CONSCIENTIOUS OBJECTIONS IN PHARMACY PRACTICE IN GREAT BRITAIN

Pharmacists who refuse to provide certain services or treatment for reasons of conscience have been criticized for failing to fulfil their professional obligations. Currently, individual pharmacists in Great Britain can withhold services or treatment for moral or religious reasons, provided they refer the patient to an alternative source. The most high‐profile cases have concerned the refusal to supply emergency hormonal contraception, which will serve as an example in this article. I propose that the pharmacy profession's policy on conscientious objections should be altered slightly. Building on the work of Brock and Wicclair, I argue that conscientious refusals should be acceptable provided that the patient is informed of the service, the patient is redirected to an alternative source, the refusal does not cause an unreasonable burden to the patient, and the reasons for the refusal are based on the core values of the profession. Finally, I argue that a principled categorical refusal by an individual pharmacist is not morally permissible. I claim that, contrary to current practice, a pharmacist cannot legitimately claim universal exemption from providing a standard service, even if that service is available elsewhere.     

Individual and collective considerations in public health: influenza vaccination in nursing homes

Many nursing homes have an influenza vaccination policy in which it is assumed that express (proxy) consent is not necessary. Tacit consent procedures are more efficient if one aims at high vaccination rates. In this paper I focus on incompetent residents and proxy consent. Tacit proxy consent for vaccination implies a deviance of standard proxy consent requirements. I analyse several arguments that may possibly support such a deviance. The primary reason to offer influenza vaccination is that vaccinated persons have a significantly reduced risk of getting the flu. This reason however cannot support the assumption that each nursing home resident is 'better off ' if she is vaccinated. Neither can it support tacit proxy consent policies. More promising are arguments that take the collective nature of infectious diseases into account. A potentially strong, but ultimately insufficient, argument for non-express consent is that vaccination contributes to prevention of harm to others. Other arguments emphasise the importance of group protection: herd immunity. I discuss three collective reasons for aiming at herd immunity: solidarity, a common interest in reducing the risk of illness, and a common interest in the prevention of an influenza outbreak. The latter argument appears to be most important. An outbreak is not just detrimental to the health of residents; it is detrimental to their everyday social life as well. Outbreaks can be seen as a collective evil. My analysis shows that there are valid (though not necessarily sufficient) moral arguments for a tacit proxy consent policy.     

Impact of vaccination and birth rate on the epidemiology of pertussis: a comparative study in 64 countries

Bordetella pertussis infection remains an important public health problem worldwide despite decades of routine vaccination. A key indicator of the impact of vaccination programmes is the inter-epidemic period, which is expected to increase with vaccine uptake if there is significant herd immunity. Based on empirical data from 64 countries across the five continents over the past 30–70 years, we document the observed relationship between the average inter-epidemic period, birth rate and vaccine coverage. We then use a mathematical model to explore the range of scenarios for duration of immunity and transmission resulting from repeat infections that are consistent with empirical evidence. Estimates of pertussis periodicity ranged between 2 and 4.6 years, with a strong association with susceptible recruitment rate, defined as birth rate × (1 − vaccine coverage). Periodicity increased by 1.27 years on average after the introduction of national vaccination programmes (95% CI: 1.13, 1.41 years), indicative of increased herd immunity. Mathematical models suggest that the observed patterns of pertussis periodicity are equally consistent with loss of immunity that is not as rapid as currently thought, or with negligible transmission generated by repeat infections. We conclude that both vaccine coverage and birth rate drive pertussis periodicity globally and that vaccination induces strong herd immunity effects. A better understanding of the role of repeat infections in pertussis transmission is critical to refine existing control strategies.     

The influence of social norms on the dynamics of vaccinating behaviour for paediatric infectious diseases

Mathematical models that couple disease dynamics and vaccinating behaviour often assume that the incentive to vaccinate disappears if disease prevalence is zero. Hence, they predict that vaccine refusal should be the rule, and elimination should be difficult or impossible. In reality, countries with non-mandatory vaccination policies have usually been able to maintain elimination or very low incidence of paediatric infectious diseases for long periods of time. Here, we show that including injunctive social norms can reconcile such behaviour-incidence models to observations. Adding social norms to a coupled behaviour-incidence model enables the model to better explain pertussis vaccine uptake and disease dynamics in the UK from 1967 to 2010, in both the vaccine-scare years and the years of high vaccine coverage. The model also illustrates how a vaccine scare can perpetuate suboptimal vaccine coverage long after perceived risk has returned to baseline, pre-vaccine-scare levels. However, at other model parameter values, social norms can perpetuate depressed vaccine coverage during a vaccine scare well beyond the time when the population''s baseline vaccine risk perception returns to pre-scare levels. Social norms can strongly suppress vaccine uptake despite frequent outbreaks, as observed in some small communities. Significant portions of the parameter space also exhibit bistability, meaning long-term outcomes depend on the initial conditions. Depending on the context, social norms can either support or hinder immunization goals.     

Delays in the primary vaccination of children.

The results of a population-based survey of 170 children''s vaccination records were used to calculate the cumulative distributions of the ages (in months) at which each dose of vaccine had been received. Considerable delays in the administration of measles-mumps-rubella (MMR) vaccine and of the fourth dose of diphtheria-pertussis-tetanus vaccine were observed, particularly in children vaccinated by private physicians rather than at public health clinics. The delay before MMR vaccination causes concern because of the frequency of measles in children aged 1 to 2 years, particularly those attending day-care centres, and the fragility of the herd immunity against this disease. Physicians should follow up patients who have missed appointments for MMR vaccination if a voluntary measles control program is to succeed.     

Disease persistence in epidemiological models: the interplay between vaccination and migration

We consider the interplay of vaccination and migration rates on disease persistence in epidemiological systems. We show that short-term and long-term migration can inhibit disease persistence. As a result, we show how migration changes how vaccination rates should be chosen to maintain herd immunity. In a system of coupled SIR models, we analyze how disease eradication depends explicitly on vaccine distribution and migration connectivity. The analysis suggests potentially novel vaccination policies that underscore the importance of optimal placement of finite resources.     

The effects of influenza vaccination of health care workers in nursing homes: insights from a mathematical model

Background

Annual influenza vaccination of institutional health care workers (HCWs) is advised in most Western countries, but adherence to this recommendation is generally low. Although protective effects of this intervention for nursing home patients have been demonstrated in some clinical trials, the exact relationship between increased vaccine uptake among HCWs and protection of patients remains unknown owing to variations between study designs, settings, intensity of influenza seasons, and failure to control all effect modifiers. Therefore, we use a mathematical model to estimate the effects of HCW vaccination in different scenarios and to identify a herd immunity threshold in a nursing home department.

Methods and Findings

We use a stochastic individual-based model with discrete time intervals to simulate influenza virus transmission in a 30-bed long-term care nursing home department. We simulate different levels of HCW vaccine uptake and study the effect on influenza virus attack rates among patients for different institutional and seasonal scenarios. Our model reveals a robust linear relationship between the number of HCWs vaccinated and the expected number of influenza virus infections among patients. In a realistic scenario, approximately 60% of influenza virus infections among patients can be prevented when the HCW vaccination rate increases from 0 to 1. A threshold for herd immunity is not detected. Due to stochastic variations, the differences in patient attack rates between departments are high and large outbreaks can occur for every level of HCW vaccine uptake.

Conclusions

The absence of herd immunity in nursing homes implies that vaccination of every additional HCW protects an additional fraction of patients. Because of large stochastic variations, results of small-sized clinical trials on the effects of HCW vaccination should be interpreted with great care. Moreover, the large variations in attack rates should be taken into account when designing future studies.     

The smallpox vaccine: a multidimensional model of choice

Following September 11, 2001, the U.S. government increased its efforts to prepare for future attacks, including those using dangerous biological agents such as smallpox. The smallpox vaccination program called for vaccinating military personnel and smallpox response teams, including healthcare workers and other first responders. The program of vaccinating healthcare workers was largely unsuccessful; few individuals volunteered to be vaccinated, highlighting the importance of understanding the factors that influence choice regarding this complex medical decision. This study examined stated choice and how it was associated with risk perceptions, knowledge, psychological distress, and general vaccine beliefs using a five-dimensional choice model. The model used multivariable modeling strategies in a sample of 256 undergraduate, graduate, and medical students. Sixty-three percent of the sample stated that they would elect to receive the smallpox vaccination. Multiple factors were related to stated choice in multivariable models, including perceived risk/worry, general vaccine beliefs, decisional conflict, and gender. However, the models were more successful at predicting acceptance of the vaccination than vaccine refusal. Although support was obtained for a multidimensional model of choice, several questions were raised by our results, including (a) whether refusal of smallpox vaccination can be more effectively characterized, possibly with additional questions; (b) whether the model translates to actual vaccination behavior; and (c) whether the model describes choice in more at-risk samples (e.g., first responders, healthcare workers). A multidimensional modeling approach should facilitate these and other studies of choice.     

The impact of specific and non-specific immunity on the ecology of Streptococcus pneumoniae and the implications for vaccination

More than 90 capsular serotypes of Streptococcus pneumoniae coexist despite competing for nasopharyngeal carriage and a gradient in fitness. The underlying mechanisms for this are poorly understood and make assessment of the likely population impact of vaccination challenging. We use an individual-based simulation model to generalize widely used deterministic models for pneumococcal competition and show that in these models short-term serotype-specific and serotype non-specific immunity could constitute the mechanism governing between-host competition and coexistence. We find that non-specific immunity induces between-host competition and that serotype-specific immunity limits a type''s competitive advantage and allows stable coexistence of multiple serotypes. Serotypes carried at low prevalence show high variance in carriage levels, which would result in apparent outbreaks if they were highly pathogenic. Vaccination against few serotypes can lead to elimination of the vaccine types and induces replacement by others. However, in simulations where the elimination of the targeted types is achieved only by a combination of vaccine effects and the competitive pressure of the non-vaccine types, a universal vaccine with similar-type-specific effectiveness can fail to eliminate pneumococcal carriage and offers limited herd immunity. Hence, if vaccine effects are insufficient to control the majority of serotypes at the same time, then exploiting the competitive pressure by selective vaccination can help control the most pathogenic serotypes.     

Irradiated vaccines for helminth control in livestock

For nearly 40 years, irradiated larval vaccines have been available for the control of parasitic bronchitis in cattle and sheep caused by Dictyocaulus spp. Despite research on a number of other host/parasite systems, no other vaccines have been commercially successful. Vaccination could provide a useful addition to other control methods in an integrated parasite management system where the criteria for vaccine success may not be complete control and sterile immunity, but a sufficient reduction in worm burden to decrease overall reinfection levels at the flock/herd level and, hence, prevent clinical disease and subclinical effects including production loss. Indeed, vaccination against Dictyocaulus spp. relies on continued natural infection to maintain levels of immunity. However, the difficulties of producing live larval vaccines are often cited as a reason why this line of research should not be pursued. This paper discusses some of the difficulties in vaccine production and offers some solutions and recommendations for those wishing to develop and register irradiated larval vaccines for other helminth diseases.     

Immunological surveys of antibodies against B. pertussis and B. parapertussis in some African and Asian countries.

Immunological surveys in African and Asian countries showed a different degree of herd immunity in the respective countries and the circulation of various types of B. pertussis. Antibodies against B. parapertussis, the second aertiological agent of whooping cough, were found in all countries in all age groups. Before planning any vaccination program, attention should be paid to the vaccine concerning the content of all types of B. pertussis, as was shown in the results of the testing of different vaccines used in Mongolia and Algeria. It is also possible to estimate the age limit for vaccination and thus economic use of the vaccine. The contemporary state of reporting whooping cough cases is very unsatisfactory.     

A spatial vaccination strategy to reduce the risk of vaccine-resistant variants

The COVID-19 pandemic demonstrated that the process of global vaccination against a novel virus can be a prolonged one. Social distancing measures, that are initially adopted to control the pandemic, are gradually relaxed as vaccination progresses and population immunity increases. The result is a prolonged period of high disease prevalence combined with a fitness advantage for vaccine-resistant variants, which together lead to a considerably increased probability for vaccine escape. A spatial vaccination strategy is proposed that has the potential to dramatically reduce this risk. Rather than dispersing the vaccination effort evenly throughout a country, distinct geographic regions of the country are sequentially vaccinated, quickly bringing each to effective herd immunity. Regions with high vaccination rates will then have low infection rates and vice versa. Since people primarily interact within their own region, spatial vaccination reduces the number of encounters between infected individuals (the source of mutations) and vaccinated individuals (who facilitate the spread of vaccine-resistant strains). Thus, spatial vaccination may help mitigate the global risk of vaccine-resistant variants.     

Lassa fever: implications of T-cell immunity for vaccine development.

Lassa fever is a re-emerging viral hemorrhagic fever, which causes significant human morbidity in endemic regions of West Africa. Attempts to vaccinate against this virus in animal models including non-human primates have revealed that eliciting a strong cellular immune response protects from clinical disease, but not infection, in the absence of measurable neutralizing antibodies. As there is renewed interest in developing a vaccine against Lassa fever for use in humans, several questions should be addressed in view of the scarce knowledge of the mechanisms of natural immunity against this disease. MHC-dependency of a vaccine relying mainly on the induction of T-cell immunity and its ability to cross-protect against different Lassa virus strains will be important issues. Furthermore, the question whether the vaccine can prevent human-to-human transmission of the virus should be discussed and the possibility that vaccination could predispose to immunopathology should be excluded. We are addressing some of the above mentioned problems concerning natural immunity through field studies in the Republic of Guinea, West Africa, and are presently studying the CD4 cell responses of Lassa antibody positive subjects on the basis of T-cell proliferation assays using recombinant Lassa virus proteins.     

Pertussis in England and Wales: an investigation of transmission dynamics and control by mass vaccination

The epidemiology of pertussis and its prospects for control by mass vaccination in England and Wales are investigated by analyses of longitudinal records on incidence and vaccine uptake, and horizontal data on age-stratified case reports. Mathematical models of the transmission dynamics of the infection that incorporate loss of natural and vaccine-induced immunity plus variable vaccine efficacy are developed, and their predictions compared with observed trends. Analyses of case reports reveal that the individual force of infection is age dependent, with peak transmission in the 5- to 10-year-old age class. A model incorporating this age dependency, along with partial vaccine efficacy and loss of vaccine-induced immunity, generates predicted patterns that best mirror observed trends since mass vaccination was inaugurated in 1957 in England and Wales. Model projections accurately mirror the failure of mass vaccination to increase the inter-epidemic period of the infection (three years) over that pertaining before control. The analysis suggests that this is due to the impact of partial vaccine efficacy. Projected trends do not accurately reflect the low levels of pertussis incidence reported between epidemics in the periods of high vaccine uptake. This is thought to arise from a combination of factors, including loss of natural and vaccine induced immunity, biases in case reporting (where reporting efficiency is positively associated with the incidence of pertussis), and seasonal variations in transmission. Model predictions suggest that the vaccination of 88% of each birth cohort before the age of 1 year will eliminate bacterial transmission, provided the vaccine confers lifelong protection against infection. If vaccine-induced immunity is significantly less than lifelong (or if vaccination fails to protect all its recipients) repeated cohort immunization is predicted to be necessary to eliminate transmission. Future research needs are discussed, and emphasis is placed on the need for more refined data on vaccine efficacy, the duration of natural and vaccine-induced immunity and the incidence of clinical pertussis and subclinical infections (perhaps by the development of reliable serological tests). Future mathematical models will need especially to incorporate seasonality in transmission.     

Pathogen adaptation under imperfect vaccination: implications for pertussis

Mass vaccination campaigns have drastically reduced the burden of infectious diseases. Unfortunately, in recent years several infectious diseases have re-emerged. Pertussis poses a well-known example. Inspired by pertussis, we study, by means of an epidemic model, the population and evolutionary dynamics of a pathogen population under the pressure of vaccination. A distinction is made between infection in immunologically naive individuals (primary infection) and infection in individuals whose immune system has been primed by vaccination or infection (secondary infection). The results show that (i) vaccination with an imperfect vaccine may not succeed in reducing the infection pressure if the transmissibility of secondary infections is higher than that of primary infections; (ii) pathogen strains that are able to evade the immunity induced by vaccination can only spread if escape mutants incur no or only a modest fitness cost and (iii) the direction of evolution depends crucially on the distribution of the different types of susceptibles in the population. We discuss the implications of these results for the design and use of vaccines that provide temporary immunity.     

SVIR epidemic models with vaccination strategies

Vaccination is important for the elimination of infectious diseases. To finish a vaccination process, doses usually should be taken several times and there must be some fixed time intervals between two doses. The vaccinees (susceptible individuals who have started the vaccination process) are different from both susceptible and recovered individuals. Considering the time for them to obtain immunity and the possibility for them to be infected before this, two SVIR models are established to describe continuous vaccination strategy and pulse vaccination strategy (PVS), respectively. It is shown that both systems exhibit strict threshold dynamics which depend on the basic reproduction number. If this number is below unity, the disease can be eradicated. And if it is above unity, the disease is endemic in the sense of global asymptotical stability of a positive equilibrium for continuous vaccination strategy and disease permanence for PVS. Mathematical results suggest that vaccination is helpful for disease control by decreasing the basic reproduction number. However, there is a necessary condition for successful elimination of disease. If the time for the vaccinees to obtain immunity or the possibility for them to be infected before this is neglected, this condition disappears and the disease can always be eradicated by some suitable vaccination strategies. This may lead to over-evaluating the effect of vaccination.     

A discrete-time model with vaccination for a measles epidemic.

A discrete-time, age-independent SIR-type epidemic model is formulated and analyzed. The effects of vaccination are also included in the model. Three mathematically important properties are verified for the model: solutions are nonnegative, the population size is time-invariant, and the epidemic concludes with all individuals either remaining susceptible or becoming immune (a property typical of SIR models). The model is applied to a measles epidemic on a university campus. The simulated results are in good agreement with the actual data if it is assumed that the population mixes nonhomogeneously. The results of the simulations indicate that a rate of immunity greater than 98% may be required to prevent an epidemic in a university population. The model has applications to other contagious diseases of SIR type. Furthermore, the simulated results of the model can easily be compared to data, and the effects of a vaccination program can be examined.     

Simple criteria for finding (nearly) optimal vaccination strategies

Strategies for best controlling the spread of the diseases with limited vaccine available are explored. I use influenza as a representative disease in point. The model describes the dynamics of influenza spread among multiple groups that have different risks and activity levels. I define a core group consisting of individuals with occupations that brings them in contact with many other people in a day. These occupations may include service industries, teachers, health care, and government workers, to name a few. High-risk individuals are those as typically designated for: children under 5 and adults over 50, people with weakened immune systems as well as emergency and health care personnel. Under certain conditions, shifting vaccination resources away from the high-risk group to the high-activity group will result in improved herd immunity in both the high-risk group and the population as whole. This results in more high-risk people protected even though less of them are being vaccinated, with the obvious implications that current vaccination policies may be far less then optimal. I show that the criteria for the optimal strategy can be derived from simple expressions gleaned from the expression for the basic reproductive number.     

Vaccine and adjuvant design for emerging viruses: mutations, deletions, segments and signaling

Vaccination is currently the most effective strategy to medically control viral diseases. However, developing vaccines is a long and expensive process, and traditional methods, such as attenuating wild-type viruses by serial passage, may not be suitable for all viruses and may lead to vaccine safety considerations, particularly in the case of the vaccination of particular patient groups, such as the immunocompromised and the elderly. In particular, developing vaccines against emerging viral pathogens adds a further level of complexity, as they may only be administered to small groups of people or only in response to a specific event or threat, limiting our ability to study and evaluate responses. In this commentary, we discuss how novel techniques may be used to engineer a new generation of vaccine candidates as we move toward a more targeted vaccine design strategy, driven by our understanding of the mechanisms of viral pathogenesis, attenuation and the signaling events which are required to develop a lasting, protective immunity. We will also briefly discuss the potential future role of vaccine adjuvants, which could be used to bridge the gap between vaccine safety, and lasting immunity from a single vaccination.