Bacterial Diarrhea Caused by Escherichia coli Species

Bacterial diarrhea caused by Escherichia coli (E. coli) species is a major public
health concern worldwide. Certain pathogenic strains of E. coli can cause
diarrhea through different mechanisms, leading to a spectrum of clinical
manifestations ranging from mild diarrhea to severe hemorrhagic colitis and
life-threatening hemolytic uremic syndrome (HUS). Understanding the
pathophysiology of E. coli-induced diarrhea is essential for effective
management and prevention strategies.

Risk Factors

Several risk factors predispose individuals to E. coli-associated diarrhea:

●​ Consumption of Contaminated Food or Water

●​ Poor Hygiene Practices
●​ Weakened Immune System
●​ Young Age and Elderly Population
●​ Travel to Endemic Areas E. coli infections, often known as "traveler’s
diarrhea."
●​ Contact with Infected Persons or Animals

Pathophysiology

Pathogenic E. coli strains cause diarrhea through various mechanisms

depending on the specific strain:

1.​ Enterotoxigenic E. coli (ETEC):

o​ Produces two key toxins: heat-labile toxin (LT) and heat-stable
toxin (ST).

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 o​ LT stimulates adenylate cyclase, increasing cyclic AMP (cAMP),
leading to chloride and water secretion into the intestinal lumen.
o​ ST activates guanylate cyclase, raising cyclic GMP (cGMP) levels,
also resulting in water loss and electrolyte imbalance.
o​ The loss of fluids and electrolytes leads to severe, watery diarrhea
characteristic of traveler’s diarrhea.
2.​ Enteropathogenic E. coli (EPEC):
o​ Attaches to enterocytes using a type III secretion system (T3SS),
injecting effector proteins that disrupt the actin cytoskeleton.
o​ Causes the formation of attaching and effacing (A/E) lesions,
leading to villus blunting and loss of absorptive surface area.
o​ Disrupts tight junctions, increasing intestinal permeability and
contributing to diarrhea.
3.​ Enterohemorrhagic E. coli (EHEC):
o​ Produces Shiga toxins (Stx1 and Stx2), which inhibit protein
synthesis by targeting ribosomal RNA, leading to cell death.
o​ Causes microvascular damage in the colonic mucosa, resulting in
hemorrhagic colitis characterized by bloody diarrhea.
o​ In severe cases, systemic absorption of Shiga toxins leads to
hemolytic uremic syndrome (HUS), causing endothelial damage in
the kidneys, leading to acute kidney injury, thrombocytopenia, and
microangiopathic hemolytic anemia.
4.​ Enteroinvasive E. coli (EIEC):
o​ Invades colonic epithelial cells similarly to Shigella, utilizing a T3SS
to promote bacterial uptake.
o​ Multiplies within the cytoplasm and spreads from cell to cell,
causing cell lysis and an intense inflammatory response.

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 o​ Leads to colonic ulceration, mucus secretion, and bloody diarrhea
with fever.
5.​ Enteroaggregative E. coli (EAEC):
o​ Forms biofilms on the intestinal mucosa, enhancing bacterial
adhesion and persistence.
o​ Produces enteroaggregative heat-stable toxin (EAST1) and
plasmid-encoded toxin (Pet), leading to prolonged secretory
diarrhea.
o​ Induces chronic inflammation and malnutrition, especially in
immunocompromised individuals and children.
6.​ Diffusely adherent E. coli (DAEC):
o​ Watery diarrhea affects Children (usually 3–5 years)
o​ Pathogenicity not conclusively demonstrated

Signs and Symptoms

The clinical presentation of E. coli-induced diarrhea varies depending on the

strain:

●​ ETEC: Profuse, non-bloody watery diarrhea, severe dehydration,

abdominal cramps, nausea, vomiting, and mild fever. Common in
travelers.
●​ EPEC: Persistent watery diarrhea, vomiting, dehydration, and
malnutrition, mainly affecting infants in developing countries.
●​ EHEC: Bloody diarrhea, severe abdominal pain, vomiting, fever, and in
severe cases, HUS (characterized by microangiopathic hemolytic anemia,
thrombocytopenia, and acute renal failure).

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 ●​ EIEC: Bloody, mucoid diarrhea with fever, tenesmus (painful defecation),
and severe colonic inflammation.
●​ EAEC: Chronic watery diarrhea with mucus, abdominal cramps, weight
loss, and malnutrition, particularly in immunocompromised patients.
●​ DAEC: Watery diarrhea affects Children (usually 3–5 years)

Diagnosis

The diagnosis of E. coli-induced diarrhea involves several laboratory tests:

1.​ Stool Culture: Identifies E. coli strains using selective media (e.g.,
MacConkey agar, Sorbitol-MacConkey for EHEC).
2.​ Molecular Testing (PCR): Detects specific virulence genes (e.g., LT and ST
genes for ETEC, Stx genes for EHEC, A/E genes for EPEC).
3.​ Enzyme-Linked Immunosorbent Assay (ELISA): Detects Shiga toxins in
stool samples for EHEC diagnosis.
4.​ Complete Blood Count (CBC) and Renal Function Tests: Essential for
detecting complications like hemolytic anemia and acute kidney injury in
EHEC infections.
5.​ Lactoferrin and Fecal Leukocyte Tests: Help differentiate between
inflammatory (EIEC, EHEC) and non-inflammatory (ETEC, EAEC) diarrhea.
6.​ Calprotectin

Note : Calprotectin is most often ordered by gastroenterologists in the context

of abdominal pain. Lactoferrin is most often ordered by primary care providers
in the context of acute diarrhea.

Treatment

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Management of E. coli-induced diarrhea depends on severity:

●​ Rehydration Therapy: Oral rehydration salts (ORS) are crucial for

preventing dehydration. Severe cases may require intravenous fluid
replacement.
●​ Antibiotics: Generally avoided in EHEC infections due to the risk of
increased toxin release and HUS development. However, they may be
used selectively for severe ETEC or EIEC cases with systemic symptoms.
●​ Zinc Supplementation: Reduces the duration and severity of diarrhea,
particularly in children.
●​ Probiotics: Can help restore gut microbiota and reduce the severity of
diarrhea.
●​ Supportive Care: Anti-motility agents (e.g., loperamide) are
contraindicated in invasive E. coli infections due to the risk of toxin
retention and worsening of symptoms.
●​ Monitoring for Complications: Patients with suspected EHEC infection
require close monitoring for signs of HUS, including reduced urine
output, pallor, and petechiae.

Prevention

Preventing E. coli infections involves multiple strategies:

●​ Food Safety Measures: Proper cooking of meat, pasteurization of milk,

thorough washing of raw fruits and vegetables, and safe food handling
practices.
●​ Improved Water Sanitation: Access to clean drinking water, boiling or
filtering water in high-risk areas, and effective wastewater management.

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 ●​ Hand Hygiene: Regular handwashing with soap and water, especially
before eating and after using the restroom.
●​ Travel Precautions: Avoiding street food, consuming bottled or purified
water, and practicing good hand hygiene in endemic areas.
●​ Vaccination Research: Ongoing studies aim to develop vaccines against
specific E. coli strains, particularly ETEC and EHEC, to prevent severe
diarrheal disease outbreaks.

Here is a detailed lecture on Vibrio cholerae, covering its introduction,

pathogenesis, clinical presentation, diagnosis, treatment, and prevention.

Cholerae

●​ Cholera, a severe diarrheal disease that is the caused by Vibrio

cholerae.
●​ Transmission occurs via contaminated water and food, particularly in
areas with poor sanitation.
●​ Endemic in parts of Africa, South Asia, and Latin America, with outbreaks
linked to natural disasters and overcrowding.

Pathogenesis

●​ Ingestion & Colonization: After ingestion, Vibrio cholerae survives

gastric acidity and colonizes the small intestine by attaching to mucosal
surfaces using toxin-coregulated pili (TCP).
●​ Toxin Production:
o​ Secretes cholera toxin (CTX), an A-B toxin.
o​ The A subunit enters enterocytes and activates adenylate cyclase,
increasing cAMP levels.

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 o​ This results in massive chloride and water secretion, leading to
profuse watery diarrhea (secretory diarrhea).
●​ Non-O1 & Non-O139 Strains: These strains can cause gastroenteritis but
do not produce cholera toxin.

Clinical Presentation

●​ Incubation period: 12 hours to 5 days.

●​ Mild to Severe Diarrhea:
o​ Asymptomatic or mild cases in some individuals.
o​ Severe cases present with:

▪​ Profuse, "rice-water" stools (colorless, odorless, mucus

flecks).

▪​ Severe dehydration and electrolyte imbalances.

▪​ Muscle cramps, sunken eyes, lethargy, and weak pulse

(hypovolemic shock).
●​ Complications:
o​ Hypovolemic shock, acute kidney injury, and death if untreated.

Diagnosis

●​ Clinical suspicion: Based on acute onset of severe watery diarrhea,

especially in endemic areas or outbreaks.
●​ Laboratory tests:
o​ Stool culture: Growth on Thiosulfate-Citrate-Bile-Sucrose (TCBS)
agar, which shows yellow colonies.

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 o​ Dark-field microscopy: Demonstrates motile, comma-shaped
bacteria.
o​ Rapid dipstick tests: Used in outbreak settings for quick
identification.
o​ PCR and ELISA: Detect cholera toxin genes (ctxA, ctxB) in research
or reference labs.

Treatment

1.​ Rehydration therapy (cornerstone of treatment)

o​ Oral rehydration solution (ORS): WHO formula (glucose, sodium,
potassium).
o​ Intravenous fluids: Ringer's lactate for severe dehydration.
2.​ Antibiotics (only for severe cases to reduce duration of diarrhea):
o​ Doxycycline (single dose) for adults.
o​ Azithromycin for pregnant women and children.
o​ Alternative: Ciprofloxacin or tetracycline.
3.​ Zinc supplementation: Helps reduce diarrhea severity and duration in
children.

Prevention

●​ Safe Water & Sanitation:

o​ Boiling or chlorinating water.
o​ Avoiding raw or undercooked seafood.
o​ Improved sewage disposal and hygiene education.
●​ Vaccination:
o​ Oral cholera vaccines (OCVs): Dukoral, Shanchol, Euvichol.

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 o​ Recommended for high-risk populations and travelers to endemic
areas.
●​ Outbreak Control:
o​ Rapid response with water purification, sanitation improvement,
and mass vaccinations.

Pathophysiology of Vibrio cholerae Infection

The disease process in cholera is primarily driven by the ability of Vibrio

cholerae to colonize the small intestine and secrete cholera toxin (CTX),
leading to massive fluid loss.

1. Ingestion and Survival in the Stomach

●​ Vibrio cholerae is ingested via contaminated food or water.

●​ Most bacteria are killed by stomach acid, but some survive, especially in
individuals with achlorhydria, malnutrition, or those using antacids.
●​ The bacteria that survive transit to the small intestine, where they begin
to multiply and adhere to the intestinal mucosa.

2. Colonization of the Small Intestine

●​ The bacteria use biofilm formation to avoid stomach acidity and

adhesins to attach to epithelial cells of the intestine, adhesion
preventing them from being flushed away by peristalsis.
●​ The mucinase enzyme helps degrade the protective mucus layer,
facilitating bacterial adhesion.

3. Cholera Toxin (CTX) Production

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 ●​ Once attached, Vibrio cholerae secretes cholera toxin (CTX), which is
encoded by a bacteriophage.
●​ The cholera toxin is an A-B type exotoxin, consisting of:
o​ A subunit (active portion)
o​ B subunit (binding portion)

4. Cellular Mechanism of Cholera Toxin

●​ The B subunit binds to GM1 ganglioside receptors on intestinal

epithelial cells, allowing the A subunit to enter the cell.
●​ Inside the cell, the A subunit activates adenylate cyclase
●​ Adenylate cyclase converts ATP to cyclic AMP (cAMP), leading to an
excessive increase in intracellular cAMP levels.

5. Hypersecretion of Water & Electrolytes

●​ Elevated cAMP activates chloride channel, leading to:

o​ Massive efflux of chloride (Cl⁻) ions into the intestinal lumen.
o​ Inhibition of sodium (Na⁺) absorption, preventing fluid
reabsorption.
o​ Water follows chloride ions osmotically, resulting in profuse
watery diarrhea.

6. Clinical Consequences of Fluid Loss

●​ The body loses up to 1 liter of fluid per hour, leading to:

o​ Severe dehydration
o​ Hypovolemia → decreased blood volume and hypotension

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 o​ Electrolyte imbalance → hypokalemia (low potassium), metabolic
acidosis
o​ Muscle cramps, weakness, and cardiac arrhythmias
o​ If untreated, can lead to hypovolemic shock, organ failure, and
death

Salmonellosis (typhoid fever)

Salmonella typhi and Salmonella paratyphi cause, and other Salmonella species
are associated with gastroenteritis, enterocolitis, and focal infections including
meningitis, septic arthritis, cholangitis, and pneumonia.

Epidemiology

It is considered primarily a food-borne infection. The major route of

transmission is by the “5 Fs”: flies, food, fingers, feces, and fomites. Large
outbreaks of Salmonella species–induced enterocolitis are frequently derived
from institutional dinners and contaminated food and water supply. The two
most common serotypes that result in enterocolitis are Salmonella enteritidis
and Salmonella typhimurium. Nonhuman reservoirs play a crucial role in
transmission of this disease, with up to 80% of outbreaks being caused by
animals or animal products. Poultry has the highest incidence of Salmonella
contamination (40% turkeys, 50% chickens, and 20% of commercial egg
whites). Household pets, especially turtles and lizards, have also been
implicated in outbreaks of Salmonella. Infectivity of a specific strain is related
to its serotype and inoculum quantity.

S. typhi is the primary cause of typhoid fever, it's only natural reservoir is
humans. Identification of an infection could indicate the presence of a carrier
state; therefore, public health authorities should be notified so that chronic

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carriers can be registered and the microorganism typed so that outbreaks can
be traced.

Clinical Features

Nontyphoidal Salmonella infections arise with nausea, vomiting, abdominal

cramps, and diarrhea. The diarrhea can vary from loose stools to dysentery
with grossly bloody and purulent feces. Symptoms arise 8 to 48 hours after
ingestion of contaminated food. The illness lasts for 3 to 5 days in patients
manifesting with gastroenteritis and 2 to 3 weeks in patients who develop
enterocolitis. Toxic megacolon is a known complication of Salmonella colitis.
Bacteremia occurs in up to 10% of patients and can result in focal infections
such as meningitis, arteritis, endocarditis, osteomyelitis, septic arthritis, and
focal abscesses. Predisposing factors that increase the risk of salmonellosis
include:

Sickle cell anemia, Hemolytic anemias (malaria), immunosuppression

(corticosteroids, chemotherapy, and acquired immunodeficiency syndrome
[AIDS]), low gastric acidity (H2 receptor blockers and resection of the stomach),
and patients at extremes of age (infants < 1 year old and elderly patients > 60
years old).

A chronic carrier state is seen in less than 1% of infected individuals and is

usually associated with structural abnormalities of the biliary tract, such as
cholelithiasis, or the urinary tract, such as nephrolithiasis.

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