Salmonellosis

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Salmonella invading a host cell. From: http://commons.wikimedia.org/wiki/File:SalmonellaNIAID.jpg

Etiology/Bacteriology

Taxonomy

Kingdom: Bacteria

Phylum: Proteobacteria

Class: Gammaproteobacteria

Order: Enteroacteriales

Family: Enterobacteriacea

Genus: Salmonella

Species: Typhimurium

Description

Salmonella typhimurium are gram negative bacilli that are non-spore forming and facultative anaerobes. This bacteria is predominately motile with peritrichous flagella. Salmonella typhimurium in particular causes gastroenteritis in human hosts. This organism is easy to identify in a laboratory setting. All Salmonella are oxidase negative, and most are lactose negative and produce hydrogen sulfide. [11] Salmonella can be acquired by eating or drinking contaminated food and water. It is especially common on turtles, and poultry. Salmonella enters the body by being ingested, and then makes its way through the stomach acid to its niche in the intestines. Because Salmonella does not contain an acid virulence factor, many of the bacteria are killed on their passage through the stomach. This is why an approximate does of 100,000 bacterial cells must be ingested in order to cause disease. In the intestines, there are many bacteria already colonized.Salmonella has many adhesion factors that allow it to better adhere to the mucosal layer. Approximately 94 million people report Salmonella typhimurium infections per year, with 155,000 deaths as a result. The disease is characterized by severe abdominal cramping, vomiting and diarrhea. In order to further confirm a Salmonella typhimurium infection, a stool sample or blood sample will be taken to be grown in a pure culture. After confirmation, of a severe infection proper antibiotics will be prescribed. To prevent Salmonella, use caution when handling raw meat by washing hands and surfaces thoroughly.

Pathogenesis

Transmission

Salmonella is generally transmitted by the fecal oral route of transmission. Generally this occurs through the improper handling of contaminated foods. Specifically precarious foods include contaminated raw beef, poultry, eggs, milk, and vegetables. Salmonella can also be transmitted zoonotically via birds. Other cases have been reported that were contracted from pet turtles, lizards, and snakes.[8]

Colonization

After Salmonella bacteria are ingested they pass through the gastrointestinal tract, avoiding the gastric mucosal barrier to invade the mucosa of the small and large intestines where they begin to produce AvrA toxin which suppresses the host’s innate immune system [9]. The invasion of Salmonella into the host’s intestinal cells cause the release of proinflammatory cytokines by the host’s immune system which induce the inflammatory response, leading to severe diarrhea.[10]

Infectious Dose and Incubation Period

The number of Salmonella organisms that need to be ingested in order to cause disease in a human host is approximately just over 100,000 bacterial cells[11]. The incubation period, or the time it takes for an individual to present with symptoms after ingestion, is between 12 hours and three days. [4]

Virulence Factors

Salmonella bacteria invade the epithelial cells of the human intestines. These bacteria have at least 16 adhesion factors which allow them to better adhere to human intestines where they make their home. Salmonella has acquired at least 5 SPI's (Salmonella Pathogenicity Islands) via horizontal gene transfer which contribute to its virulence [9]. Specifically, SPI-1 and SPI-2 are the main contributors to Salmonella's virulence. Salmonella uses a type three secretion system (TTSS) to inject its outer proteins into the host's intestinal cells. Once it has invaded the host cell, Salmonella mature within the cell inside of "Salmonella containing vacuoles" (SCVs) thereby evading the hosts immune response to its foreign presence.[11]

Clinical features

Incidence and Mortality

In the United States, approximately 40,000 cases of Salmonella typhimurium are reported annually, with 400 deaths occurring annually as a consequence of these infections. Worldwide, 93.8 million cases of Salmonella are reported annually, with approximately 155,000 deaths occurring as a consequence of these infections. [1][2]

Symptoms

The symptoms of Salmonellosis generally appear 12 to 72 hours after infection. The symptoms of Salmonellosis include self-limiting diarrhea, fever, abdominal cramps, and vomiting. Symptoms generally persist for 4-7 days after infection. In immunocompromised individuals, specifically infants and elderly patients, the diarrhea may become severe enough that the individual must be hospitalized in order to replenish fluids and electrolytes via IV. Although most symptoms in non-high-risk patients will fade a week after the initial infection, it may take months to re-establish the normal gut microbiota of the digestive tract. [3[4]

Diagnosis

Salmonella typhimurium can be detected through sterile samples. The bacteria can also be detected in the blood, urine or tissues. These tests consist of growing the bacteria in pure culture. [5] Diagnostic identification can be obtained by the growth of the bacteria on MacConkey agar and Eosin Methylene Blue agar (EMB). Both of these types of media is designed to grow gram-negative bacteria and differentiate for lactose fermentation. The test results for both of the media will appear colorless and translucent, which indicates that the bacteria is lactose negative. Salmonella typhimurium produces no gas when grown in TSI media which is used to differentiate it from other Enterobacteriaceae. [6] A fecal, blood, or other sample is placed on the agar and incubated for two to three days. After that time, the specialist can properly identify the bacteria and confirm the identity by looking at the specific biochemical reactions. [5]

Treatment

Salmonella typhimurium strains usually do not require treatment other than oral fluids, and the infection can usually be resolved in 5-7 days. One with severe diarrhea may require rehydration with intravenous fluids. Antibiotics are not routinely recommended since they tend to increase adverse effects as well as prolong Salmonella strains detected in stools. Young infants and adults over the age of 65 are at risk for severe disease or complications. One who experiences severe diarrhea, high fever, bloodstream infection or one who needs hospitalized are recommended a prescription of antibiotics. Today, antibiotic resistance is a problem among Salmonella bacteria therefore susceptibility testing can guide appropriate therapy. Popular antibiotics used for the infection include fluoroquinolones, or third generation cephalosporins and ampicillin. [7]

Prevention

There is no vaccine against Salmonella Typhimurium. Salmonella Typhimurium can be traced to many dairy, poultry, and meat products. However, the most common sources where Salmonella is found are eggs and chickens. Salmonella can also be acquired through water and foods that have been contaminated with feces. To prevent Salmonella one should use caution when handling and storing raw chicken. Make sure to keep the raw chicken separated from all other meats. Also, wash preparation tops, cutting boards, and hands thoroughly before handling or preparing other meats to prevent cross contamination. One should also use caution when cooking eggs and meat to make sure they are cooked thoroughly and to the correct internal temperature to kill any bacteria that could be present. (1) Do not eat or drink raw eggs. Milk should be pasteurized before drinking.Water should come from regulated sources or be filtered to make sure it is free of Salmonella bacteria. Reptiles(especially small turtles) and birds are notorious for carrying Salmonella on their skin. Children, the elderly, and immunocompromised individuals should stay away from these animals to protect themselves from contracting the Salmonella bacterium. (2)


(1)http://www.salmonella.org/info.html (2)http://www.cdc.gov/salmonella/general/prevention.html

Host Immune Response

The mucus lining in the intestines serves as the first line of defense against invading pathogens. Other cells in the intestines also secrete amphipathic proteins that function like antimicrobials that create another line of defense against invading pathogens. As Salmonella Typhimurium invades that mucosal lining the host inflammatory response kicks in. Salmonella Typhimurium uses the type III secretion system to invade the epithelial cells in the intestines. There is a positive feedback immune response that occurs between the Salmonella bacterium and the host immune system. The PRR's recognize the Salmonella to induce a pro-inflammatory response of cytokines, chemokines, and lipid mediators. The presence of the cytokines triggers a cascade of proteins to be released from Salmonella that positively trigger more cytokines to be released. Cytokines trigger the assembly NLRC4/NLRP3 in Salmonella which then activates Caspase-1 which leads to the release of other specific cytokines. Those cytokines then trigger the release of chemokines which creates an influx of neutrophils to the mucosal lining. Those neutrophils are important in killing the extracellular Salmonella. However, because of all the signals that have occurred for an inflammatory response the neutrophils also cause damage to the epithelial cells leading to diarrhea.

http://www.landesbioscience.com/journals/gutmicrobes/article/19141/?nocache=486795098

References

1 Centers for Disease Control (CDC). General Information Salmonella.Page last updated: April 5, 2012
2 Shannon E. Majowicz, Jennie Musto, Elaine Scallan, Frederick J. Angulo, Martyn Kirk, Sarah J. O'Brien, Timothy F. Jones, Aamir Fazil, Robert M. Hoekstra The Global Burden of Nontyphoidal Salmonella Gastroenteritis.Oxford Journals. Medicine Clinical Infectious Diseases. Food Safety. Volume 50, Issue 6Pp. 882-889.
3 Centers for Disease Control (CDC). Multistate Outbreak of Salmonella Typhimurium and Salmonella Newport Infections Linked to Cantaloupe (Final Update). Posted October 5, 2012 3:15 PM ET
4 Mayo Clinic Staff. Salmonella infection. April 16, 2011.
5 Marler Clark. PHow is Salmonella Infection Diagnosed? 2005-2013.
6 Juan Miguel Morata. Different Types of Agar.
7 National Institue of Allergy and Infectious Diseases Staff. Salmonellosis.
8 Wikipedia entry: Salmonella. page was last modified on 16 July 2013
9 Giannella RA. Salmonella. In: Baron S, editor "'Medical Microbiology. 4th edition. Galveston (TX): University of Texas Medical Branch at Galveston; 1996. Chapter 21
10 Wikipedia entry: Infectious Dose. page was last modified on 9 April 2013.
11 Rene E. Harrison, John H. Brumell,† Arian Khandani, Cecilia Bucci, Cameron C. Scott, Xiuju Jiang, B. Brett Finlay, and Sergio Grinstein "Salmonella Impairs RILP Recruitment to Rab7 during Maturation of Invasion Vacuoles" In: Mol Biol Cell. 2004 July; 15(7): 3146–3154 Wolters Kluwer Health

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Created by Rachel Acosta, Taylor Zelnicek, and Magdalene Shaughnessy, students of Tyrrell Conway at the University of Oklahoma.