Infections and Intoxications of the Intestines
Diseases
There are an enormous
number of microbes that cause disease in the intestines. Bacteria (E. coli,
Salmonella, Shigella, Campylobacter, Clostridium), viruses (
Not all of these diseases follow infection but can occur following ingestion of preformed toxin (staphylococcal food poisoning). Usually symptoms (vomiting, diarrhea) of intoxication occur soon (1-8 hr) after ingestion of the toxin. This is called intoxication.
There are several ways of categorizing this set of diseases. Some categorize them based on location in the intestines (small vs. large intestine), others by how the disease was acquired (food vs. water vs. person to person), and still others categorize these diseases based on what the infectious agent does to the host (intoxication vs. gastroenteritis vs. noninflammatory diarrhea vs. inflammatory diarrhea vs. enteric fever). All of these means of categorizing these etiologies are used to help the physician narrow down the possible causes of the symptoms. None of them work for every GI tract illness.
GI tract infections
are very common. Diarrhea is the most common cause of death in developing
countries (2.5 million deaths/year). Over 211 million cases of diarrhea occur
in
Many of these infections are self-limiting and do not require treatment. Some can spread to other sites in the body and require treatment to prevent further damage. The trick is in knowing when to treat and how to treat patients.
Etiologies
Bacteria- Staphylococcus aureus, Bacillus cereus, Clostridium perfringens, Clostridium botulinum, Escherichia coli (ETEC, EPEC, EHEC, EAEC, EIEC), Salmonella sp., Shigella sp., Campylobacter sp., Yersinia enterocolitica, Clostridium difficile, Vibrio cholerae, Vibrio parahemolyticus, Listeria monocytogenes, Aeromonas hydrophila, Plesiomonas sp.
Viruses- Rotaviruses,
Parasites- Giardia
lamblia, Entamoeba histolytica, Cryptosporidium parvum,
Cyclospora cayetanensis, Diphyllobothrium
latum, Ascaris lumbricoides, Trichuris trichiura, Taenia solium, Taenia
saginata
Intoxications
Bacteria- Staphylococcus
aureus, Bacillus cereus, Clostridium perfringens, Clostridium botulinum
Infections
Bacteria- Escherichia coli (ETEC, EPEC, EHEC, EAEC, EIEC), Salmonella sp., Shigella sp., Campylobacter sp., Yersinia enterocolitica, Clostridium difficile, Vibrio cholerae, Vibrio parahemolyticus, Listeria monocytogenes, Aeromonas hydrophila, Clostridium botulinum (children under 1 year of age eating honey)
Viruses- Rotaviruses,
Parasites- Giardia
lamblia, Entamoeba histolytica, Cryptosporidium parvum,
Cyclospora cayetanensis, Diphyllobothrium
latum, Ascaris lumbricoides, Trichuris trichiura, Taenia solium, Taenia
saginata
Small intestine infections
Bacteria- E. coli (ETEC, EPEC), Clostridium perfringens, Cholera sp., Vibrio sp.
Viruses- Rotavirus, Adenovirus,
Calicivirus, Astrovirus,
Parasites- Giardia
lamblia, Cryptosporidium parvum, Ascaris lumbricoides, Taenia solium, Taenia
saginata, Cyclospora cayetanensis
Large
intestine infections
Bacteria- E. coli (EHEC, EIEC, EAEC), Shigella sp., Salmonella
sp., Campylobacter sp., Yersinia sp., Aeromonas sp.,
Plesiomonas sp., Clostridium difficile
Parasites- Entamoeba
histolytica, Trichuris trichiura
|
Organisms that commonly cause food
poisoning |
|
|
Food History |
Organism |
|
Dairy |
Campylobacter, Salmonella
species |
|
Eggs |
Salmonella sp. |
|
Meats |
Clostridium perfringens, Bacillus cereus (diarrhea), Aeromonas, Campylobacter, and Salmonella sp. |
|
Ground beef |
E coli O157:H7 |
|
Poultry |
Campylobacter sp. |
|
Pork |
C. perfringens, Yersinia
enterocolitica |
|
Seafood |
Astrovirus, Aeromonas,
Plesiomonas, and Vibrio sp. |
|
Oysters |
Calicivirus, Plesiomonas
and Vibrio species |
|
Vegetables |
Aeromonas sp., C
perfringens |
|
Mayonnaise containing salads
and highly processed foods (cream puffs) |
Staphylococcus aureus |
|
Rice; starchy foods |
Bacillus cereus (vomiting) |
|
Canned foods; honey (children
under 1 year of age) |
Clostridium botulinum |
Knowing the stool
characteristics is very useful in narrowing down the causative agent of an
intestinal infection.
|
Stool Characteristics |
Small Bowel |
Large Bowel |
|
Appearance |
Watery |
Mucousy and/or bloody |
|
Volume |
Large |
Small |
|
Frequency |
Increased |
Increased |
|
Blood |
Possibly positive but never gross blood |
Possibly grossly bloody |
|
pH |
Possibly <5.5 |
>5.5 |
|
Reducing substances |
Possibly positive |
Negative |
|
WBCs |
<5/high power field |
Possibly >10/high power field |
|
Serum WBCs |
|
Possible leukocytosis, bandemia |
|
Organisms |
Viral Rotavirus Noroviruses |
Invasive bacteria E. coli |
|
|
Toxic bacteria E. coli Bacillus cereus |
Toxic bacteria Clostridium difficile |
|
|
Parasites Giardia species |
Parasites Entamoeba organisms |
Manifestations
The following categories will be used to provide a framework
for you to think about these diseases.
1. Food toxemia- noninflammatory
2. Viral gastroenteritis- noninflammatory
3. Bacterial gastroenteritis- noninflammatory
4. Invasive gastroenteritis
NAME OF DISEASE: Food poisoning, Food toxemia,
Botulism (only for disease due to Clostridium botulinum)
OVERVIEW:
Food
poisoning is a toxemia 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 human is required, symptomology
occurs rapidly, usually within 2-12 hours. In all but botulism symptoms occur
relatively soon after ingestion of the toxin and does NOT include a fever.
These toxins either affect the intestine (enterotoxin of C. perfringens)
or the central nervous system (neurotoxin of C. botulinum).
ETIOLOGICAL AGENTS: Staphylococcus aureus (gram+, aerobic, coccus), Bacillus cereus (gram+, aerobic, rod), Clostridium perfringens Type A (gram+, anaerobic, rod), Clostridium botulinum (gram+, anaerobic, rod)
S. aureus enterotoxins - 8 distinct antigenic types labeled SEA, SEB, SEC, SEE, SEG, SEH, SEI, SEJ. They are water-soluble, low molecular weight proteins that are heat stable (resist boiling for 30 minutes). They bind to the emetic reflex center causing nausea and vomiting.
B. cereus enterotoxins - The spore germination process of B. cereus produces two enterotoxins which cause either vomiting (emetic form) or diarrhea (diarrheal form). The type of toxin produced is dependent on the type of food that the spore germinates in. In a high carbohydrate food (rice, pasta), Type 1 disease, the emetic heat stable enterotoxin is produced causing nausea and vomiting. The heat stable enterotoxin causes vomiting through an unknown mechanism.
The diarrheal form (Type 2) resulting from the heat labile form of the enterotoxin is produced while the bacteria grow in the food or in intestine. In a high protein food (meat) the diarrheal heat labile enterotoxin is produced resulting in a diarrhea. The enterotoxin stimulates the adenyl cyclase - cyclic AMP system in intestinal epithelial cells and cause fluid accumulation in the intestine.
C. perfringens enterotoxin - This heat-labile protein binds to the brush border membrane in the small intestine. It disrupts ion transport in the ileum and jejunum altering membrane permeability. Excess amounts of ions go into the lumen with the water following them. This results in a watery diarrhea. The toxin is formed when the vegetative cells become spores. The alkaline conditions in the small intestine cause spore formation. Meat products contaminated with large numbers of organisms are needed to cause disease. Refrigeration prevents growth of organisms in the meat and reheating the meat destroys the heat-labile enterotoxin.
C. perfringens
Type C beta-toxin producing strains of this bacterium can cause a rare disease
called necrotizing enteritis or enteritis necroticans (pig-bel). This disease is
most common in
C. botulinum
neurotoxin - Seven distinct antigenic types labeled A, B, C, D, E, F, G
have been identified thus far. Human disease is associated with toxin types A,
B, E and F. Improperly canned foods are the most common source of this form of
food poisoning. The spores of C. botulinum are not destroyed and when
cooled sufficiently will start growing and making toxin. This large toxin is an
A-B type toxin. The B portion protects the toxin from being inactivated by
stomach acid and helps get the A portion inside the nerve cells. The A portion
is a metalloproteinase that blocks neurotransmission of cholinergic synapses by
preventing the release of acetylcholine at the neuro-muscular junction. This
causes a flaccid paralysis that will remain until the nerve endings regenerate.
PATHOLOGY:
There is no pathology
associated with S. aureus, C. perfringens or B. cereus toxemia. C.
perfringens toxemia can rarely with heavily contaminated foods produce a
diffuse, necrotizing enteritis of the jejunum, ileum and colon. The pathology
associated with C. botulinum is minimum, inconsistent and
non-diagnostic.
CLINICAL SYMPTOMS:
In cases of gastroenteritis it is important to differentiate toxemia from infectious diarrhea. The key features are the rapidity of onset of symptoms following ingestion of contaminated food or drink, the lack of fever and the absence of fecal leukocytes. Symptoms usually occur within 12 hours of toxin ingestion as compared to an incubation period of 24-72 hours for infections.
Botulism can take from 1-2 days before symptoms are manifest. This is because of the time it takes to get the toxin from the intestine to the nerve synapses.
S. aureus
- Vomiting (often projectile) little or no diarrhea, no fever. Symptoms occur
within 1-4 hours after ingestion of contaminated food (generally mayonnaise or
dairy products or highly salted foods). Staphylococcal food poisoning is the
most common cause of food poisoning in the
B. cereus
- Type 1: When the organism grows in starchy foods especially fried rice, there
is emetic illness 2-3 hours (less than 6 hrs; mean= 2 hrs) after ingestion and
a little diarrhea. No fever. The rice
is cooked and most of the cells are killed leaving behind the heat resistant
spores. If the cooked rice is not refrigerated the spores germinate and the
cells grow rapidly. Reheating the rice does not destroy the heat-stable
enterotoxin released by the bacterial cells.
Type 2: When the organism grows in meat, vegetables, and sauces (cream sauce, gravy) it produces the heat-labile enterotoxin. When ingested the enterotoxin can cause profuse diarrhea with a little vomiting at 10-14 hours after ingestion. No fever. The toxin is heat-labile and reheating will destroy it. A wide variety of foods including meats, milk, vegetables, and fish have been associated with the diarrheal type food poisoning.
Type 2 infections can also result in that the large numbers of the ingested bacteria can produce the heat-labile toxin resulting in the same symptoms as indicated above.
C. perfringens- 8 to 24 hrs after ingestion of the toxin the patient experiences abdominal cramping and watery diarrhea. The diarrhea generally lasts less than 24 hours. No fever. In most instances, the actual cause of poisoning by C. perfringens is temperature abuse of prepared foods. Small numbers of the organisms are often present after cooking and multiply to food poisoning levels during cool down and storage of prepared foods. Meats, meat products, and gravy are the foods most frequently implicated.
C. botulinum - Onset of symptoms between 1-2 days after ingestion of improperly canned green beans, peppers, chili or sausage. The length of the incubation period is a function of the amount and antigenic type of toxin ingested. Initial signs include blurred vision with fixed and dilated pupils, dry mouth, constipation and abdominal pain. Fever is absent. Bilateral descending weakness of the peripheral muscles develops in patients with flaccid paralysis. Death is usually attributed to respiratory failure. Patients maintain a clear sensorium throughout the illness. Complete recovery can take many months to years. With good supportive care the mortality rate is about 10%.
DIAGNOSIS:
Usually diagnosis is not necessary for the food intoxications. They rarely cause significant long-term problems and are self-limiting. The only reason to determine the food source and cause would be in the case of food poisonings resulting at public institutions (restaurants, elderly care facilities, etc.). Oftentimes the contaminated food is cultured or immunoassays are performed to detect the enterotoxins in the food.
The only fatal toxemia in this group is botulism, the emphasis should be on ruling out botulism in the diagnosis. Presumptive diagnosis of botulism is made 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 however the sample must be sent to a Public Health lab.
A differential diagnosis should include:
Guillain-Barré syndrome - this is an ascending paralysis. There are paresthesias or other sensory abnormalities and elevated cerebral spinal fluid protein. There may be a history of an antecedent viral infection.
Myasthenia gravis - this is a descending paralysis. There is accentuation of muscle fatigability during exercise and positive response to endrophomium.
Other microbial food
poisonings and gastroenteritis - there is no cranial nerve involvement in these
diseases
TREATMENT:
In toxemia due to S. aureus, B. cereus, C. perfringens no treatment is usually given. If the patient becomes dehydrated intravenous replenishment of fluids and electrolytes is 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:
1. admitted to an intensive care unit to permit monitoring of respiratory and cardiac function. Airway patency should be guaranteed by insertion of an endotracheal tube or tracheostomy before respiratory impairment becomes severe.
2. Induction of vomiting or gastric lavage is recommended if exposure has occurred within several hours.
3. Given trivalent (A, B, E) botulinum antitoxin to
neutralize unabsorbed toxin in the bloodstream.
OVERVIEW: Viral gastroenteritis is
a very common cause of diarrhea in the
Several different
viruses can cause this disease: Rotavirus, Adenovirus, Astrovirus, Calicivirus
(Noroviruses and
Noroviruses are the most common cause of gastroenteritis outbreaks in industrialized countries. Gastroenteritis caused by Norovirus infection has been described as a highly seasonal syndrome, often referred to as "winter vomiting disease". Noroviruses cause approximately 23 million cases of acute gastroenteritis each year and are the leading cause of outbreaks of gastroenteritis. Norovirus was attributed to 9 out of the 21 outbreaks of acute gastroenteritis on cruise ships reported to the CDC’s Vessel Sanitation Program from January 1, 2002, to December 2, 2002.
ETIOLOGY:
Rotavirus is in the Reoviridae family, i.e., it is a naked double-stranded RNA virus with a double icosahedral capsid.
The
Adenoviruses serotypes 40 and 41 are most
commonly associated with diarrhea in infants.
PATHOLOGY:
The viruses invade and destroy mature epithelial cells in the middle and upper villus, causing a decreased absorption of sodium and water from the bowel lumen.
SYMPTOMOLOGY:
Symptoms include low-grade fever, abdominal pain, watery diarrhea, nausea and vomiting in nearly all of these etiologies.
Rotaviruses usually cause vomiting diarrhea and fever in babies less than 2 years of age. The elderly can also have problems with this virus. The incubation period being is 2-4 days. The diarrhea can last for extended periods of time resulting in dehydration.
Adenoviruses cause symptoms similar to rotavirus infections except that the infants tend to be older. Complications can include intussusception.
Astroviruses usually cause symptoms of diarrhea (vomiting is uncommon) in children less than 5 years of age. As with Noroviruses this infection is most common in the winter.
Norovirus symptoms last 12--60 hours and are characterized by sudden onset of low-grade fever, nausea, vomiting, and watery diarrhea; the incubation period is 12--48 hours. These viruses can infect children and adults.
DIAGNOSIS:
No diagnostic tests are usually performed.
A rapid antigen test of the stool, either by EIA (>98% sensitivity and specificity) or latex agglutination tests (less sensitive and specific as compared to EIA) can be used to aid in the diagnosis of rotavirus infection.
TREATMENT:
Viral gastroenteritis is a self-limiting disease but it is often necessary to administer fluids and electrolytes. Use the following parameters to assess the degree of dehydration: blood pressure, pulse, heart rate, skin turgor, fontanelle, mucous membranes, eyes, extremities, mental status, urine output, and thirst.
Oral rehydration therapy is recommended for preventing and treating early dehydration and continued replacement therapy for ongoing loses. Shock, severe dehydration, and decreased consciousness require intravenous therapy.
Administering antiemetics and antidiarrheal agents to small children is not recommended.
Research has consistently shown that probiotics, such as Lactobacillus casei GG and Saccharomyces boulardii, reduce the frequency and/or duration of diarrhea in acute infantile gastroenteritis by 30-70%. Their role in the treatment and prevention of acute infantile gastroenteritis is still undefined.
PREVENTION:
Natural immunity is usually incomplete and multiple episodes of viral gastroenteritis can occur in infants. In time the episodes become less severe.
A previously successful vaccine for Rotavirus infection caused small bowel intussusception several weeks after vaccination and was removed from the market. Another attenuated Rotavirus vaccine is in the works and may be of use in the future.
Bacterial Gastroenteritis-
Noninflammatory (no fecal WBC’s)
Escherichia
coli INFECTION
ETIOLOGICAL AGENT:
Enterotoxigenic E. coli (ETEC)-
infantile diarrhea and Traveler’s diarrhea
Enteropathogenic E. coli (EPEC)-
diarrhea in infants less than 6 months of age
Enteroaggregative E. coli (EAEC)- a
major cause of Traveler’s diarrhea, a more persistent diarrhea
PATHOLOGY:
EPEC produces no demonstrable toxin. They
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 (type III secretory system) bacterial factors into
the host cells and cause alterations in the glycocalyx of the small bowel
epithelial cells. EPEC express rope-like bundles of filaments, termed
bundle-forming pili, which create a network of fibers that bind together the
individual organisms and are used to bind the bacterial cells to the surface of
the intestinal epithelial cells
ETEC strains colonize the small intestine and
produce a cholera-like (heat-labile; LT) toxin and a heat stable toxin (ST).
Both toxins ultimately stimulate the secretion of chloride by the host cells
resulting in a watery diarrhea.
The LT toxin is has a molecular weight of
86,000 d. It is an A-B toxin like the cholera toxin composed of one A subunit
and 5 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 contains the enzymatic function that ADP ribosylates the
GTP-binding protein. The GTP-binding protein then permanently activates
adenylate cyclase resulting in increased intracellular levels of cAMP. The cAMP
activates cAMP-dependent protein kinase (A kinase), which will cause
supranormal phosphorylation of chloride channels. Stimulation of chloride ion
secretion from secretory crypt cells and inhibition of NaCl absorption by
villus tip cells causes an increase in luminal ion content drawing water
passively through the paracellular pathway and an osmotic diarrhea.
The
Enteroaggregative E. coli (EAEC)-
Involves three stages that include; 1. Adherence to the mucosa, 2. Enhanced
mucus production that encases the bacteria forming a biofilm, 3. Followed by
elaboration of a cytotoxin, which damages the intestinal cells. They may have
the ability to colonize both the small and large intestine. Regardless of this
the symptoms of this infections are similar to most small intestinal
infections.
SYMPTOMS:
Severe diarrheal disease caused by ETEC is
generally characterized by the abrupt onset of watery diarrhea. In severe
cases, the clinical picture is identical to that of cholera except that
cramping abdominal pain is more commonly present with E. coli diarrheas
and the duration is much less, seldom lasting more than 24 hours after
initiation of fluid replacement therapy.
The non-enterotoxin producing, noninvasive E.
coli (EPEC) have thus far been incriminated only in mild diarrheal disease
in infants less than 6 months of age primarily.
EAEC is a common cause a more persistent diarrhea seen in adults and children.
DIAGNOSIS:
Diagnosis is made by isolating E. coli on MacConkey's agar and then:
1. Inoculating them into a tissue culture of mouse adrenal cells or Chinese hamster ovary cells which respond morphologically to stimulation of their adenylate cyclase systems by the LT or
2. Performing an ELISA test on toxin bound to antibody or
3. Using a DNA probe to
detect the LT gene.
TREATMENT:
Intravenous or peroral replacement of the
fluid and electrolytes lost in feces. Peroral therapy is almost always
adequate.
Tetracycline and trimethoprim - sulfamethoxazole are effective in shortening the duration of symptoms but are not essential. Bismuth subsalicylate may provide symptomatic relief (less severe abdominal cramps and less frequent stools).
Vibrio
ETIOLOGICAL AGENT:
Vibrio cholerae- This is a slightly curved gram-negative rod
which has two major groups based on the O-antigen. These are identified by
slide agglutination tests with specific antiserum. Classic epidemic cholera is
caused by the 01 serotype; all other strains are designated the non-01 strains
and they have the antigen designations 02-0139. These non-01 strains produce
sporadic and milder forms of diarrhea.
OVERVIEW:
Cholera is endemic in
PATHOLOGY:
V. cholerae is acid sensitive and the majority of ingested organisms are killed by stomach acidity; it takes ingestion of 108-1010 cells to cause disease. Those organisms that survive attach to the microvilli of the glycocalyx of epithelial cells of the jejunum and ileum. There they multiply and liberate cholera enterotoxin, mucinase and endotoxin. They do not invade the mucosa. All signs, symptoms and metabolic derangements in cholera result from the rapid loss of liquid from the gut. The increased electrolyte secretion is caused, in the absence of morphologic damage to the gut mucosa. The enterotoxin (cholera toxin) has a molecular mass of 84,000 daltons and consists of a binding (B) moiety and an activating (A) moiety. Five equal subunits with a molecular weight of 11,500 each 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 A1 subunit contains ADP-ribosyltranferase activity and catalyzes the transfer of ADP-ribose from NAD to a guanosine triphosphate (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 2 sites to cause net secretion of isotonic liquid within the small bowel lumen. The increased cyclic AMP inhibits neutral sodium chloride absorption across the glycocalyx via the cotransport mechanism; it also stimulates active chloride secretion into the gut lumen. There is no significant pathology.
CLINICAL SYMPTOMS:
Cholera- The onset is characterized by abrupt, watery diarrhea. Several liters of liquid may be lost within a few hours, rapidly leading to profound shock. Vomiting may ensue after diarrhea. The patient is cyanotic and has sunken eyes and cheeks, a scaphoid abdomen, poor skin turgor and thready or absent peripheral pulses. The voice is high pitched or inaudible; the vital signs include tachycardia, tachypnea and low or unobtainable blood pressure. The heart sounds are distant and often inaudible, and bowel sounds are hypoactive.
DIAGNOSIS:
Cholera- In endemic or epidemic areas, the working diagnosis of cholera is made based on the clinical presentation, especially the presence of "rice water" stools. Confirmative diagnosis is made by plating a stool sample on TCBS (thiosulfate-citrate-bile salt-sucrose) agar, which is selective for Vibrio, and the adrenal cell assay.
TREATMENT:
Cholera- Successful therapy requires only prompt replacement of fluids and electrolytes. Ringer's solution is most commonly used. It is given rapidly by IV injection - 50 to 100 ml per minute - until a strong radial pulse is restored. Tetracycline reduces the severity and length of disease. Chloramphenicol and furazolidone are slightly less effective.
PREVENTION:
Cholera- The only
vaccine available in the
INFANT BOTULISM - A SPECIAL CASE
C. botulinum can colonize the gastrointestinal tract of an infant less than 1 year of age. C. botulinum spores in honey used to sweeten infants milk or water, when ingested, geminate in the infants intestinal tract, colonize it and produce toxin in vivo. Constipation is the first sign of disease; the same neurological signs seen in the adult follow the constipation. Antibiotics are generally not effective and may exacerbate the illness by elimination of normal flora. Therapy is the same as for adult botulism except that antitoxin is generally not used because the disease is milder in children.
Other causes of
noninflammatory gastroenteritis
GIARDIASIS
NAME OF DISEASE: Giardiasis
OVERVIEW:
Ingestion of water containing Giardia lamblia (duodenalis) cysts. The cyst then develops into a trophozoite in the duodenum. The trophozoites adhere to the surface of the duodenum and jejunum via their adhesive disk. Acute infections can be asymptomatic or result in bloating, flatulence, and watery diarrhea. Chronic infections can lead to malabsorption and fatty diarrhea (steatorrhea).
ETIOLOGICAL AGENT:
Giardia lamblia, a flagellate with both a trophic and cystic
stage. The teardrop-shaped trophozoites have a smooth dorsal surface with a
concave ventral surface and a prominent anterior adhesive disk. There are 4
pairs of flagella directed posteriorly. The cysts are ellipsoidal and highly
refractile. This is the most common intestinal protozoan parasite of humans.
PATHOLOGY:
Ingested organisms colonize the duodenum and jejunum where they adhere to the epithelium of the microvillus, without causing significant amounts of damage. The parasite causes a small-intestine disaccharidase deficiency. Ingestion of the disaccharides causes an osmotic diarrhea with bloating, flatulence, and watery diarrhea.
If the infection
continues and gets worse malabsorption
and a fatty diarrhea can result. 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.
SYMPTOMOLOGY:
Giardia infections can result in asymptomatic
or symptomatic disease that ranges from mild watery diarrhea to severe
malabsorption syndrome. The incubation period ranges from 1-4 weeks (average 10
days). Disease onset is sudden and consists of foul-smelling, watery diarrhea;
abdominal cramps; flatulence; and steatorrhea. Spontaneous recovery can occur
after 10-14 days. However a chronic disease with multiple relapses can develop.
This is especially a problem for patients with IgA deficiency or intestinal
diverticula.
DIAGNOSIS:
Presumptive diagnosis is made on the basis of
a history of drinking non-chlorinated water and the expression of classical
clinical symptoms.
Confirmative diagnosis requires the finding of Giardia lamblia trophozoites or cysts in the feces or in an intestianl biopsy. Since the parasite is not consistently shed in the feces a fecal sample for each of three consecutive days should be examined for cysts and trophozoites. If unsuccessful the duodenum can be sampled by duodenal aspiration, string test (Entero-Test), or biopsy of the upper small intestine.
TREATMENT:
Asymptomatic carriers
and those with symptoms of infection should be treated with either Quinacrine hydrochloride or metronidazole
(Flagyl; 250 mg,
PREVENTION:
Boil all drinking water while on extended outdoor adventures. Chlorination will not kill the cysts. Proper maintaining the filtration systems at water plants is also essential.
Other
causes of noninflammatory gastroenteritis primarily associated with immunocompromised
hosts.
CRYPTOSPORIDIUM PARVUM
NAME OF DISEASE: Cryptosporidiosis
OVERVIEW:
This organism is found all over the world and inhabits a variety of animals; fish, mammals and reptiles. It is a common contaminant in water. Only 150 oocysts can cause diarrhea in 50% of the persons infected. Autoinfections and person-to-person spread (fecal-oral and anal-oral) is common. Ingestion of oocysts of Cryptosporidium parvum in immunocompromised persons is more likely to result in a persistent chronic diarrhea. It is a frequent cause of diarrhea in daycare centers and among male homosexuals. Loss of cell-mediated immunity increases the risk of infection and is a common cause of chronic diarrhea in AIDS patients.
ETIOLOGICAL AGENT:
Cryptosporidium parvum is a coccidium parasite.
PATHOLOGY:
How it causes disease is not completely
understood however, it is known that the parasite affects intestinal ion
transport and causes inflammatory damage of the microvilli resulting in
malabsorption.
SYMPTOMOLOGY:
In people 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 the diarrheal disease can be very severe
and chronic; 50 or more stools a day with tremendous amounts of fluid loss
lasting months to years. In some cases the parasite can disseminate and infect
other organ systems.
DIAGNOSIS:
The cysts are acid-fast positive and staining
a stool smear with Kinyoun acid-fast staining can be used to visualize the
parasites.
TREATMENT:
No reliable treatment
currently available. Nonspecific antidiarrheal agents may give temporary
relief.
PREVENTION: Avoid contaminated water sources and fecal-oral routes.
Other
parasitic infections causing watery diarrhea in immunocompromised patients
Cyclospora
cayetanensis, Isospora belli, and Microsporida (Enterocytozoon bieneusi)
Can
cause a noninflammatory gastroenteritis or an inflammatory disease.
ANTIMICROBIC-ASSOCIATED PSEUDOMEMBRANOUS COLITIS
OVERVIEW:
Antibiotic-associated diarrhea develops in up to 30% of hospitalized patients. Clostridium difficile is a bacterium that is resistant to most broad-spectrum antibiotics. It 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 GI tract. The organism produces small amounts of toxin A and toxin B, which only achieve cytotoxic levels when it is the predominant organism. Intestinal epithelial cells are killed, forming a pseudomembrane under these conditions.
ETIOLOGY:
Clostridium difficile is an anaerobic, Gram-positive, spore-forming rod that produces toxin A and toxin B. Both toxins are cytophilic but only toxin A is active against intestinal epithelial cells.
PATHOLOGY:
Systemic antibiotics reduce the normal flora
and interfere with bacterial breakdown of carbohydrates. The increased amounts
of undigested carbohydrates increases the osmotic load in the colon preventing
water resorption and causing watery diarrhea.
C. difficile overgrows and produced toxin A and B which
bind to and kill cells in the bowel wall. These toxins cause the cells to round
up and die by stimulation of host cell mitogen-activated protein kinases
(MAP-kinases) and inactivating proteins that regulate actin filament assembly
(small GTP-binding Rho proteins). These toxins cause depolymerization of actin
filaments, which then cause the cells to round up and detach. Shallow ulcers
will then form. Acute inflammation with pus and mucus formation results in
pseudomembrane formation. Inflammation can extend through the full thickness of
the bowel.
SYMPTOMOLOGY:
Symptoms vary from an asymptomatic carrier state to fulminant colitis. Severity appears to be related to the number of receptors for the bacterial toxin on the colon.
Watery diarrhea- most common symptomatic disease is watery diarrhea (5-15 stools per day). 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 antibiotics are started. However, symptoms may be delayed as long as 10 weeks after completion of antibiotic therapy.
Pseudomembranous colitis- the same as seen above with pseudomembranes observed by colonoscopy.
Fulminant colitis- develops in 2-3% of patients. This disease has a severe morbidity and high mortality. Diarrhea is usually present however the patient can be constipated. 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- persistent high fever, marked leukocytosis, lack of response to antibiotics and marked bowel thickening on CT scan.
DIAGNOSIS:
Diagnosis is generally made on the basis of a
history of antibiotic therapy within the past month. Culture is not usually
performed due to its expense and difficulty. ELISA for toxins A and B are
performed on the feces is rapid and relatively sensitive (70-90%). Older assays
that only detect toxin A will miss those strains that only make toxin B. About
half the time the stools contain white blood cells and are heme positive.
Endoscopy revealing the classical pathology
can make the diagnosis if the patient is unable to produce stool or if an
immediate diagnosis is requires. Care
must be taken to not perforate the colon.
TREATMENT:
Withdrawal of the antibiotic and replacement
of the intestinal flora generally suffices. If dehydrated give intravenous
fluids and electrolytes. Do not use antimotility drugs as they increase the
likelihood of full-blown colitis and toxic megacolon.
If antibiotic treatment is needed, metronidazole will kill C. difficile. Asymptomatic individuals should not be treated with metronidazole. Except in severe disease, oral vancomycin should be avoided to prevent selecting for vancomycin-resistant enterococci.
Toxic megacolon- bowel resection and ileostomy are recommended.
PREVENTION:
Standard infection controls measures must be meticulously followed to prevent the spread of the bacterial spores from patient to patient. Thorough hand washing should be emphasized. Prolonged use of broad-spectrum antibiotic treatment should be avoided. Limit the use of clindamycin (a common cause of these problems).
Inflammatory Gastroenteritis- Dysentery
This form of intestinal infection affects the large intestine. Most of these organisms are invasive and cause the host to mount an inflammatory response. Frequently the stool volume is small, contains mucus and white blood cells, and if invasion is deep enough can be heme-positive. The patient usually has a fever, complains of abdominal pain, and of pain while attempting to defecate (tenesmus).
Antimicrobial treatment of these infections can in most cases be beneficial. Treatment is not indicated when a person is infected with EHEC E. coli. Treatment releases more shiga-like toxin and makes the patient more likely to develop HUS (hemolytic uremic syndrome). Treatment with antimotility drugs to stop the dysentery is NOT a good idea.
The three most common causes of this form of gastroenteritis are Salmonella, Shigella, and Campylobacter. Other important causes include E. coli (EHEC, EIEC), Yersinia enterocolitica, and Entamoeba histolytica (a parasite).
CAMPYLOBACTERIOSIS
OVERVIEW:
Campylobacter jejuni
is a gram-negative slender, curved, and motile rod. These organisms are
comma shaped (seagull shape). It is a microaerophilic
organism, which means it has a requirement for reduced levels of oxygen. It is
relatively fragile, and sensitive to environmental stresses (e.g., 21% oxygen,
drying, heating, disinfectants, acidic conditions). Because of its
microaerophilic characteristics the organism requires 3 to 5% oxygen and 2 to
10% carbon dioxide for optimal growth conditions.
Surveys have shown that C. jejuni is the leading
cause of bacterial diarrheal illness in the
Three to five days after ingestion, overt disease occurs only if the organism penetrates the mucous coating the epithelial cells and invades the cell.
ETIOLOGICAL AGENTS:
Eight different species of Campylobacter cause gastrointestinal infections. C. jejuni is the most common cause of gastroenteritis worldwide. These are gram-negative, comma-shaped rods that commonly occur in pairs and are microaerophilic and motile.
PATHOLOGY:
Campylobacter adheres to intestinal epithelial cells and M cells. Depending on the strain the bacteria can produce a heat-labile toxin or cause the host cells to ingest the bacterial cells. If the heat labile enterotoxin is produced a watery diarrhea occurs.
If the organisms cause the host cells to ingest the bacteria an inflammatory colitis results. After adhering to the host cells the bacteria use a type III secretory system to inject bacterial proteins into the host cells. These bacteria proteins cause the host cells to ruffle and ingest the bacterial cells.
Meanwhile, some strains of the bacteria produce a toxin called shiga toxin or verotoxin that gets into the host cells cytoplasm and stops protein synthesis by removing an adenine residue from the 28S rRNA in the 60S ribosomal unit. This toxic activity causes the host cells to die. Toxin activity produces superficial ulcers in the bowel mucosa and induces an acute inflammatory response.
Immunocompromised patients, patients with chronic illnesses and those at the extremes of ages are more likely to develop a bacteremia that can be transient and go away without treatment or infect other sites (meninges, lungs, heart and blood vessels).
The syndrome produced by C. jejuni is similar to that produced by Shigella and enteroinvasive Escherichia coli (EIEC).
SYMPTOMS:
Most cases are mild and subside within 7 days (60-70%). Some last for 2 weeks (20-30%) and a few persist longer (5-10%). In one third to one half of patients, initial 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 can also occur. Symptoms include malaise, fever, abdominal cramps, tenesmus, bloody stools, and fecal leukocytes on light microscopy. The inflammatory and pathology that results are indistinguishable from the inflammation and pathology due to Shigella sp., Salmonella sp., and E. coli. Clinical findings are not diagnostic. Along with the diarrhea there is sometimes pain, malaise and fever.
DIAGNOSIS:
Presumptive diagnosis is based on the finding of gull-shaped bacteria in watery, bloody, leukocyte-filled feces. They have a characteristic darting motility.
Definitive diagnosis requires isolation of the organism from the stool or other sites of infection. This requires special media and isolation techniques. Campy-BAP or Skirrow media contain antibiotics that