Salmonellae are gram-negative, non-spore-forming, facultatively anaerobic bacilli that belong to the Enterobacteriaceae family. Classification and nomenclature of Salmonella species are confusing. On the basis of DNA hybridization studies, Salmonella isolates are classified in a single species, S. enterica. The species S. enterica contains approximately 2,500
different serotypes. Salmonella serotypes and isolates (previously known as species) were classified on the basis of host range, surface antigen structure, and biochemical characteristics, and the terms they were given appeared to designate them as separate species (e.g., S. typhimurium). The current correct taxonomic name would be S. enterica serotype Typhimurium. Commonly (although taxonomically incorrect), serotypes are designated as species (e.g., S. typhimurium).

Salmonella can be subdivided into serotypes on the basis of three types of surface antigens: cell-wall somatic or O antigens, flagellar or H antigens, and polysaccharide or Vi antigens. Generally, Salmonella serotypes were named for the city in which they were defined. Many hospital laboratories perform agglutination reactions that define specific O antigens into serogroups designated Salmonella A, B, C₁, C₂, D, and E. This grouping confirms identification of the genus and may be useful epidemiologically, but final serotyping generally requires a reference laboratory. S. typhi may be identified rapidly (serogroup D, Vi-antigen positive) by using commercially available agglutination tests, but identifying serotypes in other serogroups requires additional testing. For example both S. typhimurium, a cause of diarrhea, and S. paratyphi, a cause of enteric fever, are in serogroup B. S. typhimurium and S. enteritidis (serogroup D) are the two most common causes of human Salmonella infections in the United States. Other serotypes commonly associated with human disease include S. newport (serogroup C₂), S. heidelberg (serogroup B), S. infantis (serogroup C₁), S. hadar (serogroup C₂), and S. agona (serogroup B). The complete genome sequence has been determined for a multidrug-resistant strain of Salmonella serotype Typhi.

Animals, including poultry, livestock, and pets, including reptiles, are the major reservoirs for nontyphoidal Salmonella. Reptiles maintain fecal carriage rates of Salmonella of more than 90%, rendering salmonellosis associated with reptiles a continuing public health concern. Other sources include contaminated animal products, meat-processing plants, contaminated water, and infected humans; fruits and vegetables, including sprouts, are less common sources. Salmonella serotype Typhi infects only humans, and Salmonella serotype Paratyphi has a reservoir primarily in humans. Methods of transmission include the following: ingestion of contaminated food, milk, water, medications, or dyes; contact with infected animals; fecal-oral transmission resulting in person-to-person spread; and, rarely, contact with contaminated medical instruments or even blood or blood product transfusions such as platelets. Most cases of salmonellosis are foodborne, with outbreaks caused by ingestion of contaminated eggs, cheese, ice cream premix, juice, sprouts, dry cereal, raw almonds, and fresh fruits and vegetables. Volunteer studies using adults have shown that between 10⁵ and 10⁶ viable organisms must be ingested for clinical disease to occur, although data from foodborne outbreaks of salmonellosis indicate that the infective dose for various Salmonella serotypes and for people with immune deficiencies may be lower.

Infections with nontyphoidal strains of Salmonella are common. Approximately 40,300 cases were reported in 2004 to the Centers for Disease Control and Prevention (CDC). Salmonella is one of the most frequently reported causes of foodborne outbreaks, cases, and deaths in the United States. Before 1996, most data regarding salmonellosis in the United States were derived from a passive surveillance system. These data estimated that 800,000 to 3.7 million infections actually occurred per year in the United States. In 1996, an active surveillance system for foodborne illness, referred to as the Foodborne Diseases Active Surveillance Network (FoodNet), was established by the CDC (http://www.cdc.gov/foodnet). Since 1997, Salmonella and Campylobacter have been the two most frequent laboratory-confirmed enteric pathogens.

Age-specific attack rates peak in the first year of life and are higher for children younger than 5 years of age and for persons 25 to 64 years of age. Most reported cases of Salmonella infection are sporadic, but transmission by contaminated food and water frequently results in outbreaks of disease. Many outbreaks of Salmonella serotype Enteritidis have been associated with ingestion of contaminated eggs. Salmonella serotype Enteritidis infects the upper oviduct and contaminates the contents of eggs that appear to have intact shells. Morbidity and mortality after infection occurs more commonly in certain groups of people (Table 173.1).

Salmonella serotype Typhi colonizes only humans, and Salmonella serotype Paratyphi colonizes humans and some primates; therefore, disease can be acquired only through close contact with a person with typhoid fever or with a carrier of one of these organisms or by ingestion of food or water contaminated with human feces from a carrier. Since the early part of the twentieth century, the incidence of typhoid fever in the United States has changed dramatically. Salmonella serotype Typhi infection has become an uncommon occurrence as compared with nontyphoidal salmonellosis. Approximately 400 cases of typhoid fever are reported annually in the United States. Most cases of typhoid fever in the United States are associated with foreign travel; most domestically acquired cases result from contact with food contaminated by a chronic carrier. Worldwide, typhoid fever is a major health problem, generally in economically developing countries, with an estimated 16 million new cases and 600,000 deaths/year.

The incubation period for Salmonella gastroenteritis is 6 to 72 hours. The incubation period for enteric fever is 3 to 60 days (usually 7 to 14 days).

Exposure to gastric acid (pH less than 3.5) is lethal to Salmonella. If the number of bacteria swallowed is large enough, if gastric acid is neutralized by ingested food, or if conditions of reduced gastric acidity (achlorhydria as occurs in infants and in people with pernicious anemia, gastric surgery, or treatment with antacids, H₂-receptor antagonists,
or proton-pump inhibitors) are present, sufficient bacteria may survive passage to enter the small intestine. To become established in the intestine and to colonize the ileum and colon, Salmonella also must elude removal by intestinal motility. The use of antiperistaltic drugs can render the condition worse or can lead to systemic invasion. Alteration of the normal intestinal flora by antimicrobial agents renders the host more susceptible to salmonellosis. Lower inocula may cause disease in persons with deficiencies of host defense mechanisms, including persons with radiation-induced intestinal damage.

Symptoms of Salmonella infection are associated with mucosal invasion with inflammation or production of toxins. Some Salmonella strains elaborate a heat-labile toxin that may function as an enterotoxin or cytotoxins that inhibit protein synthesis. After attachment, organisms must resist both nonspecific and specific host defense mechanisms long enough to multiply to sufficient numbers to damage underlying cells and tissues. Once attached to mucosal cells, Salmonella organisms then can invade the mucosa. The M cells, which are specialized epithelial cells overlying Peyer patches, probably are the site of internalization of Salmonella serotype Typhi and less commonly other serotypes. Organisms then interact with macrophages and lymphocytes in Peyer patches and other lymphoid tissue in the mucosa of the small intestine. After several weeks of infection, Peyer patches enlarge and become necrotic and most likely are responsible for the abdominal pain that occurs during the course of typhoid fever. As Salmonella organisms invade through Peyer patches, they are transported in phagocytic cells to mesenteric lymph nodes and through the thoracic duct to the bloodstream; circulating bacteria are removed by reticuloendothelial cells in liver, spleen, and bone marrow. Some organisms can reach distant target organs or tissues, such as the gallbladder, where they can multiply and secondarily seed the intestine. Symptoms of typhoid fever occur when a critical number of organisms has replicated. Serotypes vary in their potential to invade the bloodstream. Infection with Salmonella serotype Typhi induces systemic and humoral immunity and cellular responses that often confer incomplete protection against relapse and reinfection. Salmonella serotypes contain a wide variety of plasmids and genes that encode virulence factors and antimicrobial resistance.