The 1942 Massive Contamination of Yellow Fever Vaccine: A Public Health Consequence of Scientific Arrogance.

In the late 1930s, the 17D vaccine against yellow fever was produced in record time. 17D was and is an excellent vaccine. Its rapid diffusion led, however, to several problems, the most important among them being the 1942 massive contamination of the vaccine distributed to the US Army by the hepatitis B virus. The US part of this story is relatively well-known, but its Brazilian part much less so. In 1940, scientists who were producing the 17D vaccine in Rio de Janeiro found that it was contaminated by an "icterus virus" that originated in normal human serum. They solved this problem through the exclusion of human serum from vaccine production, but failed to persuade their US colleagues to do the same. The Rio experts, aware of the potential pitfalls of a new technology, carefully supervised the consequences of their vaccination campaigns. They were thus able to rapidly spot problems and eliminate them. By contrast, US scientists, persuaded of their technical superiority and distrustful of warnings that originated from a "less developed" country, neglected to implement basic public health rules. A major disaster followed. (Am J Public Health. 2021;111(9): 1654-1660. https://doi.org/10.2105/AJPH.2021.306313).

[National Immunisation Programme: is vaccinating less an option?] / Rijksvaccinatieprogramma: is minder vaccineren een optie?

Many people are no longer familiar with the diseases that are part of the Dutch National Immunisation Programme (NIP). The protection given by the NIP has ensured that these diseases, most of them serious, have largely disappeared. The NIP has developed gradually, but in retrospect it was in 1957 that what we now know as the NIP started. Over the years, the NIP has gradually expanded to include various vaccines such as live attenuated vaccines, conjugate vaccines and vaccines that offer protection against chronic viral infections. Currently, the NIP offers protection against twelve different diseases. Occasionally the Netherlands still sees minor outbreaks of those diseases included in the NIP programme, generally among non-vaccinated people. It is important that the NIP is retained; stopping vaccination always leads to the return of the disease. The question is: can good protection be maintained with fewer injections? This subject is on the agenda of the Health Council Of The Netherlands for discussion in 2022.

Decrease in the prevalence of hepatitis B and D virus infections in an endemic area in Peru 23 years after the introduction of the first pilot vaccination program against hepatitis B.

In 1991, Peru launched the first vaccination program against hepatitis B in children aged under 5 years in the hyperendemic [hepatitis B virus (HBV) and hepatitis D virus (HDV)] province of Abancay. We conducted a cross-sectional study to determine the prevalence of HBV and HDV infections, 23 years after the launch of the vaccination program, as well as the post-vaccine response against hepatitis B in terms of prevalence of hepatitis B surface antibody (anti-HBs ≥10 mUI/ml). Among 3165 participants aged from 0 to 94 years, the prevalence rates of hepatitis B surface antigen (HBsAg), and hepatitis B core antibody (total anti-HBc) were 1.2% [95% confidence interval (CI) 0.85-1.64%], and 41.67% (95% CI 39.95-43.41%), respectively. The prevalence rate of anti-HBs at protective levels (≥10 mUI/ml) in individuals who HBsAg and anti-HBc negative was 66.36% (95% CI 64.15-68.51%). The prevalence rate of HBsAg in children aged <15 years was nil, and among adult HBsAg carriers, the prevalence of hepatitis D antibody (anti-HDV) was 5.26% (2/38; 95% CI 0.64-17.74). These findings showed that HBV prevalence has changed from high to low endemicity, 23 years following implementation of the vaccination program against hepatitis B, and HDV infection was not detected in those aged <30 years.

Programa nacional de inmunizacion en Chile: pasado, presente y futuro / National immunization program in Chile: past, present and future

El Programa Ampliado de Inmunizaciones (PAI) a nivel mundial nace en 1974 como iniciativa de la Organización Mundial de la Salud (OMS) y la Organización Panamericana de la Salud (OPS). En Chile, el actual Programa Nacional de Inmunizaciones (PNI) se origina en el Plan Ampliado de Inmunizaciones (PAI) establecido en el año 1978. En sus inicios, el PAI se basó en disposiciones legales definidas en 1975, que establecía las Enfermedades Trasmisibles de Vacunación Obligatoria. Desde el año 2010, el Decreto Exento N°6 promulgado el 29 de enero, se dispone la vacunación obligatoria contra enfermedades inmunoprevenibles de la población del país. Posteriormente se han realizado modificaciones al decreto exento N°6 reflejando la incorporación de nuevas vacunas al calendario, modificaciones en los grupos objetivo y/o cambios en las estrategias de vacunación, entre otros. En estas disposiciones también se establece que el Ministerio de Salud debe asegurar el acceso gratuito a vacunaciones seguras y efectivas para toda la población objetivo. El objetivo del artículo, es describir la evolución de las iniciativas de vacunación en nuestro país, desde antes de la creación del PAI, la sistematización de las estrategias de vacunación una vez que se establece el programa hasta las modificaciones realizadas en la última década.

The Expanded Program on Immunization (EPI) worldwide was created in 1974 as an initiative of the World Health Organization (WHO) and the Pan American Health Organization (PAHO). In Chile, the current National Immunization Program (PNI) originates from the Extended Inmunization Plan (EPI) established in 1978. In its beginnings, the EPI was based on legal provisions defined in 1975, which established the Communicable Diseases of Compulsory Vaccination. Since 2010, the Exempt Decree No. 6 promulgated on January 29, provides the Mandatory Vaccination against Immune preventable Diseases of the Population of the Country. Subsequently there have been modifications to the Exempt Decree No. 6 reflecting the incorporation of new vaccines to the calendar, modifications in the target groups and /or changes in vaccination strategies, among others. These provisions also state that the Ministry of Health must ensure free access to safe and effective vaccinations for the entire target population. The aim oh this article is to describe evolution of vaccination initiatives in our country, from before the creation of the EPI, the systematization of vaccination strategies once the program is established, until the modifications made in the last decade.

Global trends in measles publications.

INTRODUCTION: Beginning with the 1960s, this review analyzes trends in publications on measles indexed by the National Library of Medicine from January 1960 to mid-2018. It notes both the growth in numbers of published papers, and the increasing number and proportion of publications, in the current century, of articles on such items as costing, measles elimination, and determinants of coverage. METHODS: A two-person team extracted from the National Library of Medicine (NLM) homepage all citations on measles beginning in 1960 and continuing through mid-2018. These were then classified both by overall number and by subject matter, with tabular summaries of both by decade and by subject matter. The tabular presentation forms the basis for a discussion of the ten most frequently cited subjects, and publication trends, with a special emphasis on the current century. RESULTS: As in the past, the most often currently published items have been on coverage and its determinants, measles elimination, outbreak reports, SSPE, and SIAs. The putative relationship between vaccination and autism saw a spurt of articles in the 1990s, rapidly declining after the IOM report rejecting the causative hypothesis. CONCLUSION: There is a discussion on the sequencing of polio and measles eradication, the former unlikely before 2022, and an examination of likely research priorities as the world moves from measles control to measles eradication. There is a key role for social science in combatting vaccination reticence. The role of technical innovations, such as micropatch vaccination, is discussed.

Smallpox Vaccine and Resident Responses in Modern Shanghai: Focusing on Regional and Cultural Comparison.

In modern Shanghai, smallpox was one of the most threatening diseases with its mortality rate going up to 30 percent. In response to the disease, Dr. William Lockhart, a medical missionary of the London Missionary Society, introduced vaccination to the Chinese people in Shanghai. He built the first western style hospital in Shanghai, Renji Hospital, in 1843. At this time, native doctors also played a very important role. For example, Huang Chun-pu was in charge of the dispensary in the Chinese City in Shanghai, and he was the one who introduced vaccination under Dr. Lockhart's direction. In 1868, the Health Office of Shanghai Municipal Council began to implement a vaccination program. Around the turn of the 20th century, the Health Office of Shanghai Municipal Council managed several sub-district offices, hospitals, dispensaries, gaol, and even the traditional place like simiao for the free vaccinations. Urban residents benefited from a sanitary system, such as wide and free vaccination, compared to people who lived in rural areas. Moreover, Shanghai possessed the advantage of having the vaccine as a staple product of the Municipal Laboratory. The number of units of the vaccine issued from the Laboratory in sequence of years from 1898 to 1920 has been 115,351 on average. Unlike the International Settlement, where systematic inoculation was conducted under the leadership of the Municipal Council, the Chinese City was still reliant on charity organizations in the early 1900s. The foreign residence in the International Settlement had a strong influence from the foreign governments, and foreign doctors were well-aware of the need for the vaccination. However, the Chinese City was a Chinese enclave that was still under the traditional rule of the Qing Dynasty. In addition, the people of Shanghai had different perceptions of the smallpox vaccination, and this became an obstacle to the establishment of urban sanitation systems. Some Chinese people still relied on the traditional Chinese variolation and Chinese custom. For example, Chinese people still applied for inoculation in the spring and avoided summer and fall following traditional Chinese variolation, even though the best time to get vaccinated was in early winter before the spread of smallpox. In addition, foreigners were often more problematic than Chinese because they often overlooked the importance of vaccines and relied on drugs instead. The municipal authority, therefore, provided a wide range of free vaccinations for the poor and needy people regardless of their nationalities, and with such measures, sought to establish a stable urban sanitation system. This had been the key to the success of hygiene policies.

[Poliomyelitis in the Spanish press (1960-1975)]. / La poliomielitis en la prensa española (1960-1975).

OBJECTIVE: Vaccination has been one of the most effective preventive measures to reduce the number of diseases that affect humans. The primary objective of this study is to describe the informative treatment of polio in the written press at a time when it was of great importance. METHODS: From the digital newspaper archive of the ABC and La Vanguardia newspapers, all the information in which the concept "polio", published during the period between 1960 and 1975 was selected. RESULTS: In total there have been 961 units of analysis, 557 for the ABC newspaper and 404, for La Vanguardia. The year of greatest publication was the year 1963, coinciding with the authorization for the use of the Sabin vaccine. The need to intensify vaccination campaigns is highlighted as the number of annual cases continued to increase. CONCLUSIONS: There are no significant differences in the coverage of the newspaper ABC and La Vanguardia, following a pattern of publication very similar between them, where the Sabin vaccine appears as one of the most important scientific advances, thanks to which they allowed to protect children against to this dreaded disease, thus avoiding a major epidemic.

OBJETIVO: La vacunación ha sido una de las medidas preventivas más eficaces para disminuir el número de enfermedades que afectan a los seres humanos. El objetivo primordial de este estudio fue describir el tratamiento informativo de la poliomielitis en la prensa escrita de una época donde tuvo gran importancia. METODOS: A partir de la hemeroteca digital de los periódicos ABC y La Vanguardia se seleccionaron todas las informaciones en las que apareciera el concepto "poliomielitis", publicadas durante el periodo de tiempo comprendido entre 1960 y 1975. RESULTADOS: En total hubo 961 unidades de análisis, 557 para el periódico ABC y 404 para La Vanguardia. El año con más publicaciones fue 1963, coincidiendo con la autorización para la utilización de la vacuna Sabin. Se destaca la necesidad de intensificar las campañas de vacunación, ya que el número de casos anuales seguía aumentando. CONCLUSIONES: No existen diferencias significativas en las coberturas del periódico ABC y la de La Vanguardia, siguiendo un patrón de publicación muy parecido entre ellos, en donde la vacuna Sabin aparece como uno de los avances científicos más importantes. Gracias a ella se pudo proteger a los niños y niñas frente a esta temida enfermedad, evitando así una epidemia mayor.

Two centuries of immunisation in the UK (part 1).

The impact of immunisation is best understood through a historical lens, since so many of the diseases which placed a burden on our population have been eliminated or controlled through immunisation. The United Kingdom (UK) National Health Service (NHS), which celebrated its 70th birthday in 2018, is responsible for delivering the highly successful universal national immunisation programme. However, the first vaccines used in the UK were not part of a centrally coordinated programme until the 1960s. Resources that summarise the first 200 years of immunisation in the UK are not readily accessible. Here we provide a two part chronological insight into the history of the UK immunisation programme from primary sources. In Part I, we highlight the importance of wartime conditions, unprecedented vaccine development, and the polio outbreaks in the in driving developments in immunisation and discuss subsequent changes in the use of the original vaccines of the immunisation programme, namely, diphtheria, tetanus, pertussis, and polio. In Part 2, we discuss the formation of the Joint Committee on Vaccination and Immunisation and its role, working with public health agencies and advising the UK Governments on vaccine policy, to bring a comprehensive programme to defend the health of the population against serious infectious diseases, highlighting the importance of programme organisation and leadership.

Two centuries of immunisation in the UK (part II).

The centrally coordinated response that controlled the polio epidemics of the 1950s through immunisation led to the development of a national immunisation strategy in the UK and the formation of the Joint Committee on Vaccination and Immunisation (JCVI) in 1963, which oversees the immunisation programme and advises the UK Department of Health on new vaccine introductions. As a result of technological advances in vaccine development and scientific advances in immunology and microbiology over the 56 years since then, and the formation of a comprehensive public health surveillance system for vaccine-preventable disease, the National Health Service immunisation programme now covers 18 serious diseases of childhood, with an astonishing impact on child health. Here we consider the formation of the JCVI and the development of the national immunisation programme and review the introduction of vaccines over the past half century to defend public health.

Borders and Blood Fractions: Gamma Globulin and Canada's Fight against Polio, 1950-55.

During the early 1950s, Canada's efforts to prevent polio became heavily influenced by developments in the United States. America's foremost polio charity, the National Foundation for Infantile Paralysis, sponsored University of Pittsburgh researcher Dr. William McD. Hammon to evaluate the efficacy of a human blood fraction, gamma globulin (GG), to prevent paralytic polio. When the resulting clinical trial data appeared to show that the blood fraction offered some protection against the disease, Canadians embraced the concept for reasons of historical trust, parental demand, and public health pragmatism. They established Canada's first national immunization program to fight polio before the vaccine, as well as developed a plan to produce, evaluate, and distribute GG to epidemic areas. Despite being an expensive enterprise for a geographically vast and sparsely populated nation, Canada's GG program was extended to citizens and it became an important response to polio before a safe and effective vaccine was licensed. Although the blood fraction was not as effective at preventing polio paralysis as researchers had anticipated, its systematic use reveals how Canadian health leaders drew on transnational relationships to reduce the incidence of disease.

Trends in governmental expenditure on vaccination programmes in the Netherlands, a historical analysis.

BACKGROUND: Health economic evaluations are often required before implementing a vaccination programme. Such evaluations rarely consider the historical context of a vaccination programme. We review the financial history of vaccination programmes in the Netherlands, and compare these to demographic and macroeconomic developments as well as avoided mortality burden. METHODS: Previously uncatalogued historical expenditures on the Dutch National Immunisation Programme (NIP) and influenza vaccination were obtained from official reports. Costs were adjusted for inflation using Consumer Price Indices and expressed in Euro of 2016. Estimates on mortality burden averted were obtained from previous research and used to calculate the ratio of expenses to averted mortality burden for vaccinations against diphtheria, tetanus, pertussis, polio, measles, mumps and rubella for birth cohorts 1953-1992. RESULTS: Developments towards a uniform government funded NIP started early 1950s with vaccinations against diphtheria, pertussis and tetanus, culminating in its official launch in 1957 together with polio vaccinations. Since the 1980s, expenditure increased nearly five-fold mostly due to the addition of new vaccines, while spending on already implemented vaccinations tended to decline. Overall, expenditure increased from € 5 million in 1957 to € 93 million in 2014. Relative to total healthcare expenditure, the NIP contributed little, ranging between 0.05% and 0.14%. Spending on influenza vaccination increased from € 37 million in 1996 to € 52 million in 2014, while relative to total healthcare expenditure it decreased from 0.069% to 0.055%. In 2014, 0.15% of healthcare expenditure and € 533 per birth was spent on vaccination programmes. Overall, for birth cohorts 1953-1992, € 5.4 thousand (95% confidence interval: 4.0-7.3) was expended per year-of-life-lost averted. CONCLUSION: The actual costs per year-of-life gained are more favorable than estimated here since averted medical costs were not included. Although expenditure on vaccination programmes increased substantially, the contribution to overall healthcare expenditure remained small.

Goodbye to Polio.

Polio has all but vanished. For one Texas physician, memories of it never will.

[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.

Vaccine-preventable disease control in the People's Republic of China: 1949-2016.

BACKGROUND: China's immunization program is one of the oldest and largest in the world. Rates of vaccine-preventable diseases (VPD) are comparable to those in high-income countries. The program's evolution has been characterized by ambitious target setting and innovative strategies that have not been widely described. METHODS: We reviewed national and provincial health department archives; analyzed disease surveillance, vaccination coverage, and serosurvey data from 1950 through 2016; and, conducted in-depth interviews with senior Chinese experts involved early VPD control efforts. RESULTS: Widespread immunization began in the 1950s with smallpox, diphtheria, and Bacillus-Calmette Guerin vaccines, and in the 1960s with pertussis, tetanus, polio, measles, and Japanese encephalitis (JE) vaccines. The largest drops in absolute VPD burden occurred in the 1970s with establishment of the Rural Cooperative Medical System and a cadre of trained peasant health workers whose responsibilities included vaccinations. From 1970 to 1979, incidence per 100,000 population dropped 48% from 3.3 to 1.75 for diphtheria, 50% from 152.2 to 49.4 for pertussis, 77% from 2.5 to 0.6 for polio, 60% from 450.5 to 178.3 for measles, and 72% from 18.0 to 5.1 for JE, averting an average of 4 million VPD cases each year. Until the early 1980s, vaccines were delivered through annual winter campaigns using a coordinated 'rush-relay' system to expedite transport while leveraging vaccine thermostability. Establishment of the cold chain system during in the 1980s allowed bi-monthly vaccination rounds and more timely vaccination resulting in rates of diphtheria, pertussis, measles and meningitis falling over 90% from 1980 to 1989, while polio and JE rates fell 40-50%. In the 1990s, progress stalled as financing for public health was weakened by broad market reforms. Large investments in public health and immunizations by the central government since 2004 has led to further declines in VPD burden and increased equity. During 2011-2016, the incidence per 100,000 population was <2.0 for measles and <0.2 for pertussis, JE, meningococcal meningitis, and hepatitis A. From 1992 to 2014, the prevalence of chronic hepatitis B infection in children <5 years fell from 9.7% to 0.3%, a 97% decline. China was certified polio-free in 2000 and diphtheria was last reported in 2006. CONCLUSIONS: Long-term political commitment to immunizations as a basic right, ambitious targets, use of disease incidence as the primary metric to assess program performance, and nationwide scale-up of successful locally developed strategies that optimized use of available limited resources have been critical to China's success in controlling vaccine-preventable diseases.

The landscape of vaccines in China: history, classification, supply, and price.

BACKGROUND: Vaccine regulation in China meets World Health Organization standards, but China's vaccine industry and immunization program have some characteristics that differ from other countries. We described the history, classification, supply and prices of vaccines available and used in China, compared with high-and middle-incomes countries to illustrate the development of Chinese vaccine industry and immunization program. METHODS: Immunization policy documents were obtained from the State Council and the National Health and Family Planning Commission (NHFPC). Numbers of doses of vaccines released in China were obtained from the Biologicals Lot Release Program of the National Institutes for Food and Drug Control (NIFDC). Vaccine prices were obtained from Chinese Central Government Procurement (CCGP). International data were collected from US CDC, Public Health England, European CDC, WHO, and UNICEF. RESULTS: Between 2007 and 2015, the annual supply of vaccines in China ranged between 666 million and 1,190 million doses, with most doses produced domestically. The government's Expanded Program on Immunization (EPI) prevents 12 vaccine preventable diseases (VPD) through routine immunization. China produces vaccines that are in common use globally; however, the number of routinely-prevented diseases is fewer than in high- and middle-income countries. Contract prices for program (EPI) vaccines ranged from 0.1 to 5.7 US dollars per dose - similar to UNICEF prices. Contract prices for private-market vaccines ranged from 2.4 to 102.9 US dollars per dose - often higher than prices for comparable US, European, and UNICEF vaccines. CONCLUSION: China is a well-regulated producer of vaccines, but some vaccines that are important globally are not included in China's EPI system in China. Sustained and coordinated effort will be required to bring Chinese vaccine industry and EPI into an era of global leadership.

Mistrust in Medicine: The Rise and Fall of America's First Vaccine Institute.

In 1813, the American government passed An Act to Encourage Vaccination, the first federal endorsement of a medical practice in American history. The law tasked a federal agent with maintaining a supply of the smallpox vaccine and distributing it nationwide. James Smith, a well-respected physician and proponent of vaccination, was appointed as vaccine agent. Smith was skeptical of claims that only well-trained physicians should be allowed to perform vaccination; he felt it was a simple procedure that should be available to all American citizens. In 1822, he made a tragic error that caused several deaths and left him vulnerable to criticism from political opponents and his medical peers. This ended Smith's professional career and led to the repeal of the act itself. In this article, we use the rise and fall of James Smith to provide a historical perspective on contemporary debates surrounding delayed vaccination schedules. We explain how physicians-in the 19th century and today-have worked to build public trust in vaccination in an American culture suspicious of medical expertise.

Molecular evolution and phylodynamics of hepatitis B virus infection circulating in Iran.

Previous local and national Iranian publications indicate that all Iranian hepatitis B virus (HBV) strains belong to HBV genotype D. The aim of this study was to analyze the evolutionary history of HBV infection in Iran for the first time, based on an intensive phylodynamic study. The evolutionary parameters, time to most recent common ancestor (tMRCA), and the population dynamics of infections were investigated using the Bayesian Monte Carlo Markov chain (BMCMC). The effective sample size (ESS) and sampling convergence were then monitored. After sampling from the posterior distribution of the nucleotide substitution rate and other evolutionary parameters, the point estimations (median) of these parameters were obtained. All Iranian HBV isolates were of genotype D, sub-type ayw2. The origin of HBV is regarded as having evolved first on the eastern border, before moving westward, where Isfahan province then hosted the virus. Afterwards, the virus moved to the south and west of the country. The tMRCA of HBV in Iran was estimated to be around 1894, with a 95% credible interval between the years 1701 and 1957. The effective number of infections increased exponentially from around 1925 to 1960. Conversely, from around 1992 onwards, the effective number of HBV infections has decreased at a very high rate. Phylodynamic inference clearly demonstrates a unique homogenous pattern of HBV genotype D compatible with a steady configuration of the decreased effective number of infections in the population in recent years, possibly due to the implementation of blood donation screening and vaccination programs. Adequate molecular epidemiology databases for HBV are crucial for infection prevention and treatment programs.