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=== Immunology and vaccination === ==== Chicken cholera ==== Pasteur's first work on vaccine development was on [[chicken cholera]]. He received the bacteria samples (later called ''Pasteurella multocida'' after him) from [[Jean Joseph Henri Toussaint|Henry Toussaint]].<ref name="Plotkin pp. 35-36">{{cite book|editor1-last=Plotkin|editor1-first=Stanley A.|title=History of Vaccine Development|date=2011|publisher=Springer|isbn=978-1-4419-1339-5|pages=35–36|url=https://books.google.com/books?id=Wf2jS_4lCOAC&pg=PA39}}</ref> Being unable to conduct the experiments himself due to a stroke in 1868,<ref>{{cite book |last1=Descour |first1=L. |title=Pasteur and his work |date=1922 |publisher=Frederick A. Stokes Company |location=New York}}</ref> Pasteur relied heavily on his assistants Emile Roux and Charles Chamberland. The work with chicken cholera was initiated in 1877, and by the next year, Roux was able to maintain a stable culture using broths.<ref name=":0">{{Cite journal|last=Barranco|first=Caroline|date=28 September 2020|title=The first live attenuated vaccines|url=https://www.nature.com/articles/d42859-020-00008-5|journal=Nature Milestones|language=en|access-date=30 April 2021|archive-date=2 August 2021|archive-url=https://web.archive.org/web/20210802072726/https://www.nature.com/articles/d42859-020-00008-5|url-status=live}}</ref> As documented later by Pasteur in his notebook in March of 1880,<ref>{{cite journal |last1=Murnane |first1=John P |last2=Probert |first2=Rebecca |title=The relationship between Rose Anna Shedlock (c1850-1878) and Emile Roux (1853-1933) |journal=Journal of Medical Biography |date=August 25, 2024 |volume=online first |pages=1–8 |doi=10.1177/09677720241273568 |pmid=39183561 |doi-access=free |pmc=12056263 }}</ref><ref>{{cite book |last1=Bazin |first1=Herve |title=Vaccination: a History |date=2011 |publisher=John Libby |location=Esher, United Kingdom}}</ref> in October of 1879, being delayed in returning to the laboratory due to his daughter’s wedding and ill health, he instructed Roux to start a new chicken cholera culture using bacteria from a culture that had sat since July. The two chickens inoculated with this new culture showed some symptoms of infection, but instead of the infections being fatal, as they usually were, the chickens recovered completely. After further incubation of the culture for an additional 8 days, Roux again inoculated the same two chickens. As was also noted by Pasteur in his notebook in March of 1880, and contrary to some accounts, this time the chickens died. Thus, although the attenuated bacteria did not provide immunity, these experiments provided important clues as to how bacteria could be artificially attenuated in the laboratory. As a result, upon Pasteur’s return to the laboratory, the focus of the research was directed at creating a vaccine through attenuation. In February of 1880, Pasteur presented his results to the French Academy of Sciences as "''Sur les maladies virulentes et en particulier sur la maladie appelée vulgairement choléra des poules'' (On virulent diseases, and in particular on the disease commonly called chicken cholera)" and published it in the academy's journal (''[[Comptes rendus de l'Académie des Sciences|Comptes-Rendus hebdomadaires des séances de l'Académie des Sciences]]''). He attributed that the bacteria were weakened by contact with oxygen.<ref name="Plotkin pp. 35-36" /> He explained that bacteria kept in sealed containers never lost their virulence, and only those exposed to air in culture media could be used as vaccine. Pasteur introduced the term "attenuation" for this weakening of virulence as he presented before the academy, saying:{{blockquote|We can diminish the microbe's virulence by changing the mode of culturing. This is the crucial point of my subject. I ask the Academy not to criticize, for the time being, the confidence of my proceedings that permit me to determine the microbe's attenuation, in order to save the independence of my studies and to better assure their progress... [In conclusion] I would like to point out to the Academy two main consequences to the facts presented: the hope to culture all microbes and to find a vaccine for all infectious diseases that have repeatedly afflicted humanity, and are a major burden on agriculture and breeding of domestic animals.<ref name=":1">{{Cite journal|last=Smith|first=Kendall A.|year=2012|title=Louis pasteur, the father of immunology?|journal=Frontiers in Immunology|volume=3|pages=68|doi=10.3389/fimmu.2012.00068|pmc=3342039|pmid=22566949|doi-access=free}}</ref> }} In fact, Pasteur's vaccine against chicken cholera did not consistently produce immunity, and has subsequently been proven to be ineffective.<ref>"This way, which the genius of Pasteur had opened and which became so fruitful, soon proved to be closed with regard to the anti-pasteurellic vaccination of the hen. Difficulties arose in the regularity of attenuation and maintenance of virulence to a definite and fixed degree." (G. Lesbouyries, ''La pathologie des oiseaux'', Paris, 1941, p. 340; quoted by Hervé Bazin, ''L'Histoire des vaccinations'', John Libbey Eurotext, 2008, p. 155.)</ref> ==== Anthrax ==== Following the results with chicken cholera, Pasteur eventually utilized the immunization method developed for chicken cholera to create a vaccine for [[anthrax]], which affected [[cattle]]. In 1877, Pasteur had earlier directed his laboratory to culture the bacteria from the blood of infected animals, following the discovery of the bacterium by Robert Koch.<ref name=":1" /> [[File:Albert Edelfelt - Louis Pasteur - 1885.jpg|thumb|''Louis Pasteur in his laboratory'', painting by [[Albert Edelfelt|A. Edelfeldt]] in 1885]] When animals were infected with the bacteria, anthrax occurred, proving that the bacteria was the cause of the disease.<ref>{{cite book|last1=Keim|first1=Albert|last2=Lumet|first2=Louis|title=Louis Pasteur|date=1914|publisher=Frederick A. Stokes Company|pages=123–125|url=https://archive.org/stream/louispasteur00keim#page/122/mode/2up}}</ref> Many cattle were dying of anthrax in "cursed fields".<ref name=Schwartz /> Pasteur was told that sheep that died from anthrax were buried in the field. Pasteur thought that earthworms might have brought the bacteria to the surface. He found anthrax bacteria in earthworms' excrement, showing that he was correct.<ref name=Schwartz /> He told the farmers not to bury dead animals in the fields.<ref>{{cite book|last1=Vallery-Radot|first1=René|translator-last=Devonshire|translator-first=R. L.|title=The Life of Pasteur|date=1919|publisher=Constable & Company|location=London|pages=303–305|url=https://archive.org/stream/in.ernet.dli.2015.173907/2015.173907.The-Life-Of-Pasteur#page/n323/mode/2up}}</ref> Pasteur's interest in creating a vaccine for anthrax was greatly stimulated when on 12 July 1880, Henri Bouley read before the French Academy of Sciences a report from [[Jean Joseph Henri Toussaint|Henry Toussaint]], a [[veterinary surgeon]], who was not a member of the academy. Toussaint had developed anthrax vaccine by killing the bacilli by heating at 55 °C for 10 minutes. He tested his vaccine on eight dogs and 11 sheep, half of which died after inoculation. It was not a great success. Upon hearing the news, Pasteur immediately wrote to the academy that he could not believe that dead vaccine would work and that Toussaint's claim "overturns all the ideas I had on viruses, vaccines, etc."<ref name=":1" /> Following Pasteur's criticism, Toussaint switched to [[carbolic acid]] (phenol) to kill anthrax bacilli and tested the vaccine on sheep in August 1880. Pasteur thought that this type of killed vaccine should not work because he believed that attenuated bacteria used up nutrients that the bacteria needed to grow. He thought oxidizing bacteria when sitting in culture broth for prolonged periods made them less virulent.<ref>{{cite book|last1=Tizard|first1=Ian|editor1-last=Schultz|editor1-first=Ronald D.|title=Veterinary Vaccines and Diagnostics|date=1998|publisher=Academic Press|pages=12–14|chapter-url=https://books.google.com/books?id=i4s1YpGVFB8C&pg=PA12|chapter=Grease, Anthraxgate, and Kennel Cough: A Revisionist History of Early Veterinary Vaccines|isbn=978-0-08-052683-6}}</ref> However, Pasteur's laboratory found that anthrax bacillus was not easily weakened by culturing in air as it formed spores – unlike chicken cholera bacillus. In early 1881, his laboratory discovered that growing anthrax bacilli at about 42 °C made them unable to produce spores,<ref name="Bazin p. 196">{{cite book|last1=Bazin|first1=Hervé|title=Vaccinations: a History: From Lady Montagu to Jenner and genetic engineering|date=2011|publisher=John Libbey Eurotext|isbn=978-2-7420-1344-9|pages=196–197|url=https://books.google.com/books?id=IC8QBAAAQBAJ&pg=PA196}}</ref> and he described this method in a speech to the French Academy of Sciences on 28 February.<ref>{{cite journal|last1=Pasteur|first1=L.|last2=Chamberland|first2=C.|last3=Roux|first3=E.|title=Le vaccin de charbon|journal=Comptes Rendus Hebdomadaires des Séances de l'Académie des Sciences|year=1881|volume=92|pages=666–668|url=http://gallica.bnf.fr/ark:/12148/bpt6k7351t/f665.item.r=+COMPTES+RENDUS+++DES+S%C3%89ANCES+DE+L.langFR.zoom|language=fr|access-date=4 March 2017|archive-date=4 March 2017|archive-url=https://web.archive.org/web/20170304201227/http://gallica.bnf.fr/ark:/12148/bpt6k7351t/f665.item.r=+COMPTES+RENDUS+++DES+S%C3%89ANCES+DE+L.langFR.zoom|url-status=live}}</ref> On 21 March, despite inconsistent results, he announced successful vaccination of sheep. To this news, veterinarian Hippolyte Rossignol proposed that the Société d'agriculture de Melun organize an experiment to test Pasteur's vaccine. Pasteur signed an agreement accepting the challenge on 28 April. Pasteur's assistants, Roux and Chamberland, who were assigned the task of conducting the trial, were concerned about the unreliability of the attenuated vaccine, and therefore Chamberland secretly prepared an alternative vaccine using chemical inactivation.<ref name="Geison1995" /> Without divulging their method of preparing the vaccine to anyone but Pasteur, Roux and Chamberland performed the public experiment on May at Pouilly-le-Fort.<ref name="Geison1995" /> 58 sheep, 2 goats and 10 cattle were used, half of which were given the vaccine on 5 and 17 May; while the other half was untreated.<ref name=":2">{{Cite journal|last1=Pasteur|first1=Louis|last2=Chamberland|last3=Roux|year=2002|title=Summary report of the experiments conducted at Pouilly-le-Fort, near Melun, on the anthrax vaccination, 1881.|journal=The Yale Journal of Biology and Medicine|volume=75|issue=1|pages=59–62|pmc=2588695|pmid=12074483}}</ref> On 31 May, Roux and Chamberland next injected the animals with the fresh virulent culture of anthrax bacillus. The official result was observed and analyzed on 2 June in the presence of over 200 spectators, with Pasteur himself in attendance. The results were as Pasteur had bravely predicted: "I hypothesized that the six vaccinated cows would not become very ill, while the four unvaccinated cows would perish or at least become very ill."<ref name=":2" /> However, all vaccinated sheep and goats survived, while unvaccinated ones had died or were dying before the viewers.<ref>{{Cite journal|last=Smith|first=Kendall A.|year=2005|title=Wanted, an Anthrax vaccine: Dead or Alive?|journal=Medical Immunology|volume=4|issue=1|pages=5|doi=10.1186/1476-9433-4-5|pmc=1087873|pmid=15836780 |doi-access=free }}</ref> His report to the French Academy of Sciences on 13 June concludes:{{blockquote|[By] looking at everything from the scientific point of view, the development of a vaccination against anthrax constitutes significant progress beyond the first vaccine developed by Jenner, since the latter had never been obtained experimentally.<ref name=":2" />}}Pasteur did not directly disclose how he prepared the vaccines used at Pouilly-le-Fort.<ref>{{cite book|editor1-last=Plotkin|editor1-first=Stanley A.|title=History of Vaccine Development|date=2011|publisher=Springer|isbn=978-1-4419-1339-5|pages=37–38|url=https://books.google.com/books?id=Wf2jS_4lCOAC&pg=PA37}}</ref><ref name="Bazin p. 196" /> Although his report indicated it as a "live vaccine",<ref name=":2" /> his laboratory notebooks show that he actually used [[potassium dichromate]]-killed vaccine, as developed by Chamberland, quite similar to Toussaint's method.<ref name="Giese">{{cite book|editor1-last=Giese|editor1-first=Matthias|title=Molecular Vaccines: From Prophylaxis to Therapy|volume=1|date=2013|publisher=Springer|isbn=978-3-7091-1419-3|page=4|url=https://books.google.com/books?id=CLm8BAAAQBAJ&pg=PA4}}</ref><ref name="cohn">{{cite web| url=http://eri.louisville.edu/~eri/fos/interest1.html| title=Pasteur| author=Cohn, David V| publisher=University of Louisville| date=18 December 2006| access-date=2 December 2007| quote=Fortunately, Pasteur's colleagues Chamberland and Roux followed up the results of a research physician Jean-Joseph-Henri Toussaint, who had reported a year earlier that carbolic-acid/heated anthrax serum would immunize against anthrax. These results were difficult to reproduce and discarded although, as it turned out, Toussaint had been on the right track. This led Pasteur and his assistants to substitute an anthrax vaccine prepared by a method similar to that of Toussaint and different from what Pasteur had announced.| archive-date=23 March 2017| archive-url=https://web.archive.org/web/20170323234134/http://eri.louisville.edu/~eri/fos/interest1.html| url-status=live}}</ref><ref>{{cite book| author= Loir, A| title=Le mouvement sanitaire| year=1938| pages=18, 160| chapter=A l'ombre de Pasteur|chapter-url=https://books.google.com/books?id=WElmkgEACAAJ}}</ref> The notion of a weak form of a disease causing immunity to the virulent version was not new; this had been known for a long time for [[smallpox]]. Inoculation with smallpox ([[variolation]]) was known to result in a much less severe disease, and greatly reduced mortality, in comparison with the naturally acquired disease.<ref>{{cite book|editor1-last=Artenstein|editor1-first=Andrew W.|title=Vaccines: A Biography|date=2009|publisher=Springer|isbn=978-1-4419-1108-7|page=10|url=https://books.google.com/books?id=ewdL8ilILZAC&pg=PA10}}</ref> [[Edward Jenner]] had also studied [[vaccination]] using [[cowpox]] (''[[vaccinia]]'') to give cross-immunity to smallpox in the late 1790s, and by the early 1800s vaccination had spread to most of Europe.<ref>{{cite book|last1=Bazin|first1=Hervé|title=Vaccinations: a History: From Lady Montagu to Jenner and genetic engineering|date=2011|publisher=John Libbey Eurotext|isbn=978-2-7420-1344-9|pages=66–67, 82|url=https://books.google.com/books?id=IC8QBAAAQBAJ&pg=PA66}}</ref> The difference between smallpox vaccination and [[anthrax]] or [[chicken cholera]] vaccination was that the latter two disease organisms had been artificially weakened, so a naturally weak form of the disease organism did not need to be found.<ref name=Giese /> Pasteur's development of artificially weakened pathogens revolutionized work in infectious diseases, and he gave these artificially weakened diseases the generic name of "[[vaccine]]s", in honour of Jenner's discovery.<ref>{{cite book|last1=Vallery-Radot|first1=René|translator-last=Devonshire|translator-first=R. L.|title=The Life of Pasteur|date=1919|publisher=Constable & Company|location=London|page=332|url=https://archive.org/stream/in.ernet.dli.2015.173907/2015.173907.The-Life-Of-Pasteur#page/n351/mode/2up}}</ref> {{Main|Koch–Pasteur rivalry}} In 1876, [[Robert Koch]] had shown that ''[[Bacillus anthracis]]'' caused anthrax.<ref name="De Paolo">{{cite book|last1=De Paolo|first1=Charles|title=Epidemic Disease and Human Understanding: A Historical Analysis of Scientific and Other Writings|date=2006|publisher=McFarland|isbn=978-0-7864-2506-8|pages=103, 111–114|url=https://books.google.com/books?id=Xcz7Y9qVGQMC&pg=PA103}}</ref> In his papers published between 1878 and 1880, Pasteur only mentioned Koch's work in a footnote. Koch met Pasteur at the Seventh [[International Medical Congress]] in 1881. A few months later, Koch wrote that Pasteur had used impure cultures and made errors. In 1882, Pasteur replied to Koch in a speech, to which Koch responded aggressively.<ref name="ullmann" /> Koch stated that Pasteur tested his vaccine on unsuitable animals and that Pasteur's research was not properly scientific.<ref name=Ligon /> In 1882, Koch wrote "On the Anthrax Inoculation", in which he refuted several of Pasteur's conclusions about anthrax and criticized Pasteur for keeping his methods secret, jumping to conclusions, and being imprecise. In 1883, Pasteur wrote that he used cultures prepared in a similar way to his successful fermentation experiments and that Koch misinterpreted statistics and ignored Pasteur's work on silkworms.<ref name="De Paolo" /> ==== Swine erysipelas ==== In 1882, Pasteur sent his assistant [[Louis Thuillier]] to southern France because of an [[epizootic]] of [[swine erysipelas]].<ref>{{cite book|editor1-last=Plotkin|editor1-first=Stanley A.|title=History of Vaccine Development|date=2011|publisher=Springer|isbn=978-1-4419-1339-5|page=39|url=https://books.google.com/books?id=Wf2jS_4lCOAC&pg=PA39}}</ref> Thuillier identified the bacillus that caused the disease in March 1883.<ref name=Berche /> Pasteur and Thuillier increased the bacillus's virulence after passing it through pigeons. Then they passed the bacillus through rabbits, weakening it and obtaining a vaccine. Pasteur and Thuillier incorrectly described the bacterium as a figure-eight shape. Roux described the bacterium as stick-shaped in 1884.<ref>{{cite book|last1=Bazin|first1=Hervé|title=Vaccination: A History|date=2011|publisher=John Libbey Eurotext|isbn=978-2-7420-0775-2|page=211|url=https://books.google.com/books?id=orjaA_7sYZQC&pg=PA211}}</ref> ==== Rabies ==== [[File:Louis Pasteur Vanity Fair 8 January 1887.jpg|thumb|upright|Captioned "[[Rabies|Hydrophobia]]", caricature of Pasteur in the London magazine ''[[Vanity Fair (British magazine)|Vanity Fair]]'', January 1887<ref>{{Cite web |title=959.025 {{!}} Collections Online |url=https://collections.thackraymuseum.co.uk/object-959-025 |access-date=2024-05-29 |website=collections.thackraymuseum.co.uk}}</ref>]] Pasteur's laboratory produced the first vaccine for [[rabies]] using a method developed by his assistant Roux,<ref name="Geison1995" /> which involved growing the virus in rabbits, and then weakening it by drying the affected nerve tissue.<ref name=Schwartz /><ref name="wood">{{cite journal|last1=Wood|first1=Margaret E.|title=Biting Back|url=https://www.sciencehistory.org/distillations/magazine/biting-back|journal=Chemical Heritage Magazine|volume=28|number=2|page=7|access-date=20 March 2018|date=3 June 2016|archive-date=21 March 2018|archive-url=https://web.archive.org/web/20180321130516/https://www.sciencehistory.org/distillations/magazine/biting-back|url-status=live}}</ref> The rabies vaccine was initially created by [[Emile Roux]], a French doctor and a colleague of Pasteur, who had produced a killed vaccine using this method.<ref name=Ligon /> The vaccine had been tested in 50 dogs before its first human trial.<ref>{{cite book|first1= Sue Vander|last1=Hook |title= Louis Pasteur: Groundbreaking Chemist & Biologist |publisher= ABDO|url= https://archive.org/details/louispasteurgrou0000vand|url-access= registration|year=2011 |page=[https://archive.org/details/louispasteurgrou0000vand/page/8 8]|isbn=978-1-61714-783-8 }}</ref><ref>{{cite web|last1=Corole D|first1=Bos|title=Louis Pasteur and the Rabies Virus – Louis Pasteur Meets Joseph Meister|url=https://www.awesomestories.com/asset/view/LOUIS-PASTEUR-MEETS-JOSEPH-MEISTER-Louis-Pasteur-and-the-Rabies-Virus|publisher=Awesome Stories|access-date=22 November 2014|year=2014|archive-date=29 November 2014|archive-url=https://web.archive.org/web/20141129064133/https://www.awesomestories.com/asset/view/LOUIS-PASTEUR-MEETS-JOSEPH-MEISTER-Louis-Pasteur-and-the-Rabies-Virus|url-status=live}}</ref> This vaccine was used on 9-year-old [[Joseph Meister]], on 6 July 1885, after the boy was badly mauled by a rabid dog.<ref name="cohn" /><ref name="wood" /> This was done at some personal risk for Pasteur, since he was not a licensed physician and could have faced prosecution for treating the boy.<ref name=van /> After consulting with physicians, he decided to go ahead with the treatment.<ref name=Wasik /> Over 11 days, Meister received 13 inoculations, each inoculation using viruses that had been weakened for a shorter period of time.<ref name=Jackson /> Three months later he examined Meister and found that he was in good health.<ref name=Wasik /><ref name=trueman>{{cite web|author= Trueman C|title= Louis Pasteur|url= http://www.historylearningsite.co.uk/louis_pasteur.htm|work= HistoryLearningSite.co.uk|access-date= 3 July 2013|archive-date= 20 May 2015|archive-url= https://web.archive.org/web/20150520170850/http://www.historylearningsite.co.uk/louis_pasteur.htm|url-status= live}}</ref> Pasteur was hailed as a hero and the legal matter was not pursued.<ref name=van /> Analysis of his laboratory notebooks shows that Pasteur had treated two people before his vaccination of Meister. One survived but may not actually have had rabies, and the other died of rabies.<ref name=Jackson /><ref>{{cite book|editor1-last=Artenstein|editor1-first=Andrew W.|title=Vaccines: A Biography|date=2009|publisher=Springer|isbn=978-1-4419-1108-7|page=79|url=https://books.google.com/books?id=ewdL8ilILZAC&pg=PA79}}</ref> Pasteur began treatment of Jean-Baptiste Jupille on 20 October 1885, and the treatment was successful.<ref name=Jackson /> Later in 1885, people, including four children from the United States, went to Pasteur's laboratory to be inoculated.<ref name=Wasik /> In 1886, he treated 350 people, of which only one developed rabies.<ref name=Jackson /> The treatment's success laid the foundations for the manufacture of many other vaccines. The first of the Pasteur Institutes was also built on the basis of this achievement.<ref name="cohn" /> In ''[[The Story of San Michele]]'', [[Axel Munthe]] writes of some risks Pasteur undertook in the rabies vaccine research:<ref>{{cite book|last1=Munthe|first1=Axel|title=The Story of San Michele|date=2010|orig-year=First published 1929|publisher=Hachette UK|isbn=978-1-84854-526-7|chapter-url=https://books.google.com/books?id=XOfWJdqYoHYC|chapter=V: Patients}}</ref> {{blockquote|Pasteur himself was absolutely fearless. Anxious to secure a sample of saliva straight from the jaws of a rabid dog, I once saw him with the glass tube held between his lips draw a few drops of the deadly saliva from the mouth of a rabid bull-dog, held on the table by two assistants, their hands protected by leather gloves.}} Because of his study in germs, Pasteur encouraged doctors to sanitize their hands and equipment before surgery. Prior to this, few doctors or their assistants practiced these procedures.<ref>{{Cite journal|last=Melin|first=Maxwell David|year=2016|title=The Industrial Revolution and the Advent of Modern Surgery|url=https://ojs.stanford.edu/ojs/index.php/intersect/article/view/819|journal=Intersect: The Stanford Journal of Science, Technology, and Society|language=en|volume=9|issue=2|pages=online (1–13)|access-date=25 August 2021|archive-date=25 August 2021|archive-url=https://web.archive.org/web/20210825051413/https://ojs.stanford.edu/ojs/index.php/intersect/article/view/819|url-status=live}}</ref><ref>{{Cite journal|last=Magerl|first=Mary Ann|year=2008|title=Operating Room Sanitation: Routine Cleaning Versus Terminal Cleaning|url=https://linkinghub.elsevier.com/retrieve/pii/S1556793108000211|journal=Perioperative Nursing Clinics|language=en|volume=3|issue=2|pages=143–148|doi=10.1016/j.cpen.2008.01.007|access-date=25 August 2021|archive-date=26 May 2021|archive-url=https://web.archive.org/web/20210526013701/https://linkinghub.elsevier.com/retrieve/pii/S1556793108000211|url-status=live}}</ref> [[Ignaz Semmelweis]] and [[Joseph Lister]] had earlier practiced hand sanitizing in medical contexts in the 1860s.<ref>{{Cite journal|last1=Vermeil|first1=T.|last2=Peters|first2=A.|last3=Kilpatrick|first3=C.|last4=Pires|first4=D.|last5=Allegranzi|first5=B.|last6=Pittet|first6=D.|year=2019|title=Hand hygiene in hospitals: anatomy of a revolution|url=https://linkinghub.elsevier.com/retrieve/pii/S0195670118304821|journal=Journal of Hospital Infection|language=en|volume=101|issue=4|pages=383–392|doi=10.1016/j.jhin.2018.09.003|pmid=30237118|s2cid=52306024|access-date=25 August 2021|archive-date=19 February 2022|archive-url=https://web.archive.org/web/20220219175842/https://linkinghub.elsevier.com/retrieve/pii/S0195670118304821|url-status=live}}</ref><ref>{{Cite journal|last=Larson|first=E|year=1989|title=Innovations in health care: antisepsis as a case study.|journal=American Journal of Public Health|language=en|volume=79|issue=1|pages=92–99|doi=10.2105/AJPH.79.1.92|pmc=1349481|pmid=2642372}}</ref>
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