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Louis Pasteur is the renowned chemist and microbiologist of the 19th century involved in the development of the rabies vaccine. He worked with a researchers team in the laboratory, mainly Pierre Paul Emile Roux, and also physicians in the clinical practice approach and the defense of Pasteur's anti-rabies technique in the Académie Nationale de Médecine, Alfred Vulpian being the most notable. Pasteur's first studies on rabies are noted in his 1881 publication. But in 1885, he revealed that he had already immunized 50 dogs against rabies. Meanwhile, he was looking for human subjects. The most polemic of this search involves the second and last Emperor of Brazil, Dom Pedro II, who was a patron of the arts and sciences and followed and supported the work of the great scientist. During the reign of Dom Pedro II, the first Pasteur's Institute was founded in Rio de Janeiro, nine months before the Parisian, which had the financial support of Dom Pedro. This article deals with the interaction between the two outstanding characters, especially in the development of prophylactic treatment against rabies, and with the utilitarian aspects of this vaccine researches development against individual autonomy., Competing Interests: Conflicts of interest statement The authors declare no conflict of interest., (©2021 Pacini Editore SRL, Pisa, Italy.)

An eclectic, versatile Tuscan doctor, Eusebio Giacinto Valli (1755-1816) was a scholar of several branches of medicine, particularly public health, preventive medicine and epidemiology. His brilliant and wide-ranging education, and his intense passion for physics and chemistry, as applied to the human body, enabled him to conduct numerous studies in the field of vaccinology. He travelled to the Middle East in order to study the epidemiology of the plague and carried out experiments aimed at discovering a cure and a prophylaxis for rabies, succeeding in attenuating the rabies virus by inoculating a mixture of saliva from rabid dogs and gastric juice from frogs. Having travelled to Spain and then to Cuba, where he undertook the study of yellow fever, he died in Havana in September 1816, after injecting attenuated germs of the disease into his own body. He was buried in the great Monumental Cemetery "Cristobal Colon", where his tomb bears the epigraph: "victima de su amor à la humanidad ("a victim of his love for humanity").

Despite the criticism and reservations made about him still nowadays, Louis Pasteur may be considered one of the most important scientists of the last two centuries in public health, even if the work of the numerous scientists who preceded him have largely contributed to the successes he obtained without following too much to the rules of deontology and ethics currently in force in the world of research and medicine. He has definitively put down, by his experiments, the "theory of spontaneous generation" in force since antiquity, validated that of "germs or microbes", enacted the first rules of asepsis, while inspiring those of the antisepsis applied by Joseph Lister, and developed a certain number of vaccinations in veterinary and human medicine, including the anti-rabies, the one which made him famous all over the world. All this was not done without difficulty and Pasteur encountered for a large part of his life the misunderstanding of his contemporaries and the hostility of the medical world to which he did not belong. The authors comment in this text the movie The Story of Louis Pasteur by William Dieterle, filmed in 1936, based on the knowledge acquired since that date and doing the part of the real and the fiction., Competing Interests: The authors have no conflicts of interest to declare

Louis Pasteur's vaccine against rabies was introduced in France during 1885. A year later it became available within the United States. This article tells the story of the first use of the Pasteur vaccine in America and describes the early history of the vaccine's production and distribution across the country by Pasteur Institutes established for this purpose. Highlights of Pasteur's landmark studies on rabies are presented: research which pioneered the field of virology and the use of immunization to prevent infectious diseases., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The present article refers to the historical characterisation of Odo Bujwid's (1857-1942) research concerning the vaccine against rabies. The introduction refers to the treatment methods applied before Ludwik Pasteur's discovery. The following part refers to Odo Bujwid's own research including diagnostics, characterisation of the symptoms of disease, modification of the original Ludwik Pasteur's method and statistical information. The resume emphasizes that Odo Bujwid's scientific research was the introduction and generalisation the worldwide microbiology knowledge at the polish lands.

The Viennese surgeon Emerich Ullmann who was trained in rabies vaccination by Pasteur personally started his activity in Vienna on 28.6.1886 vaccinating persons of Austria-Hungary been bitten by rabid animals. Whereas Prof. v.Frisch of the other surgical clinic who also had visited Pasteur carried out animal experiments which urged him to disapprove Pasteur's human rabies vaccination. Ullmann vaccinated with great success but soon there appeared obstructions in Viennese medical journals and hateful discussions in the Austrian Parliament against Pasteur and Ullmann. These facts blocked the necessary financial subvention of Ullmann's self financed vaccinations and resulted in their interruption. After a mass infection of rabies in the Bukowina in 1891 the Supreme Sanitary Board formed an Epidemiologic Committee which recommended the establishment of a vaccination unit in an Austrian hospital. In July 1894 the Vaccination Unit was opened in the Viennese hospital Rudolfstiftung, where Emerich Ullmann carried out the rabies vaccinations.

As physicians, we've all learned in detail about the science behind vaccinations, but I suspect few of us have been taught about the history of vaccinations. Sure, we all know that Dr. Jonas Salk developed the poliovirus vaccine, but I wasn't aware that he inoculated himself, his wife, and his three children with his then experimental vaccine. When our editorial committee decided to focus on vaccinations as our theme for this month's Greene County Medical Society's Journal, I perused the internet for interesting topics. I came across a fascinating website, historyofvaccines.org; this website is a project of the College of Physicians of Philadelphia, touted as being the oldest professional medical organization in the United States. I credit the majority of the information in this article to the above website and the rest to the National Institutes of Health (nih.gov) website; I trust that the information is valid and true, based on the agencies behind these websites. Below are some interesting tidbits about vaccine preventable diseases that I found noteworthy to pass on to our readers.

Odessa physician Yakov Bardakh had an unusually high number of bacteriological 'firsts' to his credit: in 1886, while working at the Odessa Bacteriological Station, he was the first to test Louis Pasteur's anti-rabies vaccine on himself in order to demonstrate its safety. In the 1890s, in addition to conducting pioneering research on diphtheria, he created the first extensive course in bacteriology at the Novorossiya University--the first such course in Russia--and established the first university laboratory in Russia to specialize in bacteriology. In 1903 he created the first Medical Emergency Service in Russia., (© The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)

Despite perceived challenges to controlling an infectious disease in wildlife, oral rabies vaccination (ORV) of foxes has proved a remarkably successful tool and a prime example of a sophisticated strategy to eliminate disease from wildlife reservoirs. During the past three decades, the implementation of ORV programmes in 24 countries has led to the elimination of fox-mediated rabies from vast areas of Western and Central Europe. In this study, we evaluated the efficiency of 22 European ORV programmes between 1978 and 2010. During this period an area of almost 1.9 million km² was targeted at least once with vaccine baits, with control taking between 5 and 26 years depending upon the country. We examined factors influencing effort required both to control and eliminate fox rabies as well as cost-related issues of these programmes. The proportion of land area ever affected by rabies and an index capturing the size and overlap of successive ORV campaigns were identified as factors having statistically significant effects on the number of campaigns required to both control and eliminate rabies. Repeat comprehensive campaigns that are wholly overlapping much more rapidly eliminate infection and are less costly in the long term. Disproportionally greater effort is required in the final phase of an ORV programme, with a median of 11 additional campaigns required to eliminate disease once incidence has been reduced by 90 per cent. If successive ORV campaigns span the entire affected area, rabies will be eliminated more rapidly than if campaigns are implemented in a less comprehensive manner, therefore reducing ORV expenditure in the longer term. These findings should help improve the planning and implementation of ORV programmes, and facilitate future decision-making by veterinary authorities and policy-makers.

The article considers the initial stage of organization of antirabic care of population of Russia. The history of organization in 1886 of the five initial Pasteur stations in Russia is presented The main directions of stations functioning and assessment of their activities is given.

A major challenge for global rabies prevention and control is the lack of sufficient and affordable high quality vaccines. Such candidates should be pure, potent, safe, effective and economical to produce, with broad cross-reactivity against viral variants of public health and veterinary importance. The history of licensed human vaccines reviewed herein demonstrates clearly how the field has evolved to the current state of more passive development and postexposure management. Modern cell culture techniques provide adequate viral substrates for production of representative verified virus seeds. In contrast to outdated nervous tissue-based rabies vaccines, once a suitable substrate is identified, production of high titer virus results in a major qualitative and quantitative difference. Given the current scenario of only inactivated vaccines for humans, highly cell-adapted and stable, attenuated rabies viruses are ideal candidates for consideration to meet the need for seed viruses in the future.

The Semple antirabies vaccine was developed by David Semple in India in 1911. Semple introduced a peculiarly British approach within the Pasteurian tradition by using carbolized dead virus. This article studies this unique phase of vaccine research between 1910 and 1935 to show that in the debates and laboratory experiments around the potency and safety of vaccines, categories like "living" and "dead" were often used as ideological and moral denominations. These abstract and ideological debates were crucial in defining the final configuration of the Semple vaccine, the most popular antirabies vaccine used globally, and also in shaping international vaccination policies.

Rabies is a fatal disease transmitted by infected animals by bite, scratch, licking on broken skin or contamination of mucosis by saliva. The regimen of post-exposure prophylaxis for people not previously vaccinated, that is currently recommended by WHO, consists of a combination of wound cleaning, active immunization and passive immunization when the exposure is of category 3. Most of the products available on the market, in particular human rabies immunoglobulins, highly purified equine rabies immunoglobulins and the derived F(ab')(2) fragments, are now characterized by high potency and safety. Although the interest of passive anti-rabies immunization was first demonstrated in the first half of the 20th century, there is still an inadequate supply of these products to the target populations mostly in developing countries. Therefore, it is urgent to set-up training and information actions for healthcare personnel on the need to use passive immunotherapy and the lack of adverse effects of the related products. For the future, we hope that a scale up of production and a lower price will improve the accessibility to these products. The development of new products based on monoclonal antibodies and molecular biology, and which may be cheaper, is promising., (© Société de Biologie, 2010.)

Iconic accounts of the "bacteriological revolution" presented it as a radical change in the understanding of the natural world. Scientist had discovered that human being shared their environment with billions of invisible living beings which shape life phenomena, health and disease. They also learned to cultivate and manipulate these invisible creatures. The domestication of microorganisms in the laboratory disarmed them as enemies and occasionally transformed them into allies. This analysis of the development in French bacteriology displays a more nuanced and complex picture, with continuities as well as ruptures, and multiple levels of change. Between 1880 and 1900, the rise of "pasteurian science" did produce important changes in French society, but these changes were obtained through a variety of approaches: introduction of new experimental techniques, administrative and legal methods, training of professionals, education of the general public, and a direct political intervention.

In this review international and national historical features of rabies are presented remarking the start of preventive immunization in Chile, at year 1896, with the creation of the first service for rabies vaccination and la descentralización of preventive treatment from year 1929. Figures of human cases produced by this zoonosis between 1950 and 1986 are described, señalándose changes that occurred in local epidemiology of rabies since 1990, with an endemic pattern in bats and almost disappearance of canine rabies.

Shanghai Pasteur Institute, found in 1899, was the first institute of medical research on rabies with modern western medical science, and was also the first rabies vaccine manufacturer in China. By making use of relevant archives and documents, the authors attempt to elaborate its foundation and evolution, which focus on the fields of infectious disease prevention, popularization of vaccine inoculation, vaccine manufacturing and cultivation of Chinese medical talents. Before 1949, two branches of the Institute had been set up. It was incorporated into the newly established PLA Academy of Military Medicine Sciences in 1951. As an orient branch of the original Pasteur Institute, Shanghai Pasteur Institute inherit the sprit and methodology of the original Institute, and make great contribution to the foundation and development of Chinese modern microbiology, immunology and modern medical education.

Since 1956, red foxes (Vulpes vulpes) and, to a lesser extent, golden jackals (Canis aureus), have been the primary vectors maintaining endemic wildlife rabies in Israel. Starting in the autumn of 1998, oral rabies vaccination campaigns have been conducted in Israel targeting these two wildlife species, with increasing yearly geographical extension. Significant data have been accumulated from an area of approximately 5,200 km2 in Northern Israel. In the spring of 2003 the project was extended to 14,000 km2 and in the autumn to 21,000 km2, covering almost all inhabited areas in Israel and the West Bank. A total of two million RABORAL V-RG (Merial) vaccine-filled baits were distributed bi-annually by plane or helicopter at 14-19 baits km2. Since the onset of oral vaccination activities in 1998, annual bait acceptance in the vaccination zones has been demonstrated by biomarker detection (with tetracycline) in 55 % (429/783) of bone samples of target animals submitted for diagnosis. In 1999 to 2004, vaccine contact and induction of immunity in animals collected from the vaccination zones were reflected by seroconversion in 66 of 284 animals (23 %). By the year 2004, rabies cases declined sharply in all progressively vaccinated areas.

The Pasteur treatment for rabies is generally seen in terms of a triumphant penetration of laboratory science into clinical medicine. Similarly, the debates challenging the Pastorians have been interpreted as retrograde and inevitably vain efforts by a few disgruntled clinicians to resist scientific progress. This article revises the standard account by showing that the defenders of Pasteur perceived a serious threat to their enterprise and acted expeditiously to counter a potential crisis by adopting clinical strategies and tactics to argue for the relative safety of their method and to account for the rare failures resulting in deaths. An extensive unpublished source, the correspondence of Dr. Joseph Grancher with Pasteur, reveals this physician's leading role in successfully orchestrating the defense of Pasteur's antirabies method in January 1887 in the National Academy of Medicine. In responding to Dr. Michel Peter's accusations that the method could be dangerous and had been fatal in certain cases, Grancher invoked notions of risk inherent in all medical therapy, along with individual variability and predisposition to disease. Grancher's unpublished correspondence, supplemented by other manuscript letters, permits a textured understanding of the urgency experienced by Pasteur's team and their interactions as they worked out a strategy to defend their pioneering entry into human medicine. The suppression of autopsy evidence in one fatal case is apparent. More important, the strategy of the Pastorians implied a complementarity between the "clinic" and laboratory science, rather than any opposition.

Since the first development of a rabies vaccine by Pasteur in the late 19th century, second- and third-generation vaccines with improved efficacy and less reactogenicity have been developed for use in humans and animals. Despite the availability of safe but rather expensive vaccines based on inactivated virus propagated in diploid cell cultures, much of the human vaccinations worldwide are still carried out with nerve tissue-containing vaccines, which have various side effects. A number of experimental vaccines are under development that may provide alternative safe and potent but less expensive vaccine options. These include DNA vaccines, recombinant viral vaccines, and recombinant protein vaccines. Further testing is needed to determine if and which one of these novel vaccines will make their way into mass production and application in the future.

Since the first immunization of man against rabies in 1885 by Louis Pasteur, antirabies vaccine has been continuously improved. Treatment failures, clinical infections by the fixed virus, neuroparalytic accidents in connection with myelin were progressively eliminated. Vaccines can be standardized and accurately controlled. After the original spinal cord, adult or newborn animals brains, embryonated eggs, primary tissue cultures, diploid and permanent cell lines have been used for the vaccine production. Today, safe and potent vaccines are available. New products might be developed from the technology of genetic recombinants.

Wildlife rabies in certain parts of the United States has been increasing. With greater urbanization, many areas have seen an influx of wild animals such as raccoons and foxes that are known wildlife reservoirs of rabies. Rabies encephalitis has been a fatal illness recognized by humans throughout history. The purpose of this review is to examine the history of rabies throughout the world to elucidate the evolution of popular and scientific knowledge of the disease in animals and humans. By examining this development from a pediatric perspective, we gain insight into the prevention and treatment protocols recommended for children today. Pediatricians need to include education about prevention and treatment of rabies exposures in their anticipatory guidance sessions with families.

A historical review of the treatment of human rabies from ancient times up to the present is undertaken. An attempt is made to trace parallel between the concept of the main cause of rabies in a certain period and the kind of treatment utilized. The ancient Greek goddess Artemis was considered to be a healer of rabies; they already identified wound cauterization. People of the first century A.D. knew of the infection deriving from the saliva of a rabid dog and called it virus (in Latin). During medieval times when a magical and religious concept regarding health was prevalent, the principal protector was called St. Humbert. During the Renaissance many experiments were carried out and new information on the disease was obtained, both were basic in opening the way for new findings in the future. At that time the miasmatic and contagious theories were predominant. Pasteur strongly objected to the idea of the spontaneity of rabies. At the end of the XIXth. century and based on microbial discoveries, Pasteur brought about a great scientific revolution as regards the possibility of treating rabies by using a vaccine. At the present time, vaccines are of the nervous type or not, and the recommended dose varies. A large-number of studies on vaccination have been undertaken. In Latin America the most used are those by Fuenzalida and Palacios. At present, WHO recommends the vaccine made by cell culture.