The cholera epidemics and the development of public health in Meiji Japan. 1. Modernity, cholera, and health thought

We present here the beginnings of public health politics in Meiji Japan (1868-1912). Due to a two century isolation of Japan, public health concepts developed in the West from the end of the 18th century were foreign in premodern Japan. Due to its isolation, Japan was also relatively preserved from some acute infectious diseases such as cholera. In this paper, we investigate the role of cholera epidemics in the emergence of public health concepts in the peculiar context of Meiji Japan. We show that chronic diseases such as tuberculosis and leprosy were neglected for a long time and that the Meiji government set priority on acute infectious diseases that were considered as long as they disturbed public order. Nevertheless, some physicians and government officials considered issues of welfare and poverty. We also review some emerging concepts of social medicine. We try to show, that in Japan as well as in Western nations, public health politics were not exempt of contradictions and paradoxes and a permanent tension existed between coercitive policies and conceptions of welfare and rights to health.     

The cholera epidemics and the development of public health in Meiji Japan. 2. Strength and weakness of public health politics

We present here the beginnings of public health politics in Meiji Japan (1868-1912). Due to a two century isolation of Japan, public health concepts developed in the West from the end of the 18th century were foreign in premodern Japan. Due to its isolation, Japan was also relatively preserved from some acute infectious diseases such as cholera. In this paper, we investigate the role of cholera epidemics in the emergence of public health concepts in the peculiar context of Meiji Japan. We show that chronic diseases such as tuberculosis and leprosy were neglected for a long time and that the Meiji government set priority on acute infectious diseases that were considered as long as they disturbed public order. Nevertheless, some physicians and government officials considered issues of welfare and poverty. We also review some emerging concepts of social medicine. We try to show that in Japan as well as in western nations public health politics were not exempt of contradictions and paradoxes and a permanent tension existed between coercitive policies and conceptions of welfare and rights to health.     

The contribution of vaccination to global health: past,present and future

Vaccination has made an enormous contribution to global health. Two major infections, smallpox and rinderpest, have been eradicated. Global coverage of vaccination against many important infectious diseases of childhood has been enhanced dramatically since the creation of WHO''s Expanded Programme of Immunization in 1974 and of the Global Alliance for Vaccination and Immunization in 2000. Polio has almost been eradicated and success in controlling measles makes this infection another potential target for eradication. Despite these successes, approximately 6.6 million children still die each year and about a half of these deaths are caused by infections, including pneumonia and diarrhoea, which could be prevented by vaccination. Enhanced deployment of recently developed pneumococcal conjugate and rotavirus vaccines should, therefore, result in a further decline in childhood mortality. Development of vaccines against more complex infections, such as malaria, tuberculosis and HIV, has been challenging and achievements so far have been modest. Final success against these infections may require combination vaccinations, each component stimulating a different arm of the immune system. In the longer term, vaccines are likely to be used to prevent or modulate the course of some non-infectious diseases. Progress has already been made with therapeutic cancer vaccines and future potential targets include addiction, diabetes, hypertension and Alzheimer''s disease.     

Applied genome research in the field of human vaccines

Prophylactic vaccination has made an essential contribution to the improvement of human health over the 20th century. However, we still lack efficient vaccines against major human diseases such as malaria or tuberculosis. Today, the design of therapeutic vaccines referred to as 'pharmaccines' is actively investigated in order to treat diseases such as cancer. In that context, novel ways to rationalize and accelerate vaccine discovery are needed. A series of advances in the fields of molecular biology and computer science, have greatly accelerated the rate at which candidate vaccine antigens can be discovered. In this review, we will present and discuss how applied genome research may facilitate antigen discovery and the design of new prophylactic and therapeutic vaccines.     

Environmental hazards to children's health in the modern world

Patterns of illness in children have changed dramatically in the last century, and will continue to change in this century. The major diseases confronting children are now chronic and disabling conditions termed the "new pediatric morbidity"-asthma, leukemia and brain cancer, neurodevelopmental dysfunction and neurobehavioral abnormality, reproductive and systemic developmental problems. Chemical toxicants in the environment, poverty, and little or no access to health care are all factors contributing to life-threatening pediatric diseases; children are uniquely vulnerable to chemical toxicants because of their disproportionately heavy exposures and their inherent biological growth and development. Genetic susceptibility and environmental exposures during vulnerable periods of development are also important contributors to the etiologies of many diseases of childhood. It is vital that we develop a better understanding of the mechanisms and interactions between nutrition, infectious disease, environmental exposures, and genetic predisposition in order to develop better prevention methods. This paper briefly examines modern contributors to children's environmental health problems, efforts to date on both the regional and international level to address these challenges, and reflects upon major research needs that must be addressed in order to close the gaps that exist in our understanding of the relationship between environmental exposures and children's health.     

Development and application of synthetic peptides as vaccines

Vaccination against bacterial and viral diseases has been one of the major achievements in medicine and immunology since the beginning of this century. Extensive vaccination programs have been able to control or, in the case of smallpox, virtually wipe out some of the most dangerous infectious diseases e.g. poliomyelitis, measles, whooping cough, diphtheria and tetanus. However, as this success has been limited mainly to the developed, affluent countries, infectious diseases still remain the worlds largest health problem. Furthermore, vaccines against human parasites are non-existent. Recent advances in immunology and molecular biology including recombinant DNA technology have provided the basis for new approaches to vaccine development.     

Do Maternal Knowledge and Attitudes towards Childhood Immunizations in Rural Uganda Correlate with Complete Childhood Vaccination?

Improving childhood vaccination coverage and timeliness is a key health policy objective in many developing countries such as Uganda. Of the many factors known to influence uptake of childhood immunizations in under resourced settings, parents’ understanding and perception of childhood immunizations has largely been overlooked. The aims of this study were to survey mothers’ knowledge and attitudes towards childhood immunizations and then determine if these variables correlate with the timely vaccination coverage of their children. From September to December 2013, we conducted a cross-sectional survey of 1,000 parous women in rural Sheema district in southwest Uganda. The survey collected socio-demographic data and knowledge and attitudes towards childhood immunizations. For the women with at least one child between the age of one month and five years who also had a vaccination card available for the child (N = 302), the vaccination status of this child was assessed. 88% of these children received age-appropriate, on-time immunizations. 93.5% of the women were able to state that childhood immunizations protect children from diseases. The women not able to point this out were significantly more likely to have an under-vaccinated child (PR 1.354: 95% CI 1.018–1.802). When asked why vaccination rates may be low in their community, the two most common responses were “fearful of side effects” and “ignorance/disinterest/laziness” (44% each). The factors influencing caregivers’ demand for childhood immunizations vary widely between, and also within, developing countries. Research that elucidates local knowledge and attitudes, like this study, allows for decisions and policy pertaining to vaccination programs to be more effective at improving child vaccination rates.     

Intranasal Immunization with DOTAP Cationic Liposomes Combined with DC-Cholesterol Induces Potent Antigen-Specific Mucosal and Systemic Immune Responses in Mice

Despite the progress made by modern medicine, infectious diseases remain one of the most important threats to human health. Vaccination against pathogens is one of the primary methods used to prevent and treat infectious diseases that cause illness and death. Vaccines administered by the mucosal route are potentially a promising strategy to combat infectious diseases since mucosal surfaces are a major route of entry for most pathogens. However, this route of vaccination is not widely used in the clinic due to the lack of a safe and effective mucosal adjuvant. Therefore, the development of safe and effective mucosal adjuvants is key to preventing infectious diseases by enabling the use of mucosal vaccines in the clinic. In this study, we show that intranasal administration of a cationic liposome composed of 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) and 3β-[N-(N'',N''-dimethylaminoethane)-carbamoyl] (DC-chol) (DOTAP/DC-chol liposome) has a potent mucosal adjuvant effect in mice. Intranasal vaccination with ovalbumin (OVA) in combination with DOTAP/DC-chol liposomes induced the production of OVA-specific IgA in nasal tissues and increased serum IgG1 levels, suggesting that the cationic DOTAP/DC-chol liposome leads to the induction of a Th2 immune response. Additionally, nasal-associated lymphoid tissue and splenocytes from mice treated with OVA plus DOTAP/DC-chol liposome showed high levels of IL–4 expression. DOTAP/DC-chol liposomes also enhanced OVA uptake by CD11c⁺ dendritic cells in nasal-associated lymphoid tissue. These data demonstrate that DOTAP/DC-chol liposomes elicit immune responses via an antigen-specific Th2 reaction. These results suggest that cationic liposomes merit further development as a mucosal adjuvant for vaccination against infectious diseases.     

The complication of coinfection

Infectious disease remains one of the largest burdens on humankind. Even with modern medical and public health standards, infectious disease remained the No. 1 killer worldwide at the turn of the century. Often, the most costly disease burdens come from multiple infections at once, i.e., coinfection. Influenza, an annual infection often considered relatively harmless, can increase susceptibility to both deadly bacterial pneumonia and childhood ear infections. Major health threat HIV rarely kills a patient on its own, but instead allows for opportunistic infections and re-emergence of infections such as tuberculosis. What generates these unique relationships is not well understood; herein, we examine in detail three types of coinfection and the unique interactions between infectious agents as well as with the host in each setting. We also begin to address how we may aid further understanding of coinfection and what questions need to be addressed to help direct future treatments.     

A Computational Approach to Characterizing the Impact of Social Influence on Individuals’ Vaccination Decision Making

In modeling individuals vaccination decision making, existing studies have typically used the payoff-based (e.g., game-theoretical) approaches that evaluate the risks and benefits of vaccination. In reality, whether an individual takes vaccine or not is also influenced by the decisions of others, i.e., due to the impact of social influence. In this regard, we present a dual-perspective view on individuals decision making that incorporates both the cost analysis of vaccination and the impact of social influence. In doing so, we consider a group of individuals making their vaccination decisions by both minimizing the associated costs and evaluating the decisions of others. We apply social impact theory (SIT) to characterize the impact of social influence with respect to individuals interaction relationships. By doing so, we propose a novel modeling framework that integrates an extended SIT-based characterization of social influence with a game-theoretical analysis of cost minimization. We consider the scenario of voluntary vaccination against an influenza-like disease through a series of simulations. We investigate the steady state of individuals’ decision making, and thus, assess the impact of social influence by evaluating the coverage of vaccination for infectious diseases control. Our simulation results suggest that individuals high conformity to social influence will increase the vaccination coverage if the cost of vaccination is low, and conversely, will decrease it if the cost is high. Interestingly, if individuals are social followers, the resulting vaccination coverage would converge to a certain level, depending on individuals’ initial level of vaccination willingness rather than the associated costs. We conclude that social influence will have an impact on the control of an infectious disease as they can affect the vaccination coverage. In this respect, our work can provide a means for modeling the impact of social influence as well as for estimating the effectiveness of a voluntary vaccination program.     

Safety and risk assessment for the human superorganism

This editorial on safety evaluation and risk assessment for the human superorganism introduces a series of papers arguing for a fundamental shift in how we approach human health risk assessment. In this series emphasis is placed on the risk of infectious disease. Our 21^stst century understanding of human biology is that, as holobionts, we possess a majority of microbial cells and genes. In fact, our microbes fundamentally affect our interactions with the external environment, metabolism, physiology, and risk of both pathology and disease. As holobionts, we require our microbial partners for us to be both complete and healthy. Using the 20^th century understanding of human biology, we failed to capture the effects of the microbiome in evaluating health risks. But 21^st century risk assessments such as those associated with exposure to specific microbial pathogens need to include the human microbiome. Microbiome status will be central in determining the health risks for both individuals and populations.     

Convincing the “Herd” of immunity: Lessons from smallpox vaccination in 19th century Germany

Although vaccination is a cost-effective way to control infectious diseases, it is often met with popular resistance. Studying smallpox in 19th century Germany, this paper explores how economic incentives contribute to this phenomenon. The paper adds to the literature by combining mathematical epidemiology and unpublished archival evidence from two German states - Baden and Wurttemberg. The two states are an intriguing case because their initial conditions and vaccination laws were similar. Despite this, Baden experienced lower smallpox prevalence and higher vaccination uptake than Wurttemberg. The epidemiological model predicts that incentives to vaccinate decline rapidly when immunization reduces prevalence. The archival evidence reveals that Baden offset this decline by creating a public vaccination system which reduced costs for vaccinees and vaccinators alike. This suggests that the high fixed costs of centralized immunization policies can be compensated by economies of scale and popular acceptance.     

Vaccines for the twenty-first century society

Vaccines have been one of the major revolutions in the history of mankind and, during the twentieth century, they eliminated most of the childhood diseases that used to cause millions of deaths. In the twenty-first century, vaccines will also play a major part in safeguarding people's health. Supported by the innovations derived from new technologies, vaccines will address the new needs of a twenty-first century society characterized by increased life expectancy, emerging infections and poverty in low-income countries.     

DNA vaccines: a mini review

DNA vaccines are a major breakthrough in the field of vaccination with several advantages over traditional vaccines. Unlike traditional vaccines, DNA vaccines stimulate both arms of the immune system offering long lasting immunity. DNA vaccines not only have the potential to fight against infectious diseases such as influenza and hepatitis but they can also be used to prevent autoimmune diseases such as multiple sclerosis. In general, this article is intended as a mini-review to discuss DNA vaccination, as well as patents on different types of DNA vaccines.     

Implications of vaccination and waning immunity

For infectious diseases where immunization can offer lifelong protection, a variety of simple models can be used to explain the utility of vaccination as a control method. However, for many diseases, immunity wanes over time and is subsequently enhanced (boosted) by asymptomatic encounters with the infection. The study of this type of epidemiological process requires a model formulation that can capture both the within-host dynamics of the pathogen and immune system as well as the associated population-level transmission dynamics. Here, we parametrize such a model for measles and show how vaccination can have a range of unexpected consequences as it reduces the natural boosting of immunity as well as reducing the number of naive susceptibles. In particular, we show that moderate waning times (40–80 years) and high levels of vaccination (greater than 70%) can induce large-scale oscillations with substantial numbers of symptomatic cases being generated at the peak. In addition, we predict that, after a long disease-free period, the introduction of infection will lead to far larger epidemics than that predicted by standard models. These results have clear implications for the long-term success of any vaccination campaign and highlight the need for a sound understanding of the immunological mechanisms of immunity and vaccination.     

Sex differences in bone loss--an evolutionary perspective on a clinical problem

The dramatic increase in the world's population that has occurred over the past 100 years has come largely through reductions in death due to infectious disease. An epidemiologic transition to a preponderance of deaths due to degenerative conditions such as cardiovascular disease and cancer is occurring in the developing countries as well as in the industrialized ones. In the industrialized countries, demographic profiles now reflect the increased life expectancies of both sexes. However, female life expectancies exceed male by six or more years. Further change in mortality patterns will accompany success in the reduction of the number of mortalities attributable to such degenerative conditions as cardiovascular disease and cancer. In the 21st century, conditions associated with sensescence will be of increasing concern. Adaptive strategies that enhanced reproductive success throughout most of human evolution may now prove detrimental to human health as average life expectancies reach unprecedented length. In this environment, differences in the survival mechanisms deployed by males as opposed to females will become increasingly important.     

Illuminating the host – How RNAi screens shed light on host-pathogen interactions

Over millions of years pathogens have coevolved with their respective hosts utilizing host cell functions for survival and replication. Despite remarkable progress in developing antibiotics and vaccination strategies in the last century, infectious diseases still remain a severe threat to human health. Meanwhile, genomic research offers a new era of data-generating platforms that will dramatically enhance our knowledge of pathogens and the diseases they cause. Improvements in gene knockdown studies by RNA interference (RNAi) combined with recent developments in instrumentation and image analysis enable the use of high-throughput screening approaches to elucidate host gene functions exploited by pathogens. Although only a few RNAi-based screens focusing on host genes have been reported so far, these studies have already uncovered hundreds of genes not previously known to be involved in pathogen infection. This review describes recent progress in RNAi screening approaches, highlighting both the limitations and the tremendous potential of RNAi-based screens for the identification of essential host cell factors during infection.     

A link between the North Atlantic Oscillation and measles dynamics during the vaccination period in England and Wales

Ecologists have become aware of the role played by interannual climatic variability on the temporal dynamics of infectious diseases. In this report, I present evidence from data on measles cases in England and Wales showing that during the post-vaccination period, the interannual variability of winter weather (represented by the North Atlantic Oscillation, NAO) influences the annual dynamics of the disease. Using annual measles data from seven cities and simple logistic models, this study reveals how, after vaccination, NAO increases its effects on measles fluctuations. In addition, this study shows that vaccination may be represented as a simple vertical and lateral perturbation effect (Royama's classification), by reducing the maximum per capita growth rate and the equilibrium number of infected individuals . The results suggest that vaccination will not lead to outbreaks of measles from regular cyclic to irregular chaotic dynamics. In contrast, because of the reduction in per capita growth rates, the disease dynamics appear to be more stable than during the pre-vaccination period. The analysis of annual data on infectious diseases may be useful for detecting long-term effects of climate and complements the classical analyses and modeling based on monthly or seasonal time-step data.     

Endosymbionts of arthropods and nematodes: allies to fight infectious diseases?

Arthropods and nematodes are important protagonists in human health because either they act as vectors of pathogens (bacteria, protozoa, viruses or fungus), or are themselves parasites. Fighting infectious diseases is based essentially on vaccination (prevention) or chemotherapeutic (curative) approaches in human, but one can envisage as an alternative to reduce the number of vectors or limit their ability to spread pathogens. Such strategies controlling dissemination will undoubtedly benefit from the knowledge accumulated by recent works on powerful mechanisms developed by symbiotic insect bacteria such as Wolbachia to popagate in arthropods and nematods. This review summarizes these recent data, and indicate how these mechanisms can be manipulated to reduce the dissemination of insect vectors propagating human diseases.     

After 2015: infectious diseases in a new era of health and development

Running over timescales that span decades or centuries, the epidemiological transition provides the central narrative of global health. In this transition, a reduction in mortality is followed by a reduction in fertility, creating larger, older populations in which the main causes of illness and death are no longer acute infections of children but chronic diseases of adults. Since the year 2000, the Millennium Development Goals (MDGs) have provided a framework for accelerating the decline of infectious diseases, backed by a massive injection of foreign investment to low-income countries. Despite the successes of the MDGs era, the inhabitants of low-income countries still suffer an enormous burden of disease owing to diarrhoea, pneumonia, HIV/AIDS, tuberculosis, malaria and other pathogens. Adding to the predictable burden of endemic disease, the threat of pandemics is ever-present and global. With a view to the future, this review spotlights five aspects of the fight against infection beyond 2015, when the MDGs will be replaced by a new set of goals for poverty reduction and sustainable development. These aspects are: exploiting the biological links between infectious and non-infectious diseases; controlling infections among the new urban majority; enhancing the response to international health threats; expanding childhood immunization programmes to prevent acute and chronic diseases in adults; and working towards universal health coverage. By scanning the wider horizon now, infectious disease specialists have the chance to shape the post-2015 era of health and development.