Dynamic Modeling of Vaccinating Behavior as a Function of Individual Beliefs

Individual perception of vaccine safety is an important factor in determining a person's adherence to a vaccination program and its consequences for disease control. This perception, or belief, about the safety of a given vaccine is not a static parameter but a variable subject to environmental influence. To complicate matters, perception of risk (or safety) does not correspond to actual risk. In this paper we propose a way to include the dynamics of such beliefs into a realistic epidemiological model, yielding a more complete depiction of the mechanisms underlying the unraveling of vaccination campaigns. The methodology proposed is based on Bayesian inference and can be extended to model more complex belief systems associated with decision models. We found the method is able to produce behaviors which approximate what has been observed in real vaccine and disease scare situations. The framework presented comprises a set of useful tools for an adequate quantitative representation of a common yet complex public-health issue. These tools include representation of beliefs as Bayesian probabilities, usage of logarithmic pooling to combine probability distributions representing opinions, and usage of natural conjugate priors to efficiently compute the Bayesian posterior. This approach allowed a comprehensive treatment of the uncertainty regarding vaccination behavior in a realistic epidemiological model.     

Risk perception,risk management and safety assessment: What can governments do to increase public confidence in their vaccine system?

For decades vaccine program managers and governments have devoted many resources to addressing public vaccine concerns, vaccine risk perception, risk management and safety assessment. Despite ever growing evidence that vaccines are safe and effective, public concerns continue. Education and evidence based scientific messages have not ended concerns. How can governments and programs more effectively address the public’s vaccine concerns and increase confidence in the vaccine safety system? Vaccination hesitation has been attributed to concerns about vaccine safety, perceptions of high vaccine risks and low disease risk and consequences. Even when the public believes vaccines are important for protection many still have concerns about vaccine safety. This overview explores how heuristics affect public perception of vaccines and vaccine safety, how the public finds and uses vaccine information, and then proposes strategies for changes in the approach to vaccine safety communications. Facts and evidence confirming the safety of vaccines are not enough. Vaccine beliefs and behaviours must be shaped. This will require a shift in the what, when, how and why of vaccine risk and benefit communication content and practice. A change to a behavioural change strategy such as the WHO COMBI program that has been applied to disease eradication efforts is suggested.     

Determinants of refusal of A/H1N1 pandemic vaccination in a high risk population: a qualitative approach

Background

Our study analyses the main determinants of refusal or acceptance of the 2009 A/H1N1 vaccine in patients with cystic fibrosis, a high-risk population for severe flu infection, usually very compliant for seasonal flu vaccine.

Methodology/Principal Findings

We conducted a qualitative study based on semi-structured interviews in 3 cystic fibrosis referral centres in Paris, France. The study included 42 patients with cystic fibrosis: 24 who refused the vaccine and 18 who were vaccinated. The two groups differed quite substantially in their perceptions of vaccine- and disease-related risks. Those who refused the vaccine were motivated mainly by the fears it aroused and did not explicitly consider the 2009 A/H1N1 flu a potentially severe disease. People who were vaccinated explained their choice, first and foremost, as intended to prevent the flu''s potential consequences on respiratory cystic fibrosis disease. Moreover, they considered vaccination to be an indirect collective prevention tool. Patients who refused the vaccine mentioned multiple, contradictory information sources and did not appear to consider the recommendation of their local health care provider as predominant. On the contrary, those who were vaccinated stated that they had based their decision solely on the clear and unequivocal advice of their health care provider.

Conclusions/Significance

These results of our survey led us to formulate three main recommendations for improving adhesion to new pandemic vaccines. (1) it appears necessary to reinforce patient education about the disease and its specific risks, but also general population information about community immunity. (2) it is essential to disseminate a clear and effective message about the safety of novel vaccines. (3) this message should be conveyed by local health care providers, who should be involved in implementing immunization.     

How Is Vaccine Effectiveness Scaled by the Transmission Dynamics of Interacting Pathogen Strains with Cross-Protective Immunity?

Background

Many novel vaccines can cover only a fraction of all antigenic types of a pathogen. Vaccine effectiveness (VE) in the presence of interactions between vaccine strains and others is complicated by the interacting transmission dynamics among all strains. The present study investigated how the VE estimates measured in the field, based on estimated odds ratio or relative risks, are scaled by vaccination coverage and the transmission dynamics in the presence of cross-protective immunity between two strains, i.e. vaccine and non-vaccine strains.

Methodology/Principal Findings

Two different types of epidemiological models, i.e. with and without re-infection by the same antigenic type, were investigated. We computed the relative risk of infection and the odds ratio of vaccination, the latter of which has been measured by indirect cohort method as applied to vaccine effectiveness study of Streptococcus pneumoniae. The VE based on the relative risk was less sensitive to epidemiological dynamics such as cross-protective immunity and vaccination coverage than the VE calculated from the odds ratio, and this was especially the case for the model without re-infection. Vaccine-induced (cross-protective) immunity against a non-vaccine strain appeared to yield the highest impact on the VE estimate calculated from the odds ratio of vaccination.

Conclusion

It is essential to understand the transmission dynamics of non-vaccine strains so that epidemiological methods can appropriately measure both the direct and indirect population impact of vaccination. For pathogens with interacting antigenic types, the most valid estimates of VE, that are unlikely to be biased by the transmission dynamics, may be obtained from longitudinal prospective studies that permit estimation of the VE based on the relative risk of infection among vaccinated compared to unvaccinated individuals.     

The importance of non-pharmaceutical interventions during the COVID-19 vaccine rollout

The promise of efficacious vaccines against SARS-CoV-2 is fulfilled and vaccination campaigns have started worldwide. However, the fight against the pandemic is far from over. Here, we propose an age-structured compartmental model to study the interplay of disease transmission, vaccines rollout, and behavioural dynamics. We investigate, via in-silico simulations, individual and societal behavioural changes, possibly induced by the start of the vaccination campaigns, and manifested as a relaxation in the adoption of non-pharmaceutical interventions. We explore different vaccination rollout speeds, prioritization strategies, vaccine efficacy, as well as multiple behavioural responses. We apply our model to six countries worldwide (Egypt, Peru, Serbia, Ukraine, Canada, and Italy), selected to sample diverse socio-demographic and socio-economic contexts. To isolate the effects of age-structures and contacts patterns from the particular pandemic history of each location, we first study the model considering the same hypothetical initial epidemic scenario in all countries. We then calibrate the model using real epidemiological and mobility data for the different countries. Our findings suggest that early relaxation of safe behaviours can jeopardize the benefits brought by the vaccine in the short term: a fast vaccine distribution and policies aimed at keeping high compliance of individual safe behaviours are key to mitigate disease resurgence.     

Healthy Bodies,Toxic Medicines: College Students and the Rhetorics of Flu Vaccination

This article examines flu vaccination beliefs and practices produced during a survey of undergraduate students in Spring 2012 (IRB#10-732). This research uses the methods of rhetorical analysis — or the study of persuasive features and arguments used in language — to examine statements respondents made regarding flu and flu vaccine. In these responses, students generated unique categories of arguments about the perceived dangers of flu vaccination, including the assertion that vaccines cause disease (including illnesses and conditions other than flu), that vaccines are toxic medicines, and that vaccines carry unknown, population-wide risks that are inadequately acknowledged. This study provides insight into vaccination beliefs and rationales among a population at risk of flu (college students) and suggests that further study of this population may yield important keys to addressing flu vaccine concerns as expressed by college students. Rhetorical analysis also offers a useful set of methods to understanding vaccination beliefs and practices, adding to existing methods of study and analysis of vaccination practices and beliefs in medicine and public health.     

Veterinary and human vaccine evaluation methods

Despite the universal importance of vaccines, approaches to human and veterinary vaccine evaluation differ markedly. For human vaccines, vaccine efficacy is the proportion of vaccinated individuals protected by the vaccine against a defined outcome under ideal conditions, whereas for veterinary vaccines the term is used for a range of measures of vaccine protection. The evaluation of vaccine effectiveness, vaccine protection assessed under routine programme conditions, is largely limited to human vaccines. Challenge studies under controlled conditions and sero-conversion studies are widely used when evaluating veterinary vaccines, whereas human vaccines are generally evaluated in terms of protection against natural challenge assessed in trials or post-marketing observational studies. Although challenge studies provide a standardized platform on which to compare different vaccines, they do not capture the variation that occurs under field conditions. Field studies of vaccine effectiveness are needed to assess the performance of a vaccination programme. However, if vaccination is performed without central co-ordination, as is often the case for veterinary vaccines, evaluation will be limited. This paper reviews approaches to veterinary vaccine evaluation in comparison to evaluation methods used for human vaccines. Foot-and-mouth disease has been used to illustrate the veterinary approach. Recommendations are made for standardization of terminology and for rigorous evaluation of veterinary vaccines.     

Modeling malaria vaccines. II: Population effects of stage-specific malaria vaccines dependent on natural boosting

Population effects of malaria vaccination programs will depend on the stage specificity of the vaccine, its duration of effectiveness, whether it is responsive to natural boosting, the proportion vaccinated, and the preexisting endemic conditions. This paper develops models of infection-blocking (sporozoite), disease-modifying (merozoite), and transmission-blocking (gametic) vaccines. It explores numerically their different effects on prevalence of infection and disease when utilized in different types of immunization programs at various levels of coverage. Simulations show that possible qualitative consequences of malaria vaccination programs include decreased prevalence of infection and disease and decreased prevalence of infection without a corresponding decrease in prevalence of disease. Epidemics, either one-time or cyclical, could occur. These effects could be accompanied by changes in the age distribution of disease. Finally, vaccination could contribute to elimination of transmission. The duration of effectiveness of the malaria vaccine relative to the duration of natural immunity could have important consequences for the unvaccinated. The problem of predicting a threshold for elimination of transmission is discussed.     

Evolving public perceptions and stability in vaccine uptake

Recent vaccine scares and sudden spikes in vaccine demand remind us that the effectiveness of mass vaccination programs is governed by the public perception of vaccination. Previous work has shown that the tendency of individuals to optimize self-interest can lead to vaccination levels that are suboptimal for a community. We use game theory to relate population-level demand for vaccines to decision-making by individuals with varied beliefs about the costs of infection and vaccination. In contrast to previous work proposing that universal vaccination is impossible in a game theoretic context, we show that optimal individual behavior can vary between universal vaccination and no vaccination, depending on the relative costs and benefits to individuals. By coupling game models and epidemic models, we demonstrate that the pursuit of self-interest often leads to stable dynamics but can lead to oscillations in vaccine uptake over time. The instability is exacerbated in populations that are more homogeneous with respect to their perceptions of vaccine and infection risks. This research illustrates the importance of applying temporal models to an inherently temporal situation, namely, the time evolution of vaccine coverage in an informed population with a voluntary vaccination policy.     

Public health: the control of meningococcal disease in Quebec

A first outbreak of serogroup C meningococcal disease occurred in the province of Quebec in 1990-1992 and lead to a mass immunization campaign using polysaccharide vaccines. In 2001, a second outbreak was identified and a mass vaccination campaign was carried out, using the newly licensed conjugate vaccine. Clinical, epidemiological, economic and social studies were instrumental in the decision making for implementing these control programs.     

The Effect of Perceived Risks on the Demand for Vaccination: Results from a Discrete Choice Experiment

The demand for vaccination against infectious diseases involves a choice between vaccinating and not vaccinating, in which there is a trade-off between the benefits and costs of each option. The aim of this paper is to investigate these trade-offs and to estimate how the perceived prevalence and severity of both the disease against which the vaccine is given and any vaccine associated adverse events (VAAE) might affect demand. A Discrete Choice Experiment (DCE) was used to elicit stated preferences from a representative sample of 369 UK mothers of children below 5 years of age, for three hypothetical vaccines. Cost was included as an attribute, which enabled estimation of the willingness to pay for different vaccines having differing levels of the probability of occurrence and severity of both the infection and VAAE. The results suggest that the severity of the health effects associated with both the diseases and VAAEs exert an important influence on the demand for vaccination, whereas the probability of these events occurring was not a significant predictor. This has important implications for public health policy, which has tended to focus on the probability of these health effects as the main influence on decision making. Our results also suggest that anticipated regrets about the consequences of making the wrong decision also exert an influence on demand.     

Multiplex real-time quantitative PCR, microscopy and rapid diagnostic immuno-chromatographic tests for the detection of Plasmodium spp : performance, limit of detection analysis and quality assurance

Background

A wide range of possible malaria vaccines is being considered and there is a need to identify which vaccines should be prioritized for clinical development. An important element of the information needed for this prioritization is a prediction of the cost-effectiveness of potential vaccines in the transmission settings in which they are likely to be deployed. This analysis needs to consider a range of delivery modalities to ensure that clinical development plans can be aligned with the most appropriate deployment strategies.

Methods

The simulations are based on a previously published individual-based stochastic model for the natural history and epidemiology of Plasmodium falciparum malaria. Three different vaccine types: pre-erythrocytic vaccines (PEV), blood stage vaccines (BSV), mosquito-stage transmission-blocking vaccines (MSTBV), and combinations of these, are considered each delivered via a range of delivery modalities (Expanded Programme of Immunization – EPI-, EPI with booster, and mass vaccination combined with EPI). The cost-effectiveness ratios presented are calculated for four health outcomes, for assumed vaccine prices of US$ 2 or US$ 10 per dose, projected over a 10-year period.

Results

The simulations suggest that PEV will be more cost-effective in low transmission settings, while BSV at higher transmission settings. Combinations of BSV and PEV are more efficient than PEV, especially in moderate to high transmission settings, while compared to BSV they are more cost-effective in moderate to low transmission settings. Combinations of MSTBV and PEV or PEV and BSV improve the effectiveness and the cost-effectiveness compared to PEV and BSV alone only when applied with EPI and mass vaccinations. Adding booster doses to the EPI is unlikely to be a cost-effective alternative to delivering vaccines via the EPI for any vaccine, while mass vaccination improves effectiveness, especially in low transmission settings, and is often a more efficient alternative to the EPI. However, the costs of increasing the coverage of mass vaccination over 50% often exceed the benefits.

Conclusion

The simulations indicate malaria vaccines might be efficient malaria control interventions, and that both transmission setting and vaccine delivery modality are important to their cost-effectiveness. Alternative vaccine delivery modalities to the EPI may be more efficient than the EPI. Mass vaccination is predicted to provide substantial health benefits at low additional costs, although achieving high coverage rates can lead to substantial incremental costs.     

Acceptance of Vaccinations in Pandemic Outbreaks: A Discrete Choice Experiment

Background

Preventive measures are essential to limit the spread of new viruses; their uptake is key to their success. However, the vaccination uptake in pandemic outbreaks is often low. We aim to elicit how disease and vaccination characteristics determine preferences of the general public for new pandemic vaccinations.

Methods

In an internet-based discrete choice experiment (DCE) a representative sample of 536 participants (49% participation rate) from the Dutch population was asked for their preference for vaccination programs in hypothetical communicable disease outbreaks. We used scenarios based on two disease characteristics (susceptibility to and severity of the disease) and five vaccination program characteristics (effectiveness, safety, advice regarding vaccination, media attention, and out-of-pocket costs). The DCE design was based on a literature review, expert interviews and focus group discussions. A panel latent class logit model was used to estimate which trade-offs individuals were willing to make.

Results

All above mentioned characteristics proved to influence respondents’ preferences for vaccination. Preference heterogeneity was substantial. Females who stated that they were never in favor of vaccination made different trade-offs than males who stated that they were (possibly) willing to get vaccinated. As expected, respondents preferred and were willing to pay more for more effective vaccines, especially if the outbreak was more serious (€6–€39 for a 10% more effective vaccine). Changes in effectiveness, out-of-pocket costs and in the body that advises the vaccine all substantially influenced the predicted uptake.

Conclusions

We conclude that various disease and vaccination program characteristics influence respondents’ preferences for pandemic vaccination programs. Agencies responsible for preventive measures during pandemics can use the knowledge that out-of-pocket costs and the way advice is given affect vaccination uptake to improve their plans for future pandemic outbreaks. The preference heterogeneity shows that information regarding vaccination needs to be targeted differently depending on gender and willingness to get vaccinated.     

植物口服疫苗的研究进展

植物口服疫苗是通过转基因植物生产,通过口服的方式预防疾病的生物制品.作为一种新型疫苗,其研究开始于三十几年前.由于植物口服疫苗可以最大程度地降低传统疫苗的潜在风险,在疫苗生产中具有优势,因此拥有良好的商业生产前景.植物疫苗价格低廉,生产过程安全,可产生与注射疫苗相似效价效果,无论是在控制养殖业抗生素滥用的情况下作为替代...     

Imperfect vaccine aggravates the long-standing dilemma of voluntary vaccination

Achieving widespread population immunity by voluntary vaccination poses a major challenge for public health administration and practice. The situation is complicated even more by imperfect vaccines. How the vaccine efficacy affects individuals' vaccination behavior has yet to be fully answered. To address this issue, we combine a simple yet effective game theoretic model of vaccination behavior with an epidemiological process. Our analysis shows that, in a population of self-interested individuals, there exists an overshooting of vaccine uptake levels as the effectiveness of vaccination increases. Moreover, when the basic reproductive number, R0, exceeds a certain threshold, all individuals opt for vaccination for an intermediate region of vaccine efficacy. We further show that increasing effectiveness of vaccination always increases the number of effectively vaccinated individuals and therefore attenuates the epidemic strain. The results suggest that 'number is traded for efficiency': although increases in vaccination effectiveness lead to uptake drops due to free-riding effects, the impact of the epidemic can be better mitigated.     

Pneumococcal Transmission and Disease In Silico: A Microsimulation Model of the Indirect Effects of Vaccination

Background

The degree and time frame of indirect effects of vaccination (serotype replacement and herd immunity) are key determinants in assessing the net effectiveness of vaccination with pneumococcal conjugate vaccines (PCV) in control of pneumococcal disease. Using modelling, we aimed to quantify these effects and their dependence on coverage of vaccination and the vaccine''s efficacy against susceptibility to pneumococcal carriage.

Methods and Findings

We constructed an individual-based simulation model that explores the effects of large-scale PCV programmes and applied it in a developed country setting (Finland). A population structure with transmission of carriage taking place within relevant mixing groups (families, day care groups, schools and neighbourhoods) was considered in order to properly assess the dependency of herd immunity on coverage of vaccination and vaccine efficacy against carriage. Issues regarding potential serotype replacement were addressed by employing a novel competition structure between multiple pneumococcal serotypes. Model parameters were calibrated from pre-vaccination data about the age-specific carriage prevalence and serotype distribution. The model predicts that elimination of vaccine-type carriage and disease among those vaccinated and, due to a substantial herd effect, also among the general population takes place within 5–10 years since the onset of a PCV programme with high (90%) coverage of vaccination and moderate (50%) vaccine efficacy against acquisition of carriage. A near-complete replacement of vaccine-type carriage by non-vaccine-type carriage occurs within the same time frame.

Conclusions

The changed patterns in pneumococcal carriage after PCV vaccination predicted by the model are unequivocal. The overall effect on disease incidence depends crucially on the magnitude of age- and serotype-specific case-to-carrier ratios of the remaining serotypes relative to those of the vaccine types. Thus the availability of reliable data on the incidence of both pneumococcal carriage and disease is essential in assessing the net effectiveness of PCV vaccination in a given epidemiological setting.     

Lipid and carbohydrate based adjuvant/carriers in immunology.

This review discusses various issues regarding vaccines; what are they and how they work, safety aspects, the role of adjuvants and carriers in vaccination, synthetic peptides as immunogens, and new technologies for vaccine development and delivery including the identification of novel adjuvants for mucosal vaccine delivery. There has been a recent increase of interest in the use of lipids and carbohydrates as adjuvants, and so a particular emphasis is placed on adjuvants derived from lipids or carbohydrates, or from both.     

The evolutionary consequences of alternative types of imperfect vaccines

The emergence and spread of mutant pathogens that evade the effects of prophylactic interventions, including vaccines, threatens our ability to control infectious diseases globally. Imperfect vaccines (e.g. those used against influenza), while not providing life-long immunity, confer protection by reducing a range of pathogen life-history characteristics; conversely, mutant pathogens can gain an advantage by restoring the same range of traits in vaccinated hosts. Using an SEIR model motivated by equine influenza, we investigate the evolutionary consequences of alternative types of imperfect vaccination, by comparing the spread rate of three types of mutant pathogens, in response to three types of vaccines. All mutant types spread faster in response to a transmission-blocking vaccine, relative to vaccines that reduce the proportion of exposed vaccinated individuals becoming infectious, and to vaccines that reduce the length of the infectious period; this difference increases with increasing vaccine efficacy. We interpret our results using the first published Price equation formulation for an SEIR model, and find that our main result is explained by the effects of vaccines on the equilibrium host distribution across epidemiological classes. In particular, the proportion of vaccinated infectious individuals among all exposed and infectious hosts, which is relatively higher in the transmission-blocking vaccine scenario, is important in explaining the faster spread of mutant strains in response to that vaccine. Our work illustrates the connection between epidemiological and evolutionary dynamics, and the need to incorporate both in order to explain and interpret findings of complicated infectious disease dynamics.