Infectious colitis
Typhoid fever

Topic Completed: 1 November 2017

Minor changes: 25 February 2021

Copyright: 2003-2021,, Inc.

PubMed Search: Typhoid fever of colon

Nalini Bansal, M.D.
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Cite this page: Bansal N. Typhoid fever. website. Accessed April 10th, 2021.
Definition / general
  • Caused by Salmonella enterica organisms
  • Salmonellosis is a food borne disease caused mainly by Salmonella typhi serotype, although Salmonella paratyphi A, B, C can cause similar disease
  • Salmonella penetrate the small bowel epithelium after ingestion, enter lymphoid tissue and disseminates via the lymphatic or hematogenous route
  • Typhoid fever is characterized by severe systemic illness with fever, relative bradycardia and considerable constitutional symptoms including abdominal pain (Med J Armed Forces India 2003;59:130)
  • Causes intestinal bleeding due to ulcers in distal ileum or proximal colon (Dig Liver Dis 2004;36:141)
  • Bleeding may be massive (Dis Colon Rectum 1986;29:511)
Essential features
  • Typhoid colitis is caused by Salmonella enterica organisms, mainly S. typhi
  • S. typhi occurs only in humans
  • Salmonellosis is a food borne disease caused by ingestion of contaminated food
  • Salmonella penetrate the small bowel epithelium after ingestion, enter the lymphoid tissue and disseminates via the lymphatic or hematogenous route
  • Typhoid fever is characterized by severe systemic illness with fever, relative bradycardia and considerable constitutional symptoms including abdominal pain (Med J Armed Forces India 2003;59:130)
  • Salmonella typhi affects mainly the proximal colon causing ulceration and rarely massive bleeding (Dig Liver Dis 2004;36:141, Dis Colon Rectum 1986;29:511)
  • Typhoid Fever
  • Enteric Fever
ICD coding
  • A01.09 - typhoid fever with other complications
  • Spreads through the oral-fecal route, mostly waterborne or via food infected by carriers, rarely through oral-anal sexual contact (Clin Infect Dis 2003;37:141)
  • More common in children and young adults
  • Most prevalent in developing countries and overcrowded areas with poor sanitation
  • High incidence (more than 100 cases per 100,000 person years) in South central Asia, Southeast Asia, southern Africa (Bull World Health Organ 2004;82:346, J Glob Health 2012;2:010401)
  • In developed countries, disease is usually limited to travelers to countries where typhoid fever is endemic (Lancet Infect Dis 2005;5:623)
  • The Vi polysaccharide typhoid vaccine is ineffective against most S. paratyphi, which lack the Vi antigen targeted by the vaccine (Lancet Infect Dis 2005;5:623)
  • Most common is terminal ileum (100%), followed by ileocecal valve (57%), ascending colon (43%), transverse colon (29%) (Dig Liver Dis 2004;36:141)
  • S. typhi is a gram negative bacillus typically transmitted via the fecal-oral route
  • Entry of S. typhi into the small bowel epithelium after ingestion appears to be mediated by the cystic fibrosis transmembrane conductance regulator (CFTR)
  • S. typhi proliferates intracellularly in the submucosa, initially in the second part of the Peyer's patches, leading to hypertrophy via recruitment of mononuclear cells and lymphocytes
  • Over the next 7 - 21 days, further proliferation occurs in these organs, then organisms are released into the bile and reinfect the ileal lymphoid tissue, then organisms disseminate to the liver, spleen and reticuloendothelial system via the lymphatic system and bloodstream (Clin Exp Gastroenterol 2012;5:213)
  • Replication within the reticuloendothelial system is a hallmark of enteric fever and is responsible for the clinical findings of prostration, generalized sepsis and hepatosplenomegaly
  • An effective vaccine for S. typhi exists
  • Salmonella enterica
  • S. typhi and paratyphi A are uniquely human pathogens
Clinical features
  • Classic features are fever, abdominal pain and hematochezia
  • First week of illness: rising ("stepwise") fever associated with chills, although frank rigors are rare
    • Also relative bradycardia or pulse-temperature dissociation is common
  • Second week of illness: abdominal pain develops and "rose spots" (faint salmon- colored macules on the trunk and abdomen) may be seen
  • Third week of illness: hepatosplenomegaly, intestinal bleeding and perforation due to ileocecal lymphatic hyperplasia of the Peyer's patches may occur, together with secondary bacteremia and peritonitis (Lancet Infect Dis 2005;5:623)
  • Chronic Salmonella carriage is defined as excretion of the organism in stool or urine >12 months after acute infection
  • Classical clinical features above
  • Typhoid fever is diagnosed by blood or stool culture
  • Bone marrow culture is the most sensitive test available (Lancet 1975; 1:1211), as it remains positive even after 5 days of antibiotic therapy.
  • CBC shows leukopenia and thrombocytopenia
  • Cultures can be from blood, stool, urine, rose spots, the blood mononuclear cell platelet fraction, bone marrow, gastric or intestinal secretions
  • A positive culture for S. typhi or S. paratyphi is obtained in more than 90% of patients if blood, bone marrow and intestinal secretions are all performed
  • Because almost all S. typhi organisms in blood are associated with the mononuclear cell platelet fraction, centrifugation of blood and culture of this fraction can reduce the time for isolation of the organism but does not increase the sensitivity
  • Children also have a higher incidence of positive stool cultures than adults (60% versus 27%)
  • The duodenal string test is useful for sampling the upper GI tract (J Infect Dis 1984;149:157)
Radiology description
  • Most common colonoscopic finding is multiple variably sized punched out ulcers with slightly elevated margins
  • Also edematous hyperemic mucosal patches with hemorrhagic spots or shallow erosions
Prognostic factors
  • Without treatment, typhoid fever may be lethal even in healthy individuals, but the prognosis is worse in infants, the elderly, immunocompromised and debilitated patients
  • Prompt initiation of antibiotic therapy greatly improves patient outcome
Case reports
  • Prolonged course of antimicrobials and supportive care with transfusions
  • Antibiotic therapy for typhoid fever is obligatory and should not be delayed for confirmatory laboratory testing
  • Ceftriaxone and ciprofloxacin are currently recommended by the CDC (CDC - Typhoid Fever, accessed 28Nov17, Lancet Infect Dis 2005;5:623)
  • Third generation fluoroquinolones are also recommended but resistance has been reported
  • In the past, chloramphenicol, trimethoprim-sulfamethoxazole, cephalosporins and first generation fluoroquinolones were used but antibiotic resistance developed
  • Surgery may be necessary for intestinal perforation or gallbladder disease
  • Selective angiography and platinum coil embolization is used for severe, life threatening lower gastrointestinal hemorrhage
Clinical images

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Typhoid rash

Gross description
  • Marked enlargement of Peyer's patches and lymphoid tissue in the appendix and ascending colon leading to mucosal elevation along the axis of the ileum
  • Proximal colon shows multiple variably sized punched out ulcers with a slightly elevated margin.
  • May have edematous hyperemic mucosal patches with hemorrhagic spots or shallow erosions
  • Perforation may be found
  • Liver may have small gray, soft nodules (typhoid nodules); variable splenomegaly and lymphadenopathy
Microscopic (histologic) description
  • Neutrophils, histiocytes with cytoplasmic bacteria, nuclear debris and hemorrhage within the colonic lamina propria associated with a lymphoplasmacytic infiltrate
  • Spleen and lymph nodes: sinus histiocytosis that distorts the normal architecture
  • Liver: aggregates of histiocytes with necrotic debris
  • Typhoid nodules may also be found in bone marrow and lymph nodes
Differential diagnosis
  • Other enteric pathogens that cause acute self limited colitis including Shigella and Campylobacter
  • Long standing cases may mimic idiopathic inflammatory bowel disease
Board review style question #1
Which of the following are common sources of infection for salmonella?

A. Sexual transmission
B. Food Borne
C. Water Borne
D. B & C
Board review style answer #1
D. Both B & C
Board review style question #2
Which serotype of Salmonella occurs only in humans?

A. S. choleraesuis
B. S. typhi
C. S. typhimurium
D. None of the above
Board review style answer #2
B. S. typhi
Board review style question #3
Which site is most commonly involved by Salmonella?

A. Colon
B. Gall bladder
C. Ileum
D. Stomach
Board review style answer #3
C. Ileum
Board review style question #4
Which is the most common site of localization of S. typhi in humans?

A. Gastric epithelium
B. Interstitial cell of cajal
C. Neurons
D. Peyer’s patches
Board review style answer #4
D. Peyer’s patches
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