Salmonella enterica serovar Typhimurium

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University of Oklahoma Study Abroad Microbiology in Arezzo, Italy[1]

Scanning electron microscope image of Salmonella Typhimurium. From: Nbcnews.com [2]

Etiology/Bacteriology

Taxonomy

Description

Being zoonotic, Salmonella enterica subsp. enterica serovar Typhimurium D23580 is a rod-shaped, Gram-negative, flagellated facultative anaerobe that is mostly present in the mammalian GI tract. It is a Non-Typhoidal Salmonella serotype that causes diarrhea and paediatric blood stream infections (bacteremia). It is one of the few emerging invasive strains of Non-Typhoidal Salmonella (iNTS). This specific strain, Typhimurium D23580, was found prevalent in the sub-Saharan African population, especially among those with high prevalence of HIV, with an associated case fatality of 20–25%. [1] In relation to diarrhoeal disease, non-typhoidal Salmonella can exploit the gut mucosal inflammatory response that accompanies infection in immunocompetent individuals to gain a selective advantage over the resident gut microbiota in the inflamed gut lumen. The clinical features of this iNTS disease in Africa are diverse; the disease differs from other strains of Salmonella. Fever, hepatosplenomegaly, and respiratory symptoms are common. Features of enterocolitis are often absent. [3] Treatment consists of the administration of antibiotics; however, with caution of possible antimicrobial resistance. Whole-genome sequence analysis of 129 ST313 strains, isolated during 1988–2010 from 7 countries of sub-Saharan Africa, identified 2 dominant genetic lineages, I and II. [3] Further studies are still needed to fully understand and control this NTS strain.

Pathogenesis

Transmission/Reservoirs

Salmonella Typhimurium is generally thought to have a wide range of animal hosts, including birds, cattle and many other domesticated animals. However, recent research has led many to believe that the individual variants have a much more narrow range of possible hosts [1] . The invasive African variant has only been found to infect humans; specifically people with compromised immune systems. Since the beginning of the HIV epidemic through Sub-Saharan, invasive African Salmonella Typhimurium has been found to transfer among the most severe HIV victims as a human-to-human pathogen [2].

The most common modes of infection for Salmonella Typhimurium are by food-borne transmission especially in hospital settings [3]. Many of the most severe infections are believed to be hospital-acquired. Besides patients with severe onset HIV, malnourished children are the next most susceptible group [3].

As well as the above susceptible groups, other links have been found between those suffering from malaria, sickle cell anemia, and people recently treated with gastric acid suppression and the acquisition of Salmonella Typhimurium.

Incubation/Colonization

Invasive, African Salmonella Typhimurium does not typical cause disease in healthy individuals, but those that are immunocompromised due to other disease (eg HIV) or just for lack of overall nutrition are much more likely to be infected by the pathogen [4]. There is no conclusive data on whether the invasive or gastrointestinal forms of Salmonella Typhimurium are actually two different pathogens or if their modes of transition, colonization, or incubation differ [1].

Epidemiology

Incidents of Salmonella Typhimurium occur largely in Sub-Saharan Africa, with the highest incident rates occurring during or just after the specific area's rainy season. The median ages of those infected are 32 for adults and 22 months for children [5]. Overall, there has not been an in-depth study done into the epidemiology of either invasive or non-invasive non-typhoidal Salmonella strains [1].

Virulence Factors

The most alarming virulence factor of invasive Salmonella Typhimurium is the rapid acquisition of drug-resistance, which has led to multidrug-resistant “super” strains unaffected by common antibiotics such as ampicillin, cotrimoxazole, and chloramphenicol [4]. Invasive Salmonella Typhimurium also has many similar virulence factors to Salmonella Typhi. These include type III secretion systems, Vi antigen, many surface polysaccharides, and flagella [5].

Clinical Features

Acute gastroenteritis is the most common symptom in infected patients. This causes diarrhea, abdominal cramping, fever, and vomiting. Fever will usually subside in 72 hours, with bloody diarrhea lasting between three and seven days. These effects can be more severe or prolonged in children and the elderly. Bacteremia, or the spread of the pathogen into the blood stream, generally occurs in 5-10% of cases and can lead to more severe symptoms such as meningitis and infections of the bones and joints. This can be especially dangerous in immunocompromised patients such as those suffering from HIV or malaria [6].

Diagnosis

The classical method for confirming a salmonella infection was by testing for the presence of antibodies using a Widal aggulation test. This method is highly unreliable and in an experiment only tested positive on 38.5% of confirmed salmonella infections [7]. Since then, a new method for detecting antibodies has been developed using an enzyme immunoassay for IgM, IgG, and IgA antibodies. This method uses a commercially available lipopolysaccharaide for S. Typhimurium and S. enteritidis. This method produced a much better 88.5% positive rate of confirmed cases. An alternative culturing method can be used to confirm diagnosis by tablet diffusion on Danish Blood Agar with Rosco Neosensitabs. If this test identifies a nalidixic acid resistance, an E-test can also be used to confirm diagnosis [8].

Treatment

From 1998 through 2002, treatment for adults with suspected sepsis was empirical antibiotic treatment that included chloramphenicol and benzylpenicillin. In 2002, chloramphenicol was replaced with oral ciprofloxacin. For adults who did not respond to initial treatments or were unable to take oral medication, they were prescribed parenteral gentamicin. In 1998 to 2002, empirical treatment for childhood sepsis consists of chloramphenicol. Parenteral gentamicin was also added to the treatment from 2002 onwards. [4] Other antibiotics used for treatment are penicillin with chloramphenicol or ampicillin with gentamicin. [3]

For multidrug-resistant strains of invasive non-typhoidal salmonella, treatment drugs include third generation cephalosporins and fluoroquinolone (i.e. ciprofloxacin). [1]

In the context of HIV, recurrent invasive non-typhoidal salmonella disease declined after being treated with antiretroviral therapy. [1]

Prevention

Risk Factors

Environmental risk factors for both adults and children include rainy seasons when drinking water sources have the highest concentrations of fecal organisms. Animal contact is a risk factor especially for children. Hospitals are also places where patients can contract hospital-acquired infections. [3]

Host risk factors include age, exposure to antimicrobial agents, malaria and anemia, malnutrition, HIV infection, gastric acid suppression, sickle cell disease, and schistosomiasis. Children and infants under the age of 3 years old are particularly at rise for invasive NTS disease. Adults who are above 50 years old in industrialized countries are more susceptible to endovascular infections with NTS, and younger adults are dominated by HIV-associated NTS disease. Malnutrition and other previous/current diseases increase the risk of NTS disease by reducing immune system responses and leaving the body vulnerable to infection. [3]

Preventive measures are vaccines, improved hygiene and sanitation (washing hands), improved nutrition (safe drinking water and proper food preparation and storage), malaria control, and antiretroviral therapy programs. [1]

References

1. Feasey NA, Dougan G, Kingsley RA, Heyderman RS, Gordon MA: Invasive non-typhoidal salmonella disease: an emerging and neglected tropical disease in Africa. Lancet 2012. 379:9835::2489-99.

2. Okoro CK, Kingsley RA, Connor TR, Harris SR, Parry CM, Al-Mashhadani MN, Kariuki S, Msefula CL, Gordon MA, de Pinna E, Wain J, Heyderman RS, Obaro S, Alonso PL, Mandomando I, MacLennan CA, Tapia MD, Levine MM, Tennant SM, Parkhill J, Dougan G: Intracontinental spread of human invasive Salmonella Typhimurium pathovariants in sub-Saharan Africa. Nature Genetics 2012. 44:1215–1221.

3. Morpeth SC, Ramadhani HO, Crump JA. Invasive Non-Typhi Salmonella Disease in Africa. Clin Infect Dis. (2009) 49:4:606-611.

4. Gordon MA, Graham SM, Walsh AL, Wilson L, Phiri A, Molyneux E, Zijlstra EE, Heyderman RS, Hart CA, Molyneux ME: Epidemics of Invasive Salmonella enterica Serovar Enteritidis and S. enterica Serovar Typhimurium Infection Associated with Multidrug Resistance among Adults and Children in Malawi. Clin Infect Dis. 2008. 46:7:963-969.

5. de Jong HK, Parry CM, van der Poll T, Wiersinga WJ: Host–Pathogen Interaction in Invasive Salmonellosis. PLoS Pathog 2012. 8:10.

6. Chen HM, Wang Y, Su LH, Chiu CH: Nontyphoid Salmonella Infection: Microbiology, Clinical Features, and Antimicrobial Therapy. Pediatrics & Neonatology 2013, 54:3:147-152.

7. Isomaki O, Vuento R, Granfors K: Serological Diagnosis of Salmonella Infections by Enzyme Immunoassay. Lancet 1989, 333:8652:1411-1414.

8. Helms M, Vastrup P, Gerner-Smidt P, Mølbak K: Excess Mortality Associated with Antimicrobial Drug-Resistant Salmonella Typhimurium. Emerging Infectious Diseases 2002, 8:5:490-495.

Created by Nathan Sethman, Robertson Bootes Beasley, Amy Vu, and Teresa Vu, students of Tyrrell Conway at the University of Oklahoma.