Practice Essentials
Infections due to Salmonella species represent a major public health problem in many countries. In the United States, nontyphoidal Salmonella (NTS) is the most common pathogen implicated in food-borne gastroenteritis. [1] In most cases, NTS is a self-limiting disease that causes mild gastroenteritis; however, it can lead to a wide spectrum of complications including bacteremia, enterocolitis, and severe local infections such as meningitis and osteomyelitis. [2, 3, 4] Salmonella serotype typhi can cause serious and prolonged bacteremic illness referred to as enteric fever or typhoid fever. [5]
Pathophysiology
The extension of the disease to various organs depends on the serotype, the size of the inoculum, and the status of the host. If large enough numbers of bacteria are ingested, they can survive in the normally lethal acidic pH of the stomach. Once ingested, Salmonella can gain access to the small intestine, producing diffuse mucosal inflammation, edema, and microabscesses. Generally, most NTS do not extend beyond the lamina propria and lymphatics of the gut. Exceptions include Salmonellacholeraesuis and Salmonelladublin, which can cause bacteremia with little intestinal involvement. [6] In individuals with S typhi, areas of intestinal necrosis can ulcerate and result in perforation. In addition, this mucosal penetration allows uptake into the draining lymph nodes, contributing to blood stream infections (BSI) and subsequent invasion of the liver, spleen, and bone marrow. This process explains the delayed onset of symptoms in S typhi. [7]
Etiology
Salmonella organisms are gram-negative rod-shaped bacilli in the family Enterobacteriaceae. All Salmonella organisms are to be considered a single species (Salmonella enterica) because of their close relationship by DNA hybridization studies. [7]
Differences in lipopolysaccharide (LPS) and flagellar structure generate the antigenic variation that is reflected in the more than 2500 known serotypes that cause human disease.
Nontyphoidal Salmonella (NTS) serotypes are divided into O-antigen groups A through E. Since 1997, Salmonella enteritidis (D), S. typhimurium (B), and Salmonella newport (C2) account for about half of the culture-confirmed Salmonella isolates. The principal reservoirs for NTS organisms are poultry, livestock, reptiles, and pets. The mode of transmission is ingestion of foods of animal origin, including poultry, red meats, unpasteurized dairy products, and eggs that have been contaminated by infected animals or an infected human. [5, 8]
Recent Salmonella outbreaks have been attributed to commercially produced items, such as peanut butter, frozen pot pies, puffed vegetable snacks, and dry dog food. [9, 10, 11, 12, 13] Contact with infected reptiles, such as iguanas, pet turtles and tortoises, and ingestion of contaminated water are other modes of transmission.
S. typhi (D) is the species known to cause enteric fever (typhoid fever). S. typhi is found only in humans. In the United States, typhoid fever is usually caused by foreign travel to countries with contaminated food and drinking water or by ingestion of food contaminated by a chronic carrier. [5] Travelers visiting friends and relatives in typhoid-endemic countries may be at more risk than tourists because of a lack of precautionary measures. [14] Historically, Salmonella paratyphi (A) has been the cause of a smaller proportion of the cases of enteric fever. [15] However, China and India have experienced a substantial increase in enteric fever caused by S. paratyphi (A). [16]
Excess antibiotic use in the prior year has been associated with a higher incidence of NTS. Disruption of the microflora of the gut has been offered as a possible cause; however, an alternate explanation may be that these individuals are a more medically fragile group, requiring more antibiotics and, in general, are more susceptible to illness. [17]
Epidemiology
United States statistics
NTS caused an estimated 11% of the 9.4 million food-borne illnesses in the United States, second to norovirus. From 2006-2008, NTS was the leading cause of food-borne illnesses that resulted in hospitalization and death. [18] . Approximately 400 cases of typhoid fever are reported per year. Most of cases are a result of foreign travel, either US citizens traveling to developing countries or foreign travelers to the United States. Most cases are from travel to India or Pakistan. [19] However, over the last 10 years, US travelers to Asia, Africa, and Latin America have been especially at risk. [20]
The preliminary data from the Foodborne Diseases Active Surveillance Network (FoodNet) of the Centers for Disease Control and Prevention's (CDC's) Emerging Infections Program for 2011 revealed a steady increase in the reported incidence of Salmonella infections in the 10 US states in which active, population-based surveillance is performed. [21]
A study by Walters et al investigated turtle-associated salmonellosis outbreaks occurring in 2011-2013. The study identified 8 outbreaks totaling 473 cases from 41 states, Washington DC, and Puerto Rico. The median patient age was 4 years; 45% were Hispanic; and 28% were hospitalized. The study added that in the week preceding illness, 68% of case-patients reported turtle exposure and among these, 88% described small turtles. [22]
In 2021, the CDC investigated multistate outbreaks of Salmonella infections associated with backyard poultry. Of the 1135 persons who were infected, 268 (24%) were younger than 5 years and 140 (12%) were younger than 1 year. [23]
International statistics
The past 2 decades have seen an increase in the incidence of NTS in Europe and North America. [24] A report from the GeoSentinel Surveillance Network revealed enteric fever as the leading cause of vaccine-preventable disease in international travelers. [25] Typhoid fever is endemic in many developing areas of the world, with incidence rates estimated to be 40-50 cases per 1,000,000 population in Pakistan and India. [26] Five Asian countries are considered to be endemic for typhoid: China, India, Indonesia, Pakistan, and Vietnam. [5] However, the CDC has removed 26 countries in Eastern Europe and the Middle East from the most current recommendations for typhoid vaccination. [26, 27] Annually, the World Health Organization (WHO) estimates 16-33 million cases of typhoid fever worldwide and 500,000-600,000 deaths.
Race-, sex-, and age-related demographics
The incidence of infection for all serotyped NTS is almost twice as high in Blacks and Latinos, Salmonella typhimurium is the most common pathogen. [28]
No sex differences are noted. [28]
Attack rates are highest in persons younger than 5 years or older than 70 years. [5, 28]
Prognosis
Prognosis varies, as follows:
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Nontyphoidal salmonellosis
Prognosis of patients with simple gastroenteritis is excellent except for very young infants or patients with debilitating diseases.
The prognosis for Salmonella meningitis or endocarditis is poor.
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Typhoid fever (enteric fever)
Therapy with antibiotics has decreased the mortality rate to 1%; however, prognosis depends on the extent of complications from the disease.
Relapse is common after therapy for enteric fever.
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Chronic carrier state: Patients who continue to shed bacteria for more than 1 year (approximately 1% of patients) are considered chronic carriers.
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NTS bacteremia: Increased mortality may be associated with a higher magnitude of NTS bacteremia. [29]
Morbidity/mortality
Enteric infections account for significant morbidity and mortality in young children (aged 1-4 y). Morbidity and mortality rates are highest in infants (most dangerous in infants < 3 mo with bacteremia), elderly patients, and patients with sickle cell disease, acquired immunodeficiency syndrome (AIDS), neoplasms, or other immunosuppressive conditions. [5, 30, 31] Substantial differences in outcomes have been noted based on varying serotypes. [32]
Complications
Complications of Salmonella infection include the following:
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Nontyphoidal salmonellosis
Bacteremia
Meningitis
Pneumonia
Endocarditis/pericarditis
Osteomyelitis (most common in patients with sickle cell anemia)
Hepatic/splenic abscess
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Typhoid fever (enteric fever)
Intestinal perforation and severe hemorrhage (occurs in 1-10% of children)
Toxic encephalopathy and cerebral thrombosis
Hepatitis, pancreatitis, arthritis, and myocarditis
Patient Education
Good personal hygiene and hand washing are essential for all people involved in food handling. All medical personnel must also use standard precautions when treating patients with Salmonella to avoid patient-to-patient transmission.
For excellent patient education resources, see WebMD's Travel Vaccines and Care Directory and the Centers for Disease Control and Prevention Web site.
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Under a moderately-high magnification of 8000X, this colorized scanning electron micrograph (SEM) revealed the presence of a small grouping of gram-negative Salmonella typhimurium bacteria that had been isolated from a pure culture. Image courtesy of the Centers for Disease Control and Prevention, Bette Jensen, and Janice Haney Carr.
