Diarrhoeal diseases, infectious A09.0

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 stool in 1975 (Günther 2003).

Stool transmission was already known in the Jin dynasty in the 4th century and was successfully used for diarrhea. The first description by Eisemann et al. dates from 1958, when stool transmission was used as a therapeutic measure for pseudomembranous colitis (Lübbert / Endres 2014).

Infectious diarrhea is understood as a form of diarrhea that is specifically and exclusively caused by infectious agents. There are 3 important indications that diarrhea is inflammatory: fever, tenesmus, bloody stool (Vogelmann 2011).

Infectious diarrheal diseases are divided into several forms:

- Acute form:

- ≥ 3 defecations / d

- Stool weight > 200 g / d with reduced consistency.

• Chronic form:
  • Diarrhea lasting longer than 10 - 20 days or longer than 4 weeks (the definition is not uniform [Herold 2022])
• Dysentery:
  • diarrhea associated with blood and / or mucus discharges
• Nosocomial form:
  • diarrhea occurring for the first time in the hospital (most common pathogens are Clostridioides difficile (formerly known as Clostridium difficile) and noroviruses

(Herold 2022)

Infectious diarrhea is one of the most common diseases worldwide. In developed countries, infectious diarrhea is predominantly caused by viruses (Vogelmann 2011).

Particularly frequently ill with it are:

- Infants and young children (Posovszky 2019).

- Adults with infant or child contact

- immunocompromised persons

- homosexual men

- international travelers

- People with unhygienic living conditions (Schöpfer 2007)

Acute diarrhea is caused by infectious pathogens in more than 90% (Kasper 2015). In Germany, for example, 351,506 cases of notifiable infectious diarrheal diseases were recorded in 2009, although the number of unreported cases is significantly higher (Vogelmann 2011).

The 3 most common pathogens in Germany are:

- 1. noroviruses

- 2. campylobacter enteritis

- 3. rotaviruses (Herold 2022)

The most common pathogens worldwide causing severe diarrhea in children are rotaviruses with 70% (Suttrop 2004).

The so-called "traveler's diarrhea" in tropical or subtropical countries affects between 30 - 50 % of travelers. In more than 30% of cases, however, the pathogen cannot be detected (Herold 2022).

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In the USA, a distinction is made between 5 high-risk groups:

1. travelers (affected in up to 40 %, so-called "traveler's diarrhea")

2. after consumption of certain foods such as banquets, picnics, restaurant meals

3. immunodeficient persons with primary immunodeficiency (e.g. IgA deficiency, hypergammaglobulinemia, chronic granulomatous disease), secondary immunodeficiency (e.g. AIDS, pharmacological suppression)

4. visitors of day care centers including family members

5. institutionalized persons in hospitals, nursing facilities, etc. (Kasper 2015)

Pathogens of infectious diarrheal diseases can be:

• 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-formingEC (ETEC): These are found in approximately 25 - 35% of traveler's diarrhea cases (Herold 2022).
    • EnteroPathogenicEC (EPEC): These represent the typical pathogens of infant diarrhea (Herold 2022).
    • EnteroInvasiveEC (EIEC): They are responsible for dysentery-like diarrhea with tenesmus and mushy or bloody stools (Herold 2022).
    • EnterohemorrhagicEC (EHEC): These form so-called shigatoxins = STEC (Herold 2022) and are the most common pathogens of bloody diarrhea (Vogelmann 2011).
    • EnteroAggregativeEC (EAEC): They can cause enteritis in infants and young children (Herold 2022).
  • 1. 2. Salmonella: They are found in 5 - 10% as the causative agent 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 human-to-human 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 immunocompromised 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).

Transmission of the infectious pathogens occurs:

- fecal- oral

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

Acute inflammatory infection occurs when the ingested pathogen bypasses or overwhelms both immunologic and non-immunologic 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 Clostridioidesdifficile 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 leads to 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 these (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-forming 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, emetic syndrome occurs (Schoenenberger 2009).

Infectious diarrheal disease may present with the following clinical symptoms:

• repeated passing of liquid or unformed stools both during the day and at night
• abdominal discomfort
• nausea
• vomiting
• fever (Kasper 2015)
• Systemic manifestation:
  • reactive arthritis (formerly known as Reiter's syndrome)
  • Arthritis
  • Conjunctivitis
  • urethritis (Kasper 2015)

Clinically, one differentiates between forms with different courses:

• 1. dysenteric diarrhea: In particular, colicky pain occurs. The stools may contain admixtures of mucus and / or blood. Depending on the time course, one differentiates between:
  • 1. a. Type "bacterial dysentery": This is caused by EHEC, EIEC and Shigella. The symptoms develop acutely or peracutely (Herold 2022).
  • 1. b.Type "amoebic dysentery": This is caused by Entamoeba histolytica and shows a slowly developing symptomatology with a colicky course characterized by intervals of less symptoms (Herold 2022).

• 2. non-dysenteric diarrhea: the symptoms are generally milder, with mucus and / or undigested food residues sometimes being evacuated. Here one differentiates between the following different types:
  • 2. a. Malabsorption type: In this type, voluminous, foamy feces are excreted with occasional admixtures of undigested food and fat. The typical causative agent is Gardia lamblia, the most common agent of chronic diarrhea (Herold 2022).
  • 2. b. Type enterotoxic form: Here, acute onset of symptoms is found, which may also be accompanied by vomiting. Pathogens are enteroviruses, pathogens of "food poisoning", ETEC, Salmonella, Vibrio cholerae (Herold 2022).

With toxin producers Staphylococcus aureus, Bacillus cereus, Clostridioides perfringens, diarrhea, vomiting, and dehydration typically occur after only a few hours (Herold 2022).

The diagnosis of infectious diarrhea is made clinically. Since this form of the disease is often self-limiting, the cause of the pathogen plays a subordinate role. More significant are the circulatory situation and volume status(Lübbert 2014).

The anamnestic information can thereby provide clues to the cause of diarrhea:

• Profuse, watery stools occur with:
  • enteroadherent pathogens
  • preformed bacterial toxins
  • enterotoxin-producing bacteria
• additional severe vomiting and minimal or no fever at:
  • preformed bacterial toxins
  • enterotoxigenic bacteria
• mild vomiting, severe abdominal cramps and fever at:
  • enterotoxigenic bacteria
  • enteroadherent pathogens
• high fever, abdominal cramps in:
  • cytotoxin-forming microorganisms
  • invasive microorganisms
• bloody diarrhea (dysentery) in:
  • Entamoeba histolytica (Kasper 2015).
  • Amoebae, shigellae (together with fever [Herold 2022]).
• severe abdominal pain in
  • Yersinia (Kasper 2015)
• "rice water" diarrhea with
  • Vibrio cholerae (Herold 2022).

In the case of a tropical history, additional testing for amoebae and giardia (lamblia) should always be performed. In AIDS patients, the spectrum includes many pathogens and not infrequently multiple pathogens. The most common are cryptosporidia, microsporidia, CMV, mycobacteria (Herold 2022).

Only in the case of prolonged episodes of infectious diarrhea or certain pre-existing conditions such as renal insufficiency, cardiac insufficiency , etc. are blood tests necessary. In addition to the usual laboratory parameters, serum electrolytes and retention parameters in particular should be determined (Lübbert 2014).

Pathogen diagnostics are:

- NOT required in cases of mild diarrhea, absence of fever, immunocompetent patients without any concomitant diseases.

- absolutely necessary in comorbidities, immunocompromised patients, fever, bloody diarrhea, before antibiotic therapy, during hospitalization (Herold 2022).

A stool examination for leukocytes or the inflammation markers calprotectin or lactoferrin can provide indications of whether this is a pathogen-related, invasive inflammatory bowel disease if the clinical symptoms are unclear (Vogelmann 2011).

In stool cultures, a pathogen can usually only be detected in 1.5 - 5.6 % of cases. Since > 50 % of diarrhea is self-limited within 24 h, stool cultures should only be performed > 24 h after the onset of symptoms (Vogelmann 2011).

Diagnostics usually include the following pathogens:

- Campylobacter

- noroviruses

- Salmonella

- Shigella (Herold 2022)

- EHEC / STEC and C. difficile: in the case of bloody diarrhea, in addition to the standard culture (Vogelmann 2011).

- After a stay abroad: additionally examine for amoebae, giardia, etc. (Herold 2022).

- Clostridioides difficile: examine only in the presence of risk factors such as hospitalization, antibiotic therapy, anamnestically known infection with Clostridioides difficile, existing comorbidities (Herold 2022). In addition to the detection of C. difficile, the C. difficile toxin should also always be determined (Vogelmann 2011).

- Non-infectious diarrhea(see d.)

- chronic inflammatory bowel disease (IBD) such as ulcerative colitis, Crohn's disease

- acute cholecystitis

- angina abdominalis

- mesenteric infarction (Lübbert 2014).

In case of tropical history and fever:

- Malaria (Herold 2022)

For Yersinia enterocolitica:

- acute appendicitis (Herold 2022)

In AIDS patients:

- side effects of medication

- idiopathic diarrhea (Herold 2022)

• Infectious diarrhea can lead to:
  • Electrolyte loss
  • orthostatic circulatory disturbance up to collapse
  • dehydration
  • thromboembolism
  • acute renal failure
  • reactive arthritis
  • septic complications (Herold 2022)
  • postinfectious irritable bowel syndrome (Kasper 2015)
  • in children, (fever-associated) seizures or encephalopathy are possible (Posovszky 2019).
• Yersinia enterocolitica to:
  • Pericarditis
  • autoimmune thyroiditis
  • glomerulonephritis (Kasper 2015)
  • Arthralgias
  • erythema nodosum (Herold 2022)
  • neurological sequelae such as Guillain-Barre syndrome
  • microangiopathic complications such as HUS = hemolytic-uremic syndrome, TTP = thrombotic thrombocytopenic purpura (Posovszky 2019)
• Clostridium difficile to:
  • pseudomembranous colitis in up to 20 % (Herold 2022)
• enterohemorrhagic E. coli and shigella to:
  • Hemolytic-uremic syndrome (high mortality rate) (Kasper 2015).
• EHEC:
  • Triad with thrombocytopenia, microangiopathic hemolytic anemia, and acute renal dysfunction (Posovszky 2019).

Infectious diarrhea is largely self-limiting and heals spontaneously within a few days without any therapy (Lübbert 2014).

However, infants and young children are particularly at risk from dehydration. This can be determined for children between 0 - 8 years using the clinical dehydration score (CDS):

• 0 points:
  • normal appearance
  • Eyes normal
  • Mucous membranes and tongue moist
  • tears present
• 1 point:
  • lethargic or restless, but irritable to touch
  • thirsty
  • eyes slightly sunken
  • mucous membranes and tongue sticky
  • only a few tears present
• 2 points:
  • cold sweaty, groggy, comatose
  • eyes extremely sunken
  • mucous membranes and tongue dry
  • no more tears present

Score:

No dehydration: 0 points

Mild to mild dehydration: 1 - 4 points

Moderate to severe dehydration: 5 - 8 points (Posovszky 2019)

• Rehydration:

The first measure should be rehydration with fluids and electrolytes (Herold 2022). For this purpose, sugary and salty liquids / foods such as sweetened tea, salty cookies, rice gruel soup, etc. are suitable (Lübbert / Grimm 2014).

In a milder course, rehydration can be done orally e.g. with ORL = oral rehydration solutions, if necessary also by nasogastric tube (Posovszky 2019).

ORL is available as a ready-to-use preparation Elotrans powder or oral pedon or can be prepared as follows according to WHO recommendation:

- NaCl 2.6 g

- Na- citrate 2,9 g

- KCL 1,5 g

- Glucose 13,5 g

- Aqua ad 1.000 ml (Herold 2022)

Pure electrolyte solutions are less suitable for rehydration because salt and glucose are absorbed in the intestinal epithelium via the enterocytes together with a common transporter, but the water can only be absorbed passively (Lübbert 2014).

In adults, rehydration can be oral or i. v. depending on the initial situation (Herold 2022).

In children, 5 ml of ORL should be given orally every 1 - 2 minutes, even if additional vomiting is present.

i. v. rehydration is required in the event of:

- Failure of oral or nasogastric rehydration.

- state of shock

- severe rehydration with

- loss of > 9 % of the bw

- severe acidosis with a pH < 7 and a BE < - 15ml / l

- neurological symptoms such as lethargy or coma

- hyponatremia (Na + < 130 mmol / l)

- hypernatremia (Na + > 150 mmol / l)

- bilious vomiting

- in case of symptoms of ileus, immediate i. v. rehydration is always indicated in children (Posovszky 2019)

Inpatient treatment should also be given in cases of:

- severe underlying chronic disease such as immunodeficiency, diabetes mellitus, oncologic disease, etc.

- Infants < 3,500 g

- Infants younger than 2 months

- malnutrition and / or failure to thrive

- intestinal transport disorder such as intussusception

- persistent bloody diarrhea (Posovszky 2019).

• Isolation:

If the V. a. an infectious diarrhea exists, the patient must be isolated immediately. If the suspicion is confirmed, isolation is to be continued for up to 48 h after the patient is symptom-free. Notification to the public health department is required according to §§ 6, 7 of the Infection Protection Act for certain diseases (see "Notes") (Herold 2022).

• Microbiome transfer:

In the case of infection with Clostridioides difficile, stool transplantation in the form of endoscopic microbiome transfer can be used in pilot studies for severe, therapy-resistant courses (Lübbert / Grimm 2014).

• Nutritional buildup:

After dehydration is eliminated, food buildup should include grains and starchy foods such as rice, wheat, potatoes, pasta, etc.... Coffee, highly spiced or roasted products should be avoided for the first 2 - 3 days as well as milk and dairy products (Schöpfer 2007).

• Motility inhibitors:

Motility inhibitors such as loperamide prevent or delay excretion of pathogens and should therefore be used only for short periods, e.g., during travel (Herold 2022).

• Spasmolytics:

Spasmolytics such as N- butylscopolamine can be used for cramping abdominal pain(Herold 2022).

• Antibiotics:

Since the majority of infectious diarrhea is caused by viruses, empiric antibiotic administration must be carefully considered (Lübbert 2014).

An indication for antibiotics is given in:

- highly acute course

- fever

- severe course of the disease

- bloody diarrhea

- in infants and the elderly (Herold 2022).

Travelers' diarrhea with a mild course should not be treated with antibiotics.

In patients with comorbidities and immunosuppressed individuals, stool diagnostics should be performed beforehand if possible.

The following antibiotics have been shown to be effective:

- Ciprofloxacin:

Effective against shigella, E. coli, salmonella.

Dosage recommendation: 2 x 500 mg / d, duration of therapy: 1 - 3 or 5 days (Herold 2022).

Alternatives are: azithromycin (dosage recommendation: 500 mg / d [Suttrop 2004]), ceftriaxone (dosage recommendation: 50 - 100 mg / kg bw / d [Papan 2015])

(Herold 2022)

- Metronidazole:

Metronidazole should be used in V. a. an antibiotic-induced CDAD or PMC. Previous antibiotics that are causative of Clostridioides difficile infection should be discontinued immediately (Herold 2022).

Dosage recommendation: 3 x 500 mg p. o. for 10 days (Lübbert / Endres 2014).

An alternative is vancomycin orally. Dosage recommendation: 4 x 125 mg / d (the dose effect is equivalent to a dose of 4 x 500 mg / d [Lübbert 2014]).

Metronidazole can also be used for giardiasis and amebiasis (Herold 2022).

Depending on the clinical picture and the pathogen, surgical measures may be necessary, e.g. in the case of complications of a Clostridioides infection in intestinal perforation, toxic megacolon, peritonitis (Schneider 2007).

According to the WHO, infectious diarrhea is one of the five leading causes of death, with 5-10 million deaths worldwide, especially in developing countries. (Lübbert 2014).

Morbidity and also mortality of infectious intestinal diseases are most frequently found in children and the elderly (Vogelmann 2011). Rotavirus, for example, causes 29% of all deaths from diarrheal disease in children <5 years of age (Ploier 2013).

The highest mortality of inpatients with gastrointestinal infectious diseases is found in ICD- 10 coding code A 04, which includes C. difficile infection (Jansen 2014).

• Acute infectious diarrhea:

This usually resolves after 2 - 10 days (Herold 2022).

• Chronic diarrhea:

Chronic diarrhea is rarely bacterial in origin (Schöpfer 2007).

To avoid traveler's diarrhea, one should:

- Always boil water (also for brushing teeth)

- Drink only from original sealed containers.

Should be avoided:

- ice cubes

- ice cream

- raw or undercooked food, e.g. fish, meat, seafood

- unboiled water

- cold buffet

- sauces

- fruits not peeled by yourself

- salads

- Melons (can be splashed with water)

- Mayonnaise (Herold 2022)

Hygiene measures such as washing hands after going to the toilet and before preparing food are obligatory (Friese 2013).

Active immunizations are possible against:

- Typhoid (as live oral vaccine or parenteral death vaccine).

- Cholera (as oral live or dead vaccine for travel to endemic areas, otherwise not recommended).

- Rotavirus (by live oral vaccine especially for infants).

(Herold 2022)

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 obligation 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

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