Can varicella be eliminated by vaccination? Potential clinical and economic effects of universal childhood varicella immunisation in Germany

Varicella is a potentially serious infection not only in immunocompromised individuals but also in otherwise healthy adults and children. Vaccination plays an important role in preventing the disease and its sequelae. A universal vaccination in childhood is expected to reduce substantially the number of uncomplicated cases of varicella and decrease the number of complicated cases requiring hospitalisation. To generate data as basis for decisions of the health authorities concerning prevention of varicella, epidemiological and health-economic data were collected in two studies. Using an age-structured decision analytic model the benefits, costs and cost effectiveness of a varicella immunisation program for a period of 30 years were assessed. It was shown that after the first year of life seroprevalence rates increased steadily and reached 62% among the 4- to 5-year olds and 94% among the 10- to 11-year olds, respectively; 90% of varicella patients were younger than 12 years. A severe course was assessed for 16.3% of the cases. Overall incidence of complications was estimated to be 5.7%. A routine varicella vaccination program targeting healthy children could prevent 82.7% of varicella cases and over 4,700 major complications per year provided the coverage level was 85%. Under these conditions the elimination of varicella is predicted to be achievable within 18 years. It is expected that a combined measles, mumps, rubella and varicella vaccine could provide the required coverage. Average yearly discounted net cost savings of universal childhood vaccination are 51 million Euro with a benefit-cost ratio of 4.12. Childhood vaccination with catch-up of adolescents provides additional clinical benefits. The break-even point indicating first net savings could be achieved already 3 years after the implementation of the vaccination program. In summary, routine childhood varicella vaccination appears to be a highly efficient strategy to significantly reduce the sizeable burden of varicella and would lead to net savings from both the societal but also the payer perspective.     

Cost-effectiveness of varicella vaccination programs: an update of the literature

Varicella is one of the most common infectious diseases in childhood, caused by the varicella zoster virus. Although vaccines are available, there are only a few countries with an early-childhood vaccination program. Most countries mainly focus on vaccination of high-risk groups, such as susceptible healthcare workers. One of the main concerns with a routine early-childhood vaccination program is a potential (temporal) increase of the incidence of herpes zoster among elderly adults. In this review, we focus on the cost-effectiveness of varicella vaccination and on the methodology used in the health-economic studies. In particular, we focus on the perspective adopted, type of model used, the modeled effect on herpes zoster, the vaccine efficacy and price, and on the value of time lost by infection. The vast majority of studies show vaccination of high-risk groups - including susceptible adolescents - to be cost saving. Routine early-childhood vaccination programs are always cost saving if indirect costs of production losses are included, or cost effective, as long as the potential negative effects on zoster are not taken into account. We note that most studies included in the review used old vaccine prices and a single dose of the varicella vaccine, whereas multiple doses are now becoming the standard. Despite that, those aspects limit the timeliness of our review and we believe that the current work does provide useful insights in the cost-effectiveness of varicella vaccination.     

Public fear of vaccination: separating fact from fiction

During the last two centuries, the world has seen a substantial increase in the number and availability of vaccines for the prevention of infectious disease. Smallpox vaccine remains the most celebrated vaccine-related achievement in human history, but worldwide reductions in many other diseases including measles, mumps, rubella, polio, diphtheria, and whooping cough (Bordetella pertussis) also illustrate the power of vaccination in controlling outbreaks of contagious diseases. Ironically, as advances in vaccination successfully limit disease outbreaks, the impact that these infectious agents once had on society becomes marginalized. Public confidence in vaccination may erode because of real or perceived risks associated with immunization, and this in turn may lead to lower vaccination coverage and loss of herd immunity. Here, we will discuss some of the elements associated with public perceptions and fear of vaccination and place these into the context of how deadly several vaccine-preventable childhood diseases can be if vaccination coverage is insufficient.     

An adolescent and adult formulation combined tetanus, diphtheria and five-component pertussis vaccine

Pertussis causes substantial morbidity among adolescents and adults, as well as other persons in contact with affected individuals. In the context of widespread childhood immunization, vaccination of adolescents and adults is a relatively new strategy for reducing the disease in all age groups. ADACEL is a tetanus-diphtheria-acellular pertussis combination vaccine (incorporating pertussis toxoid, filamentous hemagglutinin, pertactin and fimbriae type 2 and 3 antigens) formulated for use in adolescents and adults based on similar products designed for infants and children. ADACEL vaccine is approved for use in Australia, Canada, Germany and the USA, and has been demonstrated to induce robust immune responses and acceptable levels of reactogenicity in clinical trials. Surveillance data from Canada, where ADACEL vaccine has been used in adolescents and adults in conjunction with ongoing childhood vaccination for several years, indicate an enhanced overall reduction in pertussis disease.     

Cost-benefit analysis of haemophilus influenzae type B immunization in Korea

An economic evaluation of Haemophilus influenzae type b (Hib) immunization was conducted to examine whether Hib immunization should be included in Korea's national immunization program. The costs and benefits included direct and indirect values and an estimation of the economic efficiency. We determined that a universal Hib immunization program in Korea would prevent 17 deaths and 280 invasive Hib cases. When we assumed the one Hib immunization cost as 26,000 won, the national Hib immunization would cost 34.6 billion won. Costs for various Hib diseases were estimated at 26.8 billion won (11.8 billion won from direct costs and 14.9 billion won from indirect costs). A benefit-cost ratio of 0.77 showed that the economic efficiency of the integration of Hib immunization in Korea is low because of the low incidence rate of Hib disease and high price of vaccine. However, if the Hib immunization cost decrease to less than 20,000 won, a benefit-cost ratio increase to 1.0 and above, integrating Hib immunization into the national immunization program with economic efficiency can be considered.     

Effectiveness of Japanese encephalitis vaccination among children in central India

Japanese encephalitis (JE) disease among children continues in central India despite vaccination implemented in the routine immunization program. Therefore, we planned to estimate the JE vaccination effectiveness among children by undertaking a 1:2 individually-matched population-based case-control study from August 2018 to October 2020. The laboratory-confirmed JE cases aged 1–15 years were enrolled along with neighborhood controls without fever and encephalitis matched on the residence area, age and sex. The JE vaccination history was enquired from parents and verified independently from the vaccination cards available at home and records at health facilities. We enrolled 35 JE cases and 70 matched controls. The vaccination effectiveness of 86.7% (95% confidence interval [CI]: 30.8–94.7) was estimated on the per-protocol analysis of 31 case-control sets. The screening method provided an effectiveness of 89.5% (CI: 78.9–94.7) on using the population vaccination coverage of 90% reported earlier in the same area. In conclusion, JE vaccination offered a moderate level of protection among children in JE medium-endemic central India, similar to reports from high-endemic areas in India. The operational aspects of vaccination program implementation need to be evaluated to assess the impact of vaccination on the disease burden of JE in medium-endemic regions of India.     

Characterization of bactericidal immune responses following vaccination with acellular pertussis vaccines in adults

Sera from six adults, collected before and after acellular pertussis vaccination, and from a placebo control were examined for the ability to elicit two bactericidal immune defenses, (i) antibody-dependent complement-mediated bacterial lysis and (ii) opsonization and phagocytosis by human neutrophils. The samples were chosen based on low preimmunization titers and strong postimmunization responses to various combinations of vaccine antigens. All but two prevaccination samples demonstrated activity indicative of complement-mediated lysis. Preimmunization activity could have been due to prior infection or childhood immunization. Immunization did not result in improved bactericidal activity for any of the individuals, and in two cases immunization caused a statistically significant decrease in complement-mediated lysis. Similarly, opsonization with the postimmunization sera failed to enhance attachment or phagocytosis of bacteria by neutrophils, and one postimmunization sample with a strong response to filamentous hemagglutinin caused an inhibition of phagocytosis that was statistically significant compared to that observed for the no-serum control. In summary, booster immunization of adults with acellular pertussis vaccines was not found to increase bactericidal activity over preimmunization levels. Identifying ways to promote bactericidal immune responses might improve the efficacy of acellular pertussis vaccines.     

Short term evaluation of a rural immunization program in Nigeria

BACKGROUND: Immunization remains the primary strategy in both the control and prevention of common childhood diseases, particularly in the developing world. Immunization and preprimary health care services were commenced in a rural community in Nigeria in 1998, when vaccine coverage for all Expanded Program on Immunization (EPI) diseases (tuberculosis, polio, diphtheria, pertussis, tetanus, measles, and hepatitis B) was considerably low with only 43% of children fully immunized. METHODS: Children aged 0-2 years and living in a rural community were recruited into the study. Data on vaccination history was collected by both vaccination card and maternal history. Three hundred and twenty-seven children were recruited into the study. Study participants were vaccinated for EPI diseases. Hepatitis-B vaccine was administered at birth, and a combined diphtheria and tetanus toxoids, and pertussis whole cell vaccine (DTP) plus hepatitis-B vaccine was administered in a single injection after six weeks. RESULTS AND CONCLUSIONS: Two years after the program was started, immunization coverage rates were 94% for BCG, 88% for DTP (third dose), and 82% for measles. All antigens showed significant improvements from baseline values (p < 0.0001). Eighty four percent of children were fully immunized against all six diseases, compared with 43% at the commencement (p < 0.0001). Hepatitis-B coverage (three doses) was 58%. The vaccination program has significantly improved vaccination coverage and could be a model for under served, non-industrialized communities.     

Acellular pertussis vaccine protects against exacerbation of allergic asthma due to Bordetella pertussis in a murine model

The prevalence of asthma and allergic disease has increased in many countries, and there has been speculation that immunization promotes allergic sensitization. Bordetella pertussis infection exacerbates allergic asthmatic responses. We investigated whether acellular pertussis vaccine (Pa) enhanced or prevented B. pertussis-induced exacerbation of allergic asthma. Groups of mice were immunized with Pa, infected with B. pertussis, and/or sensitized to ovalbumin. Immunological, pathological, and physiological changes were measured to assess the impact of immunization on immune deviation and airway function. We demonstrate that immunization did not enhance ovalbumin-specific serum immunoglobulin E production. Histopathological examination revealed that immunization reduced the severity of airway pathology associated with sensitization in the context of infection and decreased bronchial hyperreactivity upon methacholine exposure of infected and sensitized mice. These data demonstrate unequivocally the benefit of Pa immunization to health and justify selection of Pa in mass vaccination protocols. In the absence of infection, the Pa used in this study enhanced the interleukin-10 (IL-10) and IL-13 responses and influenced airway hyperresponsiveness to sensitizing antigen; however, these data do not suggest that Pa contributes to childhood asthma overall. On the contrary, wild-type virulent B. pertussis is still circulating in most countries, and our data suggest that the major influence of Pa is to protect against the powerful exacerbation of asthma-like pathology induced by B. pertussis.     

佳木斯市2018年常规免疫接种率监测结果分析

目的 了解佳木斯市常规免疫接种率监测工作情况,评价报告接种率水平并分析原因。方法 采用Excel 2007整理,用差值（D值）评价法、比值（R值）评价法、脱漏率等对佳木斯市2018年常规免疫接种数据进行分析评价。结果 佳木斯市2018年常规免疫报告接种率的及时率和完整率均为100.00%;报告接种率98%以上,乙肝疫苗首针及时接种率为99.24%;以县区为单位报告接种率95%以上,乙肝疫苗首针及时接种率≥99.20%;各疫苗估算接种率范围在82.99%~108.46%;D值评价结果为可信的有脊髓灰质炎疫苗（OPV）加强、白喉百日咳破伤风联合疫苗（DPT）加强、麻风疫苗（MR）、A群流脑第一剂（MenA1）、乙脑疫苗第一剂（JE1）、JE2、白喉破伤风联合疫苗（DT）和甲肝疫苗（HepA）;可疑的有乙肝疫苗（HepB）、OPV基础、DPT基础、麻腮风疫苗（MMR）、MenA2、A+C群流脑第一剂（MenA+C1）和MenA+C2;不可信的只有卡介苗（BCG）。R值评价为R1、R3、R4和R6值为可信;R2、R5和R7值为可疑。OPV、DPT脱漏率分别为-2.82%和-2.34%,评价为可信;各县区仅同江市DPT脱漏率为-11.79%,评价为不可信,其余县区两种疫苗的脱漏率均在合理范围。结论 佳木斯市2018年常规免疫报告接种率、乙肝疫苗首针及时接种率均较高,达到国家、省的要求。D值评价和R值评价提示佳木斯市常规免疫工作质量较高,但有应种数掌握不准确,报告接种率虚高的问题。OPV、DPT脱漏率较低,提示这两种疫苗的保护性较好,但同江市的免疫规划工作质量需进一步加强。     

The control of childhood viral infections by pulse vaccination

Pulse vaccination, the repeated application of vaccine overa defined age range, is gaining prominence as a strategy forthe elimination of childhood viral infections such as measlesand polio. However, unlike routine or continuous mass infantimmunization, epidemiological understanding of this controlmethod is in its infancy. This paper develops initial work byAgur et al. (1993) using simple steady-state and age-structureddynamic models to extend the theory of the mechanism of actionof pulse vaccination, and to explore the relationship betweenthe maximum permitted interval between pulses and key epidemiological,demographic and vaccination variables. Initially, a conceptualmodel is presented to illustrate the principles of pulse vaccinationand to make comparison with routine immunization procedures.An ordinary differential equation model, which assumes homogeneousmixing, is then used to derive equilibrium expressions for thepulse interval in relation to (i) different demographic profiles,(ii) population growth characteristics (stationary or exponentially increasing), (iii) combined routine and pulse immunization,and (iv) the age range vaccinated. Finally, simulations usingage-structured compartmental determin istic models illustratecomplex epidemiological dynamics associated with pulse vaccination,particularly where there is age heterogeneity in contact ratesin the population. The resultant uncertainty in defining anoptimal pulse interval raises concerns of a practical nature.     

Postlicensure epidemiology of childhood vaccination: the Danish experience

The efficacy, the ability to confer protection against a target disease and the safety of a vaccine are assessed in great detail before licensure. However, inherent limitations in the prelicensure assessment necessitate continued epidemiological evaluations of efficacy and safety issues after the introduction of vaccines into use. In Denmark, the opportunities available for epidemiological research are unique. In 2001, an initiative was undertaken to take advantage of these opportunities to study the postlicensure epidemiology of childhood vaccination with respect to effectiveness and safety. First, we describe the unique opportunities for postlicensure research in Denmark with respect to the data sources available and the epidemiological and statistical methods used. We then describe a number of recent postlicensure studies of effectiveness and safety that took advantage of these opportunities. Specifically, studies on the effectiveness of Haemophilus influenzae type b vaccination, the effectiveness of pertussis vaccination, the impact of a preschool pertussis booster on infant pertussis, measles-mumps-rubella vaccine and autism, thimerosal-containing vaccine and autism, measles-mumps-rubella vaccine and febrile seizures, childhood vaccination and Type 1 diabetes, and childhood vaccination and nontargeted infectious disease are discussed.     

Long-term protection in children with meningococcal C conjugate vaccination: lessons learned

Owing to an increase in group C disease, extensive prelicensure studies have been funded by both the UK Department of Health and vaccine manufacturers. These demonstrated the safety and immunogenicity of three candidate meningococcal group C conjugate (MCC) vaccines (two conjugated to CRM(197) and one to tetanus toxoid) in the targeted age groups. Induction of immunological memory in infants and young children was also demonstrated by either a low dose of polysaccharide challenge following primary immunization with MCC or by an increase in avidity indices post-primary to pre-challenge. Immune memory after infant immunization persisted to at least 4 years of age, although antibody persistence in this age group was poor. MCC vaccine was introduced into the UK routine immunization schedule at 2, 3 and 4 months of age in 1999, with a catch-up as a single dose to all children aged 1-18 years with two doses for infants aged 5-11 months. The number of group C cases fell rapidly in the targeted age groups and early analyzes showed high vaccine effectiveness in all age groups together with significant herd immunity. However, when effectiveness was measured again more than 1 year after vaccination, there was a significant decline in all age groups, most marked in infants vaccinated in the routine infant immunization program, for whom there was no demonstrable efficacy after only 1 year and then in toddlers for whom efficacy declined to 61% (95% confidence interval: -327-94) from 88% (95% confidence interval: 65-96) in the first year. However, good disease control was maintained in the UK with only low numbers of vaccine failures. The assumption that immune memory was predictive of long-term protection is incorrect, at least after vaccination in infancy. Persistence of antibody and herd immunity may be more relevant for long-term disease control.     

Hepatitis A vaccines

The global disease burden associated with hepatitis A virus (HAV) is expected to increase in the coming years due to a shift in the epidemiological pattern of the disease. A decrease in the prevalence of natural immunity is leading to an increased number of adolescents and adults susceptible to a disease that is associated with greater morbidity, mortality and treatment costs in older-age groups. Current HAV vaccines have been shown to be safe, highly immunogenic and confer long-lasting protection against HAV disease. Vaccine-induced antibodies persist for more than 12 years in vaccinated adults and mathematical modeling predicts antibody persistence for more than 25 years in over 95% of vaccine recipients. However, the cost of HAV vaccines has been prohibitive for some countries. Recent studies in countries with transitioning HAV endemicity indicate that the cost-benefit ratio of mass vaccination against HAV would be similar to other routine childhood vaccinations.     

T-Cell Responses before and after the Fifth Consecutive Acellular Pertussis Vaccination in 4-Year-Old Dutch Children

Immunization with acellular pertussis vaccine (aP) induces higher specific antibody levels and fewer adverse reactions than does immunization with the whole-cell vaccine (wP). However, antibody levels in infants induced by both types of pertussis vaccines wane already after 1 year. Therefore, long-term T-cell responses upon vaccination might play a role in protection against pertussis. In a cross-sectional study (ISRCTN65428640), we investigated T-helper (Th) cell immune responses in wP- or aP-vaccinated children before and after an aP low-dose or high-dose preschool booster at 4 years of age in The Netherlands. T cells were stimulated with pertussis vaccine antigens. The numbers of gamma interferon-producing cells and Th1, Th2, Th17, and interleukin-10 (IL-10) cytokine concentrations were determined. In addition, pertussis-specific IgE levels were measured in plasma. Children being vaccinated with aP vaccinations at 2, 3, 4, and 11 months of age still showed higher pertussis-specific T-cell responses at 4 years of age than did wP-vaccinated children. These T-cell responses failed to show a typical increase in cytokine production after a fifth aP vaccination but remained high after a low-dose booster and seemed to decline even after a high-dose booster. Importantly, elevated IgE levels were induced after this booster vaccination. In contrast, wP-vaccinated children had only low prebooster T-cell responses, and these children showed a clear postbooster T-cell memory response even after a low-dose booster vaccine. Four high-dose aP vaccinations in infancy induce high T-cell responses still present even 3 years after vaccination and enhanced IgE responses after preschool booster vaccination. Therefore, studies of changes in vaccine dosage, timing of pertussis (booster) vaccinations, and the possible association with local side effects are necessary.     

Monitoring impact and effectiveness of rotavirus vaccination

Rotavirus infection is the most common cause of severe gastroenteritis in children <5 years of age globally. Since 2009, the WHO has recommended inclusion of rotavirus vaccine in the national immunization programs of all countries. Data regarding rotavirus vaccine impact and effectiveness under conditions of routine use are important for encouraging countries to implement vaccination programs. In the absence of a national rotavirus vaccination program in France, the IVANHOE study was initiated to determine the real-world impact and effectiveness of rotavirus vaccine following introduction in a limited geographic area. This study found a twofold reduction in rotavirus hospitalizations among children <2 years of age who were age-eligible to receive rotavirus vaccine and a 98% vaccine effectiveness, highlighting the health benefits of a vaccination program.     

Booster immunization of children with an acellular pertussis vaccine enhances Th2 cytokine production and serum IgE responses against pertussis toxin but not against common allergens

Acellular pertussis vaccines (Pa) protect against severe pertussis in children. However, serum antibody responses decline quickly after immunization. Studies in animal models suggest that cell-mediated immunity also contributes to protection against Bordetella pertussis, and it has already been demonstrated that Pa induce T cells that secrete type-1 and type-2 cytokines in children. In this study we examined the persistence of the T cell response and the effect of booster immunization in 4-6-year-old children. Cell-mediated immunity to B. pertussis antigens was detected in a high proportion of children more than 42 months after their last immunization. Peripheral blood mononuclear cells (PBMC) from the majority of children secreted interferon-gamma (IFN-gamma) and a smaller proportion IL-5, in response to specific antigen stimulation in vitro. However, following booster immunization, significantly higher concentrations of IL-5, but not IFN-gamma, were produced by PBMC in response to B. pertussis antigens. Furthermore, plasma IL-4 and IL-5 concentrations were increased, whereas IFN-gamma concentrations were reduced following booster immunization. It has been suggested that childhood immunization with Th2-inducing vaccines may predispose some children to atopic disease. Although we found that pertussis toxin (PT)-specific IgE was significantly increased after booster immunization in both atopic and non-atopic children, the levels of IgE to common allergens and the prevalence of positive skin prick test were unaffected by the booster vaccination. Thus, despite the enhancement of type-2 responses to B. pertussis antigens, booster vaccination with Pa does not appear to be a risk factor for allergy.     

Parental views on vaccine safety and future vaccinations of children who experienced an adverse event following routine or seasonal influenza vaccination in 2010

To assess parental vaccine safety views and future vaccination decisions after an adverse event following immunization (AEFI) experienced by their child. A cross-sectional telephone survey was conducted of parents of children aged 0-7 y, identified in AEFI reports submitted to the South Australian Immunization Section, Department Health. The reports included childhood National Immunization Program (NIP), seasonal or pandemic influenza vaccines. Interviews were conducted following a national suspension of the 2010 seasonal trivalent influenza (STIV) vaccine. Parental attitudes toward vaccine safety, reasons for reporting the AEFI and impact on future vaccination intent were assessed. Of 179 parents interviewed, 88% were confident in the safety of vaccines in general. Parents reporting an AEFI to the STIV were more likely to state the event had influenced future vaccination decisions than the NIP vaccine reporters (65% vs 14%, p < 0.001), with 63% stating refusal or hesitance to re-vaccinate their children against influenza. Media reports of the 2010 STIV program suspension was the most common reason for reporting an AEFI for parents of children who received an influenza vaccination. The AEFI experience did not impact on parental decision to continue with routine childhood NIP schedules, regardless of whether children received influenza or NIP vaccines. In contrast, most parents whose child experienced an AEFI to the 2010 STIV stated decreased confidence in the safety of influenza vaccines, which is likely to have impacted on the uptake of seasonal influenza vaccination in 2011. Addressing influenza vaccine safety concerns to promote influenza vaccination in the community is required.     

Shifts of Bordetella pertussis variants in Sweden from 1970 to 2003, during three periods marked by different vaccination programs

The Swedish population of Bordetella pertussis strains was characterized from 1,247 isolates covering a whole-cell vaccine program up to 1979, a 17-year period without vaccination (1979 to 1996), and a period after the introduction of general vaccination among newborns with acellular pertussis vaccines (1997 to 2003). Strains were characterized by serotyping and genotyping of pertactin and ptxA and by means of pulsed-field gel electrophoresis (PFGE). With emphasis on vaccine-related markers, the vast majority of circulating strains were of nonvaccine type. There were shifts of serotype connected with shifts of vaccination program. Serotype Fim3 was most frequent during the periods with general vaccination schedules, whereas serotype Fim2 was predominant during the 17-year vaccine-free period. Pertactin 1 was predominant during the pertussis whole-cell (Pw) vaccine period but was thereafter replaced by prn2 and has not reappeared after the introduction of acellular pertussis (Pa) vaccines. ptxA (1) was predominant over all three decades. There was a significant difference in the distribution of serotypes between vaccinated and unvaccinated individuals, but not for pertactin. A few PFGE profiles were predominant over the years: BpSR25 (serotype Fim3 prn1/7) and BpSR18 (serotype Fim3 prn2) during the Pw period, BpSR1 (serotype Fim2 prn2) during the 17 years without general vaccination, and BpSR11 (serotype Fim3 prn2) after the reintroduction of general vaccination in 1996. Despite differences between the pertactin and toxin types of Pa vaccines and circulating strains, there is no evidence that there is a threat, i.e., the vaccination program so far has been effective against whooping cough, and there seems to be no impact on the effectiveness of the vaccination program from the bacterial polymorphism.     

Emerging issues in vaccine economics: perspectives from the USA

Economic studies of vaccines, including vaccine development and delivery issues, are increasingly needed to inform policy recommendations and programmatic decisions in the USA. This need arises from the increasing costs of vaccines, the complexity of the US healthcare system and the limited number of vaccine manufacturers in the market. We have developed a national research agenda in domestic and global vaccine economics by conducting key informant interviews with 42 experts and inviting ideas from an additional 128 experts. To assess priorities among the 129 ideas that were generated, we asked 15 experts representing a broad range of perspectives to rank the ideas and we analyzed their votes. The highest-ranking domestic research ideas included evaluating: the costs of vaccine shortages, the cost-effectiveness of potential human papillomavirus vaccination and adult and adolescent pertussis vaccination programs and the cost-effectiveness of universal vaccine purchase programs for adults as well as children. The highest-ranking globally-oriented ideas included developing a resource allocation model to support the best vaccination program decisions with limited funds and assessing the cost-effectiveness of HIV, rotavirus, meningococcal and malaria vaccines in developing countries. To optimize the usefulness of vaccine economics research, conceptual issues, such as how to set values for the prevention of illness and how to maximize social equity through investments in vaccines, must be addressed.