Table of Contents
Diarrhea is defined as a stool frequency of more than three stools per day that have a high water content (over 75%) and increased stool weight (about 250 g). Acute diarrhea usually lasts 2–3 days; the cause may be infection or intoxication. Prolonged diarrhea is chronic and can be caused by food intolerance, inflammatory bowel disease, or tumors.
Classification according to the emergence of diarrhea
|Diarrhea form||Pathomechanism||Possible causes|
|Secretory diarrhea||The mucosa of the intestine actively releases water or electrolytes from where water follows osmotically.||Chronic inflammatory bowel disease, food poisoning, or intake of laxatives|
|Osmotic diarrhea||Unabsorbed, osmotically active molecules, such as food ingredients or medicines, pull water into the intestinal lumen.||Lactose intolerance, celiac disease, laxative use, or sorbitol ingestion|
|Exudative diarrhea||Inflammation of the intestinal mucosa leads to the accumulation of stool with mucus and blood.||Chronic inflammatory bowel diseases or bacterial/parasitic infections|
|Hypermotile diarrhea||Increased intestinal motility leads to a reduced transit time for the stool; this reduced time leads to not enough water being withdrawn.||Irritable bowel syndrome, hyperthyroidism, or diabetic polyneuropathy|
|Steatorrhea||A decrease in the level of enzymes and bile acid leads to insufficient digestion and absorption of fats.||Exocrine pancreatic insufficiency or condition after cholecystectomy|
Food poisoning as a cause of diarrhea
Food can have a toxic effect on the human body for various reasons. The most common triggers of food poisoning are caused by toxins produced by bacteria, but even heavy metals such as lead or toxic chemicals can be present in food and may cause poisoning, with symptoms such as diarrhea.
Food poisoning with bacterial toxins
Food poisoning can be caused by the intake of bacterial toxins; the multiplication of bacteria itself is no trigger. In most cases, there is a contamination of food with Staphylococcus aureus. This contamination can occur because of a lack of hand hygiene in the preparation of food. The bacteria themselves are indeed killed by cooking, but not the enterotoxins they release. Very rapid onset of symptoms, about 30 minutes to 2 hours after eating, and an equally short duration of diarrhea symptoms are typical. Classically, several people are affected at the same time. Even Bacillus and Clostridium species can form enterotoxins and cause similar symptoms.
Other food poisonings
Other triggers of food intoxication include toxic metals such as arsenic, lead, zinc, and antimony. Even fungal toxins such as fly agaric (Amanita phalloides) and amatoxin (Amanita phalloides) lead to diarrhea, among other symptoms. Saxitoxin, which can accumulate in steamed mussels and oysters, leads to a disease pattern called paralytic shellfish poisoning, which results in nausea with vomiting and diarrhea and abdominal cramps.
In the United States
- 179 million cases per year
- 17 million foodborne
- Approximately 2 million hospitalizations
- ~ 3,000 deaths, 83% of them in the elderly population
- $6 billion in medical care and lost productivity
United States: rate per 100,000 people
- Salmonella, 13.6
- Campylobacter, 13
- Shiga toxin–producing Escherichia coli, 0.04–0.41
- Vibrio, 0.45
- Yersinia, 0.29
In foodborne infections, pathogenic germs are absorbed by the food and the microorganisms multiply in the intestine. Even pathogenic germs often produce toxins, which is why there can be no clear separation of the types of food poisoning along these lines.
Etiology of salmonellosis
Salmonella enteritis is caused by the consumption of contaminated drinking water or infected food; these situations are often the result of insufficient hygiene. The pathogen is Salmonella enteritidis; however, out of the more than 2,600 known salmonella serotypes, another 30 pathogens are gastroenteritis pathogens. In 2004, a new subspecies—Salmonella choleraesuis—was discovered. This subspecies is very resistant to antibiotics and more frequently results in death than other Salmonella species.
Various animals, including poultry, swine, and reptiles, can be carriers of the Salmonella pathogen; therefore, many foods, such as eggs, meat, milk, and mussels, can be contaminated with Salmonella. Even when adequate hygiene is observed by slaughterhouse staff, who are the chronic carriers of Salmonella, S. enteritidis can be transferred to the meat. In countries with inadequate treatment of water, the feces of infected animals can contaminate drinking water and thus serve as a source of infection.
Symptoms of S. enteritis
In most cases, infection occurs during the warm season, especially among children and elderly people, in the form of invasive gastroenteritis. Typical symptoms of S. enteritis are vomiting and diarrhea after an incubation period of a few hours up to 7 days. Patients also develop spasmodic abdominal pain. The duration of the disease is generally only a few days.
Diagnosis of salmonellosis
Stool and vomit samples are used to detect salmonellosis. Onoz agar and xylose lysine desoxycholate (XLD) agar in the culture serve as differentiation media. The classification in subtypes is based on the O antigens and is useful for epidemiologic investigations.
Salmonellosis is a notifiable infection under the Infection Protection Act.
Treatment and prophylaxis of salmonellosis
Salmonellosis should not be treated with antibiotics because this would lead to an extension of the time to bacterial elimination. In about 5% of patients, systemic infection with fever and massive fluid loss develop, making hospitalization necessary. Ciprofloxacin and ampicillin are suitable treatments for children.
A small percentage of patients who are infection with Salmonella do not eliminate it. This results in these people becoming asymptomatic chronic carriers for a long time. Asymptomatic carriers should be prohibited from being involved in activities involving food handling.
Prophylactic measures include properly cooking poultry, meat, and eggs, as well as the strict separation of cutlery and cutting boards that are used before and after cooking in order to avoid cross-contamination.
Etiology of typhoid
Salmonella typhi usually spreads by unsanitary conditions during the preparation of food and beverages. It has often led to infections among Europeans, especially during long-distance travel to Africa, Southeast Asia, and Latin America.
Disease pattern of the typhoid fever
The course of the disease can be divided into three stages. The incubation period varies, with 10 days being the average.
- Stadium incrementi occurs during the first week after infection. It results in nonspecific general symptoms such as headache, fatigue, constipation, and a stepwise increase in fever.
- Stadium fastigii occurs the second to third week of infection. After approximately 8 days, a very high fever (up to 41°C) is reached, and this persists. Relative bradycardia, leukopenia, and splenomegaly may also be seen. A reddish, spotty rash, so-called roseola, is typically prominent on the upper body and abdomen, as are disturbances of consciousness, which give the disease its name. Typhoid tongue is often seen; this is characterized by a white-gray coating in the middle of the tongue and reddish tip and edges.
Typhoid fever destroys the Peyer’s patches of the small intestine. This leads to pea soup diarrhea from the fourteenth day of infection onward. Other possible symptoms include meningitis, osteomyelitis, and bowel perforation.
- Stadium decrementi is the stage of stepwise decreasing fever.
Diagnosis of typhoid fever
The detection of Salmonella infection is dependent on the week during which the disease is investigated. One week after infection, it can be detected in blood cultures. In the second week, antibody screening of blood serum is possible. From the third week on, the organism can be cultured from stool samples.
Also, typical leukopenia is found in the blood, often along with a lack of eosinophilic granulocytes.
Treatment of typhoid fever
Treatment is carried out with ciprofloxacin or ceftriaxone of the third generation such as cephalosporins.
As is the case with salmonellosis, some affected people remain chronic carriers for up to a year, especially if they have not received antibiotics. Salmonella survives in the gallbladder and the bile ducts and may lead to gallstones.
Prophylaxis of typhoid disease
Proper hygiene is the best protection against infection, particularly in tropical locations. Therefore, people who travel to these areas should avoid consuming insufficiently cooked foods and should avoid drinking tap water. Vaccination against typhoid can be done with a dead or nonpathogenic live vaccine, but this leads to adequate protection in only about 60% of those who receive the vaccine.
Yersiniosis is an infectious disease caused by the bacterium Yersinia enterocolitica or Yersinia pseudotuberculosis. The pathogen is spread worldwide, and animals such as pigs or cattle serve as a reservoir. Therefore, the infection can spread through the contamination of meat and dairy products, as well as drinking water.
Symptoms of yersiniosis
Depending on the age at onset, other symptoms occur after infection with Yersinia.
- Yersinia gastroenteritis Occurs mainly in infants. It results in self-limiting bloody diarrhea with exsiccosis.
Pseudoappendicitis (lymphadenitis of the intestines) or Morbus Masshoff: In older children and adolescents, this results in inflammation of the intestines, with concomitant swelling of the mesenteric lymph nodes. It typically results in a lymph node conglomerate around the vermiform appendix, such that it may be misdiagnosed as appendicitis; it is often detected with fever and abdominal pain and by visualization of a mass around the appendix on a sonogram.
- Enterocolitis: The enterocolitis caused by Yersinia is invasive gastroenteritis. The bacterial cells migrate through the mucosa of the intestine and result in inflammation in the Peyer’s patches. The resulting diarrhea continues for 10–14 days and is accompanied by colicky abdominal pain.
For weeks to months following an enteral infection with Yersinia, inflammatory late-onset diseases such as reactive arthritis, pyomyositis, and persistent ileitis (pseudo-Crohn’s) are commonly noted. These late effects are very frequently associated with the human leukocyte antigen (HLA) type B27.
Diagnosis of Yersinia infection
The aim should be the direct detection of Yersinia from a culture of blood culture, stool, or infected lymph nodes. The so-called CIN (cefsulodin, irgasan, novobiocin agar) breeding ground serves as the selective agar on which porthole-shaped red colonies grow after 1–2 days.
Acute infection with Yersinia must be reported to health authorities.
Treatment of yersiniosis
Usually, only symptomatic treatment for rehydration is performed. Severe gastroenteritis and systemic infections are treated with a combination of ciprofloxacin and ceftriaxone.
Shigellosis, or bacterial dysentery, is transmitted through the fecal–oral route and mainly affects the colon.
Etiology of bacterial dysentery
Several Shigella species come into question as pathogens. They are divided into groups from A to D.
|A||S. dysenteriae||Tropics||Serious disease patterns occur because of the formation of endotoxins and exotoxins; the lethality rate is 60%.|
|B||S. flexneri||Worldwide||Mild progressive form because no exotoxin is observed|
|C||S. boydii||Middle East, North Africa||Mild course|
|D||S. sonnei||Central Europe||Summer diarrhea in children; no exotoxin; approximately 80% of cases of shigellosis|
The only reservoir for the Shigella pathogens is the human body; this means that fecal–oral transmission occurs via contaminated food and drinking water.
Symptoms of Shigella dysentery
Diarrhea occurs after an incubation period of 2–10 days. In the mild progressive form, this is referred to as white dysentery; in the severe, bloody progressive form it is known as red dysentery. Characteristically, the diarrhea is accompanied by abdominal pain and tenesmus with defecation. Loss of appetite, fever, and consequences of electrolyte loss are common. Complications of gastrointestinal bleeding and intestinal perforation may occur.
Diagnostics of shigellosis
At the beginning of the disease, catarrhal dysentery, an inflamed, swollen intestinal mucosa, is observed histologically. In severe cases, the image changes into pseudomembranous necrotizing dysentery. The histologic image then resembles chronic inflammatory bowel disease.
The diagnosis is made on the basis of clinical symptoms and a rectal smear because Shigella dies in the stool sample after a short time.
Treatment of Shigella dysentery
Treatment should be symptomatic, which means balancing the water and electrolyte losses. Also, calculated antibiotic treatment can be started with a quinolone. However, many Shigella species are affected by an R-plasmid resistant to numerous antibiotics such that a change of antibiotic treatment after an antibiogram is meaningful.
The treatment of choice for Shigella dysentery is ciprofloxacin or azithromycin.
Infection with Escherichia coli
Escherichia coli (E. coli) is the most well-known bacterium in the world, It is responsible for about 160 million diarrheal diseases and 1 million deaths per year.
Infections with enteropathogenic E. coli
Enteropathogenic E. coli (EPEC) strains are common diarrheal pathogens found in infants and young children in developing countries. Through the EPEC adhesion factor (EAF), the bacteria bind to the epithelial cells of the small intestine and inject toxins in the enterocytes using a type 3 secretion system.
Infections with enterotoxigenic E. coli
The transmission of EPEC occurs in tropical countries through contaminated food and drinking water. These strains have specific fimbriae, called colonization factors, that attach to the mucosa of the intestine. The pathogenic effect is caused by one of the cholera toxins similar to the heat-labile enterotoxin and two heat-stable (up to 100°C) toxins. Guanylate cyclase is stimulated through the toxins, among other things, whereby sodium absorption is inhibited and more water is extracted from the intestine. This often results in massive watery diarrhea, which is self-limiting; it is commonly seen as traveler’s diarrhea. In children, the dehydration can be life threatening.
Infections with enteroinvasive E. coli (EIEC)
Infection with EIEC resembles a Shigella infection. The bacteria penetrate the epithelial cells of the colon and lead to a granulocytic inflammation with the discharge of blood and mucus. Even EIEC strains have toxins, which cause additional water and electrolyte loss.
The treatment of choice for E. coli (non-Shiga toxin–producing) infections is ciprofloxacin, trimethoprim/sulfamethoxazole, or azithromycin.
Infections with enterohemorrhagic E. coli
Enterohemorrhagic E. coli (EHEC), are Shiga toxin–producing E. coli with additional pathogenicity. Even 10—100 bacteria are enough to cause food poisoning with EHEC. The infection occurs mainly via milk and raw meat, but it can also occur person to person during close contact.
The Vera toxin present in the EHEC bacteria is phage-encoded, and like the Shiga toxin, it is neurotoxic and causes necrosis. Also, EHEC has a plasmid-encoded hemolysin that triggers the hemolytic–uremic syndrome (HUS), which is also called the Gasser syndrome. This microangiopathic hemolytic anemia with thrombocytopenia and acute renal failure is caused by bacterial toxins. If only two of these symptoms are present, one indicates incomplete enteropathic HUS. With diarrhea, it is the typical HUS and is common in children. The atypical HUS, without diarrhea, occurs more commonly in adults.
The detection of EHEC is achieved through the use of the polymerase chain reaction (PCR) assay. The treatment should be symptomatic, with the administration of electrolytes and infusions and plasmapheresis. Loperamide and antibiotics are contraindicated, because they do not act against the toxins and there are indications that HUS symptoms occur more frequently when antibiotics are used. Since 2009, there has been a monoclonal antibody called eculizumab that inhibits the complement system and reduces the mortality with atypical HUS.
The suspicion or evidence of an EHEC infection is a notifiable condition under the law if HUS is present, two or more people are sick, or the sick person works in the food industry. The suspicion, the illness, and death by a bacterial HUS are also notifiable under the law.
Infections with enteroaggregative E. coli (EAEC)
The attachment to the intestinal epithelium by fimbriae results in secretory-type diarrhea caused by enterotoxins. Increased mucus production is typical, and this delays the elimination of the pathogen—the disease can drag on for weeks. In the case of immunosuppressed patients, such as patients infected with the human immunodeficiency virus (HIV), EAEC is the most frequent cause of bacterial enteritis.
Clostridium botulinum produces the most potent toxin in the world. Under anaerobic conditions, such as in animal carcasses or insufficiently heated canned food, this bacterium can multiply and produce botulinum toxin. Infants can become infected even by eating contaminated honey, because their intestinal flora has not yet fully developed.
After the intake of this poison, there is an inhibition of acetylcholine secretion at the neuromuscular junction. The eye muscles are paralyzed first, followed by other facial and pharyngeal muscles. Even vomiting and diarrhea are typical before death from suffocation or cardiac arrest. The treatment is an antiserum, which reduces mortality from about 90% to 10%.
Clostridium difficile (C. difficile) infections
C. difficile is an obligate anaerobic spore-former that occurs ubiquitously. Approximately 80% of infants and < 5% of adults are infected. The infection usually occurs nosocomially (48 hours after hospital admission until 4 weeks after dismissal) through the fecal–oral route. The diarrhea is highly contagious, and can be spread even indirectly via surfaces.
Risk factors for C. difficile infection
- Previous antibiotic therapy (in particular, clindamycin, ampicillin, and cephalosporins)
- Old age
- Therapy with proton pump inhibitor (PPI) and/or nonsteroidal antiinflammatory drugs (NSAIDs)
- Underlying gastrointestinal (GI) disease
Clinical symptoms are watery, greenish diarrhea with a foul odor, lower abdominal pain, fever, leukocytosis, and hypoalbuminemia.
To diagnose C. difficile infection, one or more of the following must be present
- Diarrhea/toxic megacolon with detection of C. difficile enterotoxin A and/or cytotoxin B or cultural evidence of toxin-producing C. difficile in the stool
- Pseudomembranous colitis found on endoscopy
- Histopathologic evidence of a C. difficile infection (CDI) found on endoscopy, colectomy, or autopsy
Detection of the toxin is the gold standard for the diagnosis, but it is seldom applied. As a routine, enzyme immunoassay (EIA) is mostly used.
The treatment of C. difficile–associated enterocolitis consists of the completion of the previous antibiotic therapy (if acceptable from a clinical perspective) and an additional antibiotic therapy in cases of persistent/severe symptoms and in old/critically ill patients or if the current antibiotic therapy needs to be continued. Suitable treatments in order to avoid the selection of vancomycin-resistant enterococci are metronidazole in uncomplicated courses and vancomycin in severe courses, during pregnancy, or in children under 10 years of age. Surgical treatment may be necessary if intestinal perforation or toxic megacolon is present.
In the case of VA (ventilator-associated) CDI, prophylaxis should be strictly observed by isolating the patient in a single room for up to 48 hours after the cessation of symptoms.
In severe cases (e.g., those requiring a stay in an intensive care unit (ICU) or surgery or in cases of recurrent infection or death from CDI < 30 days after diagnosis), local health authorities must be notified.
Cholera, or bile diarrhea and vomiting, is caused by infection with Vibrio cholerae. Transmission usually occurs through contaminated water in poorer countries that do not have adequate supplies of clean drinking water. Approximately 85% of cholera infections proceed without detection; the other 15% are associated with typical symptoms.
After an incubation period of 2–3 days, the infection results in diarrhea and vomiting; the diarrhea is interspersed with flakes of mucus and is therefore called rice-water stool. Because of massive exsiccosis, it then results in a subnormal body temperature and a typical facial expression with a pointed nose, sunken cheeks, and standing skin folds.
This is subsequently followed by general bodily reactions such as dizziness and coma. The diagnosis can be made quickly through microscopy and stool culture. The definitive diagnosis is done with the help of an antiserum. For rehydration, the World Health Organization (WHO) oral solution, consisting of glucose, sodium chloride, sodium citrate, and potassium chloride, is recommended. Also, there are several oral cholera vaccines, and these are administered in different endemic areas.
Lambliasis, or giardiasis, is an infection of the intestinal tract caused by the protozoan Giardia intestinalis. Typical symptoms of lamblia dysentery are diarrhea, flatulence, and malnutrition in cases of prolonged illness. The detection of trophozoites or cysts is done using microscopy of stool or from a biopsy sample from the intestinal tract. Even antigen detection using enzyme-linked immunosorbent assay (ELISA) or PCR is possible. It is presumed that a resolved infection can cause lactose intolerance or other food intolerances with persistent GI symptoms.
The treatment of choice is metronidazole.
Infection with Giardia is notifiable under the law.
Entamoeba histolytica passes as a cyst in the small intestine and as a four-core stage thereafter in the colon. In the colon, amoebas live in the form of trophozoites. They form cysts, which are excreted in the stool (up to 50 million per day). The minuta form of E. histolytica causes self-limited diarrhea. The magna form, on the other hand, penetrates the colonic mucosa and passes from there into the bloodstream. It then settles in the form of abscesses in many organs, including the intestines. Amebic dysentery, therefore, results in raspberry jelly–like diarrhea with abdominal pain and exsiccosis. Even peritonitis and abscess rupture in the liver is common.
The treatment of choice is metronidazole plus paromomycin.
Important Clues to the Differential Diagnosis of Diarrhea
The clinical causes of foodborne illness can vary; however, some important clues in the clinical history can make the treating doctor suspect an infectious etiology behind the patient’s diarrhea. They are summarized in the following points:
- Acute abdominal pain that is associated with fever and vomiting is often an indicator of an infectious etiology of diarrhea.
- A recent change in diet, the ingestion of new foods, or eating undercooked foods are important clues for foodborne illness.
- Patients with a long duration of symptoms are more likely to be dehydrated. Moreover, chronic diarrhea is unlikely to be infectious in etiology.
- A history of working in a child care facility puts the individual at an increased risk of viral diarrhea.
- A recent history of hospitalization in a patient who presents with diarrhea raises the suspicion of C. difficile infection.
- Patients with immunosuppression due to disease or medication who present with diarrhea are more likely to have an atypical infectious cause.
- A recent history of antibiotic use raises the suspicion of C. difficile infection.
- A recent history of travel history puts the individual at an increased risk of acquiring traveler’s diarrhea, which is infectious in etiology.
Key Recommendations for the Management of Foodborne Illness per the American Family Physician Guidelines
The American Family Physician guidelines for the management of foodborne illness, formulated in 2015, can be summarized in four main points:
- Stool cultures are the diagnostic standard for bacterial foodborne illness. They must be performed in any patient suspected to have a bacterial etiology behind their diarrhea. They are positive in up to 40% of the cases.
- A single dose of ondansetron is recommended in children with significant gastroenteritis-related vomiting.
- Patients with a foodborne illness who have diarrhea that is associated with fever and signs of invasive disease such as leukocytosis should receive empiric antibiotic therapy if their symptoms persist for more than 1 week or if hospitalization is required.