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Typhoid fever is an acute febrile illness caused by the bacterium Salmonella enterica serotype Typhi, commonly shortened to Salmonella Typhi. Humans are the only known natural host for Salmonella Typhi, and fecal-oral transmission through contaminated food and water is the most common mode of infection. In the United States, about 350 cases are reported each year, and most of these are acquired while traveling internationally.1–3


Salmonella Typhi, a Gram-negative, flagellated bacillus, appears as nonlactose fermenting on MacConkey’s agar and can be further identified by phenotypic properties as well as by serotyping based on somatic (O) and flagellar (H) antigens. Most freshly isolated strains also have a capsular Vi antigen.4 In the Kauffman-White scheme, Salmonella Typhi is a member of Salmonella group O:9, and usually possesses a single H antigen, d; in some cases, H:z66 or H:j, which genetically are related to d, are expressed instead.5,6 The organism survives in water and sewage, but is readily killed by boiling, pasteurization, or chlorination.7

Controlled human infection models have provided information about the dose and course of infection. In studies of volunteers, ingesting as few as 105 bacteria can lead to clinical illness in some persons, and ingestion of 106 organisms results in 50% of subjects becoming ill.8 With concurrent administration of a sodium bicarbonate solution, an inoculum of 103 or 104 cfu resulted in attack rates of 55% and 65%, respectively.9 Incubation periods are usually 7–14 days (range 3–56 days) and higher inoculum is associated with a higher attack rate.8,9 In an early challenge study, higher inoculum was also associated with shorter median incubation periods.8 However, subsequent human challenge studies have suggested that inoculum size, while associated with time to asymptomatic bacteremia, is unrelated to time to symptom onset.9,11 Partial immunity follows clinical illness, but reinfection and illness can still occur after a large oral dose. In human vaccine studies, whereas anti-Vi antibodies protected some individuals from infection, antibody titers and bactericidal activity did not correlate with resistance to reinfection or occurrence of relapse but did shorten or lessen severity of the disease.9,10


Typhoid fever is classically described as an acute, systemic illness with fever and abdominal pain, but symptoms can also be nonspecific and insidious in onset. Nonspecific symptoms include headache, constipation, malaise, chills, and myalgia.7,11 Fever increases gradually from low-grade during the first week of illness to as high as 39–40°C by the third to fourth day of illness.11 Many patients cough for the first few days of illness, and some report a sore throat or joint pain. Splenomegaly, leukopenia, and abdominal distention and tenderness are generally present. By the end of the first week of illness, up to 30% of patients develop rose spots—small, salmon-colored spots—on the trunk caused by bacterial ...

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