Editing Typhoid fever (section)

==History==

=== Early descriptions ===
The [[plague of Athens]], during the [[Peloponnesian War]], was most likely an outbreak of typhoid fever.<ref name=":1" /> During the war, [[Athenians]] retreated into a walled-in city to escape attack from the [[Sparta]]ns. This massive influx of humans into a concentrated space overwhelmed the water supply and waste infrastructure, likely leading to unsanitary conditions as fresh water became harder to obtain and waste became more difficult to collect and remove beyond the city walls.<ref name=":1" /> In 2006, examining the remains of a mass burial site from Athens from around the time of the plague (~430 B.C.) revealed that fragments of DNA similar to that of modern-day [[Salmonella enterica subsp. enterica|''S.'' Typhi]] were detected, whereas ''[[Yersinia pestis]]'' (plague), ''[[Rickettsia prowazekii]]'' (typhus), ''[[Mycobacterium tuberculosis]]'', [[Cowpox|cowpox virus]], and ''[[Bartonella henselae]]'' were not detected in any of the remains tested.<ref name=":10">{{cite journal | vauthors = Papagrigorakis MJ, Yapijakis C, Synodinos PN, Baziotopoulou-Valavani E | title = DNA examination of ancient dental pulp incriminates typhoid fever as a probable cause of the Plague of Athens | journal = International Journal of Infectious Diseases | volume = 10 | issue = 3 | pages = 206–14 | date = May 2006 | pmid = 16412683 | doi = 10.1016/j.ijid.2005.09.001 | doi-access = free }}</ref>

===Definition and evidence of transmission===
The French doctors [[Pierre Bretonneau|Pierre-Fidele Bretonneau]] and [[Pierre Charles Alexandre Louis|Pierre-Charles-Alexandre Louis]] are credited with describing typhoid fever as a specific disease, unique from [[typhus]]. Both doctors performed autopsies on individuals who died in Paris due to fever – and indicated that many had lesions on the [[Peyer's patch]]es which correlated with distinct symptoms before death.<ref name=":1">{{Cite book| vauthors = Adler R, Mara E |url=https://www.worldcat.org/oclc/934938999|title=Typhoid fever: a history|date=2016 |isbn=978-0-7864-9781-2|location=Jefferson, North Carolina |publisher=McFarland & Company |oclc=934938999}}</ref> British medics were skeptical of the differentiation between typhoid and typhus because both were endemic to Britain at that time. However, in France, only typhoid was present circulating in the population.<ref name=":1" /> Pierre-Charlles-Alexandre Louis also performed case studies and statistical analysis to demonstrate that typhoid was contagious – and that persons who already had the disease seemed to be protected.<ref name=":1" /> Afterward, several American doctors confirmed these findings, and then [[Sir William Jenner, 1st Baronet|Sir William Jenner]] convinced any remaining skeptics that typhoid is a specific disease recognizable by lesions in the Peyer's patches by examining sixty-six autopsies from fever patients and concluding that the symptoms of headaches, diarrhea, rash spots, and abdominal pain were present only in patients who were found to have intestinal lesions after death; these observations solidified the association of the disease with the intestinal tract and gave the first clue to the route of transmission.<ref name=":1" />

In 1847, [[William Budd]] learned of an epidemic of typhoid fever in Clifton, and identified that all 13 of 34 residents who had contracted the disease drew their drinking water from the same well.<ref name=":1" /> Notably, this observation was two years before [[John Snow]] first published an early version of his theory that contaminated water was the central conduit for transmitting [[cholera]]. Budd later became health officer of [[Bristol]] ensured a clean water supply, and documented further evidence of typhoid as a water-borne illness throughout his career.<ref name=":1" />

===Cause===
Polish scientist [[Tadeusz Browicz]] described a short bacillus in the organs and feces of typhoid victims in 1874.<ref>{{cite journal | vauthors = Stachura J, Gałazka K | title = History and current status of Polish gastroenterological pathology | journal = Journal of Physiology and Pharmacology | volume = 54 | pages = 183–92 | date = December 2003 | issue = Suppl 3 | pmid = 15075472 | url = https://pubmed.ncbi.nlm.nih.gov/15075472 }}</ref> Browicz was able to isolate and grow the bacilli but did not go as far as to insinuate or prove that they caused the disease.<ref name=":1" />

In April 1880, three months before Eberth's publication, [[Edwin Klebs]] described short and [[Filamentation|filamentous]] bacilli in the [[Peyer's patch]]es in typhoid victims.<ref>{{Cite journal|date=1918-09-07|title=Typhoid Fever Considered as a Problem of Scientific Medicine.|url=|journal=JAMA: The Journal of the American Medical Association|volume=71|issue=10|pages=847|doi=10.1001/jama.1918.02600360063023|hdl=2027/coo1.ark:/13960/t9d516735|issn=0098-7484|hdl-access=free}}</ref> The bacterium's role in disease was speculated but not confirmed.<ref name=":1" />

In 1880, [[Karl Joseph Eberth]] described a bacillus that he suspected was the cause of typhoid.<ref>
{{cite journal | vauthors = Eberth CJ | date = 1880 | url = http://babel.hathitrust.org/cgi/pt?id=hvd.32044093330488;view=1up;seq=74 | title = Die Organismen in den Organen bei Typhus abdominalis | trans-title = Organisms in the [internal] organs in cases of Typhus abdominalis | language = de | journal = Archiv für pathologische Anatomie und Physiologie | volume = 81 | pages = 58–74 }}</ref><ref>
{{cite journal | vauthors = Eberth CJ | date = 1881 | url = http://babel.hathitrust.org/cgi/pt?id=hvd.32044103035598;view=1up;seq=512  | title = Neue Untersuchungen über den Bacillus des Abdominaltyphus | trans-title = New investigations into the bacilli of abdominal typhoid | language = de | journal = Archiv für pathologische Anatomie und Physiologie | volume = 83 | pages = 486–501 }}</ref><ref>
Eberth's findings were verified by [[Robert Koch]] {{cite journal | vauthors = Koch R | date = 1881 | url = https://books.google.com/books?id=lD1AAAAAYAAJ&pg=PA1 | title = Zur Untersuchung von pathogenen Organismen | language = de | trans-title = On the investigation of pathogenic organisms | archive-url = https://web.archive.org/web/20170423081253/https://books.google.com/books?id=lD1AAAAAYAAJ&pg=PA45 | archive-date=2017-04-23 | journal = Mitteilungen aus dem Kaiserlichen Gesundheitsamte | volume = 1 | pages = 1–49 }}</ref>  Eberth is given credit for discovering the bacterium definitively by successfully isolating the same bacterium from 18 of 40 typhoid victims and failing to discover the bacterium present in any "control" victims of other diseases.<ref name=":1" /> In 1884, pathologist [[Georg Theodor August Gaffky]] (1850–1918) confirmed Eberth's findings.<ref>{{cite journal  | vauthors = Gaffky G | title = Zur aetiologie des abdominaltyphus. | trans-title = On the etiology of abdominal typhus | journal = Mitteillungen aus dem Kaiserlichen Gesundheitsamt | language = de | date = 1884 | volume = 2 | pages = 372–420 | url = https://books.google.com/books?id=Y6lQAAAAYAAJ&pg=PA372 | archive-url = https://web.archive.org/web/20170423042158/https://books.google.com/books?id=Y6lQAAAAYAAJ&pg=PA372 | archive-date=2017-04-23 }}</ref> Gaffky isolated the same bacterium as Eberth from the spleen of a typhoid victim, and was able to grow the bacterium on solid media.<ref name=":1" /> The organism was given names such as Eberth's bacillus, ''Eberthella'' Typhi, and Gaffky-Eberth bacillus.<ref name=":1" /> Today, the bacillus that causes typhoid fever goes by the scientific name ''[[Salmonella enterica]]'' serovar Typhi.<ref>{{Cite book|title=Atlas of Human Infectious Diseases|date=2012|publisher=John Wiley & Sons| vauthors = Wertheim HF, Horby P, Woodall JP |isbn=978-1-4443-5467-6 |edition = 1st |location=New York, NY|oclc=897547171}}</ref>

=== Chlorination of water ===
Most developed countries had declining rates of typhoid fever throughout the first half of the 20th century due to vaccinations and advances in public sanitation and hygiene. In 1893, attempts were made to chlorinate the water supply in [[Hamburg]], Germany, and in 1897 [[Maidstone]], England, was the first town to have its entire water supply chlorinated.<ref>{{cite journal |title=Typhoid Epidemic at Maidstone|date=October 1897|journal=Journal of the Sanitary Institute|volume=18|pages=388}}</ref>  In 1905, following an outbreak of typhoid fever, the City of [[Lincoln, England]], instituted permanent water chlorination.<ref>{{cite web |url=http://www.icis.com/Articles/2008/08/25/9150211/chlorine-cleans-water-for-millions-but-comes-under-attack-after-health.html|title=A miracle for public health?|access-date=2012-12-17}}</ref>  The first permanent disinfection of drinking water in the US was made in 1908 to the [[Jersey City, New Jersey]], water supply. Credit for the decision to build the chlorination system has been given to [[John L. Leal]].<ref>{{cite book | vauthors = Leal JL | date = 1909 | chapter = The Sterilization Plant of the Jersey City Water Supply Company at Boonton, N.J. | title = Proceedings American Water Works Association. | pages = 100–9 }}</ref> The [[Water chlorination|chlorination]] facility was designed by [[George W. Fuller]].<ref>{{cite book | vauthors = Fuller GW | date = 1909 | chapter = Description of the Process and Plant of the Jersey City Water Supply Company for the Sterilization of the Water of the Boonton Reservoir. | title = Proceedings American Water Works Association | pages = 110–34 }}</ref>

Outbreaks in traveling military groups led to the creation of the Lyster bag in 1915: a bag with a faucet that can be hung from a tree or pole, filled with water, and comes with a chlorination tablet to drop into the water.<ref name=":1" /> The Lyster bag was essential for the survival of American soldiers in the [[Vietnam War]].<ref name=":1" />

=== Direct transmission and carriers ===
[[File:Mary Mallon in hospital.jpg|thumb|upright=1.3|[[Mary Mallon]] ("Typhoid Mary") in a hospital bed (foreground): She was forcibly quarantined as a carrier of typhoid fever in 1907 for three years and then again from 1915 until she died in 1938.|right]]
There were several occurrences of [[Milk delivery|milk delivery men]] spreading typhoid fever throughout the communities they served. Although typhoid is not spread through milk itself, there were several examples of milk distributors in many locations watering their milk down with contaminated water, or cleaning the glass bottles the milk was placed in with contaminated water.<ref name=":1" /><ref name=":2" /> [[Boston]] had two such cases around the turn of the 20th century.<ref name=":2">{{Cite web |date=2007-11-05|title=Typhoid Milkman|url=http://rememberjamaicaplain.blogspot.com/2007/11/typhoid-milkman.html|access-date=2021-06-24|website=Remember Jamaica Plain?}}</ref> In 1899, there were 24 cases of typhoid traced to a single milkman, whose wife had died of typhoid fever a week before the outbreak.<ref name=":2" /> In 1908, J.J. Fallon, who was also a milkman, died of typhoid fever.<ref name=":2" />  Following his death and confirmation of the typhoid fever diagnosis, the city conducted an investigation of typhoid symptoms and cases along his route and found evidence of a significant outbreak. A month after the outbreak was first reported, the [[The Boston Globe|''Boston Globe'']] published a short statement declaring the outbreak over, stating "[a]t Jamaica Plain there is a slight increase, the total being 272 cases. Throughout the city, there is a total of 348 cases."<ref name=":2" /> There was at least one death reported during this outbreak: Mrs. Sophia S. Engstrom, aged 46.<ref name=":2" /> Typhoid continued to ravage the [[Jamaica Plain]] neighborhood in particular throughout 1908, and several more people were reported dead due to typhoid fever, although these cases were not explicitly linked to the outbreak.<ref name=":2" /> The Jamaica Plain neighborhood at that time was home to many working-class and poor immigrants, mostly from [[Ireland]].<ref>{{Cite book| vauthors = Von Hoffman A |url=http://worldcat.org/oclc/1036707621|title=Local attachments: the making of an American urban neighborhood, 1850 to 1920|date=1996|publisher=Johns Hopkins University Press|oclc=1036707621}}</ref>

The most notorious carrier of typhoid fever, but by no means the most destructive, was [[Mary Mallon]], known as Typhoid Mary.<ref name="Nova">{{cite web |title=Nova: The Most Dangerous Woman in America |website=[[PBS]] |url=https://www.pbs.org/wgbh/nova/typhoid/letter.html |url-status=live |archive-url=https://web.archive.org/web/20100426042928/http://www.pbs.org/wgbh/nova/typhoid/letter.html |archive-date=2010-04-26 }}</ref><ref name=":7">{{Cite web|title=Short Wave: Typhoid Mary: Lessons From An Infamous Quarantine on Apple Podcasts|url=https://podcasts.apple.com/kh/podcast/typhoid-mary-lessons-from-an-infamous-quarantine/id1482575855?i=1000482300467|access-date=2021-06-28|website=Apple Podcasts|language=en-GB}}</ref> Although other cases of human-to-human spread of typhoid were known at the time, the concept of an asymptomatic carrier, who was able to transmit disease, had only been hypothesized and not yet identified or proven.<ref name=":1" /> Mary Mallon became the first known example of an [[asymptomatic carrier]] of an infectious disease, making typhoid fever the first known disease being transmissible through asymptomatic hosts.<ref name=":1" /> The cases and deaths caused by Mallon were mainly upper-class families in New York City.<ref name=":1" /> At the time of Mallon's tenure as a personal cook for upper-class families, New York City reported 3,000 to 4,500 cases of typhoid fever annually.<ref name=":1" /> In the summer of 1906, two daughters of a wealthy family and maids working in their home became ill with typhoid fever.<ref name=":1" /> After investigating their home water sources and ruling out water contamination, the family hired civil engineer [[George Soper]] to conduct an investigation of the possible source of typhoid fever in the home.<ref name=":1" /> Soper described himself as an "epidemic fighter".<ref name=":1" /> His investigation ruled out many sources of food, and led him to question if the cook the family hired just prior to their household outbreak, Mallon, was the source.<ref name=":1" /> Since she had already left and begun employment elsewhere, he proceeded to track her down in order to obtain a stool sample.<ref name=":1" />  When he was able to finally meet Mallon in person he described her by saying "Mary had a good figure and might have been called athletic had she not been a little too heavy."<ref name=":4">{{Cite journal| vauthors = Soper GA | date=October 1939|title=The Curious Career of Typhoid Mary|journal=Bulletin of the New York Academy of Medicine|volume=15|issue=10|pages=698–712|issn=0028-7091|pmc=1911442|pmid=19312127}}</ref> In recounts of Soper's pursuit of Mallon, his only remorse appears to be that he was not given enough credit for his relentless pursuit and publication of her personal identifying information, stating that the media "rob[s] me of whatever credit belongs to the discovery of the first typhoid fever carrier to be found in America."<ref name=":4"/> Ultimately, 51 cases and 3 deaths were suspected to be caused by Mallon.<ref>{{Cite web| vauthors = Klein C |title=10 Things You May Not Know About 'Typhoid Mary'|url=https://www.history.com/news/10-things-you-may-not-know-about-typhoid-mary|access-date=2021-06-28|website=HISTORY|language=en}}</ref><ref name=":7" />

In 1924, the city of [[Portland, Oregon]], experienced an outbreak of typhoid fever, consisting of 26 cases and 5 deaths, all deaths due to intestinal [[hemorrhage]].<ref name=":3">{{cite journal | vauthors = Sears HJ, Garhart RW, Mack DW | title = A Milk Borne Epidemic of Typhoid Fever Traced to a Urinary Carrier | journal = American Journal of Public Health | volume = 14 | issue = 10 | pages = 848–54 | date = October 1924 | pmid = 18011334 | pmc = 1355026 | doi = 10.2105/ajph.14.10.848 }}</ref> All cases were concluded to be due to a single milk farm worker, who was shedding large amounts of the typhoid pathogen in his urine.<ref name=":3" /> Misidentification of the disease, due to inaccurate Widal test results, delayed identification of the carrier and proper treatment.<ref name=":3" /> Ultimately, it took four samplings of different secretions from all of the dairy workers in order to successfully identify the carrier.<ref name=":3" /> Upon discovery, the dairy worker was forcibly quarantined for seven weeks, and regular samples were taken, most of the time the stool samples yielding no typhoid and often the urine yielding the pathogen.<ref name=":3" /> The carrier was reported as being 72 years old and appearing in excellent health with no symptoms.<ref name=":3" /> Pharmaceutical treatment decreased the amount of bacteria secreted, however, the infection was never fully cleared from the urine, and the carrier was released "under orders never again to engage in the handling of foods for human consumption."<ref name=":3" /> At the time of release, the authors noted "for more than fifty years he has earned his living chiefly by milking cows and knows little of other forms of labor, it must be expected that the closest surveillance will be necessary to make certain that he does not again engage in this occupation."<ref name=":3" />

Overall, in the early 20th century the medical profession began to identify disease carriers and evidence of transmission independent of water contamination.<ref name=":1" /> In a 1933 [[American Medical Association]] publication, physicians' treatment of asymptomatic carriers is best summarized by the opening line "Carriers of typhoid bacilli are a menace".<ref name=":6">{{Cite journal|date=1933-06-10 |journal=Journal of the American Medical Association|volume=100|issue=23|pages=1866|doi=10.1001/jama.1933.02740230044012|issn=0002-9955|title=Typhoid Carriers and Their Treatment}}</ref> Within the same publication, the first official estimate of typhoid carriers is given: 2–5% of all typhoid patients, and distinguished between temporary carriers and chronic carriers.<ref name=":6" /> The authors further estimate that there are four to five chronic female carriers to every one male carrier, although offered no data to explain this assertion of a gender difference in the rate of typhoid carriers.<ref name=":6" /> As far as treatment, the authors suggest: "When recognized, carriers must be instructed as to the disposal of excreta as well as to the importance of personal cleanliness. They should be forbidden to handle food or drink intended for others, and their movements and whereabouts must be reported to the public health officers".<ref name=":6" />
[[File:Typhoid LAcounty 2016.jpg|thumb|New Typhoid carrier cases reported in L.A. County between 2006 and 2016<ref name="LA county typhoid 2016" />]]
Today, typhoid [[Asymptomatic carrier|carriers]] exist all over the world, but the highest incidence of [[asymptomatic]] infection is likely to occur in South/Southeast Asian and Sub-Saharan countries.<ref name="LA county typhoid 2016" /><ref>{{cite journal | vauthors = Stanaway JD, Reiner RC, Blacker BF, Goldberg EM, Khalil IA, Troeger CE, etal | title = The global burden of typhoid and paratyphoid fevers: a systematic analysis for the Global Burden of Disease Study 2017 | journal = The Lancet. Infectious Diseases | volume = 19 | issue = 4 | pages = 369–381 | date = April 2019 | pmid = 30792131 | pmc = 6437314 | doi = 10.1016/S1473-3099(18)30685-6 }}</ref> The [[Los Angeles County Department of Public Health|Los Angeles County department of public health]] tracks typhoid carriers and reports the number of carriers identified within the county yearly; between 2006 and 2016 0–4 new cases of typhoid carriers were identified per year.<ref name="LA county typhoid 2016" /> Cases of typhoid fever [[Infectious disease reporting|must be reported]] within one working day from identification. As of 2018, chronic typhoid carriers must sign a "Carrier Agreement" and are required to test for typhoid shedding twice yearly, ideally every 6 months.<ref name=":8">{{Cite web |website=Los Angeles Department of Public Health |title=Acute Communicable Disease Control Manual (B-73): Typhoid Fever Carrier |date=June 2018 |url=http://publichealth.lacounty.gov/acd/procs/b73/DiseaseChapters/B73Typhoidfevercarrier.pdf|access-date=June 27, 2021}}</ref> Carriers may be released from their agreements upon fulfilling "release" requirements, based on completion of a personalized treatment plan designed with medical professionals.<ref name=":8" /> Fecal or gallbladder carrier release requirements: 6 consecutive negative feces and urine specimens submitted at 1-month or greater intervals beginning at least 7 days after completion of therapy.<ref name=":8" /> Urinary or kidney carrier release requirements: 6 consecutive negative urine specimens submitted at 1-month or greater intervals beginning at least 7 days after completion of therapy.<ref name=":8" />

Due to the nature of asymptomatic cases, many questions remain about how individuals can tolerate infection for long periods, how to identify such cases, and efficient options for treatment. Researchers are working to understand asymptomatic infection with ''[[Salmonella]]'' species by studying infections in laboratory animals, which will ultimately lead to improved prevention and treatment options for typhoid carriers. In 2002, John Gunn described the ability of ''[[Salmonella]]'' sp. to form [[biofilm]]s on [[gallstone]]s in mice, providing a model for studying carriage in the gallbladder.<ref>{{cite journal | vauthors = Prouty AM, Schwesinger WH, Gunn JS | title = Biofilm formation and interaction with the surfaces of gallstones by Salmonella spp | journal = Infection and Immunity | volume = 70 | issue = 5 | pages = 2640–9 | date = May 2002 | pmid = 11953406 | pmc = 127943 | doi = 10.1128/iai.70.5.2640-2649.2002}}</ref> [[Denise Monack]] and [[Stanley Falkow]] described a mouse model of asymptomatic intestinal and systemic infection in 2004, and [[Denise monack|Monack]] went on to demonstrate that a subpopulation of [[superspreaders]] are responsible for the majority of transmission to new hosts, following the [[Pareto principle|80/20 rule]] of disease transmission, and that the intestinal microbiota likely plays a role in transmission.<ref name=":9">{{cite journal | vauthors = Monack DM, Bouley DM, Falkow S | title = Salmonella typhimurium persists within macrophages in the mesenteric lymph nodes of chronically infected Nramp1+/+ mice and can be reactivated by IFNgamma neutralization | journal = The Journal of Experimental Medicine | volume = 199 | issue = 2 | pages = 231–41 | date = January 2004 | pmid = 14734525 | doi = 10.1084/jem.20031319 | pmc = 2211772 }}</ref><ref>{{cite journal | vauthors = Lawley TD, Bouley DM, Hoy YE, Gerke C, Relman DA, Monack DM | title = Host transmission of Salmonella enterica serovar Typhimurium is controlled by virulence factors and indigenous intestinal microbiota | journal = Infection and Immunity | volume = 76 | issue = 1 | pages = 403–16 | date = January 2008 | pmid = 17967858 | pmc = 2223630 | doi = 10.1128/iai.01189-07}}</ref> [[Denise monack|Monack]]'s mouse model allows long-term carriage of ''Salmonella'' in [[mesenteric lymph nodes]], [[spleen]] and [[liver]].<ref name=":9" />

=== Vaccine development ===
[[File:Almroth Wright c1900.jpg|thumb|upright=1.3|[[Almroth Edward Wright]] developed the first effective typhoid vaccine.]]
British bacteriologist [[Almroth Edward Wright]] first developed an effective typhoid vaccine at the Army Medical School in [[Netley]], [[Hampshire]]. It was introduced in 1896 and used successfully by the British during the [[Second Boer War]] in South Africa.<ref>{{cite web|title=Sir Almroth Edward Wright|url=http://www.britannica.com/EBchecked/topic/649457/Sir-Almroth-Edward-Wright|url-status=live|archive-url=https://web.archive.org/web/20131111031313/http://www.britannica.com/EBchecked/topic/649457/Sir-Almroth-Edward-Wright|archive-date=2013-11-11|website=Encyclopædia Britannica}}</ref> At that time, typhoid often killed more soldiers at war than were lost due to enemy combat. Wright further developed his vaccine at a newly opened research department at [[St Mary's Hospital (London)|St Mary's Hospital]] Medical School in London in 1902, where he established a method for measuring protective substances ([[opsonin]]) in human blood.<ref>{{Cite journal|vauthors=Wright AE, Douglas SR|date=1904-01-31|title=An experimental investigation of the rôle of the blood fluids in connection with phagocytosis|journal=Proceedings of the Royal Society of London|language=en|volume=72|issue=477–486|pages=357–370|doi=10.1098/rspl.1903.0062|s2cid=84388525 |issn=0370-1662|doi-access=}}</ref> Wright's version of the typhoid vaccine was produced by growing the bacterium at [[Thermoregulation|body temperature]] in broth, then heating the bacteria to 60&nbsp;°C to "heat inactivate" the pathogen, killing it, while keeping the surface [[antigen]]s intact. The heat-killed bacteria was then injected into a patient.<ref name=":1" /> To show evidence of the vaccine's efficacy, Wright then collected serum samples from patients several weeks post-vaccination, and tested their serum's ability to [[Agglutination (biology)|agglutinate]] live typhoid bacteria. A "positive" result was represented by clumping of bacteria, indicating that the body was producing anti-serum (now called [[Antibody|antibodies]]) against the pathogen.<ref name=":1" />

Citing the example of the Second Boer War, during which many soldiers died from easily preventable diseases, Wright convinced the [[British Army]] that 10 million vaccine doses should be produced for the troops being sent to the [[Western Front (World War I)|Western Front]], thereby saving up to half a million lives during [[World War I]].<ref>{{cite web|title=Library and Archive Catalogue|url=http://www2.royalsociety.org/DServe/dserve.exe?dsqIni=Dserve.ini&dsqApp=Archive&dsqCmd=Show.tcl&dsqDb=Persons&dsqPos=5&dsqSearch=%28Surname%3D%27wright%27%29|access-date=1 November 2010|publisher=Royal Society}}{{Dead link|date=July 2018|bot=InternetArchiveBot|fix-attempted=no}}</ref> The British Army was the only combatant at the outbreak of the war to have its troops fully immunized against the bacterium. For the first time, their casualties due to combat exceeded those from disease.<ref>{{cite web|date=2014-11-11|title=Medical lessons from World War I underscore need to keep developing antimicrobial drugs|url=https://www.minnpost.com/second-opinion/2014/11/medical-lessons-world-war-i-underscore-need-keep-developing-antimicrobial-dru|url-status=live|archive-url=https://web.archive.org/web/20160130210117/https://www.minnpost.com/second-opinion/2014/11/medical-lessons-world-war-i-underscore-need-keep-developing-antimicrobial-dru|archive-date=30 January 2016|access-date=8 September 2017|website=MinnPost}}</ref>

In 1909, [[Frederick F. Russell]], a [[U.S. Army]] physician, adopted Wright's typhoid vaccine for use with the Army, and two years later, his vaccination program became the first in which an entire army was immunized. It eliminated typhoid as a significant cause of morbidity and mortality in the U.S. military.<ref name="USAMRMC">{{cite book|url=http://technologytransfer.amedd.army.mil/assets/docs/marketing/USAMRMC_history.pdf|title=USAMRMC: 50 Years of Dedication to the Warfighter 1958–2008|publisher=U.S. Army Medical Research & Material Command (2008)|year=2008|page=5|asin=B003WYKJNY|access-date=2013-03-27|archive-url=https://web.archive.org/web/20130214210353/http://technologytransfer.amedd.army.mil/assets/docs/marketing/USAMRMC_history.pdf|archive-date=2013-02-14|url-status=dead}}</ref> Typhoid vaccination for members of the American military became mandatory in 1911.<ref name=":1" /> Before the vaccine, the rate of typhoid fever in the military was 14,000 or greater per 100,000 soldiers. By World War I, the rate of typhoid in American soldiers was 37 per 100,000.<ref name=":1" />

During the Second World War, the United States Army authorized the use of a trivalent vaccine – containing heat-inactivated Typhoid, [[Paratyphoid fever|Paratyphi]] A and [[Paratyphoid fever|Paratyphi]] B pathogens.<ref name=":1" />

In 1934, the discovery of the [[Vi capsular polysaccharide vaccine|Vi capsular]] antigen by [[Arthur Felix]] and [[Miss S. R. Margaret Pitt]] enabled the development of the safer Vi Antigen vaccine – which is widely in use today.<ref>{{Cite journal|vauthors=Felix A, Pitt RM|date=July 1934|title=A New Antigen of B. Typhosus|journal=The Lancet|language=en|volume=224|issue=5787|pages=186–191|doi=10.1016/S0140-6736(00)44360-6}}</ref> Arthur Felix and Margaret Pitt also isolated the strain Ty2, which became the parent strain of [[Ty21a]], the strain used as a live-attenuated vaccine for typhoid fever today.<ref>{{Cite journal|vauthors=Craigie J|date=1957-11-01|title=Arthur Felix, 1887–1956|journal=Biographical Memoirs of Fellows of the Royal Society|volume=3|pages=53–79|doi=10.1098/rsbm.1957.0005|s2cid=72753150 |doi-access=}}</ref>

=== Antibiotics and resistance ===
[[Chloramphenicol]] was isolated from ''[[Streptomyces]]'' by [[David Gottlieb (biologist)|David Gotlieb]] during the 1940s.<ref name=":1" /> In 1948, American army doctors tested its efficacy in treating typhoid patients in [[Kuala Lumpur]], Malaysia.<ref name=":1" /> Individuals who received a full course of treatment cleared the infection, whereas patients given a lower dose had a relapse.<ref name=":1" /> Asymptomatic carriers continued to shed bacilli despite chloramphenicol treatment – only ill patients were improved with chloramphenicol.<ref name=":1" /> Resistance to chloramphenicol became frequent in Southeast Asia by the 1950s, and today chloramphenicol is only used as a last resort due to the high prevalence of resistance.<ref name=":1" />