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Salmonella (typhoid and nontyphoidal)

Elliot Weisenberg, M.D.

Topic Completed: 1 November 2015

Minor changes: 30 September 2020

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PubMed Search: Salmonella [title] colon

Elliot Weisenberg, M.D.
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Table of Contents
Definition / general | Essential features | Terminology | Epidemiology | Sites | Pathophysiology | Etiology | Clinical features | Diagnosis | Prognostic factors | Case reports | Treatment | Gross description | Microscopic (histologic) description | Microscopic (histologic) images | Differential diagnosis | Additional references
Cite this page: Weisenberg E. Salmonella (typhoid and nontyphoidal). PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/colonsalmonella.html. Accessed January 22nd, 2021.
Definition / general
  • Disease caused by Salmonella species infection
  • While overlap exists, species causing typhoid fever and nontyphoidal species are often categorized separately
Essential features
  • Salmonellosis is considered a food borne disease
  • Typhoid fever:
    • Sometimes known as enteric fever, is a life threatening illness caused by Salmonella typhi sometimes called Salmonella enterica serotype Typhi or S. paratyphi
    • Infects from 20 to 30 million people a year, mostly in the developing world
    • In industrialized countries, it is usually encountered in travelers
  • Nontyphoid species:
    • Usually cause acute, self limited gastroenteritis
    • The Centers for Disease Control and Prevention (CDC) estimates that one million cases, 19,000 hospitalizations, and 450 deaths occur each year in the United States
    • Tens of millions of cases occur worldwide each year causing an estimated 100,000 deaths
    • Disease is spread through ingestion of contaminated food or water, most often in a sporadic fashion but sometimes through foodborne outbreaks that often are associated with suboptimal sanitary practices or food preparation
Terminology
  • Salmonella is named after the veterinarian Elmer Daniel Salmon
  • Salmonella are gram negative rods
  • Salmonella species bacteria are serotyped based on the chemical content of the O antigens found on the surface and the protein content of part of the flagella known as the H antigen
  • Over 2500 serotypes have been described; however, under 100 are known to be associated with human disease
  • Serotyping is currently done by molecular methods
  • S. typhi and S. paratyphi are associated with typhoid fever
  • Some of the more common nontyphoidal species are:
    • S. enteritidis
    • S. typhimurium
    • S. muenchen
    • S. adnatum and S. give
    • S. paratyphi may also cause nontyphoidal disease
Epidemiology
  • Worldwide over 20 million cases of typhoid fever occur each year, mostly in the developing world
  • Approximately 1800 cases of typhoid fever occur in the United States annually, mostly in travelers
  • From 1.0 to 1.2 million cases of nontyphoidal illness occur in the United States each year, causing about 19,000 hospitalizations and 450 deaths
  • Tens of millions of nontyphoidal illness occur worldwide, causing over 100,000 deaths each year
  • Disease occurs from ingestion of bacteria, usually in food or water, eggs, milk, meat, poultry
  • Vegetables contaminated with animal feces are commonly implicated
  • Food borne outbreaks, often associated with less than sanitary conditions, are common sources of disease
    • However, in the United States approximately 60% of cases occur sporadically
  • Fecal oral transmission may occur; disease after contact with infected animals is another source
  • Salmonellosis is a common cause of traveler diarrhea
  • All serotypes at least in theory may cause human disease
  • Serotypes may or may not be host specific
  • When serotypes specific to other species infect humans. severe disease may result
  • S. typhi is restricted to humans
  • Risk factors for infection include:
    • Lack of access to clean water
    • Poor sanitation. especially regarding food handling
    • Flooding
    • Ingestion of plants fertilized with sewage
    • Urban environments
    • Sexual transmission has been reported
  • Both typhoidal and nontyphoidal salmonellosis may occur in health care workers when proper hand hygiene is not practiced
  • Travelers to the developing world are often infected with S. paratyphi; vaccination against S. typhi is common prior to travel
Sites
  • S. typhi may infect the entire gastrointestinal tract but typically is found in the terminal ileum, appendix and ascending colon; nontyphoidal Salmonella infects the small and large bowel
  • S. typhi typically spreads to the liver, spleen, bone marrow and lymph nodes
  • Extraintestinal spread is uncommon in nontyphoidal Salmonella but may occur with severe disease
Pathophysiology
  • Salmonella possess cellular mechanisms enabling bacterial proteins to be transferred to enterocytes and M cells with subsequent growth within endosomes
  • Subsequent events include an inflammatory response with neutrophil recruitment and mucosal damage
  • The host immune response typically controls nontyphoidal infection; however, the very young, elderly, debilitated and immunosuppressed may lack the response necessary to control infection
  • S. typhi more commonly invades M cells
  • Bacteria are phagocytosed by histiocytes in underlying lymphoid tissue
  • The bacteria proliferate and widely disseminate through blood vessels and lymphatic channels
Etiology
  • Salmonella are gram negative bacilli
  • S. typhi is found only in humans
  • Nontyphoidal species are found in humans, domestic and wild animals
  • In general, infection occurs through ingestion of contaminated food or water or the fecal-oral route
  • Nontyphoidal Salmonella are commonly found in food and companion animals including poultry, cattle, swine, parrots, cats, dogs and turtles
  • Eggs, milk, meat, poultry and contaminated vegetables are commonly implicated
  • Direct person to person transmission as well as transmission from pets may occur
    • In this setting, the source of the transmission may not appear ill
Clinical features
  • Symptoms of nontyphoidal salmonellosis generally start 12 - 36 hours after ingestion of bacteria but may occur after 6 - 72 hours
  • Ingestion of very few organisms may cause disease
  • Typically patients suffer self limited illness characterized by diarrhea, abdominal pain, fever, nausea and occasionally vomiting that is unpleasant but rarely life threatening
  • May be life threatening In infants, elderly, immunocompromised or debilitated patients, due to dehydration or dissemination of bacteria
  • Very rarely, toxic megacolon may complicate infection
  • Individuals with achlorhydria or hypochlorhydria from drugs, chronic Helicobacter pylori infection or other causes are at higher risk of infection
  • Some patients develop a reactive arthritis that may last for months and lead to chronic arthritis

  • Typhoid fever causes symptoms shortly after bacteria are ingested
  • Patients suffer from severe abdominal pain, bloody diarrhea, bloating, anorexia, nausea, vomiting, headache
  • A brief asymptomatic period is followed by bacteremia with fever and flu-like illness
  • Blood cultures are almost always positive at this time and antibiotic therapy may be lifesaving
  • With disease progression in untreated patients, high fever and abdominal pain occurs that may mimic appendicitis; lasts for about two weeks
  • If patients survive, symptoms slowly abate
  • Possible extraintestinal complications include CNS disease, endocarditis, myocarditis, pneumonia, cholecystitis, osteomyelitis (patients with sickle cell disease are particularly prone to osteomyelitis)
  • Disease relapses may occur
Diagnosis
  • Nontyphoidal salmonellosis traditionally has been diagnosed by stool culture although many patients do not seek medical attention
  • Recently a PCR based assay has been introduced that, in addition to Salmonella species bacteria, also detects Camplyobacter group, Shigella species, Vibrio group, Yersinia enterocolitica, Shiga toxin 1 and 2, Norovirus G1 / GII, Rotavirus A and Aeromonas species
  • Serotyping is done to characterize disease outbreaks
  • Typhoid fever is diagnosed by blood or stool culture
  • In the developing world where laboratory facilities may not be readily available, disease may be treated empirically
Prognostic factors
  • Nontyphoidal salmonellosis is almost always a self limited infection, except in infants, the elderly, immunocompromised and debilitated patients
  • Antibiotic therapy is usually efficacious in these patients, although antibiotic resistance is a growing problem
  • 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; although again, antibiotic resistance is a growing problem
Case reports
Treatment
  • Nontyphoidal Salmonella usually:
    • Only requires supportive care, particularly hydration
    • Antibiotics are indicated for severe disease and vulnerable patients
    • Ceftriaxone and ciprofloxacin are currently recommended by the CDC
    • Antibiotic resistance is a growing problem
  • Antibiotic therapy for typhoid fever is obligatory and should not be delayed for confirmatory laboratory testing
    • In the past, chloramphenicol, trimethoprim-sulfamethoxazole, cephalosporins and first generation fluoroquinolones were used but antibiotic resistance developed
    • Currently, third generation fluoroquinolones are recommended but resistance has been reported
    • Surgery may be necessary for intestinal perforation or gallbladder disease
    • An effective vaccine for S. typhi exists
  • WHO recommendations for the public and travelers include:
    • Ensure food is properly cooked and hot when served
    • Avoid raw milk and products made from raw milk
    • Avoid ice unless made from safe water
    • Use disinfecting tablets for water unless its purity is certain
    • Wash hands thoroughly with soap and water after contact with pets or farm animals and after using the toilet
    • Wash fruits and vegetables thoroughly and if possible, peel fruits and vegetables unless optimal sanitary practices are known to have taken place
  • Recommendations for food handlers and producers include:
    • Maintain a clean workspace
    • Separate raw and cooked food
    • Cook food thoroughly
    • Keep food at safe temperatures
    • Use safe water and raw materials
    • Practice good personal hygiene
    • Do not work if have fever, diarrhea, vomiting or infected skin lesions
    • Protect fields from animal contamination
Gross description
  • Colonoscopy in patients with mild nontyphoidal salmonellosis shows nonspecific findings including edema and petechial hemorrhage; more severe disease is associated with friability and ulceration
  • Typhoid fever causes marked enlargement of Peyer patches and lymphoid tissue in the appendix and ascending colon leading to mucosal elevation along the axis of the ileum
  • Perforation may occur
  • Small gray, soft nodules (typhoid nodules) may be present in the liver
  • There is splenomegaly and lymphadenopathy
Microscopic (histologic) description
  • Nontyphoidal salmonellosis is rarely biopsied
  • The findings are a non-specific acute self limited colitis
  • The crypt architecture is maintained, there are increased mixed inflammatory cells within the lamina propria in a patchy distribution with foci of cryptitis and possible crypt abscesses
  • Long standing cases may demonstrate architectural distortion raising the spectre of idiopathic inflammatory bowel disease
    • This is also true of S. typhimurium infection
  • Knowledge of culture results is necessary to render a specific diagnosis

  • S. typhi shows neutrophils, histiocytes with cytoplasmic bacteria, nuclear debris and hemorrhage within the lamina propria associated with a lymphoplasmacytic infiltrate
  • The spleen and lymph nodes show sinus histiocytosis that distorts the normal architecture
  • Typhoid nodules in the liver show aggregates of histiocytes with necrotic debris
  • Typhoid nodules may also be found in bone marrow and lymph nodes
Microscopic (histologic) images

Contributed by Elliot Weisenberg, M.D.
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Acute self limited colitis



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Typhoid nodules

Differential diagnosis
  • The differential diagnosis of nontyphoidal salmonellosis includes other enteric pathogens that cause acute self limited colitis including Shigella and Campylobacter
  • Long standing cases may mimic idiopathic inflammatory bowel disease
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