Nontyphoid Salmonella

Robert Koch and Karl Joseph Eberth, 1880

The salmonellae are named after the American bacteriologist Danile Salmon.

Enteritic salmonellae, like typhoid salmonellae, are petrich flagellated (i.e. distributed over the entire cell surface) and thus motile, Gram-negative rod-shaped bacteria that cannot be distinguished microscopically from other Gram-negative rod-shaped bacteria. As a rule, they cannot ferment lactose. Basically, Salmonella are classified according to the White-Kauffmann-Le Minor scheme (formerly Kauffmann-White scheme) on the basis of the structure of their surface (O) and flagellar (H) antigens and differentiated into serovars on the basis of an antigenic formula. The following antigens are relevant to the serovar classification of Salmonella:

• O antigens (surface antigens; Note: The O originally stood only for "without puff", meaning these bacteria do not swarm on an agar plate): More than 60 different types exist.
• H antigens (flagellar antigens): Their antigenic structure is characterized by 2 distinct protein groups: H1 antigens and H2 antigens.Both phases can occur singly or together. The H1 antigens are marked with lower case letters. Since these are not sufficient, they are also numbered (e.g. z1, z2 etc.). The H-antigens of phase H2 are identified by lower case letters and numbers.
• K-antigens (capsular antigen; also called Vi antigen, an additional surface antigen, which was initially held primarily responsible for virulence; however, it represents a special case of a capsular antigen) occur only rarely, but they characterize the Typhi and Paratyphi varieties.

Enteritic salmonellae include Salmonella Enteritidis (= S. enterica subsp. Enterica Serovar Enteritidis), Salmonella Typhimurium, S. Virchow, S. London, S. Choleraesuis, S. Abortusovis. Most of the salmonellae in this group are typical zoonotic pathogens, i.e. they cause illness in humans and animals. Salmonellae adapt in different extreme host and non-host environments at both genetic and phenotypic levels, leading to their better survival and spread. The uncontrolled and improper use of antibiotics against various Salmonella serovars has not only led to the emergence of various multidrug resistant strains but also to the emergence of hyperinfective Salmonella strains, which further complicates the severity of disease manifestation and treatment (Pradhan D et al. 2019).

Infection by oral ingestion: Infection by enteric salmonella is a classical food-associated disease (A02.0). S. Enteritidis is transmitted mainly via inadequately heated eggs and dishes made from them (e.g. tiramisu, egg foam, creams, ice cream, mayonnaise). S. Typhimurium is more likely to be transmitted via raw meat or inadequately heated meat products. Infection occurs directly through oral ingestion of the pathogen (food, drinking water) or through "cross-contaminated" food (by touching infected people, contact with contaminated surfaces, or contaminated other food). Direct transmission from person to person is only possible under very poor hygienic conditions.

The infection dose for adult humans is between¹⁰³ and¹⁰⁶ pathogens, unless the salmonellae are found in foods with a high fat content (e.g. cheese, chocolate, salami) or in spices, in which case illnesses are already possible with < 100 germs. A low dose of infection is also sufficient in cases of immune deficiency (infants, small children, old people).

Resistance to cold: Salmonella can multiply between 10°C and 47°C, in some cases already from 6-8°C. Freezing does not kill salmonella (e.g.: ice cream) and it can survive for several months in food (e.g.: spices such as paprika or coconut flakes) or in the environment.

In order to achieve a sufficiently high infectious dose, the salmonellae must first multiply in a foodstuff for a period of time (generation time approx. 20 min at 37°C, 60 min at room temperature). Enteritis results from a massive invasion of the mucosa of the small intestine with the germ. The bacterial invasion occurs on the one hand through the M-cells of the Peyer`s plaques which pass them transcytotically into the interstitium. Subsequently, the Salmonellae are phagocytosed by macrophages. There they can survive or even multiply.

Another pathway is via the enterocytes of the intestinal wall. Salmonellae bind to the EGF receptor (epidermal growth factor). This binding leads to a change in the cytoskeleton of the cell. The cell forms cytoplasmic extensions that enclose and internalize the pathogen like a ruffle. The pathogens are released on the other side of the epithelium, migrate into the submucosa to be phagocytosed by macrophages.

In general, the infection remains localized (in contrast to the typhoid Salmonella). Only in immunocompromised individuals and children can generalization occur. The production of endotoxins plays a minor role in the pathogenesis of this infection.

Incubationperiod: It ranges from 6-72 hours (usually from 12-36 hours) for enteric salmonellae and depends on the infectious dose and serovar (for typhoid salmonellae it ranges from 3 days to 4 to 8 weeks). The incubation period depends on the infectious dose.

Incidence: In Germany, the incidence for Salmonella enteritis is 65/100,000 . Worldwide, salmonellae are frequent pathogens of bacterial diarrhoeal diseases in humans and animals.

Seasonal incidence: Salmonellosis occurs more frequently in late summer. S. Enteritidis with approx. 60% and S. Typhimurium with approx. 20% were isolated most frequently.

The infections have been decreasing for years. This is partly due to the fact that, for example, outbreak clarifications are mandatory in the poultry industry and there is a compulsory vaccination against S. Enteritidis in the laying hen sector and a ban on egg marketing in the event of positive S. Enteritidis or S. Typhimurium detection.

Self-limiting gastroenteritis: While infections with typhoid salmonellae are classified as serious systemic diseases, enteric salmonella infections usually present as acute but uncomplicated, febrile and self-limiting gastroenteritis with nausea and vomiting, headache and muscle pain, violent diarrhoea, not bloody. Fever: 38-39°C.Duration: Fever less than 2 days. Diarrhoea less than 7 days. Rarely, bacteremia occurs with or without extraintestinal focal infection, which usually does not require antibiotic therapy. The lethality is low in otherwise healthy individuals and is about 0.1% (Hof H et al. 2019).

Complication - Extraintestinal manifestations: Immunocompromised adult patients may develop extraintestinal manifestations of nontyphoidal salmonellosis in adulthood (Weiss SH et al (1986). They are then associated with a more severe course of disease and more frequent or prolonged hospitalization than the enteritic course (Chen PL et al.(2012). In a study by a Spanish study group at a primary care hospital, 8% of all salmonelloses showed an extraintestinal site of manifestation (Rodriguez M et al. (1998). A preceding gastroenteritic symptomatology was not always present. Salmonella was most frequently detected in the blood without any other infectious focus. Furthermore, focal infections were detectable in the urinary tract, the lower respiratory tract, intra-abdominal and at vascular, osteoarticular and central nervous manifestation sites (Rodriguez M et al. 2006; Huang DB et al. 2005). In addition, endocarditis and soft tissue abscesses have been described (Abbott SL et al 2012). An increased risk for the occurrence of extraintestinal focal salmonellosis in general is also associated with a number of host factors:

• Age > 50 years
• Autoimmune diseases (e.g. systemic lupus erythematosus (Gerona JG et al. 2009), granulomatous polyangiitis).
• Immunosuppressed (e.g. immunosuppressive therapy -continuous therapy with corticosteroids, chemotherapeutic treatment) or HIV infection, an antibody deficiency syndrome, alcoholism, hematologic neoplasms, metastatic solid malignancies (Chan JC et al. 1991, Souglakos J et al. 2002; Sperber SJ et al. 1987; Mamishi S et al. 20109).

Enteritic salmonellae: Salmonellae are detected from stool, vomit or suspicious food by means of cultural cultivation of the pathogens. If a systemic course is suspected, blood cultures are taken. Serotyping (Kauffmann-White scheme) of the Salmonella strain is then carried out in the reference laboratory in order to identify the source and route of infection. A stool culture should be performed in case of prolonged diarrhea (> 3 days) or blood accumulation in the stool.

The therapy of enteric, nontyphoidal salmonella consists of fluid and electrolyte replacement. In uncomplicated, gastroenteritic courses of salmonellosis, antibiotic therapy is not indicated as it would prolong the excretion of the pathogen. In severe cases (sepsis or SIRS = systemic inflammatory response syndrome), antibiotic therapy is indicated. Antimicrobial therapy may also be considered for gastroenteritis in infants, small children, the elderly and patients with immune deficiencies or diseases of the heart valves or vessels.

Due to increasing resistance of the pathogens, the therapy should be carried out according to the antibiogram. For therapy, 3rd generation cephalosporins, trimethoprim/sulfamethoxazole, ampicillin, azithromycin or, in adults, quinolones are available (Hof H et al. 2019).

Any suspicion of salmonella enteritis must be reported to the public health department (obligation to report). Anyone who works in schools, kindergartens or similar community facilities or in food establishments may no longer work in certain cases even if a salmonella infection is suspected. The public health department monitors sick persons and only allows them to work again when no salmonellae can be detected in three stool samples (see below Salmonellosis hygiene regulations).

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