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 reduce the growth of other enteric microorganisms. These media should be incubated in 5% oxygen and 10% carbon dioxide at 42°C.
TREATMENT:
Most C jejuni infections are mild and self-limited. Usually, they do not usually require antibiotic therapy. Correction of electrolyte abnormalities and oral rehydration are usually sufficient.
Treatment is reserved
for compromised hosts or persons with fever, increasing bloody diarrhea, or symptoms
that last longer than 1 week. C jejuni is usually sensitive to
erythromycin, gentamicin, tetracycline, ciprofloxacin, and clindamycin.
Shigellosis-
Bacillary Dysentery
OVERVIEW:
Shigellosis is primarily transmitted by the
fecal-oral route. Around 300,000 cases of shigellosis occur each year in the
Despite modern environmental hygiene shigellosis persists because
1. Shigella is present in large numbers around the bases of toilets used by infected persons.
2. They readily pass through toilet paper onto the fingers.
3. As few as 200 ingested organisms can cause disease.
4. They can be spread by horseflies
5. Closed population groups often have substandard sanitation (e.g., prisoner-of-war camps, homes for mentally retarded, Indian reservations)
ETIOLOGICAL AGENTS:
Fifty Shigella species fall into one of four serological groups.
Only two serological
groups are common in the
Group B - S. flexneri, a species
commonly isolated in the
Group D - S. sonnei, the most commonly
isolated cause of shigellosis in the
Shigella is a nonmotile, nonlactose fermenting
gram-negative rod whose natural habitat is the intestine of humans and other
primates. Shigellae are closely related to Escherichia coli and share
antigens and toxin-producing capability with them. Unlike Salmonella and
Campylobacter Shigella are quite resistant to killing by stomach
acid. As a result, as few as 200 Shigella can infect the large intestine.
The disease occurs when virulent
Shigella organisms attach to, and penetrate, epithelial cells of the
intestinal mucosa. After invasion, they multiply intracellularly, and spread to
contiguous epithelial cells resulting in tissue destruction. Some strains
produce enterotoxin and Shiga toxin (very much like the verotoxin of E. coli
O157:H7).
Shigellosis
is mainly a disease of children between 1 and 4 years of age. It is transmitted
by the 4-F's: food, fingers, feces and flies.
PATHOLOGY:
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 bacteria proteins cause the host cells to ruffle and ingest the bacterial cells. Once in the cells the bacteria uses 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 the bacteria reach the periphery of the cell it pushes outward to form membrane projections that are then ingested by adjacent cells.
Meanwhile, the bacteria are producing 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.
The cell-to-cell travel and toxin activity produces superficial ulcers in the bowel mucosa and induces an extensive acute inflammatory response. This inflammatory response usually prevents entry of the bacteria into the bloodstream.
SYMPTOMS:
After an incubation period of 36-72 hours,
the initial non-specific symptoms of fever (39-39oC) and cramping
abdominal pain are prominent.
Watery diarrhea usually appears after 48 hours, with dysentery (bloody, mucous containing, small volume stools, pain is experienced when trying to defecate) 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 the feces are bloody, mucoid and small volume.
Fluid and electrolyte loss may be quite significant, particularly in pediatric and geriatric populations. Escherichia coli septicemia may be initiated by shigellosis. Shigella only rarely gets into the bloodstream.
DIAGNOSIS:
Presumptive diagnosis is based on the acute onset of fever and diarrhea with bloody and mucoid feces. Definitive diagnosis requires the isolation of Shigella from the 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. The stool usually contains white blood cells and is positive for lactoferrin
Shigella is commonly isolated on S-S agar (Salmonella - Shigella
agar).
TREATMENT:
Shigellosis is usually a self-limited disease however to shorten the course of the illness and prevent person-to-person spread of the illness treatment with trimethoprim-sulfamethoxazole or ciprofloxacin is usually recommended. Fluid and electrolyte replacement is necessary in severe cases. Antidiarrheal compounds which inhibit peristalsis, are CONTRAINDICATED.
Salmonellosis
OVERVIEW:
About 2 to 4 million cases of salmonellosis occur in the
Although extensive debate centers on how to name the various strains of Salmonella I will be using a sort of hybrid of the most current system. Basically, there is one species S. enterica with over 2460 unique serogroups (ex. S. enterica serovar typhimurium or S. enterica serovar enteritidis). There are exceptions to this rule. The Salmonella that cause enteric fevers will be referred to as S. paratyphi and S. typhi.
All of the strains of Salmonella, except S. paratyphi and S. typhi, colonize virtually all animals. Salmonella are commonly found inhabiting the intestines of chickens, reptiles, birds, and humans. Transmission from animals to humans (turtles, iguanas) and from animal food products to humans (raw meats, poultry, eggs, milk and dairy products, fish, shrimp, frog legs, yeast, coconut, sauces and salad dressing, cake mixes, cream-filled desserts and toppings, dried gelatin, peanut butter, cocoa, and chocolate) is common.
S. paratyphi and S. typhi are only found in humans. A certain number of humans infected with these organisms become chronic carriers after the organisms colonize their gallbladder.
ETIOLOGIC AGENTS:
Salmonella enterica serovar (thousands of names; S. typhimurium, S. enteritidis, S. cholerasuis)- salmonellosis= diarrhea, fever, and/or abdominal cramps.
Salmonella typhi and Salmonella paratyphi- enteric fevers= paratyphoid fever and typhoid fever= 1st week gradually increasing fever, headache, myalgias, malaise, anorexia, constipation (sometimes diarrhea) followed in the 2nd week by diarrhea, splenomegaly, high fever, etc.
PATHOLOGY:
Salmonella are sensitive to killing by
gastric acid. Therefore, it requires large number of organisms to cause an
infection. If for any number of reasons the acid in the stomach is reduced or
neutralized fewer organisms are required.
If they survive the stomach’s acidity the bacteria will attach to the epithelial cell in the small intestine and colon. Once attached 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 in large vacuoles. In the vacuoles the bacteria replicate and eventually cause the cells to lyse. They escape into the extracellular environment and gain entry into the mesenteric lymph nodes and in some get into the bloodstream. Most infections result in fever, abdominal pain, and diarrhea.
Some Salmonella are better at getting in the bloodstream than others. They cause little damage in the intestine and little if any diarrhea. S. typhi and S. paratyphi are very good at getting into the blood stream. They both cause enteric fever or typhoid fever (S. typhi) and paratyphoid fever (S. paratyphi).
Some Salmonella (S. enterica serovar cholerasuis) are better at getting in the bloodstream and can cause nontyphoidal Salmonella bacteremias.
Since large numbers of organisms are required to cause infection most infections are acquired by ingestion of heavily contaminated foods. Salmonellosis is more common in the summer where warmer temperatures allow for rapid growth of the organisms in the contaminated foods.
SYMPTOMS:
Enteritis- is the most common form of salmonellosis. Symptoms appear 6-48 hours after ingestion of the contaminated food or water. Initially the patient has nausea, abdominal cramps, vomiting and nonbloody diarrhea. They also have signs of systemic involvement in that they will have fever, headache and myalgias. Symptoms last from 2 days to 1 week and usually spontaneously resolve.
Septicemia- All Salmonella serovars can cause bacteremia. The following strains are most likely to cause bacteremia; S. typhi, S. paratyphi, and S. enterica serovar cholerasuis. The risk of bacteremia is higher in pediatric and geriatric patients and in immunocompromised patients (AIDS). The clinical presentation is just like any other gram-negative sepsis (see SIRS to Septic Shock lecture).
Enteric fever- S. typhi produces typhoid fever. S. paratyphi A, S. schottmuelleri, and S. hirschfeldii cause paratyphoid fever. These bacteria pass through the cells lining the intestines and are engulfed by macrophages. They replicate after being taken to the liver, spleen, and bone marrow. Ten to 14 after ingestion the patients experience a gradually increasing fever with headache, myalgias, malaise, and anorexia. These symptoms persist for a week or so and then are followed by diarrhea. These disease manifestations correspond to an initial bacteremic phase, followed by colonization of the gallbladder and then reinfection of the intestines. S. typhi also causes skin lesions called rose spots and symptoms tend to be more severe than those seen with the causes of paratyphoid fever.
Asymptomatic colonization- Those Salmonella responsible for the enteric fevers can chronically colonize the gallbladder serving as a reservoir to infect other people. They can be colonized for up to a year following resolution of symptoms. This can occur in 1-5% of those infected.
DIAGNOSIS:
Compared to shigellosis there is a less vigorous inflammatory response. Therefore there are fewer fecal leukocytes seen in the stools. Isolation of the organisms from the stool using S-S agar is necessary for a definitive diagnosis.
TREATMENT:
Enteritis is self-limiting in most people. Treatment appears to prolong carriage of the bacteria and does not appear to shorten the course of the illness. However, certain patient should be treated due to their greater likelihood of developing bacteremia, endocarditis, and/or osteomyelitis. These patients include: neonates, persons over 50 years of age, immunocompromised patients, patients with Sickle-cell disease, patients with prosthetic valves or vascular grafts.
Patients with enteric fevers warrant immediate antibiotic therapy (ciprofloxacin or ceftriaxone).
Fluid and electrolyte replacement is necessary
in severe cases. Antidiarrheal compounds which inhibit peristalsis, are
CONTRAINDICATED.
PREVENTION:
People traveling
to countries with high rates of typhoid fever should be vaccinated. Two typhoid
vaccines are available for use in the United States: an oral, live, attenuated
vaccine (Vivotif Berna vaccine, manufactured from the Ty21a strain of S.
typhi by the Swiss Serum and Vaccine Institute) and a Vi capsular
polysaccharide vaccine (ViCPS) (Typhim Vi, manufactured by Aventis Pasteur) for
intramuscular use. Both vaccines have been shown to protect 50%–80% of
recipients.
Primary vaccination with oral Ty21a vaccine consists of a total of four capsules, one taken every other day. The capsules should be kept refrigerated (not frozen), and all four doses must be taken to achieve maximum efficacy. Each capsule should be taken with cool liquid no warmer than 37° C (98.6° F), approximately 1 hour before a meal. This regimen should be completed 1 week before potential exposure. The vaccine manufacturer recommends that Ty21a not be administered to infants or children <6 years of age. Boosters should be given every 5 years.Primary vaccination with ViCPS consists of one 0.5-mL (25-µg) dose administered intramuscularly. The manufacturer does not recommend the vaccine for infants <2 years of age. One dose of vaccine should be given at least 2 weeks before expected exposure. Boosters should be given every 2 years.
ESCHERICHIA
COLI INFLAMMATORY
GASTROENTERITIS
OVERVIEW:
The common Escherichia coli strains carried
in the human intestine have minimal or no invasive ability. The enteroinvasive E.
coli (EIEC) has acquired certain genetic traits from Shigella sp.
that allow it the same invasive capabilities that certain Shigella sp.
possess.
EHEC strains have acquired the genes to express Shiga-toxins. These toxins causes cell death, edema and hemorrhage in the lamina propria. This results in a hemorrhagic colitis (HC) and can in some cases extend to the kidneys resulting in hemolytic uremic syndrome (HUS). The most common cause of HC and HUS is EHEC serotype O157:H7. However other serotypes of E. coli can cause HC and HUS.
ETIOLOGY:
E. coli 0157:H7 is a facultative, Gram-negative, motile, rod-shaped bacterium that cannot ferment sorbitol.
There is nothing really unique about the physiology of the non-O157:H7 EHEC and EIEC strains.
PATHOLOGY:
EHEC- The majority of the pathology occurs in the ascending and transverse colon lamina propria. 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- It is very similar to what has been described during Shigella infections. Most of the time in the case of EIEC only watery diarrhea is seen. However, a watery diarrhea followed by the onset of scanty dysenteric stools containing blood and mucus can occur. This is very similar to most Shigella infections.
SYMPTOMOLOGY:
EHEC- The symptomology of HC includes severe
crampy abdominal pain, watery diarrhea followed by grossly bloody diarrhea and little or no fever. The symptomology if
HUS includes the triad of acute renal failure, thrombocytopenia, and
microangiopathic hemolytic anemia. HC usually precedes HUS.
EIEC- A watery diarrhea that can on occasion result in dysenteric stools.
DIAGNOSIS:
Isolation and identification of the etiologic agent is necessary for definitive diagnosis. To grow EHEC O157:H7 the carbohydrate sorbitol must be included in the medium.
TREATMENT:
EHEC- Avoid antimotility drugs and use of
antibiotics. Many believe that administration of antibiotics kills the bacteria
releasing more toxin and increasing the chances that HUS will develop.
EIEC- Usually is self-limiting however in
severe cases treatment with trimethoprim-sulfoxazole or a fluoroquinolone or
ciprofloxacin can be used. Again avoid antimotility drugs.
Vibrio
ETIOLOGICAL AGENT:
Vibro parahaemolyticus- Also a slightly curved rod that like V.
cholerae is halophilic and grows in estuaries marine environments attaching
to plankton and shellfish. Hemolytic strains of V. parahaemolyticus are
virulent.
OVERVIEW:
V. parahaemolyticus- following ingestion of inadequately cooked or uncooked (sushi) seafood the organisms colonize the small intestine and produce an enterotoxin that causes some inflammation and a mild to moderately severe watery diarrhea.
PATHOLOGY:
V. parahaemolyticus- Produces an enterotoxin that produces mild inflammation and diarrhea.
CLINICAL SYMPTOMS:
V. parahaemolyticus- causes watery diarrhea often with abdominal cramping, nausea, vomiting fever and chills. In about 25% of cases a bloody diarrhea can occur.
DIAGNOSIS:
V. parahaemolyticus- not usually done. Culture the stool on TCBS medium.
TREATMENT:
V. parahaemolyticus- oral rehydration
PREVENTION:
V. parahaemolyticus- Only eat cooked seafood.
AMEBIASIS
OVERVIEW:
Infection is acquired by ingestion of cysts
of E. histolytica in contaminated food or water. Excystation occurs in
the small intestine, and trophozoites establish themselves in the lumen of the
proximal colon. Oftentimes they establish residence in the colon without
causing symptoms. Symptoms only result from invasion of the colon by
trophozoites.
When mucosal resistance is lowered, trophozoites can invade colonic epithelium. Ameboid movement and amebic enzymes such as proteases, hyaluronidase and mucopolysaccharidases facilitate penetration from the surface or within crypts of the mucosa. Eventually the venules and lymphatics are penetrated and the trophozoites gain access to the liver via the portal vein. The liver becomes the chief site of extraintestinal amebic disease.
Involvement of nonhepatic extraintestinal
organs is much less frequent. Trophozoites may disseminate to other organs,
especially from a liver abscess, by direct rupture into lung, pleural cavity or
pericardium, or through the bloodstream to 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.
ETIOLOGICAL AGENT:
Entamoeba histolytica is the cause of amebiasis or amebic dysentery. It occurs in two forms: the motile amoeboid trophozoite, the cyst form. The cyst form is responsible for person-to-person transmission of the parasite. The ameboid trophozoite is the only form present in tissue. The cytoplasm is granular and may contain red blood cells (presence of intracytoplasmic red blood cells is pathognomonic).
PATHOLOGY:
The major lesions are colonic ulcers, colonic granulomas, diffuse hepatitis, hepatic abscess, brain abscess and rectal ulcerations. The primary lesions of the intestinal tract are ulcerations in the cecum, appendix and adjacent ascending colon. The unique feature of these ulcers is that they are flask-shaped. These lesions enlarge, gradually losing their characteristic form, and develop elevated margins with a white exudate on the base of the ulcer.
The organisms in the hepatic microcirculation produce necrosis of the endothelium and penetrate into the periportal sinusoids, where they may digest pathways into the hepatic lobules. Initially there is no inflammatory reaction but 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 similar to those in the liver. Skin ulcerations show little inflammatory reaction.
The trophozoites adhere to the intestinal epithelial cells surface exposed lectins. After adherence, trophozoites invade the colonic epithelium to produce the ulcerative flask-shaped lesions typical of intestinal amebiasis. The trophozoites of E histolytica lyse the target cells using the parasite's ionophore-like protein to induce a leak of ions (ie, Na+, K+, Ca+) from the target cell cytoplasm. A number of hemolysins, encoded by plasmid and cytotoxic to the intestinal mucosal cells, have been described in E histolytica. An extracellular cysteine kinase causes proteolytic destruction of the tissue, producing flask-shaped ulcers. Phorbol esters and protein kinase C activators augment the cytolytic activity of the parasite.
SYMPTOMS:
After an incubation period of 1-5 days, the disease begins with a prodromal episode of diarrhea, abdominal cramps, nausea, vomiting and tenesmus; there may be vague abdominal discomfort, general malaise, loss of appetite, lose of weight and mental apathy. The feces may be watery or formed, but with dysentery they are generally watery, containing mucous and blood.
Amebic liver abscess presents with an abrupt onset of high fever and right upper quadrant abdominal pain, usually lasting fewer than 10 days. The pain is constant and may radiate to the right scapula and shoulder. It may become pleuritic and may increase when the patient lies on the right side. In left lobe liver abscess, the pain may be predominantly epigastric and may radiate to the left shoulder. Anorexia, nausea, and vomiting may occur.
DIAGNOSIS:
The diagnosis of amebiasis is made by
identifying E. histolytica in the feces or in tissues obtained from
lesions. Leukocytosis without eosinophilia is common.
Serology for antibodies to the parasite is useful in extraintestinal infections. Chest radiograph, CT scan and MRI is also useful in visualizing extra-intestinal amebic abscesses. A brown milkshake-like material is oftentimes obtained from liver abscesses
TREATMENT:
The choice of amebicides is based on the location and severity of infection:
Asymptomatic intestinal infection –
paromomycin or iodoquinol
Patient with diarrhea/dysentery; mild to moderate disease- metronidazole followed by either paromomycin or iodoquinol
Severe or
extraintestinal disease- metronidazole followed by paromomycin
Pleural involvement may require
drainage via a chest tube or thoracotomy. Only large liver abscesses (greater
than 12 cm) should be treated surgically.
Food
Borne Infections and Incubation Times
In food poisoning the time from
ingestion to start of symptoms is useful in pointing to the possible causes of
the patient’s problems. Not of these infections result in GI tract symptoms.
Short incubation (ie, within
1 day, usually <16 h)
Intermediate
incubation (1-3 days)
A. Prevention is the best approach
in dealing with these diseases.
1. Avoid eating undercooked meat or seafood
2. Avoid consuming unpasteurized milk or soft cheeses
3. Avoid drinking untreated water
4. Ensure the daycares your patients utilize practice proper hygiene and have the proper number of workers
5. Warn travelers of the possible GI challenges they will encounter when traveling
6. Offer the typhoid vaccine to travelers going to countries with a lot of typhoid fever
B. If a patient comes in with
diarrhea what do you do?
1. Initiate rehydration (use oral rehydration therapy whenever possible)
2. Perform a thorough clinical and epidemiological evaluation for any significant diarrheal illness. Significant diarrheal illnesses include; profuse dehydrating, bloody or febrile diarrhea, or illness in infants, elderly or immunocompromised patients.
a. Determine when the illness began
b. Obtain stool characteristics (frequency and quantity)
c. Symptoms or signs of hypovolemia
d. Travel history
e. Does the patient attend a day care?
f. Has the patient ingested raw or undercooked meat, raw seafood, or raw milk?
g. Are any of the patient’s contacts ill?
h. What are the patients’ sexual preferences and sexual contacts?
i. Any medications?
j. Any other medical conditions?
3. Perform selective fecal studies (see figure below)
4. Institute selective therapy for:
a. Traveler’s diarrhea- antibiotics
b. Shigellosis- antibiotics
c. Campylobacter infection- antibiotics
5. Avoid administering antimotility agents with bloody diarrhea or proven infection with Shiga toxin-producing E. coli.
6. Selectively administer available vaccines for travelers to (or residents of) areas where typhoid is endemic.