ACUTE INFECTIOUS DIARRHEA

Definition

Diarrhea: more than 3 unformed stools/24 h or

increased stool volumen >300 g/24 h

Diarrhea

• Acute (several hours or days), chronic (several days

or months)

• Osmotic, secretory, motility-related, mixed

• Infective, non-infective
 The importance of acute diarrheal diseases

• The second most common diseases worldwide (after

acute respiratory infections)

• Leading cause of morbidity and major cause of

mortality in children living in nondeveloped countries
 Bacteria

• Salmonella spp.

• Shigella spp.

• Campylobacter spp.

• Yersinia enterocolitica

• E.coli

• V. Cholerae

• Clostridium (difficile, perfringens)

 Viruses

• Rotavirus

• Norwalk (Norovirus)

• Adenovirus

• Calicivirus

• Astrovirus

• Coronavirus

• CMV
 Parasites

• Entamoeba hystolitica

• Giardia (Lamblia) intestinalis

• Isospora belli

• Cryptosporidium parvum

• Cyclospora cayetanensis
 Diarrhea

Epidemiology

Host Virulence
defenses factors
 Epidemiology

• Age

(children<5 years of age, older adults)

• Cultural and personal habits

(food preparation, personal hygiene…)

• Location

(day-care centers, chronic-care institutions, hospitals-

C.difficile)

• Traveler`s history- 20-50% of people who travel to

tropical regions experience diarrhea
 Host defenses

• Normal bowel flora

• Gastric acid

• Intestinal motility

• Immunity
 Normal bowel flora

• Bacteria that normally inhabit the intestine act as an

important host defense by preventing colonization of
potential enteric pathogens

• More than 600 species

(99% are anaerobic bacteria)

 Gastric acid

• The risk for enteric infections is increased in

patients who have undergone gastric surgery and
those treated with antacids or H-2 blockers

• Salmonella, Shigella, Giardia and helmintic infections

are common among those patients

• Rotavirus is highly stable to acid

 Intestinal motility

• Normal peristalsis is the major mechanism for

clearance of bacteria from the intestines

• When intestinal motility is impared, the frequency of

bacterial overgrowth and infection with enteric
pathogens is much increased

• Patients treated with antimotility agents experience

prolonged fever and shedding of organisms and higher
frequency of bacteremia
 Immunity

• The wide spectrum of viral, bacterial, fungal and

parasitic infections in patients with AIDS highlights
the importance of cellular immunity in protecting
normal host from these pathogens
 Immunity

• Humoral immunity consists of systemic IgG and IgM

as well as secretory IgA

• Binding of bacterial antigens to the M cells and their

presentation to subepithelial lymphoid tissue lead to
the proliferation of lymphocytes which populate
mucosal tissues as IgA-secreting plasma cells
 Virulence factors

Enteric pathogens have developed a variety of tactics to

overcome host defenses

• Inoculum size

• Adherence

• Toxin production

• Invasion
 Inoculum size

• In case of Shigella, enterohemorrhagic E. coli, Giardia

and Entamoeba as few as 10-100 bacteria or cysts can
produce infection

• About 1 million Vibrio cholerae organisms must be

ingested to cause disease
 Adherence

• The initial step in the pathogenic process is the

adherence to the gastrointestinal mucosa

• Organisms colonize the mucosa and compete with the

normal bowel flora which is an important advantage in
causing disease
 Toxin production

• Enterotoxins cause watery diarrhea by acting directly

on secretory mechanisms

• Cytotoxins cause destruction of mucosal cells and

associated inflammatory diarrhea

• Neurotoxins act directly on the central or peripheral

nervous system

• Some toxins act by more than one mechanism

 Cholera toxin
A subunit catalyzes the ADP
ribosylation of a GTP-binding
protein

Persistent activation of
adenylate cyclase

Increase of cyclic AMP

Increased Cl- secretion and

decreased Na+ absorption

Loss of fluid and diarrhea

A subunit contains the enzymatic activity

B subunit pentamer binds toxin to the enterocyte
surface receptor
 Other toxins

• Enterotoxigenic E.coli produces heat-labile

enterotoxin (LT) which is similar to cholera toxin and
heat-stable enterotoxin (ST) which acts by elevation
of cyclic GMP
 Other toxins

• Cytotoxins destroy intestinal mucosal cells and

produce the syndrome of dysentery (Shigella,
Clostridium, E.coli)

• Neurotoxins are produced outside the host and cause

the symptoms soon after ingestion (Staph. aureus,
Bacillus cereus, Clostridium botulinum)
 Invasion

• Invasion and inflammation of the mucosa with

destruction of epithelial cells (Shigella, EIEC)

• Invasion and inflammation without destruction of

enterocytes (Salmonella)

• Penetration of the intact intestinal mucosa,

multiplication in Peyer`s patches and intestinal lymph
nodes, dissemination through the bloodstream to
cause enteric fever (S. typhi, Y.enterocolitica)
 Fecal leukocytes

• White blood cells in a

stool sample stained
with Methylene blue
 Types of enteric infections
Type of Non- Inflammatory Penetrating
infection inflammatory
Mechanisms Toxin production Invasion Invasion/
penetration
Location Proximal small Colon Distal small
bowel bowel
Fever No Fever Fever
Abdominal pain No Abdominal Minimal
cramping, tenesmus abdominal pain
Illnes Watery diarrhea Dysentery (blood, Enteric fever
mucus)
Fecal No PMN Mononuclear
leukocytes
Microorganism V.cholerae, E.coli, Shigella, E.coli, S. typhi,
S. aureus, Campylobacter, paratyphi A,B,C
Rotavirus,Giardia C.difficile, Yersinia
Cryptosporidium Salmonella,
E.hystolitica
 Approach to the patient

• History : clinical presentation

• Physical examination: signs of dehydration (dry

mouth, thirst, decreased urine output, hypotension,
tachycardia, confusion, shock), careful abdominal
examination to exclude surgical conditions

• Diagnostic approach: distinction between

inflammatory and noninflammatory disease
 Laboratory analyses

• Blood count

• Biochemical analysis (azotemia, loss of electrolytes,

acidosis)

• Inflammatory parameters (CRP, fibrinogen)

• Malabsorption (protein, albumin,Fe)

 Diagnosis

• Stool culture (selective growth medium)

• Fresh stool examination for parasites

• Rapid ELISA stool tests for C.diff. toxin A and B

• Stool test for detection of Shiga- toxin

• ELISA stool tests (Rotavirus)

• PCR

• Serologic blood testing (E.hystolitica)

• Blood culture (S.typhi)

 Treatment

• Rehydration

Mild diarrhea- oral rehydration

Severe diarrhea- intravenous rehydration

• Antimicrobial drugs- dysentery, serious inflammatory

diarrhea with high fever, bacteremia, complications

• Probiotics-live microorganisms that act as inhibitors

of pathogens in the intestine
BACTERIAL FOOD POISONING
 Staphylococcus aureus

• Source: infected human carriers (nose, mouth, skin)

• Food contamination (ham, polutry, mayonnaise, ice

cream)

• Bacteria multiplies and produces heat-stable

Staphylococcal enterotoxin B

• Pathogenesis: symptoms are mediated through the

autonomous nervous system
 Staphylococcus aureus

Clinical presentation

• Short incubation period (1-6 hours)

• Nausea, vomiting, diarrhea, abdominal cramps

• No fever

• Illness lasts less than 24 hours

 Staphylococcus aureus

Diagnosis

• Diagnosis is generally based only on the signs and

symptoms of the disease

• Staph.aureus can be identified in stool or vomit, and

bacteria and toxin can be detected in food

• Testing is usually reserved for outbreaks involving

several people

• Therapy: adequate rehydration

 Bacillus cereus

• A Gram-positive facultatively aerobic sporeformer

• The vomiting (emetic) form of illness is caused by a

low molecular weight, heat-stable peptide (similar to
staphylococcal enterotoxin B)

• The diarrheal form of illness is caused by a large

molecular weight protein (similar to E.coli type of
enterotoxin)
 Bacillus cereus

Emetic form

• Source: rice (heat –resistant spores, heat-stable

toxin)

• Incubation period 1-6 hours

• Clinical presentation: the same as in Staphylococcal

food poisoning
 Bacillus cereus

Diarrheal form

• Sources: meat, vegetables, beans, cereals

• Incubation period 8-16 hours

• Clinical presentation: diarrhea, abdominal cramps,

vomiting and fever uncommon

• Illness is self-limited rarely lasting for more than 24

hours
 Bacillus cereus

• Diagnosis: isolation of a B. cereus serotype known to

cause foodborne illness from the suspect food or
from the feces or vomitus of the patient

• Therapy: nonspecific- rehydration

 Clostridium perfringens

• A Gram-positive anaerobic, spore forming bacteria

• Sources: beef, poultry, legumes

• Clostridium perfringens enterotoxin (CPE) is produced

in intestinal tract
 Clostridium perfringens

• Incubation period 8-14 hours

• Clinical presentation: diarrhea, abdominal cramps,

rarely vomiting

• Diagnosis: testing contaminated food or stool for

Clostridium perfringens and detection of enterotoxin
in contaminated food and feces

• Therapy: adequate rehydration

 Vibrio parahemolyticus

• Source: raw seafood, in the summer months

• Incubation period 12-24 h

• Clinical presentation: abdominal cramps and diarrhea,

rarely dysentery-like illness with bloody or mucoid
stools

• Treatment: adequate rehydration, in serious cases

antibiotics
VIRAL GASTROENTERITIS
 Gastrointestinal viruses
Virus type Genome Risk groups Seasonality Diagnosis Therapy
structure
Rotavirus RNA Children<3 Winter ELISA Oral rehydration
years
Adenovirus DNA Children<3 Year-round ELISA Oral rehydration
years

Calicivirus RNA Children - EM Oral rehydration

Astrovirus RNA Children, Winter EM Oral rehydration

immunocomp
romised pt.
Norwalk-like RNA Children, Winter EM Oral rehydration
adults
Parvovirus DNA - Year-round EM None

Picornavirus RNA - - Culture,EM None

Coronavirus RNA - - EM None

 Rotavirus

• RNA virus, member of

the Reoviridae family

• EM picture of mutiple
rotavirus particles
 Epidemiology

• Most important cause of severe diarrhea in infants

and children<3 years old

• Mild diarrhea in adults: family members of affected

infants, geriatric patients and immunocompromised
hosts

• 10% of cases of traveler‘s diarrhea

• Infection is seasonal, occuring in the cooler winter

months
 Pathogenesis

• Virus is spread by the fecal-oral route

• Virus infects and kills epithelial mature villus cells of

the small intestine

• Lack of absorption of carbohydrates and other

nutrients results in osmotic diarrhea
 Clinical presentation

• Vomiting, diarrhea (rarely with mucus)

• Fever >390C (one third of the patients)

• In older patients infection is mostly subclinical

 Diagnosis

• ELISA – detection of rotavirus antigen in fecal

specimens

• PCR (only for research purposes)

 Treatment

• Standard oral rehydration therapy

• Intravenous rehydration in serious cases

• Multivalent rotavirus vaccine (for children under the

age of 6 months)
 Norwalk-like virus (Norovirus)

• Epidemics of non-bacterial gastroenteritis

• Waterborne epidemics in nursing home, cruise ship,

camps

• Traveler‘s diarrhea

• Infection is common year-round with a clear winter

peak
 Pathogenesis

• Virus infects epithelial cells of the small intestine

• Carbohydrate malabsorption, mild steatorrhea,

decreased levels of brush border enzymes
 Clinical presentation

• Incubation period 18-72 hours

• Nausea, abdominal cramps, vomiting, diarrhea

• Fever, headache, myalgias are common

• The illness is mild and self-limited

 Diagnosis and treatment

• ELISA and PCR- based assays

• Oral and intravenous rehydration

DYSENTERY
 Definition

• Acute infectious inflammatory colitis which is

characterized by frequent passage of small-volume
stools consisting of blood and mucus
 Dysentery

• Differential diagnosis:

Shigella, enterohemorrhagic E.coli (EHEC),

enteroinvasive E. coli (EIEC), Campylobacter jejuni,
Salmonella enteritidis, Clostridium difficile,
Entamoeba histolytica, Cytomegalovirus,
noninfectious conditions (ulcerative colitis)
 Shigellosis

• Gram-negative nonmotile bacilli, members of the

family Enterobacteriaceae

• Four species:

S. dysenteriae

S. flexneri

S. sonnei

S. boydii
 Epidemiology

• 140 million cases and almost 600,000 deaths among

children under age of 5 years in developing countries

• Natural pathogen for humans

 Epidemiology

• Fecal-oral route of transmission

Direct contact (day-care centers, centers for

retarded children, household transmission or by anal-
oral sexual practices among gay men)

Indirect infection(food, water, flies-pools, lakes,

cruise ships, military personnel)
 Pathogenesis

• Infective dose 10-100 bacteria

• Oral ingestion, passing the gastric acid barrier

• Attachment to colonic cells, entry by an endocytic

mechanism, movement to the cell membrane, cell-to-
cell spread of infection

• Intracellular multiplication causes cell damage and

death resulting in mucosal ulcerations
Pathogenesis
 Pathogenesis

Virulence factors

• 120-140 MDa plasmid responsible for invasion and

spreading of bacteria among colonic cells (also
present in EIEC)

• Shigella enterotoxins ShET-1 and-2 alter electrolyte

transport and cause fluid secretion, and they also act
as cytotoxins by destroying epithelial cells
 Pathogenesis

Virulence factors

• Shiga-toxin – enterotoxin produced by S.dysenteriae

type 1, also plays a role in microangiopathic
complications (also present in EHEC)
 Clinical presentation

• Incubation period 24-48 hours

• 25% of patients have no symptoms

• 25% have mild fever

• 25% have fever and self-limited watery diarrhea

• 25% have fever and watery diarrhea that progress to

bloody diarrhea (dysentery)
Bloody diarrhea with mucus
 Clinical presentation

• Abdominal cramps

• Tenesmus- the painful straining with stooling that

may lead to rectal prolapse

• Bacteremia in young children and AIDS

• Complications- toxic megacolon and perforation

• Prolonged carriage of Shigella in AIDS

 Extraintestinal manifestations

• Hemolytic-uremic syndrome (HUS)

Anemia with congestive heart failure

Anuria with renal failure

Leukemoid reaction

Thrombocytopenia

Encephalopathy

• Seizures in young children with high fever

• Reiter`s syndrome- reactive arthritis

 Diagnosis

• Stool culture (Mac Conkey agar,Salmonella-Shigella

agar, Hektoen enteric or xylose-lysine-dexycholate)

• PCR

• Enzyme immunoassay for detection of Shiga-toxin in

the stool
 Salmonella-Shigella (SS) agar

• Typical uncoloured
colonies of Shigella
(flexneri)
 Shigellosis: Endoscopy

• Endoscopy- mucosa is
hemorrhagic with
mucous discharge, focal
ulcerations and exudate
in distal colon
 Diagnosis

• Positive fecal leukocytes

• Leukocytosis

• Anemia due to blood loss

• Prerenal azotemia and acidosis (dehydration)

 Treatment

• Mild diarrhea- oral rehydration

• Dysentery- rehydration (oral, intravenous) and

antibiotics

• Many shigellae are resistant to ampicillin and

trimethoprim-sulfamethoxazole

• Drugs of choice- 4-fluoroquinolones (ciprofloxacin),

azithromycin, ceftriaxone
 Treatment

• Toxic megacolon- colectomy

• Haemolytic-uremic syndrome (HUS)- dialysis

• Prevention- adequate environmental and personal

hygiene
 Entamoeba hystolitica

• Fecal-oral infection (contaminated water and food,

anal-oral transmission among homosexuals)

• Cysts are infective, and trophozoites are responsible

for invasion and inflammation of the mucosa
 Presentation

• Mild diarrhea

• Dysentery

• Chronic diarrhea with weight loss

• Extraintestinal disease –liver abscess

 Therapy

Invazive amebiasis and abscess

• Metronidazole 3x750 mg PO 10 days

• Metronidazole 3-4x500 mg IV 10 days

Eradication of cysts

• Paromomycine 3x500 mg PO 10 days

 Campylobacteriosis

• Motile curved gram-negative rods

• Campylobacters are found in the gastrointestinal

tract of many animals and household pets

• Human is infected by using raw and undercooked

food products (poultry, milk) or through direct
contact with animals
 Clinical presentation

• Incubation period 1-7 days

• Fever, headache, myalgia (first 12-48h)

• Abdominal pain (cramping)

• Diarrhea varies from severeal watery stools to bloody

stools
 Clinical presentation

Complications:

• Bacteremia in patients with AIDS and

hypogammaglobulinemia

• Cholecystitis, pancreatitis, endocarditis, reactive

arthritis

• Guillain-Barré syndrome (Campylobacter triggers 20-

40% of all cases)
 Diagnosis

• Stool culture in Campylobacter-specific media

• Blood culture

• Direct microscopic examination of stool: organisms

with vibroid morphology
 Treatment

• Fluid and electrolyte replacement

• In case of high fever and bloody diarrhea persisting

for more than 1 week antibiotics are indicated:

erythromycin, clarithromycin, azithromycin,

ciprofloxsacin

• For systemic infections: gentamycin, imipenem,

ciprofloxsacin
E.Coli
Pathotypea Epidemiology Clinical Defining Molecular Responsible
Intestinal Pathogenic
Syndrome b
E. coli
Trait Genetic Elementc
EHEC Food, water, Hemorrhagic colitis, Shiga toxin Lambda-like Stx1-
person-to-person; hemolytic-uremic or Stx2-encoding
all ages, syndrome bacteriophage
industrialized
countries
ETEC Food, water; young Traveler's diarrhea Heat-stable and - Virulence plasmid(s)
children in and labile enterotoxins,
travelers to colonization factors
developing
countries
EPEC Person-to-person; Watery diarrhea Localized EPEC adherence
young children and adherence, factor plasmid
neonates in attaching and pathogenicity island
developing effacing lesion on (locus for
countries intestinal epithelium enterocyte
effacement)
EIEC Food, water; Dysentery Invasion of colonic Multiple genes
children in and epithelial cells, contained primarily
travelers to intracellular in large virulence
developing multiplication, cell- plasmid
countries to-cell spread
EAEC ? Food, water; Traveler's diarrhea, Aggregative/diffuse Chromosomal or
children in and acute diarrhea, adherence, plasmid-associated
travelers to persistent diarrhea virulence factors adherence and
developing regulated by AggR toxin genes
countries; all ages,
industrialized
countries
 Traveler`s diarrhea

• Ingestion of contaminated food and water

• Illness begins within first 3-5 days

• Abdominal cramps and watery diarrhea

• Disease is self-limited lasting for 1-5 days

• Causes: enterotoxigenic E.coli, Shigella, Salmonella,

Campylobacter, Vibrio spp., Giardia, Entamoeba
hystolitica, Cryptosporidium, Cyclospora, Rotavirus
 EHEC O157:H7

• Fecal-oral transmission mostly through the

contaminated water and food

• Source: digestive tract of the cattle and wild animals

(deer, swine)
 Pathogenesis and clinical presentation

• Bacteria is invasive and produces Shiga-like toxin

• Incubation period 3-4 days

• Abdominal cramps, diarrhea, blood and mucus in stool

• HUS (10%), mortality 3-5 %

 Therapy

• Symptomatic
• The use of antibiotics is contradictory
• Dialysis