Typhoidal Salmonella

Robert Koch and Karl Joseph Eberth, 1880. salmonellae are named after the American bacteriologist Danile Salmon.

Typhoid salmonellae such as S.enterica Serovar Typhi, abbreviated S.Typhi and S.enterica Serovar Paratyphi A,B. or C , abbreviated S. Paratyphi A- C are gram-negative bacteria within the family Enterobacteriaceae. They are the cause of significant morbidity and mortality worldwide. The pathogens are usually petrich flagellated (i.e., distributed over the entire cell surface) and thus motile rod-shaped bacteria that are classified according to the White-Kauffmann-Le Minor scheme (also called the Kauffmann-White scheme) based on the structure of their surface (O) and flagellar (H) antigens and differentiated into serovars on the basis of an antigenic formula. As a rule, they cannot ferment lactose. Microscopically, they cannot be distinguished from other gram-negative rod bacteria. In contrast to the non-typhoidal (enteric) salmonellae, they cause systemic infections (anthropozoonosis) of varying severity, which may be life-threatening (typhoid/paratyphoid fever).

The typhoid salmonellae (typhoid and paratyphoid) include:

• Salmonella enterica Serovar Typhi (S.Typhi for short) Causes typhoid fever.
• Salmonella enterica Serovar Paratyphus A (short S.Paratyphi A)
• Salmonella enterica Serovar Paratyphus B (S.Paratyphi B for short)
• Salmonella enterica Serovar Paratyphus C (S.Paratyphi C for short)
• Several other Salmonella varieties (S.Enteritides, S.Typhimurium, S.Hadra), which occur mainly in immunologically impaired patients.

Basically, Salmonellae 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 antigen 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 antigens; 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.

S.Typhi and S.Paratyphi occur worldwide, S.Paratyphi A and C only in tropical and subtropical regions. Diseases occur as sporadic cases, clusters of cases e.g. in families or in larger outbreaks. An increase in individual cases in a particular region may indicate an as yet unrecognized group disease with a common source of infection.

In Germany, a total of 15,732 Salmonella cases were reported to the RKI in 2018 according to the IfSG. Typically, there is a peak of illness in late summer. The highest age-specific incidences occur in children under 10 years of age, with a maximum in young children. Deaths from salmonellosis are rare in Germany (Hof H et al.2019).

The pathogen is mainly transmitted from animals to humans(zooanthroponosis). Routes of transmission and entry: orally, mostly through consumption of animal foodstuffs containing salmonella (raw or insufficiently heated meat or meat products as well as raw eggs and food containing raw eggs), vegetables or lettuce contaminated by faecal manure; more rarely drinking or bathing water.

Pathogen reservoirs: The main reservoir of Salmonella is animals, although these rarely become clinically ill. Agricultural animals such as cattle, pigs and poultry and animal foods produced from them are therefore at the top of the list of possible causes of infection. Humans are secondary hosts (Bula-Rudas FJ et al. 2015).

Route of infection: Salmonellosis is a classical food-borne infection. The infection therefore occurs through oral ingestion of the pathogen. The infectious dose is small(100-1000 bacteria are sufficient to cause an infection). The pathogens penetrate the epithelium of the small intestine, reach the regional lymph nodes where they multiply and spread haematogenously. The dominant serovar in Germany, S. Enteritidis, is transmitted mainly via insufficiently heated eggs or food and preparations containing eggs, especially if these contain raw egg.

The serovar S. Typhimurium, which is also frequently found in Germany, is often transmitted through raw meat or meat products that have not been heated or have not been heated sufficiently (e.g. minced meat, raw sausages fresh mettwurst). Even foodstuffs that are not primarily contaminated with salmonella can pose a risk of infection through contact with infected people, contact with contaminated surfaces or contaminated other foodstuffs ("cross-contamination").

Incubation period: It is 6 - 72 hours, usually 12 - 36 hours and depends on the infectious dose and serovar.

After that, the disease begins with nonspecific flu-like prodromes. If untreated, typhoid and paratyphoid present as follows:

• 1st week of illness (stage incrementi) Gradual rise in body temperature to 39-41oC.Frequent angina and bronchitis. Formation of the typical roseolae due to infectious settlements in the skin. Leucopenia, eosinopenia, splenic swelling (organ infestation), constipation.
• 2nd and 3rd week of illness (stage acmes): fever continuum around 40oC. Headache, delirium, massive (pea-pulp-like) diarrhoea. AZ markedly reduced. Pneumonia, myocarditis and toxic circulatory collapse may cause death.
• Metastatic pathogen colonization occasionally forms the basis for osteomyelitis or spondylitis, which may take years to manifest clinically.
• 4th and 5th week (stage decrementi): AZ improves, fever minima fall, maxima remain high. Critical stage because of necrosis in the area of Peyer's plaques, massive intestinal bleeding and perforation peritonitis with exitus are threatening.
• Beyond the 6th week (relapses): Stabilisation of the AZ, body temperature normalises. Healing phase.

Disease sequelae: Excretion of typhoid salmonella takes on average one month in adults, 7 weeks or longer in children < 5 years. The bile ducts, especially the gallbladder, can harbour germs for a long time after recovery. These may be excreted in the stool for the rest of the patient's life. People who still harbor pathogens in their stool 10 weeks after healing are referred to as permanent excretors. This is the case in 2-5% of infected persons.

The pathogen is usually detected from stool, rectal swabs, vomit, but also from suspicious food. Blood cultures are indicated if systemic courses are suspected. Indications for microbiological stool diagnostics include prolonged diarrhea (> 3 days), visible blood in the stool or hospitalization. After cultural cultivation, biochemical and serological identification of the pathogen is carried out in the laboratory. The examination takes 2 - 3 days, but with the help of various rapid diagnostics a well-founded tentative diagnosis can be made within one day.

The antibodies formed can be detected serologically from about the end of the first week of illness using the Gruber-Widal reaction. High antibody titres (1:400-800) are not achieved until the third week of illness. If therapy with antibiotics is started early, this detection can remain negative.

Other bacterial (e.g. Shigella, Yersinia, Campylobacter, enterohaemorrhagic E. coli, Clostridium difficile), viral (e.g. noroviruses, adenoviruses, rotaviruses) and parasitic diarrhoeal pathogens (e.g. amoebae, lambliae) may be considered.

Non-infectious causes such as colon irritable.

In the case of gastroenteritis, antibiotic therapy is not given, as this can prolong bacterial excretion. Normally, only the loss of fluids and electrolytes must be compensated.

In severe cases of systemic inflammatory response syndrome (SIRS) or sepsis, antimicrobial therapy is indicated.

Patientsat risk: Because of possible complications that cannot be excluded, antimicrobial therapy should be considered in the case of gastroenteritic manifestations in patients in the 1st year of life, in the elderly, in persons with congenital or acquired immunodeficiencies and in patients with known abnormalities of heart valves or vessels.

Resistance development: Due to the increasing development of resistance in non-typhoidal Salmonella, resistance testing of the pathogen is then generally recommended. Depending on the results of the resistance test, 3rd generation cephalosporins, co-trimoxazole, ampicillin or (in adults) fluoroquinolones such as ciprofloxacin can be used. These are also suitable for the treatment of permanent excretions (duration of excretion longer than 1 year), which occur only very rarely in nontyphoid salmonelloses. In such cases, however, possible predisposing factors such as gallstones or kidney stones should first be clarified and, if necessary, specifically treated. Afterwards, the success of the therapy should be proven by appropriate diagnostics.

See also Salmonella, infection control and hygiene measures.

Fecal carriage of Salmonella is an important factor in the spread of the organism to healthy people. The most important measures to prevent the spread and outbreak of Salmonella infections and typhoid fever are appropriate hygiene protocols for food processing and handling and hand hygiene (see also Salmonella Infection Prevention and Hygiene Measures). In Europe and the United States, 2 vaccines against Salmonella Typhi are commercially available. WHO recommends the use of these vaccines in endemic areas (travel recommendation) and for outbreak control (Bula-Rudas FJ et al. 2015).

• The distinction between paratyphoid fever and typhoid abdominalis is not clinically possible; it is merely a question of pathogen detection.
• Current case figures on salmonellosis and other epidemiological parameters can be found in the current Infektionsepidemiologisches Jahrbuch of the Robert Koch Institute at www.rki.de/jahrbuch.

• For the detection of infection sources and tracing of infection routes and chains for epidemiologically important serovars, especially S. Paratyphi B, S. Enteritidis and S. Typhimurium, there is the possibility of further fine differentiation by lysotype, biochemical and genotypic methods (e.g. pulsed field gel electrophoresis - PFGE). These tests are performed at the National Reference Center for Salmonella and other enteritis pathogens.

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8. Robert Koch Institute: Infectious Disease Epidemiology Yearbook for 2019, Berlin, 2020.
9. World Health Organization/Food and Agriculture Organization (WHO/FAO): Safe preparation, storage and handling of powdered infant formula - Guidelines. 2006