Smallpox Readiness: Modern Strategies Against an Ancient Disease.

This Viewpoint highlights the potential for unintentional or deliberate release of variola virus (smallpox), discusses current medical countermeasures for smallpox, and calls for greater flexibility from the US and its partners in developing safe, reliable, affordable, and equitable countermeasures.

Importancia de las vacunas en salud pública: hitos y nuevos desafíos / The importance of vaccines in public health: milestones and new challenges

La creación del Programa de Inmunizaciones en el mundo ha sido una de las estrategias de salud pública más valorada y que contribuye a la equidad. Este programa fue lanzado por la Organización Mundial de la Salud en 1974, posteriormente en el año 1977 fue implementado por la Organización Panamericana de la Salud para los países de la región de América y en Chile fue a partir de 1979, poniendo a disposición un esquema contra 6 enfermedades inmunoprevenibles. Es un programa de Bien Público de cobertura nacional, gratuito para toda la población objeto para cada una de las vacunas, que cuenta con respaldo político, independiente de los cambios de gobierno y con financiamiento nacional en un 100%. Uno de los pilares de éxito de los programas es lograr altas coberturas de vacunación. En el caso de sarampión, dado la alta tasa de reproducción del agente y su condición de enfermedad en fase de eliminación, se requieren coberturas superiores a 95%. Aunque el principal indicador indirecto de desarrollo del programa es la tercera dosis de vacuna contra DFT (Difteria, Pertussis acelular, Tétanos). Aunque han transcurrido 45 años de existencia de los Programas de Inmunización, cinco de las Enfermedades Inmunoprevenibles forman parte de las 10 principales amenazas para la salud mundial. El presente artículo desarrolla parte de la historia del Programa Ampliado de Inmunizaciones de América y de Chile desde su génesis, destacando la importancia de los 12 componentes mínimos que forman parte de las actividades del programa y los hitos que han demostrado el valor, los beneficios de la vacunación, relatando ejemplos como viruela, poliomielitis, sarampión. Por último, se señalan las amenazas y posibles estrategias de superación.

The creation of the Immunization Program in the world has been one of the most valued public health strategies and one that contributes to equity. This Program was launched by the World Health Organization in 1974, later in 1977 it was implemented by the Panamerican Health Organization for the countries of the Americas region and in Chile since 1979, making available a scheme against 6 immunopreventable diseases. It is a program of Public Good of national coverage, free for all the target population for each of the vaccines, which has political support, independent of changes in government and 100% national financing. One of the corner stone of success of the programs is to achieve high vaccination coverage. In the case of measles, given the high rate of reproduction of the agent and its disease condition in the phase of elimination, coverage of more than 95% its needed. Although the main indirect indicator of program development is the third dose of DPT (Difteria, Acellular Pertussis, Tetanus) vaccine. Although 45 years of the existence of Immunization Programs have passed, five of the Immunopreventable Diseases are part of the 10 main risks to world health. This article develops part of the history of the Expanded Program of Immunizations of America and Chile since its genesis, highlighting the importance of the 12 limited components that are part of the activities of the program and the milestones that have experienced the value, benefits of vaccination, such as smallpox, polio, measles. Finally, the threats and possible strategies for overcoming them are pointed out.

The Smallpox Epidemics in America in the 1700s and the Role of the Surgeons: Lessons to be Learned During the Global Outbreak of COVID-19.

Today's COVID-19 pandemic offers many similarities with previous pandemics hitting our country. In particular, the smallpox epidemics during the 1700s threatened the lives of multitudes and created panic and fear in the society, similar to the situation caused by the coronavirus. Remedies that were instituted, especially inoculations, were met with opposition and even violence when first introduced. The newspapers were filled with headlines reflecting the disputes. There was a "six feet rule" during the smallpox epidemics, although it had a different meaning than today. Politicians and other leaders of the society were engaged in the war against the infection. Boston became involved in the fight against the smallpox by Dr. Zabdiel Boylston's and Rev. Cotton Mather's introduction of inoculations. When George Washington realized the benefits of the procedure and ordered mass inoculations of the Continental Army, it became an important factor in winning not only the fight against smallpox but the Revolutionary War as well. Looking back at history, realizing that we have survived previous outbreaks of devastating diseases, can provide hope during the current pandemic.

The Delay in the Licensing of Protozoal Vaccines: A Comparative History.

Although viruses and bacteria have been known as agents of diseases since 1546, 250 years went by until the first vaccines against these pathogens were developed (1796 and 1800s). In contrast, Malaria, which is a protozoan-neglected disease, has been known since the 5th century BCE and, despite 2,500 years having passed since then, no human vaccine has yet been licensed for Malaria. Additionally, no modern human vaccine is currently licensed against Visceral or Cutaneous leishmaniasis. Vaccination against Malaria evolved from the inoculation of irradiated sporozoites through the bite of Anopheles mosquitoes in 1930's, which failed to give protection, to the use of controlled human Malaria infection (CHMI) provoked by live sporozoites of Plasmodium falciparum and curtailed with specific chemotherapy since 1940's. Although the use of CHMI for vaccination was relatively efficacious, it has some ethical limitations and was substituted by the use of injected recombinant vaccines expressing the main antigens of the parasite cycle, starting in 1980. Pre-erythrocytic (PEV), Blood stage (BSV), transmission-blocking (TBV), antitoxic (AT), and pregnancy-associated Malaria vaccines are under development. Currently, the RTS,S-PEV vaccine, based on the circumsporozoite protein, is the only one that has arrived at the Phase III trial stage. The "R" stands for the central repeat region of Plasmodium (P.) falciparum circumsporozoite protein (CSP); the "T" for the T-cell epitopes of the CSP; and the "S" for hepatitis B surface antigen (HBsAg). In Africa, this latter vaccine achieved only 36.7% vaccine efficacy (VE) in 5-7 years old children and was associated with an increase in clinical cases in one assay. Therefore, in spite of 35 years of research, there is no currently licensed vaccine against Malaria. In contrast, more progress has been achieved regarding prevention of leishmaniasis by vaccine, which also started with the use of live vaccines. For ethical reasons, these were substituted by second-generation subunit or recombinant DNA and protein vaccines. Currently, there is one live vaccine for humans licensed in Uzbekistan, and four licensed veterinary vaccines against visceral leishmaniasis: Leishmune® (76-80% VE) and CaniLeish® (68.4% VE), which give protection against strong endpoints (severe disease and deaths under natural conditions), and, under less severe endpoints (parasitologically and PCR-positive cases), Leishtec® developed 71.4% VE in a low infective pressure area but only 35.7% VE and transient protection in a high infective pressure area, while Letifend® promoted 72% VE. A human recombinant vaccine based on the Nucleoside hydrolase NH36 of Leishmania (L.) donovani, the main antigen of the Leishmune® vaccine, and the sterol 24-c-methyltransferase (SMT) from L. (L.) infantum has reached the Phase I clinical trial phase but has not yet been licensed against the disease. This review describes the history of vaccine development and is focused on licensed formulations that have been used in preventive medicine. Special attention has been given to the delay in the development and licensing of human vaccines against Protozoan infections, which show high incidence worldwide and still remain severe threats to Public Health.

Measles and the Modern History of Vaccination.

The modern era of vaccination was heralded with the licensure of the first 2 measles vaccines in 1963. This new era was distinct from the preceding era of vaccination for 4 main reasons. First, federal leadership in support of immunization at the local level grew. Second, immunization proponents championed the required vaccination of children as the best means of ensuring a protected population. Third, immunization proponents championed the idea that mass vaccination would not only help manage infectious diseases but also eradicate them. Fourth, the focus of local and federally supported immunization initiatives began to extend to the "mild" and "moderate" diseases of childhood (eg, measles), so-called because they were seen as less severe than previous targets of mass vaccination, such as smallpox, polio, and diphtheria. This article follows the history of measles to explore immunization successes and challenges in this modern era, because measles was the first of the mild and moderate diseases to become the target of a federally supported eradication-through-vaccination campaign, one that relied heavily on the preemptive, required vaccination of children. Its story thus epitomizes the range of political, epidemiological, cultural, and communications challenges to mass immunization in the modern era of vaccination.

[The battle in Madrid over poliomyelitis vaccines (1963): science, ideology and power in the first mass immunization campaign in Spain]. / La batalla de Madrid por las vacunas antipoliomielitis (1963): ciencia, ideología y poder en la primera campaña de inmunización masiva en España.

Between 1958 and 1963, Spain witnessed the highest ever incidence of poliomyelitis (2000 cases and 200 deaths per year). Although Salk's inactivated vaccine had arrived in Spain in 1957, the government took no decisive action to administer it to the entire population at risk. Neither was Sabin's attenuated vaccine administered, available in Europe from 1960. While other countries adopted one or the other, in Spain rivalry arose over the two vaccines, with mixed results. The Salk vaccine was administered to a small percentage of the population at risk through the Compulsory Sickness Insurance scheme (Spanish initials: SOE), while at the same time a research team at the National School of Health led by Florencio Pérez Gallardo (1917-2006) carried out a model epidemiological study that demonstrated the superiority of the Sabin vaccine. In 1963, the SOE launched a national campaign with the Salk vaccine promoted by the paediatrician Juan Bosch Marín (1902-1995), a representative of the most conservative structure of the Franco regime. The dispute over which vaccine was best reached its peak in early 1963 at various scientific conferences in Madrid. Bosch Marín's group argued in favour of his campaign and the Salk vaccine, while Pérez Gallardo did the same for the oral vaccine, achieving a substantial impact by inviting Sabin himself to speak. By the end of the year, following a pilot study, the first mass oral vaccination campaign against polio was introduced in Spain.

Effect of vaccination programmes on mortality burden among children and young adults in the Netherlands during the 20th century: a historical analysis.

BACKGROUND: In the 20th century, childhood mortality decreased rapidly, and vaccination programmes are frequently suggested as a contributing factor. However, quantification of this contribution is subject to debate or absent. We present historical data from the Netherlands that allow us to quantify the reduction in childhood mortality burden for vaccine-preventable diseases in this period as a function of vaccination coverage. METHODS: We retrieved cause-specific and age-specific historical mortality data from Statistics Netherlands from 1903 to 2012 (for Dutch birth cohorts born from 1903 to 1992), and data for vaccination coverage since the start of vaccination programmes from the Dutch Health Care Inspectorate and the Dutch National Institute for Public Health and the Environment. We also obtained birth and migration data from Statistics Netherlands. We used a restricted mean life-time method to estimate cause-specific mortality burden among children and young adults for each birth cohort as the years of life lost up to age 20 years, excluding migration as a variable because this did not affect the results. To correct for long-term trends, we calculated the cause-specific contribution to the total childhood mortality burden. FINDINGS: In the prevaccination era, the contribution to mortality burden was fairly constant for diphtheria (1·4%), pertussis (3·8%), and tetanus (0·1%). Around the start of mass vaccinations, these contributions to the mortality burden decreased rapidly to near zero. We noted similar patterns for poliomyelitis, mumps, and rubella. The number of deaths due to measles around the start of vaccination in the Netherlands were too few to detect an accelerated rate of decrease after mass vaccinations were started. We estimate that mass vaccination programmes averted 148 000 years of life lost up to age 20 years (95% prediction interval 110 000-201 000) among children born before 1992. This corresponds to about 9000 deaths averted (6000-12 000). INTERPRETATION: Our historical time series analysis of mortality and vaccination coverage shows a strong association between increasing vaccination coverage and diminishing contribution of vaccine-preventable diseases to overall mortality. This analysis provides further evidence that mass vaccination programmes contributed to lowering childhood mortality burden. FUNDING: Dutch Ministry of Health, Welfare and Sport.

The Entangled History of Sadoka (Rinderpest) and Veterinary Science in Tanzania and the Wider World, 1891-1901.

Scholarship on the Tanzanian Rinderpest epizootic of the 1890s has assumed that German colonizers understood from the start that they were confronting the same disease that had afflicted Eurasia for centuries. Outward indicators of the epizootic, known locally as sadoka, especially wildlife destruction, were unknown in Europe, leading German veterinarians to doubt that the African disease was Rinderpest. Financial constraints and conflicting development agendas, especially tension between ranching and pastoralism, deterred early colonial applications of veterinary science that might have led to an early diagnosis. European veterinarians, guarding their authority against medical researchers, opposed inoculation therapies in the case of Rinderpest in favor of veterinary policing despite recent breakthroughs in vaccine research. The virus was not identified before reaching South Africa in 1896, but this breakthrough had little influence on policy in East Africa. Yet emergent international disease conventions directed at bubonic plague entangled with veterinary policy in East Africa.

'Fight TB with BCG': mass vaccination campaigns in the British Caribbean, 1951-6.

Based on a wide range of primary materials, including WHO reports and Colonial Office correspondence, this article examines the UNICEF/WHO-funded mass BCG campaigns that were carried out in seven Caribbean colonies between 1951 and 1956. It explores the reasons behind them, their nature and aftermath and also compares them to those in other non-European countries and discusses them within a context of decolonisation. In doing so, it not only adds to the scholarship on TB in non-European contexts, which had tended to focus on Africa and Asia, but also to the relatively new field of Caribbean medical history and the rapidly expanding body of work on international health, which has paid scant attention to the Anglophone Caribbean and the pre-independence period.

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.

Vida, engenho e arte: o acervo histórico da Fundação Oswaldo Cruz / Life skill and art: the historical collection of the Oswaldo Cruz Foundation

Livro de fotografias sobre o acervo histórico da Fiocruz, formado em mais de um século por meio de expedições científicas, campanhas sanitárias e diversas atividades de pesquisa e ensino realizadas em seus laboratórios. Fotografias históricas de Joaquim Pinto somam-se às contemporâneas de Bruno Veiga para exibição deste amplo acervo de conhecimento, que encontra-se no campus de Manguinhos, no Rio de Janeiro, onde há um castelo mourisco, além de edificações centenárias em estilo eclético e modernista. Em breves artigos, historiadores e outros especialistas contextualizam a formação de cada tipo de acervo, revelando, também, aspectos da evolução da saúde pública no Brasil.

Benefits of lethal pandemics: direct impact of contagious diseases on public administration in Hungary (1867-1914).

The reconciliation of 1867 between Austria and Hungary brought great changes to Hungarian public administration: the way towards the building up of a modern public administration had been opened. Although there was a functioning public health system and a related legislation from the late 18th century, major issues - such as balanced geographical distribution of medical personnel, fair access to medical services even in the poorer regions of the country, and the effective protection against some contagious diseases - were not resolved for decades. During the reform work of public administration since the 1870s, the lawmakers touched repeatedly the framework and functioning of the public health as well. Although the general conditions of the domain depended traditionally on the municipalities and counties due to the national importance of the matter, the government made efforts to make the functioning of the public health more efficient through centralisation. The contagious diseases continuously endangered the population, revealing the weak points in the existing public health system, thereby giving a momentum to the reforms and helping the government in its organization of prevention and clearly contributing to the legislation work.

Poliomyelitis and its elimination in Cuba: an historical overview.

INTRODUCTION: Polio was first detected in Cuba in the late 19th century among residents of the US community on the Isla de Pinos (Isle of Pines, now Isle of Youth), apparently introduced through migration from the USA. The first outbreak was reported in 1906 on the Isle, with the first epidemic reported in the former province of Las Villas in 1909. The epidemics subsequently intensified, by 1934 becoming periodic every four to five years, and accompanied by high morbidity, mortality and crippling sequelae, primarily among children. OBJECTIVE: To review and analyze the history of polio and its control in Cuba, from the disease's first appearance in 1898 until WHO/PAHO certification of elimination in 1994. METHODS: The historiological method was used; archival documents, medical records, and available polio morbidity and mortality statistics from the Ministry of Public Health's National Statistics Division before 1959 and from 1959 through 2000 were reviewed. Crude morbidity and mortality rates were calculated using population estimates at mid-period. Reports and scientific publications describing polio vaccination campaigns and their results were also reviewed, and key informants were interviewed. RESULTS: After initial introduction of polio in Cuba, five major epidemics occurred between 1932 and 1958: in 1934 (434 cases, 82 deaths); 1942 (494 cases, 58 deaths); 1946 (239 cases, 33 deaths), 1952 (492 cases, 15 deaths) and 1955 (267 cases, 8 deaths). Between 1957 and 1961 the disease's endemicity reached epidemic levels, with the last outbreak occurring in 1961, with 342 cases, 30% of them in children aged >4 years. In 1962, Cuba launched a nationwide polio vaccination campaign, the first of annual campaigns thereafter carried out in the framework of a coherent national program aimed at polio elimination. Using the Sabin oral vaccine and targeting the entire pediatric population in a single time period, five million doses were administered in the first campaign, reaching 87.5% of the target population aged 1 month through 14 years, constituting 109.4% of planned coverage. Since that year, no deaths from polio have been recorded (there were ten cases between 1963 and 1989) and WHO/PAHO certified polio elimination in Cuba in 1994. CONCLUSIONS: Cuba controlled polio with effective vaccination strategies and appropriate epidemiological measures, in the context of social, financial and political support. KEYWORDS History, poliomyelitis, epidemiology, disease control, vaccination, Sabin vaccine, Cuba.