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Infectious colitis

Salmonella (typhoid and nontyphoidal)

Authors: Nalini Bansal, M.D., Elliot Weisenberg, M.D.

Last author update: 1 November 2015

Last staff update: 14 October 2022

Copyright: 2003-2023, PathologyOutlines.com, Inc.

PubMed Search: Salmonella colon

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Table of Contents

Cite this page: Bansal N, Weisenberg E. Salmonella (typhoid and nontyphoidal). PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/colonsalmonella.html. Accessed April 1st, 2023.

Definition / general

Disease caused by Salmonella species infection
While overlap exists, species causing typhoid fever and nontyphoidal species are often categorized separately
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

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
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)

Terminology

Typhoid fever
Enteric fever
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

ICD coding

ICD-10: A01.09 - typhoid fever with other complications

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
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)

Sites

Most common is terminal ileum (100%), followed by ileocecal valve (57%), ascending colon (43%), transverse colon (29%) (Dig Liver Dis 2004;36:141)
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
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 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

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
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 patches may occur, together with secondary bacteremia and peritonitis (Lancet Infect Dis 2005;5:623)
- Perforation is four times more common in males than females (Am J Epidemiol 2004;160:46)
Chronic Salmonella carriage is defined as excretion of the organism in stool or urine >12 months after acute infection

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
Bone marrow culture is the most sensitive test available, as it remains positive even after 5 days of antibiotic therapy (Lancet 1975; 1:1211)

Laboratory

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

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

Nontyphoidal Salmonella:
- Infant with large bowel obstruction as presentation of salmonella enterocolitis (Pediatr Surg Int 2000;16:525)
- 37 week old infant boy with Salmonella berta meningitis (J Perinatol 2014;34:798)
- 51 year old man with Salmonella dublin infection (Eur J Gastroenterol Hepatol 2001;13:587)
- 57 year old man with endovascular infection with Salmonella group C (Germs 2015;5:99)
- 62 year old man with toxic megacolon due to Salmonella (Int J Colorectal Dis 2002;17:275)
- Family outbreaks of nontyphoidal salmonellosis (Case Rep Infect Dis 2015;2015:864640)
- Toxic megacolon in Salmonella colitis (Acta Paediatr Taiwan 2000;41:43)
Typhoidal Salmonella:
- 10 year old child with Salmonella typhi coinfection with dengue fever (J Infect Dev Ctries 2015;9:1033)
- 18 year old man with acute scrotal ulcers in typhoid fever (Trop Med Health 2015;43:69)
- 30 year old man with gastrointestinal bleeding from paratyphoid A fever (World J Gastroenterol 2015;21:1040)
- Breast abscess by Salmonella paratyphi (J Clin Diagn Res 2015;9:DD03)

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
- 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 and Paratyphoid Fever [Accessed 28 November 2017], 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
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

Clinical images

Images hosted on other servers:

Typhoid rash

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.

Acute self limited colitis

Images hosted on other servers:

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

Additional references