Editing Typhoid fever (section)

=== 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" />