Intoxications and Infections of the Small Intestine

Numerous bacteria, viruses, and parasites cause diseases in the intestines that result in diarrhea or dysentery, 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 1).

Table 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 Clostridium difficile Listeria monocytogenes
Viruses	Rotaviruses Norwalk virus Noroviruses (Norwalk-like viruses) Adenoviruses Astroviruses
Parasites	Cryptosporidium parvum Giardia lamblia Entamoeba histolytica

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 2).

Table 2. Organisms that Cause Intoxication or Infection
Intoxications	Staphylococcus aureus Bacillus cereus Clostridium perfringens Clostridium botulinum
Infections	Escherichia coli Salmonella Shigella Campylobacter Clostridium difficile Vibrio cholerae Listeria monocytogenes Rotaviruses Norwalk virus Adenoviruses Astroviruses Caliciviruses Noroviruses Cryptosporidium parvum Giardia lamblia Entamoeba histolytica

Diarrhea is an important symptom of intestinal disease and is the most common cause of death in developing countries (2.5 million deaths per year). Over 211 million cases of diarrhea occur in the U.S. every year. 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).

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 poisoning, viral gastroenteritis, bacterial gastroenteritis, and parasitic gastroenteritis. Invasive gastroenteritis, which primarily involves the large intestine, will be discussed later in this handout.

Food poisoning is an intoxication associated with the ingestion of preformed microbial toxins. It is not an infection. 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. Botulism has an incubation time (> 12 h) that is longer than the incubation times seen with the other causes of food poisoning (usually less than 12 h).

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

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.

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 poisoning occurs when the organism grows in meat, vegetables, and sauces, producing a heat-labile enterotoxin. When ingested, the enterotoxin can cause profuse diarrhea within 10–12 hours after ingestion of the toxin.
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.
Clostridium botulinum toxin produces symptoms 1–2 days after ingestion of improperly home-canned vegetables or sausage. Botulism is the only intoxication that has an incubation period of over 12 hours because of the amount of time required for the toxin to spread from the intestine to the nerve synapses. Initial symptoms include blurred vision with fixed and dilated pupils, dry mouth, constipation, and abdominal pain. A bilateral descending weakness of the peripheral muscles develops resulting in flaccid paralysis. Death is usually attributed to respiratory failure. Patients maintain a clear sensorium throughout the illness.

Staphylococcal food poisoning is the most common cause of food poisoning in the U.S. Staphylococcal food poisoning occurs most often in foods that require hand preparation, such as potato salad, ham salad, and sandwich spreads.
B cereus outbreaks are relatively uncommon and 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 toxemia.
C perfringens is found in soil and dust and in the gastrointestinal tract of animals and humans. 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.
C botulinum is relatively rare, with only 15–40 cases of botulism diagnosed yearly in the U.S. Botulism causes death in approximately 30% of patients. Botulism usually occurs in home-canned foods. Recent use of botulinum toxin for cosmetic purposes has resulted in several cases of botulism when using improperly diluted, unlicensed concentrated toxin preparations.

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 vomiting through an unknown mechanism.

The diarrheal form of B cereus type II, which results from the heat-labile enterotoxins hemolysin BL (HBL) and nonhemolytic enterotoxin, is produced as the bacteria grow in the food or 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; 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.

C botulinum produces seven antigenically distinct types of neurotoxin; human disease is associated with toxin types A, B, E, and F. If the spores of C botulinum are not destroyed during the canning process, when cooled sufficiently, the spores will germinate and the resulting vegetative cells will produce toxin. This large toxin is an A-B type toxin. The B portion protects the toxin from being inactivated by stomach acid and forms a pore in the membrane of the nerve cell to allow entry of the A portion into the cell. The A portion is a metalloproteinase that blocks neurotransmission of cholinergic synapses by preventing the release of acetylcholine at the neuromuscular junction and causing a flaccid paralysis that remains until the nerve endings regenerate.

Except for botulism, diagnosis of the source of food intoxication usually is 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. Table 3 lists foods and the pathogens they are likely to contain.

Table 3. Organisms that Commonly Cause Food Poisoning
Food Source	Organism
Dairy	Campylobacter, Salmonella
Eggs	Salmonella
Meats	Clostridium perfringens, Bacillus cereus, Campylobacter, Salmonella
Ground beef; leafy green vegetables	E coli O157:H7
Poultry	Campylobacter
Pork	Clostridium perfringens
Seafood	Astrovirus, 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 eclairs, sandwich fillings)	Staphylococcus aureus
Rice; starchy foods	Bacillus cereus
Home-canned foods; honey (in children < 1 year of age)	Clostridium botulinum

The only fatal food poisoning is botulism. Emphasis should be placed on ruling out botulism in the diagnosis. Presumptive diagnosis of botulism is determined by the presence of a rapidly descending paralysis. A history of ingestion of home-canned food or honey is helpful. Anaerobic culture of the organism from the food source and demonstration of toxin production using a mouse bioassay can be performed, but the sample must be sent to a public health laboratory for analysis.

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.

Patients with signs or symptoms compatible with botulism or patients who are known to have eaten food shown by laboratory testing to contain the toxin should be admitted to an intensive care unit to permit monitoring of respiratory and cardiac function. Patients should be induced to vomit or gastric lavage should be performed if exposure has occurred within several hours and given trivalent (A, B, E) botulinum antitoxin to neutralize unabsorbed toxin in the bloodstream.

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. Botulism can be prevented by proper canning of foods, by avoiding tasting of canned food before cooking, and by boiling canned foods for 10 minutes before eating to destroy any neurotoxins that may have been produced.

Viral gastroenteritis is one of several common causes of diarrhea in the United States, and can be caused by rotavirus, adenovirus, astrovirus, and caliciviruses.

Rotavirus is a naked double-stranded RNA virus. The Caliciviridae family contains several naked single-stranded RNA-containing viruses that cause gastroenteritis The viruses in the Caliciviridae family that cause gastroenteritis are Norwalk virus and noroviruses (formerly called Norwalk-like viruses). 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.

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

Table 4. Organisms that Cause Viral Gastroenteritis
Cause	Comments
Rotaviruses	Usually cause disease in children < 2 years of age Most common cause of infant diarrhea The incubation period being is 2–4 days Diarrhea can last 4–8 days, resulting in dehydration Most common in the winter
Norovirus	Symptoms last 12–60 hours Incubation period is 12–48 hours Most common cause overall of viral gastroenteritis Infect children and adults Most common in the winter (winter vomiting syndrome)
Norwalk virus	Symptoms similar to norovirus infections Causes symptoms in children and adults Most common in summer
Astroviruses	Usually cause symptoms in children < 5 years of age (vomiting is uncommon) Most common in the winter
Adenoviruses	Cause symptoms similar to rotavirus infections except that the infants tend to be older Complications can include intussusception.

Rotavirus is the 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.
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.

Norwalk virus infection affects older children and adults.
Norwalk virus replicates 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.”
Noroviruses are found in the stool or vomit of infected persons. It is highly contagious and can spread rapidly.
The Norwalk virus and 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.

Rotavirus, adenovirus, astrovirus, 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.

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.

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. Persons who are infected with norovirus should not prepare food while they are symptomatic and for 3 days after they recover from the illness.

Bacterial gastroenteritis results in large volume watery diarrhea and abdominal cramps. Although vomiting is common in viral gastroenteritis, it is much 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 any fecal leukocytes.

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).

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.

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.

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 (AMP). 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 and then disrupt the microvilli (effacement). They then intimately adhere to the host cells and inject, by a type III secretory system, bacterial factors into the host cells and 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.

EAEC infection involves three stages that include adherence to the intestinal mucosa: (1) enhanced mucus production that encases the bacteria in a biofilm on the surface of the intestinal mucosa; (2) followed by elaboration of a cytotoxin, which kills the intestinal cells; and (3) damage causes the watery diarrhea.

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.

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 5) and infections of the large intestine.

Table 5. Stool Characteristics Useful in the Diagnosis of Intestinal Diseases
Stool Characteristics	Small Bowel	Large Bowel
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, Norwalk virus, Noroviruses	Invasive bacteria- Escherichia coli, Shigella species, Salmonella species, Campylobacter species, Yersinia species
	Toxic bacteria- Escherichia coli, Clostridium perfringens, Vibrio cholerae, Bacillus cereus	Toxic bacteria- Clostridium difficile
	Parasites- Giardia lamblia, Cryptosporidium parvum	Parasites- Entamoeba histolytica

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. If antibiotics are needed, ciprofloxacin or levofloxacin are usually prescribed. Rifaximin has been approved for the treatment of traveler’s diarrhea caused by noninvasive strains of E coli. Bismuth subsalicylate may provide symptomatic relief, with less severe abdominal cramps and less frequent stools.

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.

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.

V cholerae is a slightly 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).

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

Table 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

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.

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.

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. Tetracycline reduces the severity and length of disease.

Botulism in infants younger than 1 year of age can follow either ingestion of the preformed toxin, as discussed above (see food poisoning), or after ingestion of C botulinum spores.

C botulinum can colonize the gastrointestinal tract of an infant younger than 1 year of age, producing the botulism toxin in the intestines.

Constipation is the first sign of disease, followed by the same neurologic signs discussed in the section on food poisoning.

The C botulinum spores are ingested; due to the lower acidity of the infant’s stomach, spores can survive passage into the intestines. The spores geminate in the infant’s small intestine, colonize it, and produce botulinum toxin in the intestine. The toxin then travels to the myoneural junctions and inhibits release of acetylcholine, causing a flaccid paralysis.

Presumptive diagnosis of botulism is determined by the presence of a rapidly descending paralysis. A history of ingestion of honey is helpful. Culture of the organism from the food and demonstration of toxin production can be performed (see food poisoning).

Antibiotics generally are not effective and may exacerbate the illness by elimination of normal flora. Therapy is the same as for adult botulism (see food poisoning) except that antitoxin is generally not used because the disease is milder in children.

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

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).

G lamblia (also called G intestinalis) 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.

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.

Ingestion of water containing G lamblia cysts causes infection. The cyst then develops into a trophozoite in the duodenum. The trophozoites adhere to the epithelium of the microvillus using their adhesive disks. Adherence of the parasite to the wall of the intestine does not cause a significant amount of damage; however, the parasite does cause 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.

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.

Asymptomatic carriers and persons with symptoms of giardiasis infection should be treated with metronidazole, nitazoxanide, or quinacrine hydrochloride for 10 days. 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.

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.

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

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.

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.

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

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 with nitazoxanide. Nonspecific antidiarrheal agents may provide temporary relief for patients where the infection will resolve without antiparasitic treatment. Contaminated water sources should be avoided.