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=== Research === {{see also|Cholera vaccine}} [[File:Robert Koch (Deutsche Cholera-Expedition in Ägypten 1884).jpg|thumb|upright=1.3|[[Robert Koch]] (third from the right) on a cholera research expedition in [[Egypt]] in 1884, one year after he identified ''V. cholerae'']] [[File:How to avoid the Cholera 1848.jpg|thumb|upright=1.3|''How to avoid the cholera'' leaflet; [[Aberystwyth]]; August 1849]] One of the major contributions to fighting cholera was made by the physician and pioneer medical scientist [[John Snow (physician)|John Snow]] (1813–1858), who in 1854 found a link between cholera and contaminated drinking water.<ref name="Rosenberg">{{cite book |author=Rosenberg, Charles E. |title=The cholera years: the United States in 1832, 1849 and 1866 |publisher=University of Chicago Press |location=Chicago |year=1987 |isbn=978-0-226-72677-9}}</ref> Dr. Snow proposed a microbial origin for epidemic cholera in 1849. In his major "state of the art" review of 1855, he proposed a substantially complete and correct model for the cause of the disease. In two pioneering epidemiological field studies, he was able to demonstrate human [[sewage]] contamination was the most probable disease vector in two [[1854 Broad Street cholera outbreak|major epidemics in London in 1854]].<ref>John Snow, [https://books.google.com/books?id=-N0_AAAAcAAJ&pg=PP5 ''The mode of communication of cholera''] {{webarchive|url=https://web.archive.org/web/20151106215135/https://books.google.com/books?id=-N0_AAAAcAAJ&pg=PP5 |date=2015-11-06 }}, 2nd ed. (London, England: John Churchill, 1855).</ref> His model was not immediately accepted, but it was increasingly seen as plausible as medical microbiology developed over the next 30 years or so. For his work on cholera, John Snow is often regarded as the "Father of Epidemiology".<ref>{{Cite web|date=14 March 2017|title=John Snow: A Legacy of Disease Detectives|url=https://blogs.cdc.gov/publichealthmatters/2017/03/a-legacy-of-disease-detectives/|access-date=2021-01-20|website=US Centers for Disease Control and Prevention|language=en-us}}</ref><ref>{{Cite web|title=Father of Modern Epidemiology|url=https://www.ph.ucla.edu/epi/snow/fatherofepidemiology.html|access-date=2021-01-20|website=www.ph.ucla.edu}}</ref><ref>{{Cite web|date=|title=John Snow|url=https://www.historyofvaccines.org/index.php/content/john-snow|access-date=2021-01-20|website=History of Vaccines|language=en|archive-date=2021-01-28|archive-url=https://web.archive.org/web/20210128091350/https://www.historyofvaccines.org/index.php/content/john-snow|url-status=dead}}</ref> The bacterium was isolated in 1854 by Italian anatomist [[Filippo Pacini]],<ref>{{cite journal |first1=Fillipo |last1=Pacini |year=1854 |url=https://books.google.com/books?id=xdtQAAAAcAAJ&pg=PA397 |title=Osservazioni microscopiche e deduzioni patologiche sul cholera asiatico |archive-url=https://web.archive.org/web/20151118081405/https://books.google.com/books?id=xdtQAAAAcAAJ&pg=PA397 |archive-date=18 November 2015 |trans-title=Microscopic observations and pathological deductions on Asiatic cholera |language=it |journal=Gazzetta Medica Italiana |volume=4 |issue=50 |pages=397–401; 405–412 }} Reprinted as: {{cite book |last1=Pacini |first1=Filippo |title=Osservazioni microscopiche e deduzioni patologiche sul cholera asiatico |date=1854 |publisher=Federigo Bencini |url=https://books.google.com/books?id=F9s_AAAAcAAJ |language=it }}</ref> but its exact nature and his results were not widely known. In the same year, the [[Catalonia|Catalan]] [[Joaquim Balcells i Pascual]] discovered the bacterium.<ref name="Real Academia de la Historia 2018">{{cite web|year=2018|editor=[[Real Academia de la Historia]]|title=Joaquín Balcells y Pasqual|url=http://dbe.rah.es/biografias/18541/joaquin-balcells-y-pasqual|archive-url=https://web.archive.org/web/20190708211444/http://dbe.rah.es/biografias/18541/joaquin-balcells-y-pasqual|archive-date=2019-07-08|access-date=2020-08-01|language=es}}</ref><ref>{{cite web|year=2015|editor=[[:ca:Col·legi Oficial de Metges de Barcelona|Col·legi Oficial de Metges de Barcelona]]|title=Joaquim Balcells i Pascual|url=http://www.galeriametges.cat/galeria-fitxa.php?icod=EGMM|archive-url=https://web.archive.org/web/20200801110910/http://www.galeriametges.cat/galeria-fitxa.php?icod=EGMM|archive-date=2020-08-01|access-date=2020-08-01|language=ca}}</ref> In 1856 [[António Augusto da Costa Simões]] and [[José Ferreira de Macedo Pinto]], two Portuguese researchers, are believed to have done the same.<ref name="Real Academia de la Historia 2018" /><ref>{{cite book|author1=da Costa Simões, António Augusto|url=http://webopac.sib.uc.pt|title=Relatório da Direcção do Hospital de Cholericos de N.S. da Conceição em Coimbra|author2=de Macedo Pinto, José Ferreira|publisher=Imprensa da Universidade. The link leads to a library catalogue where the book can be found|year=1856|location=Coimbra|language=pt}}</ref> Between the mid-1850s and the 1900s, cities in developed nations made massive investment in clean water supply and well-separated sewage treatment infrastructures. This eliminated the threat of cholera epidemics from the major developed cities in the world. In 1883, [[Robert Koch]] identified ''V. cholerae'' with a microscope as the bacillus causing the disease.<ref>{{cite book |last1=Aberth |first1=John |title=Plagues in World History |date=2011 |publisher=Rowman & Littlefield Publishers |isbn=978-1-4422-0796-7 |page=101 }}</ref> [[Hemendra Nath Chatterjee]], a Bengali scientist, was the first to formulate and demonstrate the effectiveness of [[oral rehydration salt]] (ORS) to treat [[diarrhea]]. In his 1953 paper, published in ''[[The Lancet]]'', he states that [[promethazine]] can stop [[vomiting]] during cholera and then oral rehydration is possible. The formulation of the fluid replacement solution was 4 g of [[sodium chloride]], 25 g of [[glucose]] and 1000 ml of [[water]].<ref>{{cite journal | vauthors = Ruxin JN | title = Magic bullet: the history of oral rehydration therapy | journal = Medical History | volume = 38 | issue = 4 | pages = 363–97 | date = October 1994 | pmid = 7808099 | pmc = 1036912 | doi = 10.1017/s0025727300036905 }}</ref><ref>{{cite journal | vauthors = Chatterjee HN | title = Control of vomiting in cholera and oral replacement of fluid | journal = Lancet | volume = 265 | issue = 6795 | pages = 1063 | date = November 1953 | pmid = 13110052 | doi = 10.1016/s0140-6736(53)90668-0 }}</ref> [[File:Medical Scientist Prof. Sambhu Nath De.png|thumb|Prof. [[Sambhu Nath De]], who discovered the [[cholera toxin]] and successfully demonstrated the transmission of cholera pathogen by ''bacterial enteric toxin'']] [[Indian people|Indian]] medical scientist [[Sambhu Nath De]] discovered the [[cholera toxin]], the ''[[animal model]] of cholera'', and successfully demonstrated the method of transmission of cholera pathogen ''Vibrio cholerae''.<ref>{{Cite web|url=https://inmemoryglobal.com/remembrance/sambhu-nath-de/|title=Sambhu Nath De|website=Inmemory|language=en-US|access-date=2019-12-05|archive-url=https://web.archive.org/web/20191205035801/https://inmemoryglobal.com/remembrance/sambhu-nath-de/|archive-date=2019-12-05|url-status=usurped}}</ref> [[Robert Allan Phillips]], working at US [[Naval Medical Research Unit Two]] in Southeast Asia, evaluated the pathophysiology of the disease using modern laboratory chemistry techniques. He developed a protocol for rehydration. His research led the [[Lasker Foundation]] to award him its prize in 1967.<ref>{{cite web |url= http://www.laskerfoundation.org/awards/show/treatment-of-cholera/ |title= Albert Lasker Clinical Medical Research Award |publisher= Lasker Foundation |access-date= June 30, 2017 |url-status= dead |archive-url= https://web.archive.org/web/20170901014519/http://www.laskerfoundation.org/awards/show/treatment-of-cholera/ |archive-date= September 1, 2017 }}</ref> More recently, in 2002, Alam, ''et al.'', studied stool samples from patients at the [[International Centre for Diarrhoeal Disease Research, Bangladesh|International Centre for Diarrhoeal Disease]] in [[Dhaka, Bangladesh]]. From the various experiments they conducted, the researchers found a correlation between the passage of ''V. cholerae'' through the human digestive system and an increased infectivity state. Furthermore, the researchers found the bacterium creates a hyperinfected state where [[gene]]s that control biosynthesis of [[amino acid]]s, [[iron]] uptake systems, and formation of periplasmic nitrate reductase complexes were induced just before defecation. These induced characteristics allow the cholera vibrios to survive in the "rice water" stools, an environment of limited oxygen and iron, of patients with a cholera infection.<ref name="Merrell2002">{{cite journal | vauthors = Merrell DS, Butler SM, Qadri F, Dolganov NA, Alam A, Cohen MB, Calderwood SB, Schoolnik GK, Camilli A | title = Host-induced epidemic spread of the cholera bacterium | journal = Nature | volume = 417 | issue = 6889 | pages = 642–5 | date = June 2002 | pmid = 12050664 | pmc = 2776822 | doi = 10.1038/nature00778 | bibcode = 2002Natur.417..642M }}</ref>
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