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 referencesCite this page: Weisenberg E. Salmonella (typhoid and nontyphoidal). PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/colonsalmonella.html. Accessed April 19th, 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
- 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
- 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
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
- Kumar: Robbins & Cotran Pathologic Basis of Disease, 9th Edition, Bennett: Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases, 8th Edition, 2014, Odze: Surgical Pathology of the GI Tract, Liver, Biliary Tract, and Pancreas, 1st Edition, Kradin: Diagnostic Pathology of Infectious Disease, 1st Edition, 2010, WHO - Salmonella, WHO - Typhoid fever, CDC - Salmonella, CDC - Typhoid Fever, CDC - Multidrug Resistant Salmonella