OVERVIEW

Numerous bacteria, viruses, and parasites cause diseases in the intestines that result in diarrhea, dysentery, constipation or perianal irritation. They may also cause nausea, vomiting, and abdominal cramping. If the infection is in the small intestine, symptoms include watery diarrhea and vomiting. Infections in the large intestine can cause diarrhea and can result in an invasive and inflammatory disease called dysentery (small fecal volume with mucus and blood) (Table SI-1).

Table SI-1. Organisms that Cause Intestinal Disease
Type of Organism	Organism
Bacteria	Staphylococcus aureus Bacillus cereus Clostridium perfringens Clostridium botulinum Vibrio cholerae Escherichia coli Salmonella Shigella Campylobacter Clostridioides difficile Listeria monocytogenes
Viruses	Rotaviruses Caliciviruses (Norovirus, Sapovirus and Astrovirus) Adenoviruses
Parasites	Cryptosporidium parvum Cyclospora cayetanensis Giardia lamblia

Not all of these diseases occur after an infection, but they can occur after ingestion of preformed toxin. Usually symptoms of intoxication such as nausea, vomiting, and diarrhea occur soon after ingestion of the toxin (1–8 h). Symptoms of an intestinal infection tend to occur much later (24–72 h) than symptoms following intoxication (Table SI-2).

Table SI-2. Organisms that Cause Intoxication or Infection
Intoxications	Staphylococcus aureus Bacillus cereus Clostridium perfringens Clostridium botulinum
Infections	Escherichia coli Salmonella Shigella Campylobacter Clostridioides difficile Vibrio cholerae Listeria monocytogenes Rotaviruses Adenoviruses Caliciviruses (Astroviruses, Sapovirus and Noroviruses) Cryptosporidium parvum Cyclospora cayetanensis Giardia lamblia

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Approximately 270 million cases of diarrhea in adults result in about 600,000 hospitalizations and 3000 deaths annually in the U.S. An etiologic agent is identified in less than 10% of these cases. Most adults have at least one episode of diarrhea each year, and children have an average of two to three episodes per year. Worldwide, diarrhea kills 2,195 children every day—more than AIDS, malaria, and measles combined. Diarrheal diseases account for 1 in 9 child deaths worldwide, making diarrhea the second leading cause of death among children under the age of 5.

Pathogens causing diarrhea can be transmitted to humans in three basic ways: in food, in water, and person to person. Many of these infections are self-limiting and do not require treatment; however, some can spread to other sites in the body and require treatment to prevent complications (e.g., bacteremia).

Table SI-3. Organisms that Cause Gastrointestinal Signs and Symptoms and the Foods They Commonly Contaminate
Food Source	Organism
Dairy	Campylobacter, Salmonella
Eggs	Salmonella
Meats	Clostridium perfringens, Bacillus cereus, Campylobacter, Salmonella
Ground beef; leafy green vegetables	E coli O157:H7,  Cyclospora cayetanensis
Poultry	Campylobacter, Salmonella
Pork	Clostridium  perfringens
Seafood	Calicivirus, Vibrio
Oysters	Calicivirus, Vibrio
Vegetables	Clostridium perfringens
Foods that require a lot of handling (e.g., salads such as egg, tuna, chicken, potato, and macaroni, bakery products such as cream-filled pastries, cream pies, and chocolate éclairs, sandwich fillings)	Staphylococcus aureus
Rice; starchy foods	Bacillus cereus
Home-canned foods; honey (in children < 1 year of age)	Clostridium botulinum

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

This section of the handout will include discussion of diseases that primarily affect the small intestine and will be divided into the following topics: food intoxication, viral gastroenteritis, bacterial gastroenteritis, and parasitic gastroenteritis. Invasive gastroenteritis, which primarily involves the large intestine, will be discussed later in this handout.

This section of the handout will include discussion of diseases that primarily affect the small intestine and will be divided into the following topics: food intoxication, viral gastroenteritis, bacterial gastroenteritis, and parasitic gastroenteritis. Invasive gastroenteritis, which primarily involves the large intestine, will be discussed later in this handout.

FOOD INTOXICATION and INFECTION

One form of food poisoning is an intoxication associated with the ingestion of preformed microbial toxins. These food poisonings are not infections. Since the toxins are ingested preformed and no microbial growth within the body is required, the incubation times are very short (within 2–12 h) and there is no fever. One of the forms of food borne infection discussed here is an infection but is included since it does not cause a fever during its infection; B. cereus Type II. Botulism is frequently discussed in intoxication because it is intoxication. However, it manifests itself as a neurological disease in the clinic and I have left this disease for Dr. Stuart to discuss and for you to remember.

Etiology

Food toxemia is primarily due to bacteria, which include Staphylococcus aureus (gram-positive aerobic coccus), Bacillus cereus (gram-positive aerobic rod), and Clostridium perfringens type A (gram-positive anaerobic rod).

Manifestations

In cases of gastroenteritis caused by food poisoning, it is important to differentiate toxemia from infectious diarrhea. The key features that are unique to toxemia are rapid onset of symptoms following ingestion of contaminated food or drink, lack of fever, and absence of fecal leukocytes. Symptoms of toxemia usually occur within 12 hours after toxin ingestion, compared to an incubation period of 24–72 hours for infections.

Some unique aspects of causes of food poisoning

·         Staphylococcus aureus produces toxins that cause vomiting (often projectile) but little or no diarrhea. Symptoms occur within 1–4 hours after ingestion of contaminated food.

·         Bacillus cereus can cause two different types of food poisoning. Type I occurs when the organism grows in starchy foods (especially fried rice), and an emetic illness is seen within 2–3 hours after ingestion. Type II B cereus food borne infection occurs when the spores survive cooking and are then ingested when consuming meat, vegetables, and sauces. The spores germinate in the intestine and produce a heat-labile enterotoxin. The enterotoxin can cause profuse diarrhea within 10–12 hours after ingestion of the toxin. Note longer incubation time since this is an infection.

·         Clostridium perfringens causes abdominal cramping and watery diarrhea that usually occurs within 8–12 hours after ingestion of its toxin; the diarrhea generally lasts less than 24 hours.

Epidemiology

·         S aureus Staphylococcal food poisoning results in 240,000 illnesses/yr, 1,100 hospitalizations/yr and 6 deaths/yr. Staphylococcal food poisoning occurs most often in foods that require hand preparation, such as potato salad, ham salad, and sandwich spreads.

·         B cereus outbreaks result in 63,000 illness/yr and 20 hospitalizations/yr, as a result, of this intoxication. Intoxications with B cereus are associated with many foods. Fried rice is a leading cause of emetic food poisoning (B cereus type I) in the U.S. Other starchy foods such as potato, pasta, and cheese products have also been associated with this form of food toxemia. Meats, milk, vegetables, and fish have been associated with the diarrheal B cereus type II food borne infection.

·         C perfringens is found in soil and dust and in the gastrointestinal tract of animals and humans. This organism causes approximately 970,000 illness/yr, 440 hospitalizations/yr and 6 deaths/yr. This organism produces heat-resistant spores that can survive cooking and grow to large numbers if the cooked food is held between 4°C and 60°C for an extensive amount of time. Meat and poultry dishes and sauces and gravies are foods most frequently associated with this form of food toxemia.

Pathogenesis

S aureus produces eight distinct antigenic types of enterotoxin. They are water-soluble, low-molecular weight proteins that are heat stable (resist boiling for 30 minutes). Staphylococcal enterotoxins cause 5-hydroxytryptamine (serotonin) to be released in the intestine, which then binds to 5-hydroxytryptamine receptors on vagal afferent neurons and causes emesis.

B cereus produces several different enterotoxins during spore germination, which cause either vomiting or diarrhea. The type of toxin produced is dependent on the type of food in which the spore germinates. In high-carbohydrate foods such as rice or pasta, an emetic heat-stable enterotoxin is produced causing nausea and vomiting or B cereus type I food poisoning. The heat-stable enterotoxin depsipeptide cereulide causes nausea and vomiting by binding to and activation of 5-HT₃ receptors (5-hydroxytryptamine, or serotonin receptors) that increase afferent vagus nerve stimulation.

The diarrheal form of B cereus type II, which results when the heat-labile enterotoxins hemolysin BL (HBL) and nonhemolytic enterotoxin, are produced as the bacteria grow in the intestine. In a high-protein food, the diarrheal heat-labile enterotoxins result in diarrhea. These enterotoxins stimulate the adenyl cyclase-cyclic adenosine monophosphate system in intestinal epithelial cells and cause fluid accumulation in the intestine.

C perfringens enterotoxin binds to the brush-border membrane in the small intestine and disrupts ion transport in the ileum and jejunum, altering membrane permeability. Excess amounts of ions and water enter the lumen, resulting in a watery diarrhea. The toxin is formed when the vegetative cells become spores; alkaline conditions in the small intestine cause spore formation. Meat products contaminated with large numbers of organisms are needed to cause disease. Refrigeration prevents growth of organisms in meat, and reheating meat destroys the heat-labile enterotoxin. 

Diagnosis

Diagnosis of the source of food intoxication is usually not performed. Most food intoxications rarely cause significant long-term problems and are self-limiting. The only reason to determine the food source and cause is in the case of food poisonings resulting from food eaten at public institutions such as restaurants or elder-care facilities. In such cases, the contaminated food is often cultured or immunoassays are performed to detect the enterotoxins in the food. Certain foods are more likely to be contaminated with a particular pathogen.

Treatment and Prevention

There is usually no treatment given for toxemia due to S aureus, B cereus, or C perfringens. If the patient becomes dehydrated, intravenous replenishment of fluids and electrolytes are administered.

Good personal hygiene while handling foods will help prevent S aureus from contaminating foods, and refrigeration of raw and cooked foods will prevent the growth of these bacteria. To prevent food toxemia caused by C perfringens, hot foods should be served immediately or held above 46°C. After cooking, large quantities of food should be divided into smaller portions and refrigerated immediately. The food should be reheated to 60°C prior to serving. Adhering to these methods will also prevent food poisonings due to B cereus.

VIRAL GASTROENTERITIS

Viral gastroenteritis is one of several common causes of diarrhea in the United States, and can be caused by adenovirus, caliciviruses (norovirus and sapovirus), SARS CoV-2, and rotavirus.

Etiology

Rotavirus is a naked double-stranded RNA virus. The Caliciviridae family contains several naked RNA-containing viruses that cause gastroenteritis The viruses in the Caliciviridae family that cause gastroenteritis are Noroviruses, Sapovirus and Astroviruses. Noroviruses are naked positive-sense single-stranded RNA viruses that can be round with a ragged outline (Norwalk virus) or have a cup-shaped indentation. Sapovirus is a naked positive-sense single-stranded RNA virus with an icosahedral symmetry (Sapporo virus). The Astroviruses are naked positive-sense single-stranded RNA viruses that are similar in appearance to a five- or six-pointed star. Adenoviruses serotypes 40 and 41 are the only DNA viruses that cause gastroenteritis.

Manifestations

Following infection with any of the viruses mentioned above (i.e., rotavirus, SARS CoV-2, adenovirus, and caliciviruses), symptoms of viral gastroenteritis can include low-grade fever, abdominal pain, watery diarrhea, and nausea and vomiting (Table SI-4).

Table SI-4. Organisms that Cause Viral Gastroenteritis
Cause	Comments
Rotaviruses	Usually cause disease in children < 2 years of age Second common cause of infant diarrhea; < 2 yrs of age The incubation period being is 2–4 days  Diarrhea can last 4–8 days, resulting in dehydration Most common in the winter
Norovirus (also called Norwalk virus)	Symptoms last 12–60 hours; Intense vomiting with dehydrating diarrhea lasting 1 to 3 days Incubation period is 12–48 hours Most common cause overall of viral gastroenteritis Most common cause of diarrhea of all ages Symptoms in children and adults Most common in the winter (winter vomiting syndrome)
SARS CoV-2 (Severe Acute Respiratory Syndrome CoronaVirus-2)	33% of mild COVID-19 (COronaVIrus Disease- 2019) patients have digestive system symptoms including diarrhea, nausea, vomiting, anorexia, loss of taste (ageusia) and loss of smell (anosmia). If the patient has digestive system symptoms a little over half have respiratory symptoms too. In 20% of patients with COVID-19 diarrhea is the first symptom. Ageusia and anosmia are unique to this virus and rarely occur in the other viruses listed here.
Sapovirus	Like Norovirus; less common than norovirus; less vomiting compared to norovirus gastroenteritis
Astroviruses	Usually cause diarrhea in infants and children, institutionalized elderly adults and the immunocompromised patients (vomiting is uncommon). Most common in the winter
Adenoviruses (types 40 and 41)	Cause symptoms similar to rotavirus infections except that the infants tend to be older Complications can include intussusception.

Epidemiology

·         Each year, more than 3.5 million infants develop acute viral gastroenteritis resulting in more than 500,000 office visits, 55,000 hospitalizations, and 30 deaths.

·         Of a total of 13.8 million cases of food-related illness from all causes, rotavirus, adenovirus, and caliciviruses cause 9.2 million cases of illness each year.

Rotavirus

·         Rotavirus is the second most common cause of severe diarrhea among children younger than 2 years of age, resulting in the hospitalization of approximately 55,000 children per year in the United States and mortality in over 600,000 children per year worldwide. Rotavirus infections are more common in the winter. In adults, the disease tends to be mild.

·         It is the second most common cause of viral gastroenteritis in children younger than 5 years of age

·         Rotaviruses replicate in the intestine of most domestic and many wild animals.

·         The most common mode of transmission of rotavirus is via the fecal-oral route. The virus is stable in the environment, and transmission can occur through ingestion of contaminated water or food and contact with contaminated surfaces.

Noroviruses

·         Noroviruses replicate in the intestine of most domestic and many wild animals.

·         Noroviruses are the most common cause of outbreaks of gastroenteritis in industrialized countries. Gastroenteritis caused by Norovirus infection is a highly seasonal syndrome, and is often referred to as “winter vomiting disease.”

·         Norovirus is the most common cause of viral gastroenteritis of all ages

·         Norovirus causes 150 deaths, 15,000 hospitalizations and 5.5 million illnesses per year.

·         Persons over 65 are at greatest risk of norovirus-associated death.

·         Children < 5 are have the highest rates of norovirus-associated medical care visits.

·         Noroviruses are found in the stool or vomit of infected persons. It is highly contagious and can spread rapidly. 

·         Noroviruses are transmitted via the fecal-oral route by food handlers directly from person to person, through contaminated food or water, or by contact with contaminated surfaces or fomites.

Coronavirus (SARS CoV-2)

·         SARS CoV-2 causes digestive symptoms (ex., nausea, vomiting, diarrhea, anorexia) in around 33% of patients with mild COVID-19.

·         Digestive symptoms can occur alone or with respiratory symptoms (e.g., dry cough, dyspnea, shortness of breath)

·         Vomiting is more common in children (6.5% to 66.7%) with COVID-19 than adults (3.6% to 15.9%)

·         Nausea can occur in 1-30% of patients with COVID-19.

·         Anorexia occurs in 40-50% of patients with COVID-19.

• Patients presenting with olfactory dysfunction (ex. anosmia, hyposmia or dysosmia) and gustatory dysfunction (ex. Ageusia, hypogeusia, dysgeusia) were 41.0% and 38.2%, respectively. More likely to occur in younger patients.

Sapovirus

·         Around 15,000 human infections and 87 hospitalizations each year.

·         Replicate in swine and can contaminate shellfish.

·         Transmitted by fecal-oral route person-to-person, contact with contaminated surfaces or fomites and ingestion of contaminated shellfish.

·         Many cases seen in adult residents of long-term care facilities and young children who attend daycare.

Astroviruses

·         Around 15,000 human infections and 87 hospitalizations each year.

·         Astroviruses have been isolated from birds, cats, dogs, pigs, sheep, cows, and man.

·         Like rotaviruses, astrovirus infections occur throughout the year with peaks during the winter months.

·         Most astrovirus infections are detected in children younger than 5 years of age, with the majority of children younger than 1 year of age.

Adenoviruses

·         Transmission of adenoviruses can be by direct contact, fecal-oral route, or occasionally they are waterborne.

·         Adenovirus types 40 and 41 can cause infantile gastroenteritis and may account for 5-15% of case of gastroenteritis in young children.

Pathogenesis

Rotavirus, adenovirus, and caliciviruses invade and destroy mature epithelial cells in the middle and upper villus, causing decreased absorption of sodium and water from the bowel lumen. Noroviruses bind to the histocompatibility blood group antigens expressed on epithelial cells of the intestine. SARS CoV-2 binds to ACE-2 (angiotensin converting enzyme-2) on the surface of epithelial cells lining the gastrointestinal tract. Rotavirus infect cells in the villi of the small intestine. The Rotavirus multiplies in the cells cytoplasm and damages the host cell’s transport systems. One viral protein NSP4 is a viral enterotoxin that induces fluid secretion via a calcium dependent signal transduction pathway. Adenovirus infects epithelial cells of the intestine.

Diagnosis

Diagnostic tests usually are not performed to identify the causes of viral gastroenteritis. However, a rapid antigen test of stool, either by enzyme immunosorbent assay or the latex agglutination test, can be used to aid in the diagnosis of rotavirus infection. Nucleic acid amplification tests can be used to detect SARS CoV-2 RNA in feces.

Therapy and Prevention

Viral gastroenteritis is a self-limiting disease, but it is often necessary to administer fluids and electrolytes to patients to prevent dehydration. Oral rehydration therapy is recommended for preventing and treating early dehydration. Shock, severe dehydration, and decreased consciousness require intravenous therapy. Administering antiemetics and antidiarrheal agents to small children is not recommended.

Natural immunity is usually incomplete, and multiple episodes of viral gastroenteritis can occur in infants. In time, the episodes become less severe. Two highly effective rotavirus vaccines are currently available and should be given to infants at 2, 4, and 6 months of age. Human trials for a norovirus vaccine began in 2016. Persons who are infected with Norovirus should not prepare food while they are symptomatic and for 3 days after they recover from the illness.

NONINFLAMMATORY BACTERIAL GASTROENTERITIS

Bacterial gastroenteritis results in large volume watery diarrhea and abdominal cramps. Although vomiting is common in viral gastroenteritis, it is less common in bacterial gastroenteritis. The bacteria that cause bacterial gastroenteritis colonize the surface of the small intestine but do not invade the mucosa. Bacterial gastroenteritis is a noninflammatory diarrhea; fecal specimens do NOT contain significant numbers of fecal leukocytes.

Escherichia coli INFECTIONS

Bacterial gastroenteritis due to E coli is a common malady of people traveling outside the U.S. and is caused by three different types of E coli: enterotoxigenic E coli (ETEC), enteroaggregative E coli (EAEC), and enteropathogenic E coli (EPEC).

Etiology

ETEC and EAEC both cause what is commonly known as traveler’s diarrhea. ETEC can also cause diarrhea in infants; EPEC thus far has been incriminated only in mild diarrheal disease in infants primarily younger than 6 months of age. The definition of classic travelers’ diarrhea is three or more diarrheal stools per day, along with at least one other clinical sign, such as abdominal cramps, fever, nausea or vomiting.

Manifestations

Severe disease caused by ETEC and EAEC is characterized by abrupt onset of watery diarrhea and abdominal cramping. The duration of diarrhea caused by ETEC is about 24 hours after initiation of fluid replacement therapy. The duration of diarrhea caused by EAEC is several days before resolution.

Pathogenesis

ETEC strains colonize the small intestine and produce two enterotoxins called LT (heat labile toxin) and ST (heat stable toxin). Both toxins ultimately stimulate the secretion of chloride by the host cells, which results in a watery diarrhea. LT is an A-B toxin similar to the cholera toxin—it is composed of one A subunit and five B subunits. The B subunits bind to GM₁ ganglioside on the host cell. Following endocytosis of the bound toxin, the A subunit is released into the cytoplasm and adenosine diphosphate-ribosylates the guanosine triphosphate (GTP)-binding protein. The GTP-binding protein then activates adenylate cyclase, resulting in increased intracellular levels of cyclic adenosine monophosphate (cAMP). Cyclic AMP activates cyclic AMP-dependent protein kinase (A kinase), causing supranormal phosphorylation of chloride channels. The stimulation of chloride ion secretion from secretory crypt cells and inhibition of sodium chloride absorption by villus tip cells causes an increase in luminal ion content, drawing water passively through the paracellular pathway and resulting in an osmotic diarrhea.

ST is quite different from LT. ST is a peptide of 18 or 19 amino acids. ST binds to a membrane-spanning enzyme called guanylate cyclase. Guanylate cyclase is located in the apical membrane of intestinal epithelial cells and binding of ST to the extracellular domains of the protein stimulates its intracellular enzymatic activity. This causes increases in intracellular cyclic guanosine monophosphate, which ultimately stimulates chloride ion secretion or inhibition of NaCl adsorption, or both. Once again, an osmotic diarrhea occurs.

EPEC produces no demonstrable toxin. EPEC strains cause what is termed an attaching-and-effacing histopathology in the small intestine. These E coli strains are adherent to the epithelial cells using bundle-forming pili and then disrupt the microvilli (effacement). They intimately adhere to the host cells and inject, by a type III secretory system, bacterial factors into the host cells that cause alterations in the glycocalyx of the epithelial cells in the small bowel. EPEC express rope-like bundles of filaments, termed bundle-forming pili, which create a network of fibers that bind the individual organisms together and are used to bind the bacterial cells to the surface of the intestinal epithelial cells. One of the injected proteins translocated intimin receptor (Tir) is inserted into the host epithelial cell membrane. When intimin from EPEC binds to Tir it causes polymerization of host cell actin, accumulation of cytoskeletal elements beneath the attached bacterial cells, loss of surface integrity and cell death.

EAEC strains autoaggregate into a “stacked-brick” arrangement using aggregative adherence fimbriae I (AAFI). EAEC infection involves adherence to the intestinal mucosa using AAFI, enhancing mucus production by the host cells that encases the bacteria in a biofilm on the surface of the intestinal mucosa, and production of toxins (enteroaggregative heat stable toxin and another plasmid encoded toxin). Both toxins induce fluid secretion and the prolonged watery diarrhea associated with this infection.

Epidemiology

·         E coli are the most common cause of traveler’s diarrhea, resulting in 50 million cases in persons traveling to developing countries. It is believed that there are about 50,000 cases of traveler’s diarrhea each day worldwide.

·         ETEC is the most common bacterial cause of a type of bacterial gastroenteritis called traveler’s diarrhea. EAEC causes about 25% of cases of traveler’s diarrhea.

·         Persons traveling to high-risk areas worldwide are more likely to acquire traveler’s diarrhea. An average of 30–50% of travelers to high-risk areas will develop traveler’s diarrhea during a 1- to 2-week stay.

·         Traveler’s diarrhea is a clinical syndrome resulting from microbial contamination of ingested food and water. It can occur during or shortly after travel, and usually affects persons traveling from an area with a well-developed hygiene and sanitation infrastructure to a less developed one.

Diagnosis

Bacterial gastroenteritis is usually a self-limiting disease, and diagnosis is determined on clinical grounds. Definitive diagnosis of ETEC infections can be made by isolating the bacteria from stool samples on MacConkey agar and assaying for the toxins by enzyme-linked immunoassay (ELISA) or with a DNA probe to detect the toxin genes. Knowing the characteristics of the fecal sample can be useful in distinguishing between infections of the small intestine (Table SI-5) and infections of the large intestine.

Table SI-5. Stool Characteristics Useful in the Diagnosis of Intestinal Diseases
Stool Characteristics	Non-inflammatory Intestinal Infection	Inflammatory (invasive) Intestinal Infection
Appearance	Watery	Mucous and/or bloody
Volume	Large	Small
Frequency	Increased	Increased
Blood	May be positive but not visibly bloody	Can be visibly bloody
pH	< 5.5	> 5.5
White blood cells	< 5 cells per high power field	> 10 cells per high power field
Serum leukocytes	Normal	Can have a leukocytosis if an invasive infection
Organisms	Viral Rotavirus Adenovirus Calicivirus (Astrovirus, Sapovirus, Norovirus)	Invasive bacteria Escherichia coli Shigella species Salmonella species Campylobacter species Yersinia species
	Toxic bacteria Escherichia coli Clostridium perfringens Vibrio cholerae Bacillus cereus	Toxic bacteria Clostridioides difficile
	Parasites Giardia lamblia Cryptosporidium parvum Cyclospora cayetenensis	Parasites Entamoeba histolytica

Treatment and Prevention

Treatment of gastroenteritis caused by E coli usually involves oral replacement of the fluid and electrolytes lost in feces. Peroral therapy is almost always adequate; however, if severe, intravenous treatment may be necessary. See pharmacology notes for current recommendations.

For travelers to high-risk areas, several approaches should be encouraged to minimize the risk of getting traveler’s diarrhea. These include instructions regarding food and beverage selection, use of bismuth subsalicylate for prophylaxis, and use of prophylactic antibiotics (e.g., rifaximin). Other means of preventing these infections include eating foods that are freshly cooked and served piping hot and avoiding water, ice, milk, or beverages diluted with water (e.g., reconstituted fruit juices) and foods washed in water, such as salads. Other foods that are considered risky include raw or undercooked meat and seafood and raw fruits and vegetables. Prophylactic antibiotics are not recommended for most travelers, but may be considered for short-term travelers who are high-risk hosts (immunosuppressed or immunocompromised patients) or persons taking critical trips (e.g., trips due to deaths in the family, essential business trips, rescue efforts after a catastrophe) during which even a short bout of diarrhea could adversely affect the purpose of the trip.

Vibrio parahaemolyticus INFECTIONS

This organism is found worldwide in marine and estuarine environments.

Etiology

V parahaemolyticus is a curved gram-negative rod that is a facultative anaerobe. It is oxidase positive and requires salt to grow.

Manifestations

The severity of this infection can vary from a self-limiting diarrhea to a mild, cholera-like illness. Usually disease occurs after an incubation period of 5 to 72 hours (average 24 hr). The diarrhea is watery and explosive. Associated symptoms include; headache, abdominal cramps, nausea, vomiting and a low-grade fever. Symptoms usually last about 72 hours and most patients recover with not sequelae.

Epidemiology

·         Infections are associated with ingestion of raw shellfish taken from marine or estuarine environments.

·         Most common cause of seafood associated gastroenteritis in the US. The most common cause of bacterial gastroenteritis in Japan and Southeast Asia.

·         Around 35,000 illnesses, 100 hospitalizations and 4 deaths result from this infection each year in the US.

Pathology

Pathogenic strains produce a thermostable hemolysin (Kanagawa hemolysin) that induces chloride ion secretion in epithelial cells by increasing intracellular calcium levels.

Diagnosis

In endemic or epidemic areas, the diagnosis is based on the clinical presentation. Definitive diagnosis is determined by plating a fecal sample on TCBS (thiosulfate-citrate-bile salt-sucrose) agar, which is selective for Vibrio and differentiates V cholerae (yellow on TCBS) from the other vibrios (green on TCBS). The green colonies of V parahaemolyticus when plated on blood agar plates containing human blood erythrocytes will produce beta hemolysis (Kanagawa positive). Beta hemolysis does not occur when sheep blood is used to make the blood agar plates.

Treatment and Prevention

Treatment of gastroenteritis caused by V parahaemolyticus usually involves oral replacement of the fluid and electrolytes lost in feces. Antibiotics will shorten the course of the infection. See pharmacology notes for current recommendations. Proper cooking of shellfish will prevent these infections. No vaccine is available.

CHOLERA

The Vibrio cholerae organism is ingested with water or food and causes an acute illness due to an enterotoxin elaborated by V cholerae, which have colonized the small bowel. In its most severe form, there is rapid loss of liquid and electrolytes from the gastrointestinal tract, resulting in hypovolemic shock, metabolic acidosis, and death.

Etiology

V cholerae is a curved gram-negative rod. This organism produces lipopolysaccharide (LPS) and is subdivided into 140 serogroups (O1 to O140) based on differences in LPS. Only the O1 and O139 serogroups produce cholera toxin and cause the most severe form of cholera. The O1 serogroup is further subdivided into serotypes (Inaba, Ogawa, and Hikojima) and biotypes (classical and el tor).

Manifestations

The onset of cholera is abrupt and results in large amounts of watery diarrhea (Table SI-6). Several liters of liquid may be lost within a few hours, rapidly leading to profound shock.

Table SI-6. Manifestations of Cholera

Profuse watery diarrhea Vomiting may occur after diarrhea

Severe cases of cholera The patient may be cyanotic and have sunken eyes and cheeks, a scaphoid abdomen, poor skin turgor, and thready or absent peripheral pulses The voice may be high pitched or inaudible Vital signs include tachycardia, tachypnea and low or unobtainable blood pressure Heart sounds are distant and can oftentimes be inaudible Bowel sounds are indicative of hypoactive intestines

 

 

 

 

 

 

 

 

 

Epidemiology

Epidemiology

·         Cholera is endemic in Louisiana, and in India, West Bengal, and Bangladesh.

·         Only about 1–10 cases of cholera occur each year in the U.S., and patients usually have a history of travel to countries with endemic cholera.

·         The organism is usually ingested in contaminated water or food (e.g., shellfish and crabs).

Pathology

V cholerae is acid sensitive, and most ingested organisms are killed by stomach acidity. About 10⁸–10¹⁰ bacterial cells must be ingested to cause disease. The organisms that survive passage through the stomach attach to the microvilli of the glycocalyx of epithelial cells of the jejunum and ileum, where they multiply and liberate cholera enterotoxin, mucinase, and endotoxin. They do not invade the mucosa. All signs, symptoms, and metabolic derangements in cases of cholera result from rapid loss of liquid from the small intestine.

The enterotoxin (cholera toxin) consists of a binding (B) moiety and an activating (A) moiety. Five equal subunits make up the B moiety. On exposure to small bowel epithelial cells, each B subunit rapidly binds to GM₁ monosialoganglioside in the gut cell wall. Following binding, the A moiety migrates through the epithelial cell membrane. The A moiety contains adenosine diphosphate (ADP) ribosyltranferase activity and catalyzes the transfer of ADP-ribose from nicotinamide adenine dinucleotide (NAD) to a GTP-binding protein that regulates adenylate cyclase activity. The ADP-ribosylation of GTP-binding protein inhibits the GTP turnoff reaction and causes a sustained increase in adenylate cyclase activity. The resultant increased intracellular cyclic AMP acts at two sites to cause net secretion of isotonic liquid within the small bowel lumen. First, the increased cyclic AMP inhibits sodium chloride absorption across the glycocalyx via the cotransport mechanism; and second, the increase in cyclic AMP stimulates active chloride secretion into the gut lumen. Water in the tissues follows the ions, causing the profuse watery diarrhea. There is no significant damage to the cells lining the intestine.

Diagnosis

In endemic or epidemic areas, the diagnosis of cholera is determined based on the clinical presentation, especially the presence of “rice water” stools. Definitive diagnosis is determined by plating a fecal sample on TCBS (thiosulfate-citrate-bile salt-sucrose) agar, which is selective for Vibrio and differentiates V cholerae (yellow on TCBS) from the other vibrios (green on TCBS). An adrenal cell assay can also be used to detect the toxin.

Treatment and Prevention

Successful therapy of cholera requires prompt replacement of fluids and electrolytes. Oral rehydration therapy is usually the first therapy attempted; however, if the dehydration cannot be corrected by oral administration of fluids, intravenous administration of fluids can be given. See pharmacology notes for current antimicrobial agent recommendations.

PARASITIC GASTROENTERITIS

Giardia lamblia, Cyclospora cayetenensis, and Cryptosporidium parvum are protozoan parasites that cause watery diarrhea worldwide.

GIARDIASIS

Acute infections of giardiasis can be asymptomatic or they can result in bloating, flatulence, and watery diarrhea. Chronic infections can lead to malabsorption and steatorrhea (fatty diarrhea).

Etiology

G lamblia (also called G intestinalis or G duodenalis) is a protozoan flagellate that produces both a cyst to survive harsh environmental conditions and a trophozoite, which is only viable in the intestine. The cyst germinates in the intestine to produce the trophozoites. The teardrop-shaped trophozoites have a smooth dorsal surface with a concave ventral surface and a prominent anterior adhesive disk. The cysts are ellipsoidal.

Manifestations

Giardiasis can result in asymptomatic or symptomatic disease that ranges from mild watery diarrhea to severe malabsorption syndrome. The incubation period ranges from 1 to 4 weeks. Disease onset is sudden and consists of foul-smelling watery diarrhea, abdominal cramps, flatulence, and steatorrhea. Spontaneous recovery can occur within 10 to 14 days; however, a chronic disease with multiple relapses can develop.

Epidemiology

·         Giardiasis is the most common intestinal protozoan parasite of humans in the U.S. About 5000–7000 cases of giardiasis occur each year in the U.S.

·         The parasite lives in the intestines of humans and in domestic and undomesticated mammals.

·         Ingestion of water containing G lamblia cysts can cause infection. The cyst is the infectious form of the parasite.

·         Most persons are infected via the fecal-oral route of transmission.

Pathology

Ingestion of water containing G lamblia cysts causes infection. Cyst formation is essential for the parasite to survive in the environment outside the host’s intestines. The cyst then develops into a trophozoite in the duodenum. Flagella help the parasite to make contact with host enterocytes. Taglin (trypsin-induced Giardia lectin) and GLAM-1 (Giardia lamblia adherence molecule- 1) are lectins that help the parasite adhere to the surface of the enterocyte. The trophozoites adhere to the epithelium of the microvillus using these lectins and are held in place by their adhesive disks. Adherence of the parasite to the wall of the intestine does not cause a significant amount of damage; however, the parasite causes a disaccharidase deficiency in the small intestine. The epithelial cells lining the microvilli do not absorb ingested disaccharides, causing an osmotic diarrhea with bloating, flatulence, and watery diarrhea.

Severe G lamblia infections can result in malabsorption and steatorrhea. Pathologic changes are mild in most cases, but shortening and thickening of the villi associated with acute focal inflammatory changes in the mucosal epithelium may be seen initially and are followed by chronic inflammatory infiltrates in the lamina propria.

 Diagnosis

Presumptive diagnosis is made on the basis of a history of drinking water that is not chlorinated and the expression of classic clinical symptoms. Confirmative diagnosis requires detecting G lamblia trophozoites or cysts in feces. Because the parasite is not consistently shed in feces, a fecal sample collected on each of three consecutive days should be examined for cysts and trophozoites. If neither cysts nor trophozoites are found, the duodenum can be sampled by duodenal aspiration, string test (Entero-Test), or biopsy of the upper small intestine.

Treatment and Prevention

See pharmacology notes for current treatment recommendations. All drinking water should be boiled when on extended outdoor trips. Chlorination will not kill the cysts. Proper maintenance of filtration systems at water plants is essential.

CYCLOSPORIASIS

Cyclospora cayetanensis is a protozoan parasite common in developing countries. Water contaminated with feces is an important source of infection. Water-borne infections are common in developing countries and in travelers to these countries. Imported fresh vegetables (lettuce), herbs (basil), and fruits (raspberries) washed with contaminated water are the most common means of acquiring this parasite in the U.S.

Etiology

Cyclospora cayetanensis is a single celled coccidian parasite. The infectious form of the organism is a sporulated oocyst.

Manifestations

Symptoms vary from asymptomatic to prolonged diarrhea of greater than one month duration. Common symptoms include; low grade fever, diarrhea, fatigue, flatulence and belching. The illness can be self-limiting, can wax and wane, or in many cases result in prolonged diarrhea, anorexia, upper gastrointestinal symptoms (bloating, nausea), myalgia, fatigue, and in some cases weight loss. Fatigue and myalgia may persist after the gastrointestinal symptoms have gone away.

Epidemiology

·         All cases in the US have resulted from imported fresh fruits, vegetables, or herbs that have been washed in the country of origin with water contaminated with feces.

·         Cyclosporiasis is endemic in tropical and subtropical countries.

·         The infectious stage of this parasite is the sporulated oocyst.

·         An infected person sheds the unsporulated noninfectious oocyst in their feces. It takes several days to weeks for the oocyst to mature to the sporulated oocyst.

·         Therefore, this organism is NOT passed person to person.

·         Water-borne means of transmission are most common in endemic countries. Food-borne means of transmission are most common in the U.S.

Pathogenesis

The parasite binds to the epithelial cells lining the small intestine and causes a secretory diarrhea. How it does this is currently unknown. Symptoms are not due to damage of the intestinal mucosa.

Diagnosis

Consider cyclosporiasis in patients with prolonged diarrhea (longer than a month) with or without travel to endemic countries. Staining the feces with a modified acid-fast stain results in variably staining acid-fast oocysts (staining varies from unstained to light pink to deep red) or in fluorescent oocysts using ultraviolet light microscopy. If cyclosporiasis is suspected you need to ask the lab to specifically look for the organism. Routine stool ova and parasite exams are usually negative.

Treatment and Prevention

See pharmacology notes for current treatment recommendations. Drink only bottled water and avoid fresh fruits you can’t peel and vegetables when traveling to developing countries. Avoid imported fresh fruits and vegetables.

CRYPTOSPORIDOSIS

Cryptosporidium parvum is a protozoan parasite that primarily affects immunocompromised persons. C parvum can cause a severe and chronic diarrhea in HIV-infected patients and is an AIDS-defining condition.

Etiology

C parvum is a coccidian single-celled parasite that stains red using the acid-fast staining technique.

Manifestations

In persons with normal immune function, an asymptomatic carrier state can occur as well as a self-limiting watery diarrhea. Spontaneous remission usually occurs in about 10 days. However, in the immunocompromised person, the diarrheal disease can be severe and chronic (≥ 50 stools a day for months to years), and can result in large amounts of fluid loss.

Epidemiology

·         C parvum occurs worldwide and inhabits the intestines of a variety of animals, fish, mammals, and reptiles, and is a common contaminant in water.

·         Ingestion of oocysts of C parvum in immunocompromised persons is more likely to result in a persistent chronic diarrhea.

·         Only 150 oocysts can cause diarrhea in humans.

·         It is a frequent cause of diarrhea in daycare centers and among male homosexuals.

·         Autoinfections and person-to-person spread (fecal-oral and anal-oral) is common.

Pathogenesis

The pathogenesis of C parvum is not completely understood; however, it is known that the parasite affects intestinal ion transport and causes inflammatory damage of the microvilli, which results in malabsorption of the small intestine. Loss of cell-mediated immunity increases the risk of infection and is a common cause of chronic diarrhea in AIDS patients.

Diagnosis

The oocysts of C parvum are acid-fast positive; a stool smear stained with a modified acid-fast stain can be used to visualize the parasites. The parasites stain red.

Treatment and Prevention

C parvum infection is usually self-limiting in persons with normal immune functioning and does not require medication; however, immunocompromised individuals with chronic C parvum infection can be treated (see pharmacology notes for current treatment recommendations). Nonspecific antidiarrheal agents may provide temporary relief for patients where the infection will resolve without antiparasitic treatment. Contaminated water sources should be avoided.