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Diarrhea
Ning Li
Department of Infectious Diseases
Huashan Hospital
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• Diarrheal illness is one of the leading causes of death worldwide.
• It is most commonly encountered in develeoping countries.
• Can be life-threatening in infants, young children, and elderly people.
Most individuals with this illness can be managed as outpatients.
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The pathogens that cause diarrhea can be transmitted
through food
through water
through person-to-person
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diarrhea
Acute
bacterial
Antibioticassociatd
chronic
viral
parasitic
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Acute diarrhea
Bacterial
viral
Antibioticassociatd
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Bacterial diarrhea
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Microbiology,pathogenesis,and epidemiology
salmonella
shigella
camylobacter
Escherichia coli
Vibrio
parahaemolyticus
yersinia
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case1
• A 52-year-old black woman with rheumatoid arthritis
• complaints of fever and diarrhea for the preceding 24 hours.
• hospitalized for neck surgery and received a 10-day course of a broadspectrum antibiotic (ceftazidime).
• developed a fever to 38.9C associated with shaking chills and
persistent severe watery diarrhea (25 to 30 bowel movements daily).
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• noted abdominal cramps, nausea, vomiting, and anorexia.
• Medications: asparin and large quantities of antacids.
• Epidemioly: Her son had brought her an egg salad sandwich, which
they shared 16 hours before onset of the illness. Her son also has
severe diarrhea.
• Physical examination: T 39℃, BP70/50 mm Hg, P 120/min,R 20/min
• moderately ill-appearing, with dry mucous membranes and a dry,
fissured tongue. Abdomenal exam revealed hyperactive bowel sounds
and mild diffuse tenderness
• No skin lesions were seen.
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• Laboratory findings: WBC 7100/mm3, with 10% PMNs, 63% bands,
19% lymphocytes; blood urea nitrogen of 63 mg/dL; and serum
creatinine of 2.1 mg/dL. Methylene blue smear of the stool: few PMNs
and few mononuclear cells. Gram stain: mixed flora. Stool culture:
Salmonella enteritidis.
The case summarizes the characteristics of the most common
bacterial causes of diarrhea.
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Salmonella Gastroenteritis
1. Gram-negative bacillus, does not ferment lactose, motile.
2. S.typhoidal: infect human
S.nontyphoidal: infect both wide and domestic animal
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Salmonella
3. Attaches to intestinal and colonic cells, and injects proteins that
stimulate internalization.
4. Spreads to mesenteric nodes; Salmonella choleraesuis and S. typhi
often enter the bloodstream, and cause bacteremia.
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Salmonella
5. Salmonella organisms is acid-sensitive, with 104 to 108 organisms
required for infection. Risk factors for disease include
a) antacid use,
b) prior antibiotics (reduces competition by normal flora), and
c) depressed immune function (AIDS and transplant patients, sickle cell
disease).
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Salmonella
6. Contracted from contaminated foods (more commonly in the
summer months):
a) Chicken products (eggs, undercooked meat)
b) Contaminated processed foods (ice cream, unpasteurized goat
cheese, whitefish, contaminated fruits and vegetables)
c) Infected pet turtles, rodents, iguanas, birds
d) Contaminated water supply (S. typhi)
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case1
• A 52-year-old black woman with rheumatoid arthritis for 24 years was
admitted to the hospital with complaints of fever and diarrhea for the
preceding 24 hours.
• One month earlier she had been hospitalized for neck surgery and
received a 10-day course of a broad-spectrum antibiotic (ceftazidime).
• Medications: asparin and large quantities of antacids.
• Epidemioly: Her son had brought her an egg salad sandwich from
Famous Deli, which they shared 16 hours before onset of the illness.
Her son also has severe diarrhea.
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Shigella Dysentery
1. Gram-negative bacillus, does not ferment lactose, nonmotile.
2. Induces ruffling of host cells; once internalized, escapes to the
cytoplasm.
a) Moves through the cytoplasm and spreads from cell to cell by
polymerizing actin.
b) Accelerates cell death, forming plaques of necrotic cells.
c) Induces marked inflammation and rarely invades the bloodstream.
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3. Resistance to gastric acid means that a small numbers of organisms
(200 bacteria) can cause disease.
4. Initially grows in the small intestine, and then spreads to the colon.
5. Spreads from person to person.Daycare centers, toilet seats,
contaminated water are vectors.Can be spread by flies. Less
commonly foodborne.
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Campylobacter Gastroenteritis
1. Campylobacter is a coma-shaped gram-negative rod, microaerophilic.
2. Grows best at 42C, requires Campy-BAP selective medium or other
bowel flora overgrow. Only C. fetus can grow at 25C.
3. Internalized by and lives in monocytes and intestinal epithelial cells;
induces cell death, bowel ulceration, and intense inflammation.
4. C. fetus is carried by monocytes to the bloodstream; it resists serum
bactericidal activity and causes persistent bacteremia.
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5. Like Salmonella, Campylobacter is sensitive to gastric acid and
requires a high inoculum (more than 104 bacteria).
6. Epidemiology is similar to that of Salmonella. C. jejuni is primarily
responsible for diarrhea.
a. Survives well in chickens because of their high body temperature
(30% of carcasses test positive).
b. Carried in water, raw milk, sheep, cattle, swine, and reptiles.
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Escherichia coli Gastroenteritis
1. Serotyping identifies specific O (lipopolysaccharide) and H antigens
(flagellar proteins).
2. Five pathogenic classes have been defined:
a) Enterotoxigenic (ETEC): Produce a choleralike toxin. Spread by water
contaminated with human sewage in developing countries. Cause
of travelers’ diarrhea.
b) Enteroaggregative (EaggEC):Adhere as large aggregates. Enterotoxin
produces watery diarrhea. Cause of travelers’ diarrhea.
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c) Enteropathogenic (EPEC): Induce pedestals that cause mild
inflammation. Produce watery diarrhea primarily in children under 3
years of age. Person-to-person spread in developing countries.
d) Enterohemorrhagic (EHEC): Produce verotoxins or Shiga-like
cytotoxin. Damage vessels. The O157:H7 strain causes hemolytic–
uremic syndrome. Cattle are the primary reservoir. Spread by
undercooked hamburger, unpasteurized milk, contaminated apple
cider, and mayonnaise.
e) Enteroinvasive (EIEC): Similar to Shigella. Require large inoculum.
Seen in developing countries.
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Vibrio （V.cholera & V.parahaemolyticus）
1. Vibrio is a slightly curved gram-negative bacillus with a single
flagellum. It requires a special culture medium (tellurite taurocholate
gelatin).
2. Spread by contaminated water (103 to 106 organisms) or food (102 to
104 organisms).
3. Attaches to the small intestine, and produces cholera toxin. Binds to
a receptor that increases cyclic adenosine monophosphate, and
thereby promotes chloride and water secretion.
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4. Survives in algae, plankton, and shellfish. Can convert to dormant
state or form aggregates surrounded by biofilm (rugose).
5. Non-cholera toxin strains are seen in the Gulf of Mexico.
6. Cholera toxin strains are spread by contaminated water in India,
Bangladesh, Asia, Africa, Europe, South America (Peru), and Central
America. Outbreaks occur in the hot seasons of the year.
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About Vibrio parahaemolyticus Diarrhea
1. Thrives in salt water and concentrates in shellfish.
2. Nonhemolytic strains are nonpathogenic.
3. Produces an enterotoxin that causes moderate inflammation and
watery diarrhea.
4. Very common in Japan, being contracted from sushi.
5. Incidence may increase as sushi becomes more popular.
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Yersinia Gastroenteritis
1. Aerobic gram-negative bacillus; requires a large inoculum (109).
2. Infects terminal ileum, and resulting mesenteric node inflammation
mimics appendicitis.
3. Common in northern Europe, South America, Africa, and Asia; rare in
the United States.
4. Acquired from contaminated meat products and milk; grows at 4C.
5. Most common in children;more frequent during winter months.
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Clinical Manifestations
• Gastroenteritis
1. Incubation periods are 8 to 24 hours for Salmonella, 36 to 72 hours
for Shigella, and 4 days for EHEC.
2. Diarrhea varies in volume and consistency:
a. Watery with enteropathogenic, enterotoxigenic, enteroaggregative,
and Vibrio
b. Mucousy with Shigella
c. Bloody with Shigella, Campylobacter, EHEC, and EIEC
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3. Abdominal pain is associated with hyperactive bowel sounds and
diffuse tenderness; in some cases, severe pain may mimicking
appendicitis or cholecystitis.
4. When the colon is involved, tenesmus and pain on defecating are
seen, most commonly with Shigella.
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• Enteric Fever
1. Caused by Salmonella typhi, S.paratyphi,Campylobacter fetus, and Yersinia
enterocolitica.
2. Incubation period is 8 to 14 days, longer with lower inocula.
3. Influenza-like syndrome: headache, muscle aches, malaise, lethargy,
nonproductive cough.
4. Mild abdominal discomfort that worsens, with constipation or minimal
bloody diarrhea.
5. Progresses to high fever (40°C) and slow pulse, septic shock, and bowel
perforation.
6. Skin shows small rose-colored macules (“rose spots”).
7. Normochromic, normocytic anemia; leukopenia.
8. Positive blood cultures in 90% of patients in the first week.
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What is diarrhea?
• Definition
• three or more bowel movements in 24 hours in which the stool is loose and
takes the shape of its container
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The Diagnosis of Bacterial Diarrhea
1. Direct examination of the stool using methylene blue stain assesses
polymorphonuclear leukocyte (PMN) response.
a) Abundant PMNs are seen in Shigella, Campylobacter, and
enteroinvasive Escherichia coli infection.
b) Salmonella infections produces moderate PMNs; with S. typhi,
monocytes may be seen,
c) PMNs are also seen with amoebic dysentery and Clostridium difficile
toxin–associated diarrhea.
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2. A Gram stain showing seagull-shaped gramnegative forms indicates
Campylobacter infection.
3. Culture stools using both standard media and Campylobacterselective media.
4. E. coli strains can be identified by slide agglutination tests using
specific O antisera.
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The Treatment of Bacterial Diarrhea
1. These diseases are self-limiting, and seldom require antibiotic
treatment.
2. Fluid and electrolyte replacement are most important.
3. Avoid agents that slow peristalsis, which increases the risk of
bacteremia, and prolongs fever and the carrier state.
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4. Antibiotic treatment of Salmonella gastroenteritis prolongs the
carrier state. However, to prevent complications associated with
bacteremia, use ciprofloxacin, amoxicillin, or trimethoprim–
sulfamethoxazole to treat
a) neonates,
b) people over the age of 50 years, and
c) immunocompromised patients or those with prosthetic valves or
synthetic vascular grafts.
5. Treat enteric fever emergently with ciprofloxacin or ceftriaxone.
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6. Trimethoprim–sulfamethoxazole or ciprofloxacin reduces person-toperson spread of Shigella.
7. Erythromycin, azithromycin, or ciprofloxacin shortens the carrier
state in Campylobacter jejuni infection.
8. Yersinia is not usually treated; in severe cases,use trimethoprim–
sulfamethoxazole, ciprofloxacin, ceftriaxone.
9. Vibrio parahaemolyticus usually not treated.
10.Ciprofloxacin for 3 to 5 days shortens the course of travelers’
diarrhea.
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Prevention of Bacterial Diarrhea
1. Investigation of sources of contamination is a cost-effective
preventive measure.
2. Fecal carriage after Salmonella infection may continue for an
extended period.
a) The carrier state can often be eradicated by prolonged therapy (4 to
6 weeks) with amoxicillin or ciprofloxacin.
b) Carrier state often cannot be eliminated in patients with gallstones.
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Antibiotic-Associated diarrhea
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Antibiotic-Associated diarrhea
• Antibiotic-associated diarrhea develops in up to 30% of hospitalized
patients.
• The most frequent causative agent is C. difficile.
• This pathogen has been implicated in 20% to 30% of patients with
antibiotic-associated diarrhea and 50% to 75% of those who develop
antibiotic-associated colitis.
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The Microbiology, Pathogenesis, and
Epidemiology of Clostridium difficile
1. Obligate anaerobic, spore-forming, gram-positive rod.
2. Produces two cytotoxins, toxin A and toxin B, that bind to and kill
host cells.
3. Bowel wall necrosis leads to acute inflammation.
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4. A disease of hospitalized patients. Risk factors include
a) broad-spectrum antibiotic administration (reduces competing
normal flora; clindamycin is associated with the highest incidence,
followed by ampicillin/amoxicillin and cephalosporins).
b) cancer chemotherapy.
c) bowel enemas or stimulants, enteral feedings.
d) underlying disease in elderly patients or recent gastrointestinal
surgery.
5. Spread from patient to patient by hospital personnel through spores
carried on hands, clothes, or equipment.
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The Clinical Manifestations of Clostridium
difficile Diarrhea
1. Symptoms do not correlate with the level of toxin production.
2. Mild-to-moderate disease:
a) Watery diarrhea and crampy abdominal pain are typical.
b) Low-grade fever and mild leukocytosis are common.
c) Patients with colitis have the same symptoms, but
pseudomembranes are seen on colonoscopy.
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3. Severe disease has a high fatality rate
a) Diarrhea or constipation both possible.
b) Diffuse abdominal pain and tenderness; signs of peritonitis indicate
impending perforation.
c) Computed tomography scan may reveal toxic megacolon: bowel
dilatation to more than 7cm,air–fluid levels,bowel-wall thickening,and
thumbprinting (can mimic ischemic bowel).
d) Marked leukocytosis (25,000 to 35,000/mm3); lactic acidosis
indicates impending perforation.
e) High fatality rate.
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The Diagnosis,Treatment, and Prevention of
Clostridium difficile Diarrhea
1. Diagnosis:
a) In 50% of cases, PMNs are found in a stool smear.
b) ELISA for toxins A and B is the preferred assay. Many assays detect
only toxin A and can miss C. difficile that produces only toxin B.
c) The cytotoxicity assay remains the definitive test, but it is expensive
and takes several days.
d) Endoscopy is usually not required, and risks perforation.
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2. Treatment:
a) Drugs must be orally administered (except for metronidazole).
b) Metronidazole is the treatment of choice; intravenous metronidazole
is also effective, being excreted in bile.
c) Use vancomycin only for severe illness because of the risk of
superinfection with vancomycin-resistant enterococci.
d) Nitazoxanide comparable to metronidazole in initial trials.
e) Tolevamer binds toxins A and B, but doesn’t change bowel flora.
f ) Severe disease may require bowel resection; mortality is 30% to 50%.
g) Relapse is common because of residual spores. Re-treat with
metronidazole.
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3. Prevention:
a) Spread by hospital personnel; hand washing is critical.
b) Limiting clindamycin use may reduce the attack rate.
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Viral diarrhea
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Viral diarrhea
Viral diarrhea is the most common form of the disease, usually causing
mild self-limiting watery diarrhea.
The viruses most common associated with viral diarrhea are
noroviruses, rotaviruses, enteric adenoviruses, and astroviruses.
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Norovirus
This calicivirus blunts intestinal villi,
causes mild malabsorption, is resistant
to chlorine, is spread by contaminated
water (including swimming pools), and
primarily infects adults.
Enteric Adenoviruses
Infects infants and young children;
peaks in the summer months.
Rotavirus
Causes lactase deficiency, and
primarily infects infants. Resists hand
washing. Peaks in winter.
Astrovirus
Infects children in pediatric wards and
elderly people in nursing homes.
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Norovirus
• This calicivirus blunts intestinal villi, causes mild malabsorption
• it is resistant to chlorine, is spread by contaminated water (including
swimming pools),
• primarily infects adults.
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Rotavirus
• double-stranded RNA virus
• Causes lactase deficiency, and primarily
• infects infants
• Resists hand washing
• Peaks in winter
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Enteric Adenoviruses
• Doublestranded DNA virus
• Infects infants and young children;
• peaks in the summer months.
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Astrovirus
• single-stranded RNA astroviruses
• Infects children in pediatric wards and elderly people in nursing
homes.
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CASE 2
• A young physician arrived in Tuba City,Arizona,to work in an Indian
health service clinic. Three days later, he became ill with mild midabdominal cramps and watery diarrhea, but denied fever. He
continued working, added additional salt and fluid to his diet,and was
inconvenienced,but not incapacitated by his illness.On the third day of
symptoms, a stool smear revealed no PMNs, and a bacterial culture
grew no pathogens.
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CLINICAL MANIFESTATIONS, DIAGNOSIS, AND
TREATMENT
• Clinical spectrum varies from mild, watery diarrhea to severe nausea,
vomiting, and fever.
• No polymorphonuclear leukocytes are found in the stool.
• The infecting agents are most readily identified by their appearance
on electron microscopy.
• Commercial Enzyme-linked immunoabsorbent assays for Rotavirus
are available.
• Self-limiting diseases; use supportive care with hydration.
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CHRONIC DIARRHEA
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Parasitic Diarrhea
• Amoebiasis can mimic bacterial enterocolitis;
• other parasites (such as Giardia lamblia, Cryptosporidium, Isospora
belli, and Microsporidium) often present with complaints that mimic
viral gastroenteritis.
• not self-limiting; prolonged periods.
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AMOEBIASIS
• Caused by Entamoeba histolytica, a
parasite that contains ingested RBC.
• binds to galactose receptors, causes
flask-like ulcers.
• invade the portal vein and form
abscesses in the liver
• Dormant cysts can survive for month
• Cysts can contaminate food and water.
• Very common in developing countries.
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About the Clinical Manifestations,Diagnosis,
and Treatment of Amoebiasis
• Clinical presentation depends on the degree of invasion:
a) Watery diarrhea is associated with superficial infection.
b) Bloody diarrhea, tenesmus, abdominal pain, and tenderness with
more invasive disease.
c) Can be misdiagnosed as ulcerative colitis; corticosteroids can lead to
toxic megacolon.
d) Right upper quadrant, right shoulder pain, hepatomegaly seen with
liver abscess.
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• Diagnosis:
a) Stool smears show fewer polymorphonuclear leukocytes (PMNs)
than are seen with shigellosis (trophozoites destroy PMNs).
b) Stools are always heme-positive.
c) Alkaline phosphatase elevated in chronic, but not acute hepatic
abscess.
d) Stool examination is insensitive; fecal antigen or polymerase chain
reaction is recommended.
e) Serum is anti-amoebic antibody positive in most patients after 1
week of symptoms.
f ) Aspirate from liver abscess shows brownish, sterile liquid without
PMNs; parasite not usually seen, and antigen may not be detected.
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• Treatment:
Metronidazole for active disease;
iodoquinol or paromomycin for carrier state.
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GIARDIA LAMBLIA
1. Giardia exists as trophozoites and dormant cysts.
2. Trophozoites attach to gastrointestinal
endothelial cells, causing malabsorption and
inflammation.
3. Giardia cysts are spread by contaminated water
(and sometimes food) and person-to-person contact.
4. Infection occurs worldwide. Common in
mountainous regions of the United States.
5. A disease of campers (sterilization of water
critical for prevention), daycare centers, and
sexually active homosexuals.
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About the Clinical Manifestations,Diagnosis,
and Treatment of Giardiasis
• Clinical manifestations are usually mild The disease is self-limiting, 4
to 6 weeks.
a) Adult have mild symptoms: abdominal cramps, anorexia, watery
diarrhea, nausea, and belching.
b) Children have more severe watery diarrhea.
c) A chronic malabsorption syndrome can develop, primarily with
immunoglobulin deficiency.
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• Diagnosis:
a) Stool smear shows no polymorphonuclear leukocytes; cysts are seen
in 90% of cses after three stool exams.
b) Enzyme-linked immunoabsorbent assay or immunofluorescence
antigen are the tests of choice.
c) Endoscopy no longer necessary.
• Treat with metronidazole.
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CHRONIC DIARRHEAL ILLNESSES PRIMARILY
ASSOCIATED WITH IMMUNOCOMPROMISED HOSTS
• About Cryptosporidium, Isospora belli, and Microsporidium
1.Survive and multiply on or in the mucosal epithelial cells of the
intestine.
2. Cryptosporidium can spread by contamination of the water supply
(oocysts resist chlorination).Small numbers of oocysts—as few as 130—
can cause disease.
3. Primarily infect AIDS patients with severely depressed cell-mediated
immunity.
4. Cause watery diarrhea and abdominal cramps, dehydration, and
malnutrition.
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• Diagnosis is made by stool smear:
a) Cryptosporidium cysts are confirmed by modified Kinyoun acid–fast stain
b) Isospora belli sporocysts are transparent and acid-fast positive; they
fluoresce under ultraviolet light
c) Modified trichrome and fluorescence stains are sensitive and specific for
Microsporidium.
• Treatment:
a) Nitazoxanide for Cryptosporidium in children and chronically symptomatic
adults.
b) Trimethoprim–sulfamethoxazole for Isospora belli.
c) Fumagillin effective for Microsporidium.
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Thank you for your attention
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