiness and identify areas for improved partnerships for pandemic response.

Evaluation of the impact of shigellosis exclusion policies in childcare settings upon detection of a shigellosis outbreak.

BACKGROUND: In the event of a shigellosis outbreak in a childcare setting, exclusion policies are typically applied to afflicted children to limit shigellosis transmission. However, there is scarce evidence of their impact. METHODS: We evaluated five exclusion policies: Children return to childcare after: i) two consecutive laboratory tests (either PCR or culture) do not detect Shigella, ii) a single negative laboratory test (PCR or culture) does not detect Shigella, iii) seven days after beginning antimicrobial treatment, iv) after being symptom-free for 24 h, or v) 14 days after symptom onset. We also included four treatments to assess the policy options: i) immediate, effective treatment; ii) effective treatment after laboratory diagnosis; iii) no treatment; iv) ineffective treatment. Relying on published data, we calculated the likelihood that a child reentering childcare would be infectious, and the number of childcare-days lost per policy. RESULTS: Requiring two consecutive negative PCR tests yielded a probability of onward transmission of < 1%, with up to 17 childcare-days lost for children receiving effective treatment, and 53 days lost for those receiving ineffective treatment. CONCLUSIONS: Of the policies analyzed, requiring negative PCR testing before returning to childcare was the most effective to reduce the risk of shigellosis transmission, with one PCR test being the most effective for the least childcare-days lost.

Antiviral treatment for outpatient use during an influenza pandemic: a decision tree model of outcomes averted and cost-effectiveness.

BACKGROUND: Many countries have acquired antiviral stockpiles for pandemic influenza mitigation and a significant part of the stockpile may be focussed towards community-based treatment. METHODS: We developed a spreadsheet-based, decision tree model to assess outcomes averted and cost-effectiveness of antiviral treatment for outpatient use from the perspective of the healthcare payer in the UK. We defined five pandemic scenarios-one based on the 2009 A(H1N1) pandemic and four hypothetical scenarios varying in measures of transmissibility and severity. RESULTS: Community-based antiviral treatment was estimated to avert 14-23% of hospitalizations in an overall population of 62.28 million. Higher proportions of averted outcomes were seen in patients with high-risk conditions, when compared to non-high-risk patients. We found that antiviral treatment was cost-saving across pandemic scenarios for high-risk population groups, and cost-saving for the overall population in higher severity influenza pandemics. Antiviral effectiveness had the greatest influence on both the number of hospitalizations averted and on cost-effectiveness. CONCLUSIONS: This analysis shows that across pandemic scenarios, antiviral treatment can be cost-saving for population groups at high risk of influenza-related complications.

Exportations of Symptomatic Cases of MERS-CoV Infection to Countries outside the Middle East.

In 2012, an outbreak of infection with Middle East respiratory syndrome coronavirus (MERS-CoV), was detected in the Arabian Peninsula. Modeling can produce estimates of the expected annual number of symptomatic cases of MERS-CoV infection exported and the likelihood of exportation from source countries in the Middle East to countries outside the region.

Estimation of Severe Middle East Respiratory Syndrome Cases in the Middle East, 2012-2016.

Using data from travelers to 4 countries in the Middle East, we estimated 3,250 (95% CI 1,300-6,600) severe cases of Middle East respiratory syndrome occurred in this region during September 2012-January 2016. This number is 2.3-fold higher than the number of laboratory-confirmed cases recorded in these countries.

Potential demand for respirators and surgical masks during a hypothetical influenza pandemic in the United States.

BACKGROUND: To inform planning for an influenza pandemic, we estimated US demand for N95 filtering facepiece respirators (respirators) by healthcare and emergency services personnel and need for surgical masks by pandemic patients seeking care. METHODS: We used a spreadsheet-based model to estimate demand for 3 scenarios of respirator use: base case (usage approximately follows epidemic curve), intermediate demand (usage rises to epidemic peak and then remains constant), and maximum demand (all healthcare workers use respirators from pandemic onset). We assumed that in the base case scenario, up to 16 respirators would be required per day per intensive care unit patient and 8 per day per general ward patient. Outpatient healthcare workers and emergency services personnel would require 4 respirators per day. Patients would require 1.2 surgical masks per day. RESULTS AND CONCLUSIONS: Assuming that 20% to 30% of the population would become ill, 1.7 to 3.5 billion respirators would be needed in the base case scenario, 2.6 to 4.3 billion in the intermediate demand scenario, and up to 7.3 billion in the maximum demand scenario (for all scenarios, between 0.1 and 0.4 billion surgical masks would be required for patients). For pandemics with a lower attack rate and fewer cases (eg, 2009-like pandemic), the number of respirators needed would be higher because the pandemic would have longer duration. Providing these numbers of respirators and surgical masks represents a logistic challenge for US public health agencies. Public health officials must urgently consider alternative use strategies for respirators and surgical masks during a pandemic that may vary from current practices.

Healthcare resource utilization and costs associated with hepatitis A in the United States: a retrospective database analysis.

Aim. To investigate hepatitis A-related healthcare resource use and costs in the US.Methods. The Merative Marketscan Commercial Claims and Encounters database was retrospectively analyzed for hepatitis A-related inpatient, outpatient, and emergency department (ED) claims from January 01, 2012 to December 31, 2018. We calculated the hepatitis A incidence proportion per 100,000 enrollees, healthcare resource utilization, and costs (in 2020 USD). Results were stratified by age, gender, and select comorbidities.Results. The overall hepatitis A incidence proportion was 6.1 per 100,000 enrollees. Among individuals with ≥1 hepatitis A-related claim, the majority (92.6%) had ≥1 outpatient visit related to hepatitis A; 9.1% were hospitalized, and 4.2% had ≥1 ED visit. The mean (standard deviation [SD]) length of hospital stay was 5.2 (8.1) days; the mean (SD) number of outpatient and ED visits were 1.3 (1.3) and 1.1 (0.6), respectively. The incidence proportion per 100,000 was higher among adults than children (7.5 vs. 1.5), individuals with HIV than those without (126.7 vs. 5.9), and individuals with chronic liver disease than those without (143.6 vs. 3.8). The total mean (SD)/median (IQR) per-patient cost for hepatitis A-related care was $2,520 ($10,899)/$156 ($74-$529) with the mean cost of hospitalization was 18.7 times higher than that of outpatient care ($17,373 vs. $928).Limitations. The study data included only a commercially insured population and may not be representative of all individuals.Conclusions. In conclusion, hepatitis A is associated with a substantial economic burden among privately insured individuals in the US.

Hepatitis A is an acute liver infection caused by the hepatitis A virus. In the US, safe and effective vaccines for hepatitis A have been available since 1996. Vaccination recommendations include children (all children aged 12 to 23 months and previously unvaccinated children 2 to 18 years of age) and adults at risk of infection or severe disease (e.g., international travelers, men who have sex with men, people experiencing homelessness, those with chronic liver disease or HIV). Since 2016, the US has experienced person-to-person outbreaks of hepatitis A, primarily affecting unvaccinated individuals who use drugs or are experiencing homelessness. To better understand the impact of hepatitis A in the US, we assessed healthcare resource use and costs in patients with hepatitis A from 2012 to 2018, including 15,435 individuals with a hepatitis A-related insurance claim in the Merative Marketscan Commercial Claims and Encounters database. We found that slightly more than 6 per 100,000 enrollees had hepatitis A from 2012 to 2018 and the number of people treated for hepatitis A per 100,000 was highest for people living with HIV or chronic liver disease. The majority (92.6%) of people reported at least an outpatient visit, 9.1% were hospitalized, and 4.2% had an emergency department visit. The average cost for hepatitis A-related care was $2,520 per patient and was 18.7 times higher for hospitalized patients ($17,373) than for patients treated in outpatient care ($928). Our results are limited by the generalizability of the dataset, which is a convenience sample of private insurance claims, and unlikely to capture groups at high-risk for hepatitis A, such as individuals experiencing homelessness. In conclusion, hepatitis A leads to considerable healthcare costs for privately insured individuals in the US.

Projected Public Health Impact of a Universal Rotavirus Vaccination Program in France.

OBJECTIVE: In June 2022, French health authorities issued a universal recommendation for routine administration and reimbursement of rotavirus vaccines in infants. Given this recent recommendation by French health authorities, we sought to understand the public health impact of a universal rotavirus vaccination strategy compared with no vaccination. MATERIALS AND METHODS: A deterministic, age-structured, nonlinear dynamic transmission model, accounting for herd immunity, was developed. We considered 3 vaccination coverage scenarios: high (95%), medium (75%) and low (55%). Model parameter values were based on published modeling and epidemiological literature. Model outcomes included rotavirus gastroenteritis (RVGE) cases and healthcare resource utilization due to RVGE (hospitalizations, general practitioner or emergency department visits), as well as the number needed to vaccinate to prevent 1 RVGE case (mild or severe) and 1 RVGE-related hospitalization. Model calibration and analyses were conducted using Mathematica 11.3. RESULTS: Over 5 years following implementation, RVGE cases for children under 5 years are estimated to be reduced by 84% under a high vaccination coverage scenario, by 72% under a medium vaccination coverage scenario and by 47% under a low vaccination coverage scenario. Across all scenarios, the number needed to vaccinate to avert 1 RVGE case and hospitalization varied between 1.86-2.04 and 24.15-27.44, respectively. CONCLUSIONS: Rotavirus vaccination with high vaccination coverage in France is expected to substantially reduce the number of RVGE cases and associated healthcare resource utilization.

Systematic review of rotavirus vaccination cost-effectiveness in high income settings utilising dynamic transmission modelling techniques.

PURPOSE: This systematic review presents cost-effectiveness studies of rotavirus vaccination in high-income settings based on dynamic transmission modelling to inform policy decisions about implementing rotavirus vaccination programmes. METHODS: We searched CEA Registry, MEDLINE, Embase, Health Technology Assessment Database, Scopus, and the National Health Service Economic Evaluation Database for studies published since 2002. Full economic evaluation studies based on dynamic transmission models, focusing on high-income countries, live oral rotavirus vaccine and children ≤ 5 years of age were eligible for inclusion. Included studies were appraised for quality and risk of bias using the Consensus on Health Economic Criteria (CHEC) list and the Philips checklist. The review protocol was prospectively registered with PROSPERO (CRD42020208406). RESULTS: A total of four economic evaluations were identified. Study settings included England and Wales, France, Norway, and the United States. All studies compared either pentavalent or monovalent rotavirus vaccines to no intervention. All studies were cost-utility analyses that reported incremental cost per quality-adjusted life year (QALY) gained. Included studies consistently concluded that rotavirus vaccination is cost-effective compared with no vaccination relative to the respective country's willingness to pay threshold when herd protection benefits are incorporated in the modelling framework. CONCLUSIONS: Rotavirus vaccination was found to be cost-effective in all identified studies that used dynamic transmission models in high-income settings where child mortality rates due to rotavirus gastroenteritis are close to zero. Previous systematic reviews of economic evaluations considered mostly static models and had less conclusive findings than the current study. This review suggests that modelling choices influence cost-effectiveness results for rotavirus vaccination. Specifically, the review suggests that dynamic transmission models are more likely to account for the full impact of rotavirus vaccination than static models in cost-effectiveness analyses.

Burden of rotavirus gastroenteritis on caregivers: Findings from a systematic literature review.

Rotavirus gastroenteritis (RVGE) poses a substantial clinical, economic, and humanistic burden globally. While predominantly affecting children, the burden of RVGE extends to caregivers and families but is often overlooked. In this systematic literature review, we aim to identify and summarize methods and estimates of RVGE associated caregiver burden. Of the 190 publications identified, 10 were included. Four studies used the EuroQoL-5 Dimension instrument and its associated Visual Analog Scale and reported a decrease in caregiver health related quality of life when a child contracted RVGE, with the greatest reduction observed in caregivers of hospitalized children. Other studies utilized surveys to assess impacts on caregivers' quality of life. Caregivers of RVGE patients experienced multiple impacts beyond financial costs related to productivity and absenteeism, with disruptions to daily routines and anxiety/stress frequently reported. This review highlights the importance of including RVGE caregiver burden when evaluating interventions, such as vaccination, to decrease RVGE burden.

Comparison of performance of varicella vaccines via infectious disease modeling.

BACKGROUND: Population-level infectious disease models for varicella require vaccine parameters, namely 'take' and 'duration of protection' (defined here as vaccine performance), to quantify the impact of vaccination. Current published models for varicella use vaccine parameters derived from various methodologies which does not allow for the direct comparison of different vaccines. METHODS: We estimated take and duration of protection using deterministic compartmental models to simulate clinical trials of one- or two-dose varicella vaccination using Varivax® (V-MSD) and Varilrix® (V-GSK). We fit different models to clinical trial data on breakthrough infections and evaluated their respective goodness-of-fit using the Akaike Information Criterion (AIC). RESULTS: Based upon the clinical trial data, we estimated that 90.3% (95% CI: 87.8-92.9%) of the cohort gained permanent protection from breakthrough varicella after the first dose of V-MSD compared to 61.7% (95% CI: 58.2-65.3%) with the first dose of V-GSK. We further estimated that a total of 97.0% (95% CI: 95.2-98.8%) and 93.8% (95% CI: 92.2-95.4%) of the cohort were permanently protected after two-doses of V-MSD and V-GSK, respectively. According to the AIC, our new model (V-MSD AIC = 92.7; V-GSK AIC = 170.3) provided a better fit than an existing model (V-MSD AIC = 108.9; V-GSK AIC = 216.1). CONCLUSIONS: The model developed fits the long-term clinical trial data on breakthrough infections for both V-MSD and V-GSK, thus, allowing for the direct comparison of vaccine performance. We estimated that a single dose of V-MSD was more likely to provide permanent protection than a single dose of V-GSK, while the protection offered by two doses was similar for both vaccines.

A Comprehensive Assessment Of Child Care Vaccination Laws Across The US.

All fifty US states and Washington, D.C., require children from birth through age five to be vaccinated against certain communicable diseases as a condition of attending child care settings such as day care, Head Start, preschools, pre-kindergarten, and other early childhood programs. However, the nuances and implementation of these laws vary greatly across jurisdictions. To date, a comprehensive analysis of all child care vaccination laws in the US has not been performed. We have developed the first compilation of child care vaccination laws across the US. This compilation is the culmination of an exhaustive examination of multiple components of the laws, such as which vaccines are required, provisions that enable unvaccinated children to temporarily attend child care until they are fully vaccinated, attendance provisions for unvaccinated students during an outbreak, methods of enforcement of vaccination policy, and child care personnel vaccination requirements. This comprehensive analysis provides a critical and foundational framework to inform policy makers and public health professionals involved in policy planning and implementation and policy research. It provides a benchmark for further evaluation of existing and future vaccination laws and their impact on vaccine coverage rates.

The burden of rotavirus-associated acute gastroenteritis in the elderly: assessment of the epidemiology in the context of universal childhood vaccination programs.

INTRODUCTION: Rotaviruses (RVs) cause acute gastroenteritis (AGE) in infants and young children worldwide and also in older adults (≥60 years), however the burden among this age group is not well understood. Herd immunity through pediatric RV vaccination may reduce the burden of RVGE across all ages, however the impact of pediatric vaccination on burden in older adults is poorly understood. AREAS COVERED: This systematic review was undertaken to identify studies related to the following objectives: understand the burden of RV in older adults, RV seroprevalence, and the impact of pediatric vaccination on this burden and highlight evidence gaps to guide future research. Of studies identified, 59 studies from two databases were included in this analysis following a review by two reviewers. EXPERT OPINION: RV is an understudied disease in older adults. We found that 0-62% of patients with AGE tested positive for RV, with results varying by setting, country, and patient age. Results also suggest that pediatric vaccination benefits older adults through herd protection. Several studies showed a reduction in RV incidence after vaccination. However, there was variety in results and lack of consistency in outcomes reported. Further studies targeting older adults are needed to better characterize RV burden.

Impact of the COVID-19 pandemic on pediatric and adolescent vaccinations and well child visits in the United States: A database analysis.

BACKGROUND: The COVID-19 pandemic has disrupted healthcare, including immunization practice and well child visit attendance. Maintaining vaccination coverage is important to prevent disease outbreaks and morbidity. We assessed the impact of the COVID-19 pandemic on pediatric and adolescent vaccination administration and well child visit attendance in the United States. METHODS: This cross-sectional study used IBM MarketScan Commercial Database (IMC) with Early View (healthcare claims database) and TriNetX Dataworks Global Network (electronic medical records database) from January 2018-March 2021. Individuals ≤ 18 years of age who were enrolled during the analysis month of interest (IMC with Early View) or had ≥ 1 health encounter at a participating institution (TriNetX Dataworks) were included. We calculated the monthly percent difference between well child visit attendance and vaccine administration rates for 10 recommended pediatric/adolescent vaccines in 2020 and 2021 compared with 2018-2019. Data were stratified by the age groups 0-2 years, 4-6 years, and 9-16 years. RESULTS: In IMC with Early View, the average monthly enrollment for children 0-18 years of age was 5.2 million. In TriNetX Dataworks, 12.2 million eligible individuals were included. Well child visits and vaccinations reached the lowest point in April 2020 compared with 2018-2019. Well child visit attendance and vaccine administration rates were inversely related to age, with initial reductions highest for adolescents and lowest for ages 0-2 years. Rates rebounded in June and September 2020 and stabilized to pre-pandemic levels in Fall 2020. Rates dropped below baseline in early 2021 for groups 0-2 years and 4-6 years. CONCLUSIONS: We found substantial disruptions in well child visit attendance and vaccination administration for children and adolescents during the COVID-19 pandemic in 2020 and early 2021. Continued efforts are needed to monitor recovery and catch up to avoid outbreaks and morbidity associated with vaccine-preventable diseases.

Long-term surveillance of rotavirus vaccination after implementation of a national immunization program in Finland (2008-2018).

BACKGROUND: Rotavirus (RV) vaccination was included in the Finnish National immunization Program (NIP) in 2009. RotaTeq (RV5) has been used exclusively with a national average vaccination coverage rate (VCR) of > 90%. While previous studies have demonstrated that inpatient rotavirus gastroenteritis (RVGE) admissions declined by as much as 96% in Finnish children ≤ 5 years old following RV vaccination introduction, no study has evaluated long-term protection after vaccination in Finland. In this study, we analyze incidence of hospital outpatient visits and inpatient admissions of gastroenteritis in children up to 7 years of age. METHODS: We first describe the incidence of RVGE, viral gastroenteritis (VGE), and acute gastroenteritis (AGE) for all Finnish children born during 2008-2011. Children were stratified by the year of birth into not-eligible, partially eligible and rotavirus vaccine-eligible (born in 2008, 2009, 2010 and 2011, respectively). Hospital inpatient and outpatient data was collected from the National Care Register for all children from birth until December 31st, 2018. We also studied RVGE incidence during 2014-2017 for children<3 years of age in municipalities with VCRs of 90% and above and municipalities with VCRs below 90%. RESULTS: RVGE incidence decreased significantly soon after implementation of RV vaccination in the NIP. In vaccine-eligible cohorts, no clear peak incidence in the youngest age groups could be observed, and no RVGE cases were observed beyond 6 years after vaccination, in contrast to vaccine ineligible and partially eligible cohorts. Despite an overall high VCR in Finland, regions with high VCR had lower incidence of RVGE than regions with lower VCR. CONCLUSION: Incidence of RVGE has remained low in all age groups during the 10 years following introduction of RV vaccine in the Finnish NIP. Differences in RVGE incidence were observed in regions with high as compared with lower VCR, highlighting the importance of maintaining high vaccination coverage.

Association Between State Hepatitis A Vaccination Requirements and Hepatitis A Vaccination Rates.

Using National Immunization Survey Child and Teen (2008-2017), we associated state vaccination requirements with hepatitis A (Hep A) vaccination rates in children and adolescents. States with school entry or both childcare and school entry requirements were associated with 35%-40% higher Hep A vaccination rates, compared with states without such requirements.

Impact of Routine Childhood Immunization in Reducing Vaccine-Preventable Diseases in the United States.

BACKGROUND AND OBJECTIVES: Current routine immunizations for children aged ≤10 years in the United States in 2019 cover 14 vaccine-preventable diseases. We characterize the public-health impact of vaccination by providing updated estimates of disease incidence with and without universally recommended pediatric vaccines. METHODS: Prevaccine disease incidence was obtained from published data or calculated using annual case estimates from the prevaccine period and United States population estimates during the same period. Vaccine-era incidence was calculated as the average incidence over the most recent 5 years of available surveillance data or obtained from published estimates (if surveillance data were not available). We adjusted for underreporting and calculated the percent reduction in overall and age-specific incidence for each disease. We multiplied prevaccine and vaccine-era incidence rates by 2019 United States population estimates to calculate annual number of cases averted by vaccination. RESULTS: Routine immunization reduced the incidence of all targeted diseases, leading to reductions in incidence ranging from 17% (influenza) to 100% (diphtheria, Haemophilus influenzae type b, measles, mumps, polio, and rubella). For the 2019 United States population of 328 million people, these reductions equate to >24 million cases of vaccine-preventable disease averted. Vaccine-era disease incidence estimates remained highest for influenza (13 412 per 100 000) and Streptococcus pneumoniae-related acute otitis media (2756 per 100 000). CONCLUSIONS: Routine childhood immunization in the United States continues to yield considerable sustained reductions in incidence across all targeted diseases. Efforts to maintain and improve vaccination coverage are necessary to continue experiencing low incidence levels of vaccine-preventable diseases.