Salmonella Infection in Emergency Medicine
- Author: Michael D Owens, DO, MPH, FACEP, FAAEM; Chief Editor: Jeter (Jay) Pritchard Taylor, III, MD more...
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, Salmonella enterica. 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. In the United States, Salmonella serotype Enteritidis (22%), Salmonella serotype Newport (14%), and Salmonella serotype Typhimurium (13%) account for nearly half of the human isolates.
Salmonellosis caused by Salmonella Enteritidis is the most common bacterial infectious cause of food-borne disease in the United States. 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. 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. 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. Transmission may also occur from mother to fetus transplacentally. 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.
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. Animal studies reveal that prolonged antibiotic use may disrupt this host susceptibility as well.
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.[10, 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. Outbreaks have been associated with contaminated frozen potpies, puffed vegetable snacks, and exposure to turtles. More recently, multistate human outbreaks have been seen in contaminated dry dog food and peanut butter products.[13, 14]
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.
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.
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.
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). However, an estimated 1.4 million people in the United States are infected with nontyphoid Salmonella annually at a cost of $365 million in direct medical costs. 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.
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. 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.[15, 16] The reported 2010 incidence is 17.6 cases per 100,000.
Additionally, an estimated 500 people are infected with typhoid Salmonella annually. Most cases of documented typhoid disease in the United States are related to foreign travel to developing nations such as India (30%), Pakistan (13%), Mexico (12%), Bangladesh (8%), Philippines (8%), and Haiti (5%).
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.
The serovars responsible for typhoid or enteric fever, typhi and paratyphi, that cause systemic illness lead to an estimated 21.7 cases and 217,000 deaths worldwide, of which paratyphoid fever accounts for 5.4 million cases. Salmonella Typhi is estimated to outweigh Salmonella Paratyphi by a ratio of about 4:1 in endemic countries. Compared with tourists, travelers visiting friends or relatives in developing nations .[19, 20] Compared with tourists, travelers visiting friends or relatives in developing nations exhibit a much higher incidence of typhoid or enteric fever. Eighty percent of the total typhoid fever cases and deaths occur in Asia; the rest mainly occur in Africa and Latin America.
Twenty percent of patients require hospitalization, with an estimated death rate of 0.6%. Infection with drug-resistant nontyphoid Salmonella and Salmonella typhi increase the likelihood of hospitalization and death.
Invasive nontyphoid Salmonella infection occurs in about 5% of cases in Israel and is responsible for 400-600 deaths in the United States each year. In 2010, the CDC reported Salmonella infection was the most common foodborne disease in the United States and was associated with the most hospitalizations and deaths. Mortality for nontyphoid Salmonella a is reported to be as high as 60% in African patients with HIV. 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. 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. Depending on the serotype, roughly 1% of adults and 5% of children excrete organisms for greater than a year.
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). One quarter to one third of pediatric typhoid patients are younger than 5 years, of which 6-21% are younger than 2 years.
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 among those aged 50 years or older.
Coburn B, Grassl GA, Finlay BB. Salmonella, the host and disease: a brief review. Immunol Cell Biol. 2007 Feb-Mar. 85(2):112-8. [Medline].
Grassl GA, Finlay BB. Pathogenesis of enteric Salmonella infections. Curr Opin Gastroenterol. 2008 Jan. 24(1):22-6. [Medline].
Chambers HF. McPhee SJ, Papadakis MA, Tierney LM, eds. Current Medical Diagnosis & Treatment. 47th ed. McGraw-Hill Co; 2008. 1250-1252.
Centers for Disease Control and Prevention. Vital signs: incidence and trends of infection with pathogens transmitted commonly through food--foodborne diseases active surveillance network, 10 U.S. sites, 1996-2010. MMWR Morb Mortal Wkly Rep. 2011 Jun 10. 60(22):749-55. [Medline].
Linam WM, Gerber MA. Changing epidemiology and prevention of Salmonella infections. Pediatr Infect Dis J. 2007 Aug. 26(8):747-8. [Medline].
Peques DA, Miller SI. Salmonella Species, Including Salmonella Typhi. Mandell: Mandell, Douglas, and Bennett's Principles and Practice of Infectious Disease. 7th ed. Elsevier; 2009. chap. 223.
Centers for Disease Control and Prevention. Preliminary FoodNet data on the incidence of infection with pathogens transmitted commonly through food - 10 states, 2009. MMWR Morb Mortal Wkly Rep. 2010 Apr 16. 59(14):418-22. [Medline]. [Full Text].
Rai B, Utekar T, Ray R. Preterm delivery and neonatal meningitis due to transplacental acquisition of non-typhoidal Salmonella serovar montevideo. BMJ Case Rep. 2014 May 29. 2014:[Medline].
Croswell A, Amir E, Teggatz P, Barman M, Salzman NH. Prolonged impact of antibiotics on intestinal microbial ecology and susceptibility to enteric Salmonella infection. Infect Immun. 2009 Jul. 77(7):2741-53. [Medline]. [Full Text].
Braden CR. Salmonella enterica serotype Enteritidis and eggs: a national epidemic in the United States. Clin Infect Dis. 2006 Aug 15. 43(4):512-7. [Medline].
Jones TF, Ingram LA, Fullerton KE, et al. A case-control study of the epidemiology of sporadic Salmonella infection in infants. Pediatrics. 2006 Dec. 118(6):2380-7. [Medline].
Centers for Disease Control and Prevention. Preliminary FoodNet data on the incidence of infection with pathogens transmitted commonly through food--10 states, 2007. MMWR Morb Mortal Wkly Rep. 2008 Apr 11. 57(14):366-70. [Medline].
Centers for Disease Control and Prevention. Multistate outbreak of human Salmonella infections caused by contaminated dry dog food--United States, 2006-2007. MMWR Morb Mortal Wkly Rep. 2008 May 16. 57(19):521-4. [Medline]. [Full Text].
Centers for Disease Control and Prevention. Multistate outbreak of Salmonella infections associated with peanut butter and peanut butter-containing products--United States, 2008-2009. MMWR Morb Mortal Wkly Rep. 2009 Feb 6. 58(4):85-90. [Medline]. [Full Text].
Voetsch AC, Van Gilder TJ, Angulo FJ, et al. FoodNet estimate of the burden of illness caused by nontyphoidal Salmonella infections in the United States. Clin Infect Dis. 2004 Apr 15. 38 Suppl 3:S127-34. [Medline].
Weinberger M, Keller N. Recent trends in the epidemiology of non-typhoid Salmonella and antimicrobial resistance: the Israeli experience and worldwide review. Curr Opin Infect Dis. 2005 Dec. 18(6):513-21. [Medline].
Harish BN, Menezes GA. Antimicrobial resistance in typhoidal salmonellae. Indian J Med Microbiol. 2011 Jul-Sep. 29(3):223-9. [Medline].
Meltzer E, Schwartz E. Enteric fever: a travel medicine oriented view. Curr Opin Infect Dis. 2010 Oct. 23(5):432-7. [Medline].
Sethuraman U, Kamat D. Management of child with fever after international travel. Clin Pediatr (Phila). 2007 Apr. 46(3):222-7. [Medline].
Zaki SA, Karande S. Multidrug-resistant typhoid fever: a review. J Infect Dev Ctries. 2011 May 28. 5(5):324-37. [Medline].
Heymann DL. Control of Communicable Diseases Manual. 18th ed. American Public Health Association; 2004. 469-473.
Hedican E, Hooker C, Jenkins T, et al. Restaurant Salmonella Enteritidis outbreak associated with an asymptomatic infected food worker. J Food Prot. 2009 Nov. 72(11):2332-6. [Medline].
Brooks JT, Matyas BT, Fontana J, DeGroot MA, Beuchat LR, Hoekstra M, et al. An outbreak of Salmonella serotype Typhimurium infections with an unusually long incubation period. Foodborne Pathog Dis. 2012 Mar. 9 (3):245-8. [Medline].
Parry CM, Wijedoru L, Arjyal A, Baker S. The utility of diagnostic tests for enteric fever in endemic locations. Expert Rev Anti Infect Ther. 2011 Jun. 9(6):711-25. [Medline].
Nagaraja V, Eslick GD. Systematic review with meta-analysis: the relationship between chronic Salmonella typhi carrier status and gall-bladder cancer. Aliment Pharmacol Ther. 2014 Apr. 39 (8):745-50. [Medline].
Hatta M, Smits HL. Detection of Salmonella typhi by nested polymerase chain reaction in blood, urine, and stool samples. Am J Trop Med Hyg. 2007 Jan. 76(1):139-43. [Medline].
Bottieau E, Clerinx J, Van den Enden E, et al. Fever after a stay in the tropics: diagnostic predictors of the leading tropical conditions. Medicine (Baltimore). 2007 Jan. 86(1):18-25. [Medline].
Abubakar I, Irvine L, Aldus CF, et al. A systematic review of the clinical, public health and cost-effectiveness of rapid diagnostic tests for the detection and identification of bacterial intestinal pathogens in faeces and food. Health Technol Assess. 2007 Sep. 11(36):1-216. [Medline].
Laube T, Cortés P, Llagostera M, Alegret S, Pividori MI. Phagomagnetic immunoassay for the rapid detection of Salmonella. Appl Microbiol Biotechnol. 2013 Dec 21. [Medline].
Kuhn KG, Falkenhorst G, Ceper TH, et al. Detecting non-typhoid Salmonella in humans by ELISAs: a literature review. J Med Microbiol. 2012 Jan. 61:1-7. [Medline].
Onwuezobe IA, Oshun PO, Odigwe CC. Antimicrobials for treating symptomatic non-typhoidal Salmonella infection. Cochrane Database Syst Rev. 2012. 11:CD001167. [Medline].
Wistrom J, Jertborn M, Ekwall E, et al. Empiric treatment of acute diarrheal disease with norfloxacin. A randomized, placebo-controlled study. Swedish Study Group. Ann Intern Med. 1992 Aug 1. 117(3):202-8. [Medline].
Centers for Disease Control and Prevention. National Antimicrobial Resistance Monitoring System for Enteric Bacteria (NARMS): Human Isolates Final Report, 2004. [Full Text].
Grady R. Safety profile of quinolone antibiotics in the pediatric population. Pediatr Infect Dis J. 2003 Dec. 22(12):1128-32. [Medline].
Mølbak K. Human health consequences of antimicrobial drug-resistant Salmonella and other foodborne pathogens. Clin Infect Dis. 2005 Dec 1. 41(11):1613-20. [Medline].
Dekate P, Jayashree M, Singhi SC. Management of acute diarrhea in emergency room. Indian J Pediatr. 2013 Mar. 80(3):235-46. [Medline].
Thaver D, Zaidi AK, Critchley JA, Azmatullah A, Madni SA, Bhutta ZA. Fluoroquinolones for treating typhoid and paratyphoid fever (enteric fever). Cochrane Database Syst Rev. 2008 Oct 8. CD004530. [Medline].
Parry CM, Threlfall EJ. Antimicrobial resistance in typhoidal and nontyphoidal salmonellae. Curr Opin Infect Dis. 2008 Oct. 21(5):531-8. [Medline].
Buchwald DS, Blaser MJ. A review of human salmonellosis: II. Duration of excretion following infection with nontyphi Salmonella. Rev Infect Dis. 1984 May-Jun. 6(3):345-56. [Medline].
Corcoran M, Morris D, De Lappe N, O'Connor J, Lalor P, Dockery P. Commonly used disinfectants fail to eradicate Salmonella enterica biofilm from food contact surface materials. Appl Environ Microbiol. 2013 Dec 20. [Medline].
Gündüz GT, Gönül SA, Karapinar M. Efficacy of myrtle oil against Salmonella Typhimurium on fresh produce. Int J Food Microbiol. 2009 Mar 31. 130(2):147-50. [Medline].
Torok TJ, Tauxe RV, Wise RP, et al. A large community outbreak of salmonellosis caused by intentional contamination of restaurant salad bars. JAMA. 1997 Aug 6. 278(5):389-95. [Medline].
Adhikari B, Besser TE, Gay JM, et al. Introduction of new multidrug-resistant Salmonella enterica strains into commercial dairy herds. J Dairy Sci. 2009 Sep. 92(9):4218-28. [Medline].
Amieva MR. Important bacterial gastrointestinal pathogens in children: a pathogenesis perspective. Pediatr Clin North Am. 2005 Jun. 52(3):749-77, vi. [Medline].
Connor BA, Schwartz E. Typhoid and paratyphoid fever in travellers. Lancet Infect Dis. 2005 Oct. 5(10):623-8. [Medline].
Hoffman SL, Punjabi NH, Kumala S, et al. Reduction of mortality in chloramphenicol-treated severe typhoid fever by high-dose dexamethasone. N Engl J Med. 1984 Jan 12. 310(2):82-8. [Medline].
Parry CM, Hien TT, Dougan G, White NJ, Farrar JJ. Typhoid fever. N Engl J Med. 2002 Nov 28. 347(22):1770-82. [Medline].
Perera N, Geary C, Wiselka M, Rajakumar K, Andrew Swann R. Mixed Salmonella infection: case report and review of the literature. J Travel Med. 2007 Mar-Apr. 14(2):134-5. [Medline].
Punjabi NH, Hoffman SL, Edman DC, et al. Treatment of severe typhoid fever in children with high dose dexamethasone. Pediatr Infect Dis J. 1988 Aug. 7(8):598-600. [Medline].