Salmonella Infection in Emergency Medicine 

Salmonella are gram-negative facultative intracellular anaerobes that cause a wide spectrum of disease. This spectrum can range from a gastroenteritis, enteric fever (caused by typhoid and paratyphoid serotypes), bacteremia, focal infections, to a convalescent lifetime carrier state. The type of infection depends on the serotype of Salmonella and host factors. It maintains a broad host range and, for unknown reasons, results in different diseases in different hosts.

The image below shows Salmonella typhimurium.

Although the taxonomy of Salmonella can be confusing, all salmonella serotypes are members of a single species, Salmonellaenterica. More than 2500 serovars^{[1, 2]} have been described of which humans are almost exclusively infected by Salmonella enterica subspecies enterica serotypes typhi, typhimurium, and choleraesuis worldwide.^[3] In the United States, Salmonella Enteritidis (20%), Salmonella Typhimurium (16%), Salmonella Newport (10%), and Salmonella Javiana (6%) account for nearly one half of the human isolates.^[4]

Salmonellosis caused by Salmonella Enteritidis is the most common bacterial infectious cause of food-borne disease in the United States.^[5] Ninety-five percent of cases of Salmonella infection are food-borne; however, the incidence of direct contact exposure with animal carriers is on the rise.^[5] Once infected, salmonellosis harbors a significant morbidity and mortality. One third of untreated patients experience complications and account for three fourths of deaths associated with salmonellosis.^[3]Campylobacter and Salmonella are the most common bacterial pathogens found in stool cultures recovered from patients presenting with gastroenteritis or severe diarrhea.^{[6, 7]}

Salmonella has a widespread distribution in the environment and certain host factors make humans particularly susceptible to infection. Its increasing antimicrobial resistance, prevalence, virulence, and adaptability are a challenge worldwide.

Salmonella infections most commonly begin with ingestion of bacteria in contaminated food or water. However, direct contact with animal and human carriers has also been implicated. Reptile and amphibian carriers are the most commonly recognized sources of direct contact.^[5] Studies involving healthy human volunteers required a median dose of 1 million bacteria to produce disease. However, point outbreaks suggest as few as 200 bacteria may produce nontyphoid gastroenteritis.^[6]

Once the bacteria survive the acidic stomach, they colonize the intestine and translocate across the intestinal epithelium via 3 routes: (1) invasion of the enterocytes, (2) invasion of epithelial cells called M cells, and (3) through dendritic cells that intercalate epithelial cells. Interaction with the epithelium and resident cells promote a proinflammatory response to include cytokines, chemokines, neutrophils, macrophages, dendritic cells, and T and B cells. This inflammatory host response can actually benefit the intestinal pathogens and contribute to the nature and severity of the infection by establishing a competitive advantage against the native flora.^[2] Animal studies reveal that prolonged antibiotic use may disrupt this host susceptibility as well.^[8]

After crossing this epithelial layer, the bacteria replicate in macrophages in Peyer’s patches, mesenteric lymph nodes, and the spleen. Once colonized, the bacteria may then potentially disseminate to the lungs, gallbladder, kidneys, or central nervous system. The nontyphoid species of Salmonella tend to produce a more localized response because they are believed to lack the human-specific virulence factors. However, the typhi serotype can develop the more invasive disease resulting in bacteremia. The severity of disease is related to the serotype, number of organisms, and host factors.

Eggs and poultry are the most common sources of infection.^{[9, 5]} Ingestion of contaminated water, milk, milk products, beef, fruit, vegetables, and dairy products are also common sources. Potential sources of infection for infants with Salmonella are exposure to reptiles, riding in a shopping cart next to meat or poultry, or consuming liquid infant formula.^[10] Outbreaks have been associated with contaminated frozen potpies, puffed vegetable snacks, and exposure to turtles.^[11] More recently, multistate human outbreaks have been seen in contaminated dry dog food and peanut butter products.^{[12, 13]}

Reservoirs of the bacteria include humans, poultry, swine, cattle, rodents, and pets such as iguanas, tortoises, turtles, terrapins, chicks, dogs, and cats. Up to 90% of reptiles and amphibians harbor Salmonella in their gastrointestinal tracts and 6% of nontyphoid disease is related to direct contact with these animals.^[5]

Fecal-oral transmission from person to person in areas with poor sanitation and contaminated or nonchlorinated water is the route for enteric or typhoid fever. Humans are the only known carriers of Salmonella typhi.^[5]

Individual susceptibility to Salmonella infection increases with extremes of age, immunodeficiency states, prior antibiotic use, neoplastic disease, achlorhydria or antacid use, recent bowel surgery, and malnutrition.

Frequency

United States

Prevalence estimates vary secondary to inconsistent diagnosis and reporting techniques. It is estimated that only 3% of Salmonella infections are laboratory confirmed and reported to the Centers for Disease Control and Prevention (CDC).^[4] However, an estimated 1.4 million people in the United States are infected with nontyphoid Salmonella annually. The incidence of nontyphoid disease in the United States has been stable since 2004, but it has decreased approximately 8% from 1996-1998 levels up to 2008.^[11]

An apparent nonstatistically significant increase in Salmonella infection was noted for the year 2009 limited to serotypes Enteritidis and, Saintpaul while a decrease was noted in the Heidelberg serotype.^[4] The true burden of nontyphoid Salmonella in the United States is calculated to be 520 cases per 100,000 compared with 13.4 cases per 100,000 of laboratory-confirmed cases annually, taking into account approximately 38.6 cases of nontyphoid Salmonella for each culture-confirmed case.^{[14, 15]} The reported 2008 incidence is 16.2 cases per 100,000.^[4]

Additionally, an estimated 500 people are infected with typhoid Salmonella annually.^[5] Most cases of documented typhoid disease are related to foreign travel to developing nations such as India (30%), Pakistan (13%), Mexico (12%), Bangladesh (8%), Philippines (8%), and Haiti (5%).^[5]

International

Fully industrialized nations report frequencies of gastroenteritis similar to that of the United States. However, worldwide estimates of nontyphoid Salmonella range from 200 million to 1.3 billion, with an estimated death toll of 3 million each year.^[1]

The serovars responsible for typhoid or enteric fever, typhi and paratyphi, that cause systemic illness lead to 16-20 million cases and 200,000 deaths worldwide.^{[16, 17]} Compared with tourists, travelers visiting friends or relatives in developing nations exhibit a much higher incidence of typhoid or enteric fever.^[5]

Mortality/Morbidity

Twenty percent of patients require hospitalization, with an estimated death rate of 0.6%.^[15] Infection with drug-resistant nontyphoid Salmonella and Salmonella typhi increase the likelihood of hospitalization and death.^[15]

Invasive nontyphoid Salmonella infection occurs in about 5% of cases in Israel^[15] and is responsible for 400-600 deaths in the United States each year^[5] . Mortality for nontyphoid Salmonell a is reported to be as high as 60% in African patients with HIV.^[16] Mycotic abdominal aortic aneurysms are more common in immunocompromised and HIV patients.

Treated typhoid cases have a 2% mortality rate with a 15% relapse rate.^[3] A significant number of typhoid patients become chronic asymptomatic carriers and can shed high numbers of bacteria in the stool for a lifetime without obvious symptoms.^[16] Depending on the serotype, roughly 1% of adults and 5% of children excrete organisms for greater than a year.^[18]

Age

Attack rates are highest in persons younger than 20 years or older than 70 years. The highest rate is found in infants (130 isolates/100,000).

Neonates are at a greater risk to fecal-oral transmission secondary to relative decreased stomach acidity and buffering of ingested breastmilk and formula.

Elderly persons are at a relative greater risk to infection secondary to chronic underlying illness and weakened immunity. Nursing home residents have a particularly higher risk. The case-fatality rate (CFR) is estimated at 1.3% for nontyphoid Salmonella for those age 50 years or older.^[4]