Enteritis pathogens

Viruses were suspected of being the cause of gastroenteritis as early as the 1940s. However, the first virus was not detected until 1972, when Kapikian identified Norwalk viruses in an endemic case of diarrhea. A year later, Bishop et al. were able to detect rotaviruses by electron microscopy. Astroviruses and enteric adenoviruses were first detected in feces in 1975 (Günther 2003).

Salmonella enterica serovar Typhi was identified as the causative agent of abdominal typhoid fever by Karl Joseph Eberth and Robert Koch in 1880. Five years later, Theobald Smith and Daniel E. Salmon isolated S. enterica serovar Cholerasius. They were given the name "Salmonella" by the French bacteriologist Joseph L. M. Lignières in 1900 in honor of Daniel E. Salmon (Wagner 2011).

P. Ch. A. Louis succeeded in 1829 in the first description of the typhoid roseolae.

In 1940, after 20 years of work, Kauffman and White were able to serotype Salmonella using antigen classification. This accurate Salmonella typing scheme remains the gold standard to this day (Lang 200).

Celiac disease was first described by Samuel Gee in 1888 (Leiß 2017).

The first describer of Crohn's disease was Burrill B Crohn in 1932 in New York (Böhles 2020).

Furrer et al first described endovascular therapy for chronic mesenteric ischemia in 1980. Since then, this form of treatment has grown steadily and rapidly (Columbus 2020).

Enteritis is an inflammation of the ileum triggered by various causes, which can be acute or chronic.

Enteritis can result from:

• I. Infections with pathogens
• II. autoimmune enteritis
• III. radiation enteritis due to radiotherapy
• IV. Drug-induced enteritis
• V. Ischemic enteritis due to blockage of blood supply, also known as "mesenteric ischemia" (Lock 2021).

• I. Infectious enteritis caused by:
  • 1. bacteria and toxins such as:
    • 1.1. E. coli (e.g., in insufficiently cooked food such as ham- burger [Kasper 2015]). The 5 major pathovars of E. coli are:
      • EnteroToxin-forming EC (ETEC): These are found in approximately 25-35% of traveler's diarrhea cases (Herold 2022).
      • EnteroPathogenic EC (EPEC): They represent the typical pathogens of infant diarrhea (Herold 2022).
      • EnteroInvasive EC (EIEC): They are responsible for dysentery-like diarrhea with tenesmus and mushy or bloody stools (Herold 2022).
      • EnteroHemorrhagic EC (EHEC): These form so-called shigatoxins = STEC (Herold 2022) and are the most common causative agents of bloody diarrhea (Vogelmann 2011).
      • EnteroAggregative EC (EAEC): They can cause enteritis in infants and young children (Herold 2022).
  • 1. 2. Salmonella: They are found in 5-10% as causative agents of traveler's diarrhea (Herold 2022) and are found in chicken meat, mayonnaise, creams, eggs, seafood [Kasper 2015]).
  • 1.3. campylobacter jejuni: these are causative agents of traveler's diarrhea in 5-10% (Herold 2022) and are found, for example, in chicken meat [Kasper 2015]).
  • 1.4 Shigellae: These are also found in chicken meat (Kasper 2015). They represent between 5 - 10% the causative agents of traveler's diarrhea (Herold 2022). Shigella dysenteriae also forms so-called shigatoxins = STEC (Kettelhoit 2019).
  • 1.5 Yersinia enterocolitica (Herold 2022).
  • 1.6. Yersinia pseudotuberculosis (very rare [Herold 2022]).
  • 1.7. Clostridioides difficile: they are the causative agents of Clostridioides difficile-associated diarrhea (CDAD), the most common pathogens of nosocomial infections (Herold 2022) and occur, for example, after antibiotic administration, but person-to-person transmission is also possible (Kasper 2015)
  • 1.8 Vibrio cholerae (Herold 2022).
  • 1.9. bacillus cereus (e.g., in reheated food or rice)
  • 1.10. Listeria (e.g., in uncooked foods, soft cheeses [Kasper 2015]).

• 1. b.Toxin formers that cause food poisoning are:
  • Staphylococcus aureus: e.g. in mayonnaise, creams (Kasper 2015).
  • Bacillus cereus: e.g., in contaminated water or contaminated food (Schölmerich 2006).
  • Clostridioides perfringens: Found in contaminated food (Jung 2021).

(Herold 2022)

• 2. viruses such as:
  • 2.1 Rotaviruses: Rotaviruses cause more than 70% of infectious diarrhea in children (Herold 2022). They are transmitted, for example, fecal-orally from person to person or through food, drinking water, and also aerogenically (Suttrop 2004). Rotaviruses are considered the most serious infectious agent in children <5 years of age worldwide. They occur preferentially in the spring. The incubation period is 2-3 d (Posovszky 2019).
  • 2.2 Noroviruses: These were formerly also called "Norwalk- like- viruses". They are responsible for non-bacterial gastroenteritis in adults in up to 50% (Herold 2022). In children, they occur predominantly in winter. The incubation period is between 12 - 48 h (Posovszky 2019).
  • 2.3 Sapoviruses (former name "Sapporo-like viruses" [Günther 2003]).
  • 2.4. astroviruses (Herold 2022) with an incubation period of 4 - 5 d (Posovszky 2019).
  • 2.5. hepatitis A (e.g., in seafood [Kasper 2015])
  • 2.6. enteric adenoviruses with an incubation period of 3 - 10 d (Posovszky 2019)

• 3. protozoa such as:
  • 3.1. giardia lamblia These pathogens are often found in returnees from tropical or subtropical countries (Herold 2022). Transmission can be fecal-oral from person to person or through food or drinking water (Suttrop 2004).
  • 3.2 Entamoeba histolytica (so-called amoebic dysentery) These pathogens are also frequently found in returnees from tropical or subtropical countries (Herold 2022).
  • 3.3. cryptosporidia: they are frequently found in immunosuppressed individuals (Herold 2022) and are transmitted, for example, by food or drinking water (Suttrop 2004)
  • 3.5 Cyclospora cayetanensis (Kasper 2015).
  • 3.6 Isospora belli (Herold 2022).

First symptoms can sometimes appear weeks after infection in protozoa (Lübbert 2014).

• 4. fungi such as:
  • 4.1. candida
  • 4.2. aspergillus (Herold 2022)

Enteritis caused by fungi is practically absent in primary cases, but occurs exclusively in the context of immunosuppression (Braun 2018).

Transmission of the infectious pathogens occurs:

- fecal- oral

- by ingestion of contaminated food or water (most common route of transmission [Kasper 2015]).

Obligation to report:

According to § 6 of the Infection Protection Act (IfSG), there is a legal obligation for physicians to report suspected illness, illness, death in the case of the following pathogens
:- Botulism

- cholera

- paratyphoid fever

- typhus abdominalis

In case of illness and death in relation to the following diseases:

- Clostridioides- difficile- infection with clinically severe course. A clinically severe course exists when

- the patient is admitted to a medical facility for treatment of a community-acquired Clostridioides difficile infection,

- the patient is transferred to an intensive care unit for treatment of the Clostridioides difficile infection or its complications,

- surgical intervention, for example colectomy, is performed due to megacolon, perforation or refractory colitis, or

- the patient dies within 30 days of the diagnosis of Clostridioides difficile infection and the infection is considered a direct cause of death or a contributing cause of death (Federal Ministry of Justice).

There is an obligation to report by name in case of suspicion and illness of acute infectious gastroenteritis and microbacterial food poisoning for the following group of persons:

- if the person concerned works in the food industry

- if the illness occurs in two or more persons in whom an endemic connection is suspected or likely (Herold 2022).

A laboratory notification requirement according to § 7 of the Infection Protection Act (IfSG) additionally includes the viral pathogens of infectious diarrhea (see d.):

https://www.gesetze-im-internet.de/ifsg/__7.html

https://www.gesetze-im-internet.de/ifsg/__6.html

• II. autoimmune enteritis

This form of enteritis includes, for example, celiac disease, Crohn's disease, lupus enteritis.

Celiac disease represents a so-called chameleon of enterology. It is a lifelong chronic inflammation of the ileum (Zeitz 2021).

In Crohn's disease, as in ulcerative colitis, certain HLA alleles such as HLA- B 15, HLA- B 27, HLA- B 5 are frequently found (Adler 2013).

• III Radiation enteritis

The ileum is more sensitive to radiation than the colon. In the early stage, thickening of the mucosa, motility disorders, and possibly ulceration are found. In the late stage, stenoses, loop kinks, mucosal atrophies and (rarely) fistulas may develop after years (Bücheler 2006).

• IV. Drug-induced enteritis

Numerous drugs can trigger enteritis or enterocolitis such as NSAIDs, antibiotics, classical chemotherapeutic agents, EGF, VEGF / R and tyrosine kinase inhibitors, amphetamines, vasopressin, ergotamine, etc. (Stange 2016).

• V. Ischemic enteritis / mesenteric ischemia.

This is a life-threatening condition that leads to irreversible impaired blood flow to the intestine within a few hours. In ischemic enteritis, the stromal area of the superior mesenteric artery is affected. The lethality ranges from 50-80% (Siewert 2012).

• I. Infectious enteritis

The three most common pathogens of infectious enteritis in adults in Germany are:

- 1. noroviruses

- 2. campylobacter enteritis

- 3. rotaviruses (Herold 2022)

The most common viral enteritis pathogens in children are:

- Rotaviruses (40 %)

- Noroviruses (30 %)

The most common bacterial enteritis pathogens are Salmonella, followed by Campylobacter and Yersinia. The diseases occur preferentially in the summer months. The incidence in 2002 in Germany was on average 68 diseases / 100,000 inhabitants (Suttorp 2004).

In children, bacterial pathogens such as E. coli, Campylobacter, Salmonella, Shigella are found in about 20% as triggers of enteritis (Bald 2012).

In childhood, no pathogen can be detected in approximately 20% of patients (Bald 2012).

• II. autoimmune enteritis

- Celiac Disease:

The prevalence is between 0.4 - 0.9 % in Germany. Women are affected twice as often as men (Poralla 2022).

- M. Crohn's:

The incidence is about 2 - 8 diseases / 100,000 / year for Crohn's disease and is country-specific. For example, in Denmark it is 10 diseases / 100,000 population and in Spain 1 / 100,000.

- Ulcerative colitis:

Here the incidence ranges from 2 - 20 / 100,000 / year (Fried 2013).

• III Radiation enteritis

This occurs in up to 80% of abdomino- pelvic irradiated patients. Incidence and severity are dose-dependent (Sauerbruch 2021).

• IV. drug-induced enteritis.

Incidence varies and is drug dependent.

• V. Ischemic enteritis / mesenteric ischemia.

The acute form of progression occurs in 1% of an acute abdomen, and up to 10% in those >70 years of age (Klar 2012).

In the chronic form of progression, the incidence is estimated to be 2 - 4 patients / 100,000 population. Women are affected up to 4 times more frequently than men (Kopp 2010).

• I. Infections with pathogens

Acute inflammatory infection occurs when the ingested pathogen bypasses or overwhelms both immunologic and nonimmunologic defense mechanisms, such as gastric acid, digestive enzymes, peristalsis, mucus secretion, and suppressive resident flora (Kasper 2015).

The pathogens invade distal small intestinal segments as well as the colon, where they damage the intestinal epithelium. This triggers local inflammatory reactions and the pathogens can enter the bloodstream (Vogelmann 2011).

Changes in the intestinal flora due to antibiotics, for example, play a special role. In this case, the digestive function is restricted and / or excessive growth of pathogens such as Clostridioides difficile may occur (Kasper 2015).

Pathophysiologically, one differentiates between three forms of diarrhea:

- 1. exudative inflammatory diarrhea:

This form of diarrhea is also called inflammatory or invasive cytotoxic diarrhea. Invasion of the pathogens into the enterocytes with cell death results in an inflammatory change of the mucosa with destruction of the epithelium (Schoenenberger 2009), as is the case with Shigella. Another example is cytotoxin-induced necrosis of enterocytes, as is the case with C. difficile. Salmonellosis is also one of them (Herold 2022).

- 2. secretory diarrhea:

In this form, there is impaired intestinal ion transport due to, for example, activation of membrane-bound adenylyl cyclase by viruses or enterotoxins (such as Vibrio cholerae [Herold 2022]). The increase in enterotoxin-induced secretion of Cl- and HCO3- from the crypts and inhibition of sodium and water reabsorption at the tips of the villi result in electrolyte and fluid shifts into the intestinal lumen. The mucosa itself remains intact (Schoenenberger 2009).

- 3. neurotoxin-producing pathogens of diarrhea are:

- Staphylococcus aureus (forms enterotoxin B).

- Clostridium botulinum (forms toxins A - G [Neumeister 2009])

- Bacillus cereus (forms vomit toxin)

As a result of toxin formation, an emetic syndrome occurs (Schoenenberger 2009).

• II. autoimmune enteritis

In celiac disease, wheat gluten protein causes inflammatory remodeling of the mucosa with increased crypt depth and reduction of villi. Histologically, this causes the small intestinal mucosa to resemble the large intestinal mucosa and is referred to as "colonization" of the small intestinal mucosa (Braun 2018).

• III Radiation enteritis due to radiatio.

Radiatio initially causes edema, hyperemia, and inflammation of both the mucosa and submucosa. The damage to the mucosa may regress. In contrast, damage to the intestinal wall progresses and may cause obliterative endarteritis and fibrosis (Feuerbach 2007).

• IV. Drug-induced enteritis

NSAIDs inhibit protective prostaglandins in the intestine, leading to increased permeability and impaired blood flow to the intestine (Stange 2016).

Chemotherapeutic agents can cause toxic enteritis with damage to the small intestinal mucosa and resulting fluid loss (Stange 2016).

• V. Ischemic enteritis / mesenteric ischemia.

In this case, cardiac embolism or arterial emboli due to severe arteriosclerosis result in stenosis with lack of blood flow to the affected intestinal segment (Siewert 2012).

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