Infections of the large intestine

The major infections discussed in this section of the handout include pseudomembranous colitis, bacterial dysentery and parasitic dysentery. Bacterial dysentery includes campylobacteriosis, shigellosis, salmonellosis, yersiniosis and Escherichia coli dysentery. Parasitic dysentery is caused by Entamoeba histolytica. These infections occur primarily in the large intestine (note some of these organisms can also infect the small intestine) and can invade the surrounding tissues. Invasion of the intestine can result in blood in the feces and cause an inflammatory response with significant numbers of fecal leukocytes.

Clostridium difficile infection (CDI) is one of the most common hospital-acquired infections, and is a frequent cause of morbidity and mortality among elderly hospitalized patients. Pseudomembranous colitis usually occurs after long-term antibiotic treatment and is due to overgrowth of Clostridium difficile in the colon and production of toxin by this bacterium.

C difficile is an anaerobic gram-positive spore-forming rod that produces toxin A and toxin B.

Symptoms of pseudomembranous colitis vary from an asymptomatic carrier state to fulminant colitis. Watery diarrhea is the most common symptom. Other symptoms include crampy bilateral lower quadrant pain that decreases after bowel movements, low-grade fever, and mild peripheral blood leukocytosis. Usually the diarrhea begins 5–10 days after the initiation of antibiotic therapy; however, symptoms may be delayed as long as 10 weeks after completion of antibiotic therapy. Patients who develop pseudomembranous colitis have similar symptoms except that pseudomembranes can be observed on the mucosal surface of the colon when viewed by colonoscopy.

A fulminant colitis develops in 2–3% of patients. Patients with pseudomembranous colitis have severe morbidity and a high mortality rate. Diarrhea is usually present; however, the patient can be constipated. There is diffuse, severe abdominal pain associated with hypoactive bowel sounds, abdominal distension, and guarding. A marked peripheral blood leukocytosis is common. Perforation of the colon can result. Development of lactic acidosis usually signals impending bowel perforation and irreversible bowel damage that requires surgical intervention. Complications can include toxic megacolon and bowel perforation. Toxic megacolon results in a persistently high fever, marked leukocytosis, lack of response to antibiotics, and marked bowel thickening on CT scan.

About 500,000 cases of C difficile diarrhea or pseudomembranous colitis occur in the U.S. annually.
C difficile is a bacterium that is resistant to most broad-spectrum antibiotics and is present in the intestine of about 5% of humans. Long-term systemic antibiotic therapy reduces the number of viable bacteria in the intestine but allows C difficile to become the predominate organism in the gastrointestinal tract.
Diarrhea due to C difficile and antibiotic use develops in up to 30% of hospitalized patients. The most common antibiotics implicated include second- and third-generation cephalosporins, ampicillin, amoxicillin, and clindamycin.
Pseudomembranous colitis is primarily a disease of hospitalized patients.
The intestines of patients with pseudomembranous colitis are colonized by C difficile via the fecal-oral route.

Systemic antibiotic treatment reduces the normal flora and interferes with the bacterial breakdown of carbohydrates. The increased amounts of undigested carbohydrates increase the osmotic load in the colon by preventing water resorption and causing watery diarrhea.

If C difficile is present in the colon, it will overgrow and produce toxins A and B, which bind to and kill cells in the bowel wall. The organism produces small amounts of these toxins, which only achieve cytotoxic levels when it is the predominant organism. Disease severity is related to the number of receptors for the bacterial toxin on the epithelial cells lining the colon. Toxin A is an enterotoxin that increases permeability of the intestinal wall by disrupting intercellular tight junctions. Toxin B leads to disruption of intestinal cell cytoskeletons by causing actin within the cell to depolymerize. Toxin B causes the epithelial cells to become more round in shape (or round up) and die by stimulating host cell mitogen-activated protein kinases (MAP-kinases) and inactivating proteins that regulate actin filament assembly (small guanosine triphosphate [GTP]-binding Rho proteins). It causes depolymerization of actin filaments, which cause the cells to round up and detach and shallow ulcers to form. Acute inflammation with pus and mucus formation results in pseudomembrane formation. Inflammation can extend through the full thickness of the bowel.

Diagnosis of pseudomembranous colitis generally is determined on the basis of a history of antibiotic therapy within the past month. Culture usually is not performed due to its expense and difficulty. An enzyme-linked immunoassay (ELISA) for toxins A and B can be performed on the fecal specimen. In about 50% of cases, fecal samples contain leukocytes and are heme positive. Endoscopy revealing the pseudomembranes can confirm the diagnosis if the patient is unable to produce a fecal sample or if an immediate diagnosis is required.

Withdrawal of the antibiotic and replacement of the intestinal flora generally suffices in the treatment of pseudomembranous colitis. If dehydrated, the patient should be given intravenous fluids and electrolytes. Antimotility drugs should not be given because they increase the likelihood of full-blown colitis and toxic megacolon.

If antibiotic treatment is necessary, metronidazole or vancomycin will eradicate C difficile; however, asymptomatic persons should not be treated with these drugs. Recurrences occur in about 25% of patients. Treatment with fidaxomicin results in fewer 2nd and 3rd recurrences. Fecal bacteriotherapy (fecal transplant) have been shown to lower future recurrences in patient with 2 or more recurrences. Patients with toxic megacolon should be treated surgically; bowel resection and ileostomy are recommended.

Standard infection control measures must be meticulously followed to prevent the spread of the bacterial spores from patient to patient. Thorough hand washing should be emphasized, and prolonged use of broad-spectrum antibiotic treatment should be avoided. The use of clindamycin, a common antibiotic that can cause overgrowth of C difficile, should be limited.

Bacterial dysentery can occur in the large and small intestine. Organisms that can cause bacterial dysentery and are discussed in this section of the handout include Campylobacter, Shigella, Salmonella, Yersinia and Escherichia coli. These organisms are invasive and cause the host to mount an inflammatory response. The stool volume frequently is small and contains mucus and leukocytes; if invasion is deep enough, the stool can be heme positive. The patient usually has a fever and complains of abdominal pain and pain while attempting to defecate (tenesmus).

In most cases, antimicrobial treatment of bacterial dysentery is beneficial. Treatment with antimotility drugs to stop the bacterial dysentery is contraindicated. The three most common causative organisms of bacterial dysentery are Campylobacter, Shigella, and Salmonella. Campylobacter, Shigella, Salmonella, Yersinia and the invasive Escherichia coli (enterohemorrhagic E coli [EHEC] and enteroinvasive E coli [EIEC]) are discussed below.

Campylobacter species are gram-negative slender, curved motile rods. These organisms are comma- or S-shaped (or seagull-shaped).

There are eight different species of Campylobacter that cause gastrointestinal infections; C jejuni is the most common species associated with human infection. Campylobacter are gram-negative S-shaped or gull–wing-shaped rods that commonly occur in pairs and are microaerophilic and motile. Campylobacter are relatively fragile, and are sensitive to environmental stresses (e.g., 21% oxygen, drying, heating, disinfectants, and acidic conditions). The organisms require reduced oxygen and increased carbon dioxide and hydrogen concentrations for optimal growth. The optimal temperature for growth is 42°C.

Most cases of campylobacteriosis are mild and subside within 7 days; some cases may last for 2 weeks or longer. Symptoms include periumbilical cramping, intense abdominal pain that mimics appendicitis, malaise, myalgias, headache, and vomiting. Watery diarrhea is the most common manifestation.

Inflammatory bowel disease may occur in some patients with campylobacteriosis. Manifestations include malaise, fever, abdominal cramps, tenesmus, and bloody stools; fecal leukocytes are observed with light microscopy. The inflammation and pathology that is due to C jejuni is indistinguishable from the inflammation and pathology due to Shigella, Salmonella, and E coli. Clinical findings are not diagnostic. Complications are rare, but infections have been associated with reactive arthritis (persons with HLA-B27), hemolytic uremic syndrome (HUS), Guillain-Barré syndrome, and septicemia.

C jejuni is a leading cause of bacterial diarrheal illness in the U.S., with about 2 million cases per year. It is the second most common cause of invasive dysentery; Salmonella infections are the most common cause.
C jejuni is not carried by healthy individuals in the U.S. or Europe but can be isolated from healthy cattle, chickens, birds, and even flies. Between 4% and 20% of chicken meat sold in retail food markets is contaminated with this organism.
It is present in some nonchlorinated water sources such as streams and ponds.
Ingestion of undercooked or raw meat (e.g., poultry), unpasteurized milk, and nonchlorinated water contaminated with Campylobacter are the most common means of transmission.
About 1 million bacterial cells must be ingested to cause disease.

C jejuni adheres to intestinal epithelial cells and M cells. Depending on the bacterial strain, it can produce a heat-labile toxin or cause host cells to ingest bacterial cells. If a heat-labile enterotoxin is produced, a watery diarrhea occurs. If organisms induce the host cells to ingest the bacteria, an inflammatory colitis will usually occur. After adhering to the host cells, the bacteria use a type III secretory system to inject bacterial proteins into the host cells. These bacterial proteins cause the host cells to ruffle and ingest the bacterial cells.

Some strains of C jejuni produce a toxin called shiga toxin or verotoxin that enters the cytoplasm of the host cells and interrupts protein synthesis by removing an adenine residue from the 28S rRNA in the 60S ribosomal unit. Shiga toxin kills the host cells and results in the formation of superficial ulcers in the bowel mucosa and induces an acute inflammatory response.

Immunocompromised patients, patients with chronic illnesses, and persons at the extremes of ages are more likely to develop a bacteremia that may be transient and resolve without treatment or may infect other sites (e.g., meninges, lungs, heart, blood vessels). The clinical manifestations following C jejuni infection are similar to those caused by Shigella and EIEC.

Presumptive diagnosis of campylobacteriosis is based on the finding of gull-shaped bacteria in watery, bloody, leukocyte-filled feces. These bacteria have a characteristic darting motility. Definitive diagnosis requires isolation of the organism from stool or from other sites of infection. Isolation requires the use of campy-BAP or Skirrow media. These media contain antibiotics that reduce the growth of other enteric microorganisms.

Most C jejuni infections are mild and self-limited. They usually do not require antibiotic therapy, and correction of electrolyte abnormalities and oral rehydration are sufficient. Treatment is reserved for compromised hosts or persons with fever, increasingly bloody diarrhea, or symptoms that last longer than 1 week. C jejuni is usually sensitive to erythromycin, gentamicin, tetracycline, ciprofloxacin, and clindamycin. Properly cooking chicken, pasteurizing milk, and chlorinating drinking water will kill the bacteria and prevent infections with these bacteria.

Shigella is a common contaminant of water sources. A small number (200) of these bacteria can cause diseases in humans. Fortunately, Shigella rarely invades the bloodstream.

There about 50 Shigella species that can be classified into one of four serologic groups. Only two serologic groups are common in the U.S.: Group B, which contains S flexneri, is a species commonly isolated in the U.S.; and Group D, which contains S sonnei, is the most commonly isolated cause of shigellosis in the U.S. Shigella is a nonmotile, nonlactose fermenting gram-negative rod that is closely related to E coli and shares antigens and toxin-producing capability with them.

After an incubation period of 36–72 hours, the initial nonspecific symptoms of shigellosis are prominent and include fever (39°C) and cramping abdominal pain. Watery diarrhea usually appears after 48 hours, with dysentery (e.g., bloody mucous-containing small volume stools and tenesmus) supervening about 2 days later. Abdominal tenderness is usually general, and the abdominal wall is not rigid. Sigmoidoscopy reveals intense hyperemia, multiple small bleeding sites, loss of transverse mucosal folds, and thick, purulent mucous secretions. Tenesmus is present, and feces are bloody, mucoid, and small volume. Fluid and electrolyte loss may be relatively significant, particularly in pediatric and geriatric populations. Septicemia caused by E coli may be initiated by shigellosis.

Shigella is found only in humans and monkeys. About 300,000 cases of shigellosis occur each year in the U.S.
Shigella is quite resistant to eradication by stomach acid. As few as 200 organisms can infect the large intestine, and about 1 million organisms must infect the large intestine to cause campylobacteriosis and salmonellosis.
Shigellosis is mainly a disease of children between the ages of 1 and 4 years.
It is more common in closed population groups that have substandard sanitation (e.g., prisoner-of-war camps, homes for developmentally handicapped persons, Native American reservations).
Shigellosis is primarily transmitted by the fecal-oral route. Contaminated drinking water and person-to-person transmission are common means of spreading this bacterial infection.

Shigella adheres to intestinal epithelial cells and M cells. After adhering to the host cells, the bacteria use a type III secretory system to inject bacterial proteins into the host cells. These bacterial proteins cause the host cells to ruffle and ingest the bacterial cells. Once in the cells, the bacteria use a surface hemolysin to lyse the phagosome membrane and escape into the cytoplasm. The bacteria then use the host cells’ actin to move around inside the cell (actin rocket tails). When bacteria reach the periphery of the cell, the cell pushes outward to form membrane projections, which are then ingested by adjacent cells.

Some strains of the Shigella genus produce the shiga toxin or verotoxin, which is similar to the verotoxin of E coli O157:H7. The shiga toxin or verotoxin enters the cytoplasm of the host cells and stops protein synthesis by removing an adenine residue from the 28S rRNA in the 60S ribosomal unit. This toxic activity results in death of the host cells.

The cell-to-cell travel and toxin activity produces superficial ulcers in the bowel mucosa and induces an extensive acute inflammatory response. The inflammatory response usually prevents entry of the bacteria into the bloodstream. Unlike certain species of Salmonella (e.g., S typhi, S paratyphi A), Shigella only rarely enters the bloodstream.

Presumptive diagnosis of shigellosis is based on acute onset of fever and diarrhea with bloody and mucoid feces. Definitive diagnosis requires the isolation of Shigella from feces. Microabscesses in a rectal biopsy are suggestive of shigellosis. Diffuse involvement of the mucosa with multiple shallow ulcers 3–7 mm in diameter is suggestive of shigellosis. A rectal swab of an ulcer will reveal clumps of neutrophils, macrophages, and erythrocytes. Stool usually contains white blood cells and is positive for lactoferrin. Shigella is commonly isolated on Salmonella-Shigella agar (S-S agar).

Shigellosis is usually a self-limited disease; however, to shorten the course of the illness and prevent person-to-person spread, treatment with trimethoprim-sulfamethoxazole or ciprofloxacin usually is recommended. Fluid and electrolyte replacement is necessary in severe cases. Antidiarrheal compounds that inhibit peristalsis are CONTRAINDICATED.

To avoid acquiring shigellosis, the following precautions should be taken: drinking contaminated water or foods washed with contaminated water should be avoided; utensils and drinking glasses should not be shared with persons who are ill; hands should always be washed after changing diapers; and easy to reach hand-washing facilities should be provided in day-care centers.

Several different strains of Salmonella cause human disease. For example, some strains such as S enterica invade the tissues of the intestine but remain there and do not disseminate via the bloodstream to other organs of the body. These strains are also called the nontyphoidal strains of Salmonella. S enterica cause enteritis, which is the most common form of disease due to Salmonella.

However, other strains of Salmonella, including Salmonella Typhi, Salmonella Paratyphi A, Salmonella Schottmuelleri, and Salmonella Hirschfeldii, can invade the tissues of the intestine and are disseminated via the bloodstream to other parts of the body. These strains are also called the typhoidal strains of Salmonella. Salmonella Typhi, Salmonella Paratyphi A, Salmonella Schottmuelleri, and Salmonella Hirschfeldii cause enteric fevers and are less common than enteritis.

Salmonella are gram-negative motile rod-shaped facultative anaerobes that produce hydrogen sulfide (H2S) gas and do not ferment lactose. Table LI-1 lists the Salmonella that can cause human infections.

Table LI-1. Diseases Caused by Salmonella
Bacteria	Disease Caused
S enterica	Enteritis
S enterica serovar choleraesuis	Bacteremia
S Paratyphi A	Paratyphoid fever (enteric fever), bacteremia
S Schottmuelleri (formerly S Paratyphi B)	Paratyphoid fever (enteric fever), bacteremia
S Hirschfeldii (formerly S Paratyphi C)	Paratyphoid fever (enteric fever), bacteremia
S typhi	Typhoid fever (enteric fever), bacteremia

S enterica is the most common cause of salmonellosis. It causes enteritis, a disease that results in diarrhea, fever, and abdominal cramps. Symptoms appear about 24–48 hours after ingestion of contaminated food or water. Initially the patient experiences nausea and vomiting, abdominal cramps, and nonbloody diarrhea. There may be signs of systemic involvement because patients will have fever, headache, and myalgias. Symptoms last from 2 days to 1 week and usually resolve spontaneously. Occasionally, a patient with enteritis will have bloody diarrhea but this is uncommon.

All salmonellae can cause bacteremia. However, Salmonella Typhi, Salmonella Paratyphi A, Salmonella Schottmuelleri, and Salmonella Hirschfeldii and S enterica serovar Choleraesuis are strains that are more likely to cause bacteremia. The clinical presentation is similar to other cases of gram-negative sepsis. Symptoms of sepsis are usually nonspecific and include fever, chills, and constitutional symptoms of fatigue, malaise, anxiety, or confusion. The risk of bacteremia is higher in pediatric, geriatric, and immunocompromised patients.

Enteric fevers are caused by S Typhi (typhoid fever), S Paratyphi A, S Schottmuelleri, and S Hirschfeldii (paratyphoid fever). About 10 to 14 days after ingestion, patients experience a gradually increasing fever with headache, myalgias, malaise, and anorexia. The symptoms persist for about 1 week and are followed by diarrhea. These manifestations correspond to an initial bacteremic phase, followed by colonization of the gallbladder, and then reinfection of the intestines. Symptoms of S Typhi may be more severe than symptoms seen in patients with paratyphoid fever. S Typhi can cause skin lesions called rose spots. The strains of Salmonella responsible for enteric fevers can chronically colonize the gallbladder and serve as an infectious reservoir. Patients can be colonized and can be infectious for up to 1 year following resolution of symptoms.

About 1 million cases of salmonellosis occur in the U.S. each year, and the incidence appears to be increasing.
About 1 million bacterial cells must be ingested to cause disease. Because large numbers of organisms are required to cause infection, most infections occur following ingestion of heavily contaminated foods.
Salmonellosis is more common in the summer months when warmer temperatures allow for rapid growth of the organisms in contaminated foods.
Almost all strains of Salmonella (except Salmonella Typhi, Salmonella Paratyphi A, Salmonella Schottmuelleri, and Salmonella Hirschfeldii) colonize virtually all animals. Salmonella are commonly found inhabiting the intestines of chickens, reptiles, birds, and humans.
Salmonella Typhi, Salmonella Paratyphi A, Salmonella Schottmuelleri, and Salmonella Hirschfeldii are found only in humans.
Some humans infected with these organisms become chronic carriers after Salmonella Typhi, Salmonella Paratyphi A, Salmonella Schottmuelleri, and Salmonella Hirschfeldii the gallbladder. These carriers transmit the infection via fecal-oral routes.
Transmission from animals (e.g., turtles, iguanas) to humans and from animal food products to humans (e.g., raw meats, poultry, eggs, milk and dairy products, fish, shrimp, cream-filled desserts and toppings, peanut butter, cocoa, and chocolate) is common.

Salmonella are sensitive to killing by gastric acid. Therefore, Salmonella requires large numbers of organisms to cause an infection of the intestines. If the acid in the stomach is reduced or neutralized, fewer organisms are required. If the organisms survive the stomach’s acidity, the bacteria attach to the epithelial cells in the small intestine and colon. Once attached to the host cells, Salmonella bacteria use a type III secretory system to inject bacterial proteins into the host cells. These bacterial proteins cause the host cells to ruffle and ingest the bacterial cells in large vacuoles. In the vacuoles, the bacteria replicate and eventually cause the cells to lyse. Following host cell lysis, the bacteria escape into the extracellular environment and gain entry into the mesenteric lymph nodes and some enter the bloodstream. Most infections result in fever, abdominal pain, and diarrhea. One of the few serovars of S enterica that can enter the bloodstream and cause nontyphoidal bacteremia is S enterica serovar choleraesuis.

The strains of Salmonella that cause enteric fevers can rapidly enter the bloodstream. These strains cause only minimal damage in the intestine (little, if any, diarrhea). Salmonella Typhi, Salmonella Paratyphi A, Salmonella Schottmuelleri, and Salmonella Hirschfeldii are most invasive. These bacteria pass through the cells lining the intestines and are engulfed by macrophages. They survive in the macrophages and are carried by the macrophages to the liver, spleen and bone marrow where they replicate. Manifestations of the disease correspond to an initial bacteremic phase (gradually increasing fever with headache, myalgias, malaise, and anorexia), followed by colonization of the gallbladder and reinfection of the intestines (diarrhea).

Salmonella cause less inflammation than do Shigella. In Salmonella infections, there are fewer fecal leukocytes, and isolation of the organisms from a fecal sample using S-S agar is necessary for a definitive diagnosis. Stool samples yield non-lactose fermenting gram-negative motile rod-shaped facultative anaerobes that produce hydrogen sulfide (H2S) gas.

Enteritis is self-limiting in most people. Treatment prolongs carriage of the bacteria and does not shorten the course of the illness. However, certain patients should be treated due to their increased likelihood of developing bacteremia, endocarditis, and osteomyelitis. These groups include neonates, persons > 50 years of age, immunocompromised patients, patients with sickle-cell disease, and patients with prosthetic valves or vascular grafts Fluid and electrolyte replacement is necessary in severe cases. Antidiarrheal compounds that inhibit peristalsis are CONTRAINDICATED.

Patients with enteric fevers warrant immediate antibiotic therapy (e.g., ciprofloxacin or ceftriaxone) and in severe cases, fluid and electrolyte replacement is necessary. Antidiarrheal compounds that inhibit peristalsis are also contraindicated in enteric fevers.

Persons traveling to countries with high rates of typhoid fever should be vaccinated. Two typhoid vaccines are available for use in the U.S.: an oral live attenuated vaccine and a Vi capsular polysaccharide vaccine that is injected.

The E coli strains that normally resident in the human intestine have minimal or no invasive ability. However, enterohemorrhagic E coli (EHEC) and enteroinvasive E coli (EIEC) have acquired certain genetic traits from Shigella that allow them to possess the same invasive capabilities that Shigella possesses.

EHEC strains, also called shiga toxin-producing E coli (STEC), have acquired shiga toxin, which causes cell death, edema, and hemorrhage in the lamina propria. There are two kinds of shiga toxin (Stx-1 and Stx-2). EHEC strains can produce only one or both of the shiga toxins. The blood from the lamina propria can enter the lumen of the intestine and cause hemorrhagic colitis. Strains of EHEC that produce Stx-2 are more likely to cause kidney damage resulting in hemolytic uremic syndrome (HUS). The shiga toxin can kills glomerular endothelial cells in the kidneys this damage activates platelets and thrombin deposition. This decreased glomerular filtration and results in acute renal failure. The most common cause of hemorrhagic colitis and HUS is EHEC serotype O157:H7; however, non-O157:H7 serotypes of E coli can produce shiga toxin and cause hemorrhagic colitis and HUS.

EHEC E coli serotypes are O157:H7 and non-O157:H7. EIEC strains of E coli can also cause dysentery. EHEC and EIEC are facultative gram-negative, motile rod-shaped bacteria. E coli 0157:H7 does not ferment sorbitol, and thus can be differentiated from non-O157:H7 serotypes of E coli.

EHEC causes hemorrhagic colitis. Manifestations include severe crampy abdominal pain and watery diarrhea followed by grossly bloody diarrhea; there usually is no fever. The symptomology of HUS includes the triad of acute renal failure, thrombocytopenia, and microangiopathic hemolytic anemia. Hemorrhagic colitis usually precedes HUS. EIEC infection produces a watery diarrhea, which can result in dysenteric stools (small volume, mucous-containing bloody feces).

About 73,000 cases of EHEC infection are reported each year in the U.S. Around 60 deaths occur each year following EHEC infection
EHEC can live in the intestines of healthy cattle. Meat can be contaminated during slaughter, and organisms can be mixed into beef when it is ground.
The most common means of infection is consumption of insufficiently cooked ground beef.
Ingestion of fewer than 100 EHEC organisms can cause disease. Person-to-person transmission can also occur with this organism.
The second most common source of EHEC infection occurs following consumption of fresh leafy green vegetables (e.g., spinach, sprouts, lettuce). Other sources of infection involve consumption of salami and unpasteurized milk and juice and ingestion of sewage-contaminated water or swimming in contaminated water.
In some persons, especially children younger than 5 years of age and the elderly, infection with EHEC can also cause HUS. About 2–7% of EHEC infections lead to HUS.
In the U.S., HUS is the principal cause of acute kidney failure in children; most cases of HUS are caused by E coli O157:H7.
Infected persons can transmit the infection from person to person if hygiene or handwashing habits are inadequate, which is particularly likely among toddlers who are not toilet trained. Family members and playmates of these children are at high risk of becoming infected. Young children typically shed the organism in feces for 1–2 weeks after the illness has resolved.

Most pathology in EHEC infections occurs in the lamina propria of the ascending and transverse colons. Colonic biopsy specimens show focal necrosis and infiltration of neutrophils. Damage to the kidneys is due to the shiga toxin and results in swollen glomerular epithelial cells, fibrin deposition, and infiltrates of inflammatory cells.

EIEC can invade and destroy colonic epithelial cells. They are closely related to Shigella. After invasion of the cell EIEC lyse the phagocytic host cell vacuole and multiply in the cytoplasm. They then utilize host actin to form actin tails that helps them move about the host cell and to invade adjacent uninfected cells. This epithelial cell destruction results in the infiltration of inflammatory cells and can result in colonic ulceration.

Isolation and identification of the etiologic agent is necessary for definitive diagnosis of E coli dysentery. To grow EHEC O157:H7, the carbohydrate sorbitol must be included in the medium.

Antimotility drugs and antibiotics should NOT be given to patients to treat EHEC infections. Administration of antibiotics kills the bacteria and releases additional toxin, increasing the likelihood that the patient will develop HUS. To prevent EHEC infections, individuals should be advised to properly cook all food and to drink only pasteurized fruit juices.

EIEC infections are usually self-limiting; however, in severe cases, patients can be given trimethoprim-sulfamethoxazole or a fluoroquinolone or ciprofloxacin. Antimotility drugs should NOT be given. EIEC infections can be prevented by drinking from safe potable water sources.

Y enterocolitica is an inhabitant of animals and humans. Diseases associated with infection by this organism include diarrhea that may become dysenteric, pseudo-appendicitis, and gram-negative sepsis.

Y enterocolitica is a gram-negative facultative anaerobe. It does not ferment lactose and is urease positive. It is motile at 25 degrees C but not at 37degrees C. It can grow at 4 degrees C however; its optimum temperature for growth is 25-28 degrees C. Selective growth medium is recommended since it grows slowly at 37 degrees C. The most widely studied selective medium is cefsulodin-irgasin-novobiocin (CIN) agar, which inhibits the growth of competing flora and produces a characteristic bull’s eye appearance with a red center. This organism can be isolated from a human sample in 24 to 48 hours at 25 degrees C on CIN medium.

Diarrhea (dysentery) - The incubation period is usually 4 to 6 days (range 1 to 14 days). The onset of diarrhea is more subacute than other diarrheal pathogens. Clinical symptoms include diarrhea, abdominal pain (right lower quadrant), and fever. A small percentage of adults may also complain of bloody stools. Nausea and vomiting may also occur. The median duration of diarrhea for yersiniosis is usually longer (12-22 days). Stool shedding of organisms may persist after the diarrhea has ended. Shedding of the bacterium can range from 17 to 116 days. Some patients may have persistent diarrhea or abdominal pain up to a year following acute illness.

Bloody diarrhea is more common in children. Children will also have a high fever and vomit. Children are less likely to have abdominal pain.

Pharyngitis is an accompanying symptom in some patients. This symptom can be a helpful diagnostic clue, since no other cause of acute bacterial diarrhea routinely causes pharyngitis.

Septicemia- can occur during acute infection, particularly among infants and individuals with impaired immunity or iron-overload states. Rapid onset septic shock can occur with an overall fatality of 50%.

Pseudoappendicitis - Since Y enterocolitica colonizes the ileum and appendix, patients with abdominal pain will oftentimes complain of lower right quadrant abdominal pain that can be mistaken for acute appendicitis. Patients present with right lower abdominal pain, fever, vomiting, leukocytosis, and mild diarrhea. If surgery is performed, findings include visible inflammation around the appendix and terminal ileum and inflammation of the mesenteric lymph nodes; the appendix is normal. Yersinia can be cultured from the appendix and involved lymph nodes.

Post-infectious sequelae include erythema nodosum and reactive arthritis in patients that are Northern European and have HLA-B27 tissue type.

Y enterocolitica has been isolated from rodents, domestic animals (dogs, cats, sheep, cattle and swine).
Human infections usually result from ingestion of contaminated food or water or contact with contaminated fomites. Examples include undercooked pork, unpasteurized milk and agricultural runoff may contaminate drinking water sources.
Causes 98,000 illnesses, 530 hospitalizations, and 8 deaths each year in the US.
This organism can also be acquired from contaminated blood transfusions.

Infection requires ingestion of a large number of bacterial cells (108-109 cells). Once in the ileum the bacteria bind to M cells using adherence proteins invasion (Inv) and Yersinia adhesion A (YadA). The bacteria invade the M cells and kill them by activating apoptosis in the M cells. Cell killing can cause ulcerating of the lining of the ileum. The bacteria then go on to invade the Peyer’s patches or spread to the spleen, liver or mesenteric lymph nodes. Once in the Peyer’s patches, mesenteric lymph nodes, spleen or liver the organisms produce abscesses.

To produce abscesses this they must avoid phagocytosis. Virulent strains of Y enterocolitica possess a 70 kb plasmid that encodes a Type III secretion system. This secretion system injects proteins from the bacterium into host macrophages and neutrophils (Yersinia outer proteins or Yops). These Yops disrupt the formation of actin microfilaments in the phagocytes and prevents phagocytosis of Y enterocolitica cells.

LPS from Y enterocolitica can activate complement and antibodies produced to Y enterocolitica antigens can result in opsonization and phagocytosis. However, the bacterial outer membrane proteins YopA and AiL prevent complement binding and host antibodies from binding to the surface of Y entercolitica.

Culture the patient samples (e.g., stool, blood ) on selective media (CIN) and incubate at room temperature for several days. Look for bull’s eye appearance of the colonies (white edges with red center). Alternatively, dilute stool sample in buffered saline at pH 7.6 and incubate for 2-4 weeks at 4oC. In time the other organisms in the stool die and Y enterocolitica grows and becomes numerous enough to see its colonies when grown on MacConkey’s agar. The organism is lactose negative, urease positive, motile at 25oC but not at 37oC.

Supportive care to prevent dehydration and treat with antibiotics such as tetracycline or trimethoprim-sulfamethoxazole. Antidiarrheal compounds that inhibit peristalsis are CONTRAINDICATED. Prevent contamination of food and water by pets and other animals.

Entamoeba histolytica is the only parasite that causes dysentery, and it is relatively uncommon in the U.S. However, it does cause infections worldwide and can invade tissues contiguous to the colon.

Entamoeba histolytica is a protozoan parasite. It is an amoeba that exists in two forms: the trophozoite form and the cyst form. The motile amoeboid trophozoite is the only form present in tissue. The cyst form is the infectious form of the parasite.

After an incubation period of 1–5 days, amebiasis begins with a prodromal episode of diarrhea, abdominal cramps, nausea and vomiting, and tenesmus. Feces may be watery; in dysentery, feces are generally watery and contain mucus and blood.

Trophozoites of E histolytica can penetrate the colon and infect the liver, causing amebic liver abscess. Symptoms of amebic liver abscess include abrupt onset of high fever and right upper quadrant abdominal pain. The pain is constant and may radiate to the right scapula and shoulder. It may become pleuritic and increase when the patient lies on the right side. In abscess of the left lobe of the liver, the pain may be predominantly epigastric and radiate to the left shoulder. Anorexia and nausea and vomiting may occur.

Involvement of nonhepatic extraintestinal organs is much less frequent in amebiasis. Trophozoites may disseminate to other organs, especially when there is a liver abscess, by direct extension into the lung, pleural cavity, or pericardium or through the bloodstream to the lung or brain. Cutaneous lesions may result from direct invasion of macerated epithelium in the perianal area when trophozoite-containing liquid feces contaminate the skin.

The distribution of the parasite E histolytica is worldwide, with higher incidence in developing countries.
In industrialized countries, high-risk groups include male homosexuals, overseas travelers outside the U.S., recent immigrants, and institutionalized populations (e.g., prison inmates).
The liver is the most common site of extraintestinal amebic disease.
Amebiasis is transmitted by fecal contamination of drinking water and foods, but can also be transmitted by direct contact with fecally contaminated hands or objects as well as by sexual contact.

E histolytica exists in two different forms; an infectious cyst and a tissue dwelling trophozoite. The cyst of E histolytica is ingested and passes through the stomach and small intestine. The cyst then excysts and produces the trophozoite in the intestine and it adheres to the surface-exposed lectins of intestinal epithelial cells. After adherence, trophozoites invade the colonic epithelium. The trophozoites of E histolytica lyse the target cells using the parasite’s ionophore-like protein to induce leakage of ions (i.e., Na+, K+, Ca+) from the cytoplasm of the target cell, which causes watery diarrhea. Ameboid movement and amebic enzymes such as proteases, hemolysins, cysteine kinase, hyaluronidase, and mucopolysaccharidases facilitate penetration into the wall of the intestine. After penetrating the wall of the intestine, E histolytica will produce flask-shaped ulcers in the intestines. These ulcerations are characteristic of this disease and usually occur in the cecum, appendix, and ascending colon.

E histolytica can also produce hepatic abscess, brain abscess, and rectal ulcerations. The trophozoites eventually penetrate the venules and lymphatics in the wall of the intestine, and gain access to the liver via the portal vein. The organisms in the hepatic microcirculation produce necrosis of the endothelium and penetrate into the periportal sinusoids, where they can digest pathways into the hepatic lobules. There is no initial inflammatory reaction; however as necrosis progresses, polymorphonuclear leukocytes gradually surround the lesion without formation of a definite wall. The lesions may remain focal or progress to form large solitary abscesses. Lung and brain abscesses are less common and are similar to those seen in the liver. Skin ulcerations are usually perirectal and have only minimal inflammation.

The diagnosis of amebiasis is confirmed by identifying E histolytica in feces or in tissues obtained from lesions. If the cytoplasm of the trophozoite contains red blood cells the diagnosis of amebiasis is definitive (the presence of intracytoplasmic red blood cells is pathognomonic for E histolytica). Leukocytosis without eosinophilia is common. ELISA assays are used to detect cysts in feces.

Serology for antibodies to the parasite is useful in extraintestinal infections. Chest radiograph, CT scan, and MRI are useful in visualizing extraintestinal amebic abscesses. A brown milkshake-like (anchovy paste-like) material is often aspirated from liver abscesses.

Asymptomatic intestinal E histolytica infections can be treated with paromomycin or iodoquinol. Mild to moderate disease that includes diarrhea or dysentery can be treated with metronidazole followed by either paromomycin or iodoquinol. If the pleura surrounding the lungs are involved, drainage via a chest tube or thoracotomy may be necessary. Only large liver abscesses (> 12 cm in diameter), should be treated surgically. Contaminated water sources and behaviors that result in fecal-oral spread of the organism should be avoided.