Enteric infections

Author: Dr Amanda Peppercorn University of North Carolina Chapel Hill
2008-07-28

Yersinia enterocolitica. Source: Public Health Image Library

The topic of enteric infections encompasses all infections of the intestinal tract. Certain infections have an anatomic preference, - causing disease of the esophagus, stomach, small intestine, or large intestine, while others can involve multiple anatomic areas of the intestinal tract or involve distant organs in addition to the intestines. While many systemic illnesses are caused by infectious agents that enter via the intestinal tract and disseminate, such as acute Hepatitis (Hepatitis A or Hepatitis B viruses) or Typhoid Fever (Salmonella typhi), only infections of the intestinal tract will be discussed in this article.

Susceptibility to certain infections is determined primarily by the status of the immune system of the individual, which can be greatly affected by immunosuppressive drugs (corticosteroids, cancer chemotherapy, 6-mercaptopurine, tumor necrosis factor antagonists), organ transplantation, or HIV/AIDS. Water sources and sanitation, seasonality, environmental factors, as well as local outbreaks, determine risk of various infections geographically. Bacteria, yeast/fungi, viruses, and parasites (worms and amoeba-like protozoans) all cause enteric infections. This knol will describe by anatomic location the various infectious agents that cause intestinal disease, provide an overview of clinical syndromes associated with the various infectious agents and give a general overview of standard first-line treatment for most infections.

Table 1. Important Definitions

Esophagitis	Inflammation of the lining of the esophagus
Gastritis	Inflammation of the lining of the stomach
Gastroenteritis	Inflammation of the lining of the stomach and small intestine  resulting in acute diarrhea
Enterocolitis	Inflammation of both the lining of the small intestine and the large intestine (colon) resulting in severe diarrhea
Colitis	Inflammation of the lining of the large intestine (colon) resulting in severe diarrhea
Dysentery	Frequent, small-volume, severe bloody diarrhea often accompanied by intestinal cramping, fever, mailasie and tenesmus (painful straining and urgency to pass stool)
Proctitis	Inflammation of the anus and the distal rectum (anatomically the last part of the colon that connects the intestinal tract to the anus) resulting in pain and urgency and often bloody mucus drainage
Virus	A very small microbe that requires another organism to grow and reproduce
Bacteria	A small, free-living prokaryotic microbe
Protozoa	A free-living, relatively large, one-celled organism that is a complex eukaryote, the cell-type shared by higher organisms (eg, amoeba)
Fungus	Eukaryotic organisms with a unique cell wall component (chitin) with various forms (yeast, mold, spores)

The Esophagus

What are the causes of infectious esophagitis?

Infections of the esophagus are rarely seen in someone with a normal immune system. The most frequently diagnosed infection is candidal esophagitis, but herpes viruses and other viruses can occasionally infect the lining of the esophagus as well. Esophagitis is often seen in the setting of HIV/AIDS, hematologic malignancies (leukemia, lymphoma), cancer chemotherapy, long-term oral or inhaled corticosteroid or antibiotic use, and poorly controlled diabetes. Diagnosis of esophagitis without a known underlying condition should prompt further investigation of the immune status of the patient.

Candidal esophagitis is caused by members of the Candida species of yeast which includes Candida albicans, Candida glabrata, Candida parapsilosis, Candidatropicalis, Candida krusei and many others but Candida albicans accounts for the vast majority. Esophageal candidiasis can be accompanied by oropharyngeal candidiasis (termed “oral thrush”) making the diagnosis of this infection much easier since it is easily visible to the health care provider. Oral thrush can be asymptomatic, but extensive candidal infection, as occurs with esophagitis, usually causes significant symptoms of pain and sharp discomfort, particularly with swallowing. It can occasionally cause nausea and vomiting as well. When present in the mouth, it appears as white plaques on the mucosal surfaces which can be sent for fungal wet prep (KOH) and culture for microbiologic confirmation. However, diagnosis of esophageal candidiasis without oral involvement generally requires upper endoscopy with culture and biopsy of plaque-like lesions. Pathology will show budding yeast with pseudohyphae invading mucosal surface cells. Treatment of candidiasis can vary depending on the immune status of the host, the extent of involvement of infection, and the species of Candida. C. albicans is almost always susceptible to first-line antifungal agents such as topical solution nystatin (“swish and swallow”) which is used for prevention or mild disease or oral fluconazole for moderate-severe disease; resistance can emerge over time. 

     Several members of the herpes family can also cause disease of the esophagus. These viruses are often acquired early in life and persist in the body in latent form after initial exposure. When the immune system is suppressed, they can reactivate and can cause substantial morbidity and mortality in several parts of the body. Herpes simplex virus 1 and 2 (HSV-1 and HSV-2), Cytomegalovirus (CMV), and Varicella zoster virus (VZV) can all reactivate in the esophagus and cause extensive erosions and ulcerations. Diagnosis cannot be made based on simple visualization because they all cause an appearance of ulceration. These infections are often extremely painful and can lead to microscopic, although rarely substantial gastrointestinal bleeding. Diagnosis is made by upper endoscopy and biopsy which shows viral cytopathic effect, Cowdry intranuclear inclusions, and multinuclear giant cells (see images). Designated PCR testing (polymerase chain reaction) and viral culture will yield a specific viral diagnosis. HSV also causes gastrointestinal (GI) involvement of the lips, mouth, rectum, and peri-anal tissue (usually HSV-2 with genital/rectal and HSV-1 with oral and esophageal involvement). CMV can infect any part of the GI tract but is most commonly seen in the esophagus and large intestine and is a common cause of rectal bleeding and diarrhea, particularly in the setting of AIDS. Treatment of viral infections of the GI tract depends on the viral agent; an acyclovir-based regimen (acyclovir, valacyclovir or famciclovir) will treat HSV and VZV while CMV requires a ganciclovir-based therapy. It is not uncommon to have more than one pathogen identified at the time of diagnosis.

The Stomach

What are the causes of infectious gastritis?

The term gastritis refers to inflammation of the lining of the stomach, which can be caused by problems with acid regulation, drug effect (,eg, aspirin, non-steroidal anti-inflammatory agents), or infection. Because of the high level of acid in the stomach, few micro-organisms can survive and thrive in this environment.

Staphylococcus aureus or Bacillus cereus can thrive in thegenerally inhospitable environment of the stomach. These foodborne, toxin-mediated bacterial strains cause acute gastritis by releasing a toxin into the stomach, causing acute nausea and vomiting (“food poisoning”). They generally resolve rapidly without treatment—onset of symptoms is usually between 4-7 hours after the contaminated meal and resolution of symptoms is usually within 12 hours of onset of nausea and vomiting.

Helicobacter pylori is another bacterial pathogen that involves the stomach. This curved bacterium is able to tightly adhere to gastric epithelial cells and is protected from acid by hiding in the thick mucus layer. It has been associated with chronic infection of the stomach and duodenum leading to dyspepsia and peptic ulcer disease and rarely gastric malignancies.

The Intestines

What is gastroenteritis and enterocolitis and what are the causes?

    Gastroenteritis (“stomach flu”) is an extremely most common illness, affecting approximately 11% of the United States population in a given year. The term gastroenteritis refers to inflammation of the lining of the intestinal tract of the stomach and small intestine, although the phrase is used indiscriminately, and many infections involve just the small intestine or the small and large intestine, termed “enterocolitis.” While symptoms vary depending on the infectious agent, pathogens which primarily involve the small intestine, such as certain protozoa, viruses and cholera, typically cause watery diarrhea and mild abdominal cramps as well as nausea, vomiting, anorexia (loss of appetite) and dehydration. Most episodes of gastroenteritis are acquired by the fecal-oral route of transmission—this occurs when infected stool particles are transmitted via contamination of hands to another host who then ingests these particles and acquires infection.  Many intermediary steps are usually required, including water that has come in contact with feces and is improperly treated before drinking, food that has been poorly handled, and poor sewage treatment.

Table 2. 2005 FoodNet surveys of laboratory diagnosed cases of bacteria or protozoal causes of acute foodborne illnesses in the United States (MMWR report) and Treatment (reference 4)

Incidence per 100,000 persons of the most common pathogens	Treatment
Salmonella – 14.6	Usually not required, oral fluoroquinolone (eg, ciprofloxacin) for 3-5 days
Campylobacter – 12.7	Usually not required, macrolide antibiotics (eg, azithromycin), fluoroquinolones also effective but increasing resistance reported
Shigella – 4.7	Oral fluoroquinolone, trimethoprim-sulfamethoxazole (TS) or macrolide but many strains now resistant to TS
Cryptosporidium – 3.0	No proven effective therapy; nitazoxanide, paromomycin often prescribed
E. coli 0157:H7 – 1.1	Antibiotics may make infection/risk of hemolytic uremic syndrome worse and should be avoided
Incidence per 1 million persons for the next most common pathogens:
Yersinia – 3.6	Antibiotics not usually indicated; oral fluoroquinolone for 7-10 days in severe cases
Listeria – 3.0	Ampicillin or trimethoprim-sulfamethoxazole
Vibrio – 2.7	Doxycycline, single dose or ciprofloxacin, single dose
Cyclospora – 0.2	Trimethoprim-sulfamethoxazole double strength twice a day for 7-10 days

    Salmonella and Yersinia usually infect the distal ileum (the last part of the small intestine), but colonic (large intestine) involvement is common as well. Fever is often present and diarrhea may be watery or frankly bloody (“dysentery”). Shigella, Campylobacter, E. histolytica and CMV all cause colitis, with symptoms of lower abdominal pain, tenesmus (sensation of urgency to defecate), and fever. The stools are of smaller volume and contain blood and mucus. The majority of cases of acute infectious gastroenteritis are caused by viral pathogens, although bacteria and protozoans cause a substantial portion as well, particularly in the setting of foodborne outbreaks and in overseas traveler’s diarrhea. In a review of approximately 30,000 bacterial stool cultures performed in the United States from 1990-1992, a bacterial cause was found in only 5.6% (1) of the samples, with the rest of the episodes attributed to viral or protozoal pathogens. 

    Because of the well-recognized clinical syndrome and the brief duration of illness, most episodes of acute gastroenteritis do not require precise diagnosis of the infectious agent, however determination of the etiology can be particularly important in the setting of an outbreak. Only a small fraction of stool samples submitted for culture or parasite detection yield a pathogen and patients are often asymptomatic by the time enteric pathogens are identified. Stool examination should be performed if severe or prolonged symptoms occur, fecal leukocytes in the stool (white blood cells which are a marker of colonic tissue invasion and an inflammatory process) are present, the patient is immunocompromised, or the patient has traveled and the gastroenteritis is not self-limited. Treatment for viral agents of disease is entirely supportive, with maintenance of hydration while bacterial and protozoal infections can be treated with targeted antibiotic therapy. The major infectious agents are described below (see table 1 for complete list):

Viruses

·         Noroviruses (eg, Norwalk-like virus) account for foodborne outbreaks in diverse settings such as cruise ships, nursing homes, and hospitals, and are a common cause of overseas traveler’s diarrhea. It is estimated that over one-third of outbreaks of non-bacterial gastroenteritis in the United States are caused by these viruses.The virus is highly infectious and requires only a small number of organisms to spread among people by the fecal-oral route.  The incubation period is 24-48 hours and the average duration of symptoms is between 1-4 days, with characteristic explosive vomiting and diarrhea.  The mechanism by which these viruses induce vomiting and diarrhea is not well understood. 

·         Astroviruses have also been associated with outbreaks of gastroenteritis, predominantly in settings that involve children, such as in daycare centers and schools. It is more common in HIV-infected children or children with hematologic malignancies.

·         Rotavirus is the single most important cause of severe, dehydrating gastroenteritis in infants and children worldwide, and causes substantial morbidity and mortality in resource-poor settings where people do not have access to rapid rehydration through intravenous fluid resuscitation or oral rehydration therapy.  Based on a recent meta-analysis, rotavirus is estimated to cause approximately 111 million episodes of gastroenteritis requiring only home care, 25 million clinic visits, 2 million hospitalizations, and 352,000–592,000 deaths (median, 440,000 deaths) in children <5 years of age. By age 5, nearly every child will have an episode of rotavirus gastroenteritis, 1 in 5 will visit a clinic, 1 in 65 will be hospitalized, and approximately 1 in 293 will die. Children in the poorest countries account for 82% of rotavirus deaths(2).  Adolescents and adults are protected by development of protective antibodies when exposed in early childhood.  A childhood vaccine against rotavirus (RotaTeq) was recently approved and implemented into routine pediatric care in the United States.

·         Enteric adenovirus (serotypes 40 and 41) cause approximately 5-10% of pediatric gastroenteritis in the United States.

Bacteria

·         Campylobacter jejuni accounts for approximately 2.3% of all episodes of gastroenteritis and close to 50% of all cases of bacterial gastroenteritis.  It is most commonly acquired from undercooked contaminated poultry.  Diarrhea is usually watery but can occasionally become hemorrhagic, and abdominal pain, cramping, and fever are often present. Unique to C. jejuni infection is its association with post-infectious reactive arthritis and Guillain-Barre syndrome, an ascending paralysis, felt to be caused by antibody cross-reactivity and auto-immunity.

·         Salmonella enteritidis and Salmonella typhimurium are commonly associated with ingestion of poultry, eggs, and milk products as well as meats, contaminated fresh produce, and other food products (4).  Additionally, several animals can transmit this bacteria, such as turtles.  Like C. jejuni, Salmonellosis usually presents as watery diarrhea but can become hemorrhagic if colitis (inflammation of the large intestine) develops.  Salmonella can infect all adults and children but certain factors put people at increased risk. These include lymphoproliferative disorders, young age, and altered intestinal flora due to surgery, inflammatory bowel disease, or recent antibiotic use. Rarely, these bacteria can enter the bloodstream and develop distant sites of infection in the bone (often associated with Sickle Cell Disease), the brain, or in the lining of the blood vessels (endovascular infection).

·         Shigella species are known as the classic cause of “dysentery,” or bloody diarrhea.  Shigella species cause infection with transmission of as few as 10 organisms and can spread by food or the fecal-oral route.  Shigella produces a well-studied toxin, termed “shiga toxin” which can cause a systemic syndrome seen primarily in children called the “hemolytic uremic syndrome” that affects the blood cells, causing anemia and kidney damage. 

·         Vibrio cholera, the etiologic agent of cholera infection, is an important cause of infectious diarrhea worldwide and leads to substantial mortality in locations where access to fluid resuscitation is not feasible.   It is predominantly contracted via exposure to infected water.  While cholera is not a problem currently in the United States, Vibrio cholera bacteria have been isolated in the Gulf of Mexico, and has caused epidemics in South America.  V. cholera produces profuse watery diarrhea by release of a potent enterotoxin which inhibits salt absorption from the intestinal lining, leading to massive fluid secretion and loss into the gut lumen (3).  The toxin produces virtually no inflammatory response.  As with rotavirus, the cornerstones of management include estimation of the volume depletion and timely replacement of fluid and electrolyte deficits.  This can be achieved by intravenous fluids or by the standard World Health Organization formula, available in packets, which includes sodium chloride, sodium bicarbonate, glucose, potassium chloride, and water.  Antibiotic therapy with tetracycline may shorten the duration of illness and reduce shedding of the bacteria and further transmission.  Vibrio parahaemolyticus is a cause of worldwide diarrheal disease and is found in coastal areas of the United States, where contaminated shellfish transmit the disease .

·         Escherichia coli species account for a number of gastrointestinal syndromes.  Most E. coli species colonize the intestines and live as normal human gut flora.  However, several toxins and unique virulence factors give different strains of E. coli the ability to cause human disease:

o        Enterotoxigenic E. coli—causes watery diarrhea, and is the most common bacterial cause of traveler’s diarrhea, mediated by release of a toxin similar to cholera toxin.

o        Enteropathogenic E. coli—associated with infantile watery diarrhea

o        Enterohemorrhagic E. coli—causes a hemorrhagic colitis.  The E. coli 0157:H7 serotype is associated with production of a toxin similar to the toxin of Shigella species, the “shiga-like” toxin, and is the most commonly identified cause of the hemolytic uremic syndrome (HUS) in the United States.  Epidemics have been traced to contaminated beef but transmission through other food products, such as unpasteurized apple cider and raspberries (infected by contamination of animal feces), have also been reported.  This has also been associated with petting zoos (5) Antibiotics have not been shown to be helpful and potentially increase the risk of developing HUS, soshould be avoided (6).

o        Enteroinvasive E. coli—agent of travel diarrhea and dysentery

o        Enteroaggregative E. coli—agent that causes persistent diarrhea in children and people with AIDS

·         Yersinia enterocolitica infection is most common in developed countries such as the United States, and is associated with water or foodborne outbreaks.

·         Clostridium perfringens is a cause of watery diarrhea.  It is a foodborne toxin-mediated process caused by release of toxin from a large number of ingested bacteria.  The spores of C. perfringens can germinate in many types of foods and can be associated with unhygienic canning procedures.

·         Listeria monocytogenes is a cause of abdominal pain, cramping, and diarrhea.  It is seen primarily in immunocompromised individuals and is particularly harmful in the setting of pregnancy—the relative immunodeficiency in the third trimester puts women at 17-fold risk of disseminated infection and transmission to the fetus can result in stillbirth.  It has been associated with outbreaks of deli meats and is commonly associated with unpasteurized dairy products. After ingestion, Listeria may cause isolated intestinal disease but also may disseminate to the bloodstream and distant organs such as the central nervous system, resulting in meningitis.

Protozoa

·         Cryptosporidium parvum is the most common parasitic cause of acute foodborne diarrhea in the United States.  In the person with an intact immune system, Cryptosporidium causes severe dehydrating diarrhea that is self-limited.  In people with AIDS or other immunocompromised hosts, it may become persistent and debilitating, particularly because there is no effective treatment other than correction of the host’s immune system.  Transmission occurs via spread from animals or humans or from contaminated food and water sources.

·         Giardia lamblia causes both epidemic and sporadic disease and is a common cause of water and foodborne diarrhea, particularly unfiltered water supplies, even if chlorinated.  This is true even in fast flowing streams which can be contaminated by animal feces.  As with Cryptosporidium, immunocompromised hosts can develop chronic recurrent giardiasis.  The time course is prolonged, even in the normal host, with onset within 9-14 days and symptom resolution by 4-6 weeks.  Many infections are asymptomatic but most have a mild watery diarrhea with or without cramping, flatulence, and malabsorption. Diagnosis is made by visualization of cysts in the stool or a stool antigen test. Treatment is with metronidazole 250 mg three times daily for 10 days but there is an 8-20% failure rate.

·         Entamoeba histolytica is a worldwide cause of infectious enterocolitis and is more prevalent in areas with poor sanitary conditions, infecting up to 10% of the world’s population.  In the United States, it is more commonly seen as an infectious agent in migrant workers from Central America, overseas travelers, and in men who have sex with men.  Symptoms range from asymptomatic carrier state to mild diarrhea to severe dysentery.  Symptoms are slow to develop, ranging from 1-3 weeks, and can persist for several weeks to months.  In severe cases, toxic megacolon may develop with fulminant colitis which may lead to perforation. A rare complication is the development of amoebomas (tumor-like masses in the lining of the intestinal tract), which may cause intestinal obstruction and can be palpated on physical examination. Liver abscess is a common complication, often seen in people who never had intestinal symptoms.  The abscess is usually found as a solitary mass in the right lobe of the liver.  Ultrasound or computer tomographic imaging will reveal a hepatic abscess without specific characteristics but aspiration of contents will reveal trophozoites consistent with Entamoeba infection.  Diagnosis of intestinal amoebiasis can be made by simple stool examination for characteristic cysts or by blood test for entamoeba antibody.  In the setting of colitis, colonoscopy reveals involvement of the cecum (the last part of the small intestine which connects to the large intestine) and colon with characteristic “flask” ulcers with a wider base beneath the superficial epithelium.  Biopsy reveals classic trophozoites, necrotic debris and eosinophil cells.

·         Cyclospora cayetanensis has been associated with outbreaks of contaminated raspberries and basil.  It causes a small intestine watery diarrhea.  Like giardiasis, infection with Cyclospora may cause several weeks of symptoms, which can include fatigue and malaise in addition to diarrhea.  Cyclospora can develop a chronic unrelenting infection in the setting of AIDS and other conditions that inhibit the immune system.  Cyclospora is easily treated with trimethoprim-sulfamethoxazole for 7-10 days but relapse may occur.  Isospora and Microsporidia are two other infectious parasites that cause a clinical syndrome similar to Cryptosporidia and Cyclospora, and are also more commonly seen in the setting of immunosuppression and AIDS.  Isospora is also treated with trimethoprim-sulfamethoxazole and Microsporidia with albendazole for a prolonged course (up to 3 months).  For all of these infections, diagnosis can be made based on examination of stool cysts which each have a characteristic appearance and for staining with an acid-fast stain.

The Anus and Rectum

What infections cause proctitis?

Proctitis is infection and inflammation of the rectum and anus.  Sexually transmitted infections such as herpes (Herpes simplex virus), syphilis (Treponema pallidum), genital warts (condyloma acuminata, caused by Human papilloma virus) gonorrhea (Neisseria gonorrhea) and chlamydia (Chlamydia trachomatis) are introduced into the rectum during anal intercourse and cause rectal and anal disease that may be asymptomatic or may cause symptoms of purulent discharge, pain, itching, and rectal bleeding (see images). Diagnosis, in certain circumstances, can be made by culture of adherent mucus.  Treatment is the same as for genital involvement (reference sexually transmitted infection knol). 

Lymphogranularum venereum (LGV) (caused by a specific serovar of Chlamydia trachomatis) causes persistent infection with fever and enlargement of local lymph nodes, which may suppurate and form tracts into other tissues if untreated.  Anal ulcerations and strictures may be mistaken for Crohn’s disease (reference Crohn’s disease knol).  LGV is diagnosed by specific antibody detection and requires 3 weeks of treatment with doxycycline or tetracycline. 

What other important diseases of the intestinal tract are there?

Many other infections affect the intestinal tract.  Four important infectious agents that do not fit well into other classifications include Mycobacterium tuberculosis, Mycobacterium avium intracellulare, Histoplasma capsulatum and Clostridium difficile. 

·         Mycobacterium tuberculosis (or rarely Mycobacterium bovis) infects the gastrointestinal tract after ingested organisms penetrate normal mucosa.  This is an uncommon manifestation of tuberculosis which is predominantly a pulmonary disease, although tuberculosis can affect the lymph nodes, brain, kidneys, uterus, and many other organs.  Gastrointestinal tuberculosis can cause fever, gastrointestinal bleeding, abdominal pain, and weight loss and can result in ulceration, stricture, mass lesions (tubercles), and fistula formation.  Thickening of the bowel and lymphadenopathy are often present.  The cecum and terminal ileum are most commonly infected, but any part of the intestinal tract can be involved.  Disease is often segmental and mimics Crohn’s disease.  Histologically, necrotizing granulomas with acid-fast bacilli confirm the diagnosis.

·         Mycobacterium Avium Complex (MAC) infection is a common manifestation of end-stage AIDS.  MAC involves the gastrointestinal tract as part of a systemic infection of the blood and lymph nodes.  It rarely causes serious infection in immunocompetent individuals.  MAC infection causes watery diarrhea, abdominal cramping, fever, and weight loss.  Diagnosis is made by culture of blood or stool and treatment requires a prolonged course of a macrolide-based regimen that often requires 2 or 3 antibiotics followed by preventive treatment with azithromycin until the immune system can be restored by the administration of HIV medications.

·         Histoplasma capsulatum is a fungus found in the soil of certain geographic locations, such as the central river valleys in the United States and parts of Central and South America.  Infection follows inhalation of spores and lung disease is the most common site of infection.  However, in the setting of immunosuppression, the fungus can spread throughout the body including the brain and has a predilection for the gastrointestinal tract where it can cause ulcerations and rectocolitis.  The mouth is also a common site of disease, with ulcerations and mass-like lesions that can be mistaken for oral cancer.  Diagnosis is made based on culture of blood, bone marrow, or lymph node, by biopsy showing classic intracellular organisms and non-caseating granulomas, or by antigen (urine and blood) or antibody test.  Therapy for disseminated histoplasmosis depends on whether or not the brain and meninges are involved.  It requires a prolonged course of intravenous amphotericin, followed by oral itraconazole indefinitely, until the immune system of the individual can be restored by cancer or HIV treatment.

·         Clostridium difficile is a hardy, spore-forming bacterium that emerges as an important pathogen following administration of antibiotics.  Clindamycin and ampicillin were most strongly indicted in early studies but virtually every antibiotic has been associated with C. difficile colitis. In recent years, the fluoroquinolone class of antibiotics (levofloxacin, ciprofloxacin, moxifloxacin) has become an important cause.  C. difficile causes disease by release of its toxins, which are directly toxic to the lining of the intestinal tract, causing fluid loss and severe inflammation.  Severe disease results in pseudomembranous colitis in which the lesions appear whitish-yellow with plaques and nodules consisting of necrotic cells visualized by colonoscopy (see images).  Antibiotics presumably induce C. difficile colitis by suppressing normal gut flora and allowing C. difficile to grow, colonize, and produce toxin.  Although people in the community may be colonized, acquisition in the hospital setting is much more common.  The diagnosis can be delayed because of the confusion with the mild form of diarrhea that is commonly induced by use of antibiotics.  Culture of the stool for C. difficile is not useful due to the presence of many non-toxin producing strains that may inhabit the colon.  Therefore, diagnosis is made by various tests looking directly for the toxin (agglutination ELISA tests, stool cytotoxin assay).  Treatment includes discontinuation of the offending antibiotic (if possible) and a 10-14-day course of oral metronidazole or vancomycin.Relapse is common.

What helminthes (worms) infect the intestinal tract and what symptoms do they cause?

            Several environmental helminthes can cause significant gastrointestinal disease as part of their life cycle.  Symptoms and severity depend on the particular organisms and the stage of disease that involves the intestinal tract. All of these infestations occur by exposure through skin or by ingestion of contaminated food and water, thus the importance of wearing shoes when walking in moist soil, avoidance of swimming in ponds and lakes exposed to sewage, and avoidance ofingestion of fruit, vegetables, or local water in areas with poor sanitary standards. Some of the more common helminthes that cause human disease involving the gut are discussed below:

·         Anisakiasis is caused by ingestion of raw or improperly cooked seafood containing larvae of Anisakidae (see image).  Many seafood are infected and humans are accidental hosts.  Ingestion can result in trivial infestation of the esophagus and throat, or in mucosal invasion of the stomach and intestine.  Symptoms of invasive disease are usually rapid in onset and include abdominal pain, nausea, vomiting, and hives.  Endoscopy is required for both diagnosis and treatment (removal of the larvae).  Chronic infestation can cause eosinophilic granulomas (7).  No specific medication is known to be effective in treatment of anisakiasis.

·         Strongyloidiasis is caused by the ubiquitous nematode (round worm). Strongyloides stercoralis which is found around the world, primarily in temperate climates, including the warmer parts of the United States.  Strongyloides inhabits moist soil which can penetrate skin or be ingested. The larvae ultimately penetrate the small intestinal mucosa where they mature into adult worms that ultimately produce eggs that pass into the feces.  A cycle of auto-infection via the skin of the anal region creates the potential for decades of infection; in immunocompromised hosts, a syndrome of “hyperinfection” can develop which can be fatal.  Uncomplicated strongyloidiasis usually causes no symptoms; occasionally abdominal cramping, watery diarrhea, and malabsorption may develop.  The changes of ulceration, stenosis, and mucosal fold thickening may be mistaken for Crohn’s Disease (reference Crohn’s knol).  Diagnosis can be made upon finding larvae in the stool or tissues or by antibody blood test.  Treatment depends on the clinical syndrome and several parasitic antibiotics may be effective.

·         Ascaris lumbricoides, a large roundworm found throughout the world, infects more than one billion people. , Humans are infected when fertilized eggs are ingested by infected water or food sources.  Mature eggs hatch in the duodenum (first part of small intestine), then penetrate the lymphatic system, travel to the lungs, up the bronchial tree and are then swallowed back into the intestinal tract. There, the adults mature and lay huge numbers of eggs. Most patients are asymptomatic, although lung symptoms can occur during the pulmonary phase, and heavy infestation of the gut can cause intestinal obstruction or migrate into the pancreas and liver.  Diagnosis can be made on endoscopy, bronchoscopy (by visualization of larvae in the lungs), or by passing of the adult worms in the stool.  Treatment is with albendazole. (see image)

·         Whipworm, or Trichuris trichiura, are easily identified in stool specimens.  Infection occurs by ingestion of embryonated eggs in contaminated food or water which directly hatch in the small intestine.  Symptoms are usually absent and treatment is also with albendazole or mebendazole. (see image)

·         Hookworm is caused by two worms, Necator americanus and Ancylostoma duodenale which live in mammals such as cats and dogs.  Both larvae can penetrate skin with migration via the venous system to the lungs and back to the intestinal system, as seen in ascariasis above.  Abdominal pain and anemia may ensue but the majority of people are asymptomatic.  Treatment is with albendazole.

·         Enterobius vermicularis, or pinworm, is a small, threadlike worm that enjoys a worldwide distribution, including cosmopolitan regions. It is most often seen in children.  Adult worms live primarily in the cecum (last part of the small intestine) but migrate at night to the perianal region, where they deposit eggs, which cause intense itching.  Eggs are immediately infectious so household spread is common.  Diagnosis is made by the “scotch tape” test (see image) which demonstrates microscopic eggs from the perianal region.  Treatment is with albendazole or mebendazole.

What intestinal infections are associated with HIV/AIDS?

            Chronic diarrhea is a common clinical feature of patients with HIV/AIDS.  Often, HIV medications account for intestinal symptoms of diarrhea, nausea, and cramping, however the cell-mediated immunodeficiency caused by advanced HIV infection/AIDS predisposes patients to several infectious pathogens.  Several studies from the pre-HIV treatment era found that Cryptosporidia and cytomegalovirus were the most frequently encountered cause of infectious diarrhea, followed by Salmonella, Mycobacterium avium complex (MAC), and Entamoeba histolytica, respectively.  Giardiasis, Herpes simplex esophagitis and proctitis, Campylobacter, Candidiasis, Histoplasmosis, Cyclospora, Isospora, and Microspora also cause substantial infection in those with HIV/AIDS (8-10).  Kaposi's sarcoma, a vascular tumor seen much more commonly in the setting of HIV/AIDS, is associated with the Kaposi's sarcoma virus (KSV, also called Human Herpes virus 8 HHV-8) can involve any part of the intestinal tract as well (see image).  Mycobacterium tuberculosis causes active and disseminated infection in the setting of HIV/AIDS and can involve the intestinal tract as well.  In large cohort studies, over one third of patients were found to be simultaneously infected with more than one infectious agent (10).  The rate of opportunistic infections, including the many causes of enteric infections listed above, are much less commonly seen in people who have access to HIV medications and whose immune systems are better preserved.

Conclusion

Most cases of enteric infection cause acute, self-limited diarrhea but can lead to substantial morbidity and mortality in children, those who are immunosuppressed, and in developing countries where access to adequate rehydration therapy is limited.  The majority of infections are acquired by the oral-fecal route with contamination of water and food sources.  When traveling overseas, avoidance of exposure to local water sources including ice and fresh fruit and vegetables can be protective.  In the United States, a practice of good hand hygiene with frequent hand washing, particularly if exposed to hospital, nursing home, or daycare centers may prevent infection.  Lastly, ensuring that meat and fish are handled properly and cooked adequately is recommended.

In most cases, a precise diagnosis is not made and symptoms resolve quickly.  However, specific identification of the causative organism and targeted treatment is recommended in those with dysentery or prolonged symptoms, and can be achieved in the case of bacterial or protozoan infection with examination of the stool for fecal leukocytes, acid-fast staining, examination for parasitic cysts, and culture.  Many other infectious processes, including Clostridium difficile, tuberculosis, and helminthic infections cause substantial morbidity and mortality worldwide and require aggressive preventive efforts, specific diagnosis, and treatment.

Table 3. Pathogens that cause enteric infections

Bacteria Escherichia coli Campylobacter jejuni Vibrio species (parahaemolyticus, cholerae) Aeromonas hydrophilia Mycobacterium Avium Complex Mycobacterium tuberculosis Shigella species Salmonella species Clostridium difficile Plesiomonas shigelloides Yersinia enterocolitica Chlamydia (Lymphogranularum venerium/LGV) Helicobacter pylori Staphylococcus aureus Bacillus cereus Clostridium perfringens Listeria monocytogenes

Viruses Rotavirus Noroviruses Enteric adenovirus Astrovirus Cytomegalovirus Herpes Simplex Virus Cytomegalovirus Varicella Zoster Virus

Fungi/Yeast ·         Candida ·         Histoplasma capsulatum

Protozoa ·         Giardia ·         Entamoeba histolytica ·         Cryptosporidium ·         Isospora ·         Microspora ·         Cyclospora

Helminths (worms) Ascariasis Strongyloides Anisakiasis Enterobius Hookworm (Necator Americanus and Ancylostoma duodenale) Whipworm (Trichuriasis)

 

References:

1)      Slutsker L, Ries AA, Greene KD et al.  Escherichia coli 0157:H7 diarrhea in the United States: Clinical and epidemiologic features.  Ann Intern Med 1997; 126:505.

2)      Parashar UD, et al.  Global illness and deaths caused by rotavirus disease in children.  Emerging Infectious Diseases 2003; 9: 565.

3)      Field M, Rao M, Chang E.  Intestinal electrolyte transport in diarrheal disease. NEJM 1989; 321: 800-806

4)      Morbidity and Mortality Weekly Report 2006.  Preliminary FoodNet data on the incidence of infection with pathogens transmitted commonly through food—10 states, United States, 2005. 55:392.

5)      Heuvelink AE et al. Escherichia coli 0157 infection associated with a petting zoo.  Epidemiologic infection 2002; 129: 295.

6)      Wong CS, Jelacic S, Habeeb RL et al.  The risk of the hemolytic-uremic syndrome after antibiotic treatment of Escherichia coli 0157:H7 infections.  NEJM 2000; 342:1930.

7)      Sugimachi K, Inokucchi K, Ooiwa T et al.  Acute gastric anisakiasis.  JAMA 1985 ; 253 : 1012-1014.

8)      Smith PD, Lane HC, Gill VJ et al.  Intestinal infections in patients with the acquired immunodeficiency syndrome (AIDS).  Ann Intern Med 1988; 108: 328-333.

9)      Antony MA, Brandt LJ, Klein RS, et al.  Infectious diarrhea in patients with AIDS.  Dig Dis Sci 1988; 33: 1141-1146.

10)   Rene E, March C, Regneir B, et al.  Intestinal infections in patient with acquired immunodefiency syndrome.  A prospective study in 132 patients.  Dig Dis Sci 1989; 34: 773-780.

Weblinks:

1)      Partners Infectious Disease Images (www.idimages.org)

2)      The American College of Gastroenterology (www.acg.gi.org)

3)      CDC website: advice for travelers and outbreaks (www.cdc.gov)