History of vaccine and immunization: Vaccine-hesitancy discussion in Germany in XIX century.

Vaccination is the most celebrated and denigrated achievement of medicine and public health - not only today, but since Edward Jenner's time (1798). In fact, the idea of injecting a mild form of "disease" into a healthy person was attacked even earlier than the discovery of vaccines. The forerunner of Jenner's vaccination with bovine lymph was the inoculation of smallpox material from person to person, which, known in Europe since the beginning of the eighteenth century, was a target of harsh criticism. The reasons for criticizing the Jennerian vaccination and its mandatory practice were medical, anthropological, biological (vaccination is not safe), religious and ethical (it is wrong to inoculate a healthy person with disease), and political (vaccination is a threat to individual freedom). As such, anti-vaccination groups emerged in England, where inoculation was adopted early, as well as overall in Europe and in the United States. This paper focuses on the lesser known debate that arose in Germany in the years 1852-53 about the medical practice of vaccination. This is an a important topic of public health that has aroused a wide debate and comparison especially in recent years and now with pandemic on Sars-Cov-2 (Covid-19) and will probably be the subject of further reflection and consideration in the coming years.

Prevention and Treatment of Monkeypox: A Systematic Review of Preclinical Studies.

The outbreak of monkeypox, coupled with the onslaught of the COVID-19 pandemic is a critical communicable disease. This study aimed to systematically identify and review research done on preclinical studies focusing on the potential monkeypox treatment and immunization. The presented juxtaposition of efficacy of potential treatments and vaccination that had been tested in preclinical trials could serve as a useful primer of monkeypox virus. The literature identified using key terms such as monkeypox virus or management or vaccine stringed using Boolean operators was systematically reviewed. Pubmed, SCOPUS, Cochrane, and preprint databases were used, and screening was performed in accordance with PRISMA guidelines. A total of 467 results from registered databases and 116 from grey literature databases were screened. Of these results, 72 studies from registered databases and three grey literature studies underwent full-text screening for eligibility. In this systematic review, a total of 27 articles were eligible according to the inclusion criteria and were used. Tecovirimat, known as TPOXX or ST-246, is an antiviral drug indicated for smallpox infection whereas brincidofovir inhibits the viral DNA polymerase after incorporation into viral DNA. The ability of tecovirimat in providing protection to poxvirus-challenged animals from death had been demonstrated in a number of animal studies. Non-inferior with regard to immunogenicity was reported for the live smallpox/monkeypox vaccine compared with a single dose of a licensed live smallpox vaccine. The trial involving the live vaccine showed a geometric mean titre of vaccinia-neutralizing antibodies post two weeks of the second dose of the live smallpox/monkeypox vaccine. Of note, up to the third generation of smallpox vaccines-particularly JYNNEOS and Lc16m8-have been developed as preventive measures for MPXV infection and these vaccines had been demonstrated to have improved safety compared to the earlier generations.

Military Epidemics, Then and Now: Smallpox and COVID-19.

We compared the COVID-19 experience in the first year of the current pandemic in the US with the smallpox experience of the 18th century, focusing on the US military but recognizing civilian and military populations are not separate and distinct. Despite the epidemics being separated by 21/2 centuries and with great advancements in technology having occurred over that time, we observed similarities which led us to several conclusions: • Infectious disease outbreaks will continue to occur and novel agents, naturally occurring or manipulated by humans, will threaten military and civilian populations nationally and globally. • Infectious disease outbreaks can affect both military and civilian populations, persist for long periods, and be catastrophic to military peacetime and wartime operations. • Effective surveillance is a prerequisite for early identification and subsequent meaningful responses to novel and reemerging threat agents and diseases. • Socio-cultural, religious, or political factors may limit the implementation of effective interventions in military or civilian populations. Public health officials must assess impediments to implementation of interventions and develop plans to overcome them.

Prevention of monkeypox with vaccines: a rapid review.

The largest outbreak of monkeypox in history began in May, 2022, and has rapidly spread across the globe ever since. The purpose of this Review is to briefly describe human immune responses to orthopoxviruses; provide an overview of the vaccines available to combat this outbreak; and discuss the various clinical data and animal studies evaluating protective immunity to monkeypox elicited by vaccinia virus-based smallpox vaccines, address ongoing concerns regarding the outbreak, and provide suggestions for the appropriate use of vaccines as an outbreak control measure. Data showing clinical effectiveness (~85%) of smallpox vaccines against monkeypox come from surveillance studies conducted in central Africa in the 1980s and later during outbreaks in the same area. These data are supported by a large number of animal studies (primarily in non-human primates) with live virus challenge by various inoculation routes. These studies uniformly showed a high degree of protection and immunity against monkeypox virus following vaccination with various smallpox vaccines. Smallpox vaccines represent an effective countermeasure that can be used to control monkeypox outbreaks. However, smallpox vaccines do cause side-effects and the replication-competent, second-generation vaccines have contraindications. Third-generation vaccines, although safer for use in immunocompromised populations, require two doses, which is an impediment to rapid outbreak response. Lessons learned from the COVID-19 pandemic should be used to inform our collective response to this monkeypox outbreak and to future outbreaks.

Vaccination in the 19th century in Italy and the role of the catholic church in public health: a historical overview.

Using the case of the vaccine against smallpox as an example, this article explores how the attitude and the politics of the Vatican State towards vaccination changed between the 18th and 19th century. Despite some notable exceptions, the Catholic Church became progressively involved in supporting vaccination in Italy, exerting its temporal and spiritual authority to develop healthcare policies and to convince a population that still considered the vaccine as potentially harmful. The brief historical overview on vaccine and vaccination shows that during the XIX century the Catholic church and in particular, the political decision of the Pope, engaged temporal and spiritual power, high authority and persuasive influence to encourage the population, more than anyone the hesitant people, to get vaccine against smallpox. Although with the due differences determined by the path of time and by the scientific, educational and social advances of modern-day, this view from the past can provide us, with actual COVID pandemic, a reason of deep thinking and also how to face the present COVID-19 pandemic and to prepare for forcoming future. Actually, it shows us how the terrible smallpox epidemic was handled and finally overcome, thanks to vaccination.

Historical review: Towards the 50th anniversary of the last major smallpox outbreak (Yugoslavia, 1972).

In 1972, Yugoslavia experienced the largest outbreak of smallpox in the history of Europe following the Second World War and its first smallpox outbreak after 1930. The origin of the infection is believed to be a pilgrim who visited countries in the Middle East. In this epidemic in Yugoslavia, from 16th February to 11th April 1972, a total of 175 people fell ill, 35 (20%) of whom died. Measures against the outbreak were based on the strategy that was common in the final phase of the smallpox eradication program. It started with active surveillance and rapid identification of new cases. Measures, such as mass vaccination and quarantine of direct contacts, were promptly taken. In a few weeks, 18 million people had been vaccinated and approximately 15,000 had been quarantined. Yugoslavia was declared free of smallpox on 9th May 1972. The global community today is confronted with serious threats from infectious diseases, which can appear as outbreaks and pandemics.

Pacific Eclipse - A tabletop exercise on smallpox pandemic response.

BACKGROUND: In December 2019, we ran Pacific Eclipse, a pandemic tabletop exercise using smallpox originating in Fiji as a case study. Pacific Eclipse brought together international stakeholders from health, defence, law enforcement, emergency management and a range of other organisations. AIM: To review potential gaps in preparedness and identify modifiable factors which could prevent a pandemic or mitigate the impact of a pandemic. METHODS: Pacific Eclipse was held on December 9-10 in Washington DC, Phoenix and Honolulu simultaneously. The scenario began in Fiji and becomes a pandemic. Mathematical modelling of smallpox transmission was used to simulate the epidemic under different conditions and to test the effect of interventions. Live polling, using Poll Everywhere software that participants downloaded onto their smart phones, was used to gather participant decisions as the scenario unfolded. Stakeholders from state and federal government and non-government organisations from The United States, The United Kingdom, Australia, New Zealand, Canada, as well as industry and non-government organisations attended. RESULTS: The scenario progressed in three phases and participants were able to make decisions during each phase using live polling. The polling showed very diverse and sometimes conflicting decision making. Factors influential to pandemic severity were identified and categorised as modifiable or unmodifiable. A series of recommendations were made on the modifiable determinants of pandemic severity and how these can be incorporated into pandemic planning. These included preventing an attack through intelligence, law enforcement and legislation, improved speed of diagnosis, speed and completeness of case finding and case isolation, speed and security of vaccination response (including stockpiling), speed and completeness of contact tracing, protecting critical infrastructure and business continuity, non-pharmaceutical interventions (social distancing, PPE, border control) and protecting first responders. DISCUSSION: Pacific Eclipse illustrated the impact of a pandemic of smallpox under different response scenarios, which were validated to some extent by the COVID-19 pandemic. The framework developed from the scenario draws out modifiable determinants of pandemic severity which can inform pandemic planning for the ongoing COVID-19 pandemic and for future pandemics.

The nineteenth-century experience of the kingdom of the two Sicilies on mandatory vaccination: An Italian phenomenon?

The current health emergency caused by COVID-19 disease shows several similarities with well-known epidemics of the past. The knowledge of their management and overcoming could give us useful tools to face the present COVID-19 pandemic. The Bourbon king Ferdinand I planned the first free large-scale mass vaccination programme conducted in Italy and one of the first in Europe to counteract smallpox. The vaccination campaign was characterized by many difficulties and the efforts made by the Southern Kingdoms governors were enormous. For example, the "ante litteram communication campaign", aimed at convincing the so-called "hesitant" people and at confuting the arguments of vaccination opponents, was impressive. In 1821, the compulsory vaccination significantly reduced smallpox infections and death rates. Subsequently, several experiences followed this initiative, not without doubts and debates. Smallpox was finally eradicated worldwide only on the 9th December 1979. Despite to other countries, the "mandatory vaccination" is a topic often debated by Italian scientific and social communities.

The first major vaccination campaign against smallpox in Lombardy: the mass vaccination campaign against coronavirus nothing new only terminology.

Terminology, technology, communication and organizational strategies are different but we tried to compare the mass vaccination campaign against smallpox with the one we are doing against coronavirus.

America's Original Immunization Controversy: The Tercentenary of the Boston Smallpox Epidemic of 1721.

The CoVID-19 pandemic marks the 300th anniversary of the Boston smallpox epidemic of 1721, America's first immunization controversy. Puritan minister Cotton Mather learned of inoculation for smallpox from Onesimus, a man enslaved to him. When the disease broke out in May 1721, Mather urged Boston's physicians to inoculate all those vulnerable to the disease. Zabdiel Boylston, alone among his colleagues, decided to proceed with the procedure, igniting a heated debate that occasionally grew violent. The division between the advocates and detractors of inoculation were as deep as religion and politics. Puritan ministers supported inoculation, asserting their right to control the lives of their flock. Challenging them were a secular class of medical professionals that proclaimed primacy in medical matters. The controversy was inflamed by a nascent newspaper industry eager to profit from the fear of contagion and the passionate debate. Despite the furor and physical risk to himself and his family Boylston inoculated 282 persons, of whom only 6 died (2.1%). Of the 5759 townspeople who contracted smallpox during the epidemic, there were 844 deaths (14.7%). In America's first effort at preventive medicine Boylston established the efficacy of inoculation, which helped support its acceptance in England, and later in the century, the adoption of Edward Jenner's technique of vaccination in 1796.

Vaccine hesitancy and other obstacles to COVID-19 control: lessons from smallpox.

The world confronts today a disease which was unknown as recently as early 2019. Now that there is a safe and effective vaccine against COVID-19, lessons can usefully be drawn from previous well documented vaccination efforts. Of these, the best documented and most successful is the Smallpox Eradication Program (SEP). A review was made of publications by major players in smallpox eradication, respecting the important differences between the disease, this review revealed several points of connection. Cultural factors loomed large both in the eradication of smallpox and progress, to date, in the control of COVID-19. Other points of similarity included political commitment, the set-up of strong surveillance mechanisms, and assurance of uniformly high quality vaccines tested and approved by the World Health Organization. The future of COVID-19 control depends, in part, on lessons learned from previous vaccination efforts. A review of those efforts will avoid repetition of past errors and permit adoption of best practices from the past. Such analyses must, of course, respect the important differences between COVID-19 and smallpox.

Countering the potential re-emergence of a deadly infectious disease-Information warfare, identifying strategic threats, launching countermeasures.

OBJECTIVES: Eradicated infectious diseases like smallpox can re-emerge through accident or the designs of bioterrorists, and cause heavy casualties. Presently, the populace is largely susceptible as only a small percentage is vaccinated, and their immunity is likely to have waned. And when the disease re-emerges, the susceptible individuals may be manipulated by disinformation on Social Media to refuse vaccines. Thus, a combination of countermeasures consisting of antiviral drugs and vaccines and a range of policies for their application need to be investigated. Opinions regarding whether to receive vaccines evolve over time through social exchanges via networks that overlap with but are not identical to the disease propagation networks. These couple the spread of the biological and information contagion and necessitate a joint investigation of the two. METHODS: We develop a computationally tractable metapopulation epidemiological model that captures the joint spatio-temporal evolution of an infectious disease (e.g., smallpox, COVID-19) and opinion dynamics. RESULTS: Considering smallpox, the computations based on the model show that opinion dynamics have a substantial impact on the fatality count. Towards understanding how perpetrators are likely to seed the infection, we identify a) the initial distribution of infected individuals that maximize the overall fatality count; and b) which habitation structures are more vulnerable to outbreaks. We assess the relative efficacy of different countermeasures and conclude that a combination of vaccines and drugs minimize the fatalities, and by itself, drugs reduce fatalities more than the vaccine. Accordingly, we assess the impact of increase in the supply of drugs and identify the most effective among a collection of policies for administering of drugs for various parameter combinations. Many of the observed patterns are stable to variations of a diverse set of parameters. CONCLUSIONS: Our findings provide a quantitative foundation for various important elements of public health discourse that have largely been conducted qualitatively.

The contributions of William Money MRCS to smallpox vaccination and control - A little-known story.

This history of vaccinology article outlines the work of William Money (1790-1843), who conducted a study related to smallpox disease, immunity, and vaccination. His hitherto unpublished study demonstrated that smallpox could be contracted more than once; notably, results from his studies showed that vaccination was not dangerous. He was also the author of a celebrated Vade Mecum in human anatomy. Here, we outline the work he conducted in England: from serving as the house surgeon at Northampton Infirmary to his post as a surgeon at the Royal Metropolitan Hospital in London.