What is the definition of acute diarrhea?
3 or more loose stools per day lasting less than 2 weeks.
Chronic diarrhea: persists greater than 4 weeks
What is the major difference between inflammatory and non-inflammatory diarrhea?
Inflammatory diarrhea is marked by the presence of blood (aka dysentery) while non-inflammatory diarrhea is more marked by watery diarrhea
What are some general characteristics of inflammatory diarrhea?
–WBCs and RBCs seen in stool
–Fever is common
–Small volume diarrhea
–Colon is commonly affected
What are some general characteristics of non-inflammatory diarrhea?
–No cells in stool
–Large volume diarrhea
–Small intestine is commonly affected
What are the main causes of non-inflammatory diarrhea?
•Enterotoxigenic E. coli
•Enteropathogenic E. coli
•Enteroaggregative E. coli
Describe Enterotoxigenic E. Coli
This infection typically occurs via contaminated food/water and is a major cause of traveler's diarrhea
How does ETEC present?
Watery diarrhea, ranging from mild to severe, and typically lasting 1-5 days
Describe the pathogenesis of ETEC
ETEC produces heat-labile toxin (LT) and heat-stabile toxin (ST)
Describe LT of ETEC
LT is similar to Cholera toxin. It stimulates adenylate cyclase and increases intracellular cyclic AMP, resulting in secretion of chloride from intestinal crypt cells and inhibition of absorption of sodium chloride at the villous tips. Secretion of free water into the intestinal lumen follows, manifesting clinically as watery diarrhea
Describe ST of ETEC
ST activates enterocyte cyclic GMP, also leading to stimulation of chloride secretion and inhibition of sodium chloride absorption. End result again is secretion of free water into the intestinal lumen and watery diarrhea
Describe Enteropathogenic E. Coli (EPEC)
This infection produces a profuse, watery diarrhea that can be severe with vomiting and dehydration and is most commonly associated with illness in children under 6 mo.-2 yo in developing countries
Describe the pathogenesis of EPEC
•Organism characterized by ability to produce attaching and effacing lesions and formation of pedestal like structures (LEE)
–No Shiga toxin produced
Describe EAEC (enteroaggregative E. Coli)
•Cause of diarrhea in children and adults in both developed and developing countries
–Also can affect HIV patients in developing countries (and probably developed countries)
–Can cause traveler’s diarrhea
•Pathogenesis not well understood
What are some other kinds of E. Coli infections?
-Nosocomial (can lead to sepsis)
-Neonatal meningitis due to encapsulated strains (K1-antigen)
-Uropathogenic E. Coli (UPEC)
UPEC causes 90% of UTIs (more common in females) with symptoms including urgency, frequency, fysuria, pyuria, suprapubic pain, and fever
How is UPEC UTI diagnosed?
–Diagnosis: bacteria in urine
•>105 per ml in females
•>103 per ml in males
What are the virulence factors used by UPEC?
–Virulence factors include a P fimbriae (also called PAP pili), and a capsule (K antigen)
This is a comma-shaped, gram - rod that is motile due to a polar flagellum and is oxidase POSITIVE
Where is vibrio commonly found?
In saltwater (disease common in warm months)
What are the significant human vibrio pathogens?
How is Vibrio cholerae transmitted?
Transmitted primarily through fecally contaminated drinking water, less often food and is known for becoming rampant/epidemic in areas devastated by natural/man-made disasters (i.e. earthquakes, etc.) and in areas with poor sanitation, malnutrition, overcrowding, and/or inadequate medical services
•Marked season variation in incidence of infection in most climates due to rapid growth of Vibrio bacteria in warmer temperatures
Epidemiology of Vibrio cholerae
5-10 mill cases/yr
Endemic in Asia, Africa, S. America, and Indian subcontinent
What are the reservoirs of Vibrio cholerae?
Humans, marine shellfish
What is serotyping of Vibrio cholerae based on?
200+ serotypes based on the O antigen
What Vibrio cholerase serotypes are responsible for epidemic and pandemic cholera?
O1 (two biotypes: E1 Tor and Classic) and O139
Describe the pathogenesis of Vibrio Cholerae
Pathogenesis is dependent on colonization of the small intestine (which requires a LARGE no. of bacteria to be ingested because VC is sensitive to stomach acid- high infectious dose) and secretion of toxins
How does VC adhere to small intestine cells?
Adherence to cells of brush border of the gut is related to secretion of the bacterial enzyme mucinase which dissolves glycoprotein covering over the intestinal cells.
What does VC do once mucinase allows it to adhere to brush border epithelial cells?
–Organism then multiplies and secretes cholera toxin – AB toxin
Describe Cholera AB toxin
•5 B (binding) subunits: binds to ganglioside receptor on the surface of the enterocyte.
•1 A (active) subunit: inserted into the cytosol and catalyzes addition of ADP-ribose to the Gs (stimulatory G) protein. Causes persistent stimulation of adenylate cyclase.
–As a result, cyclic AMP is overproduced and activates cyclic AMP-dependent protein kinase which phosphorylates ion transporters in the cell membrane, resulting in the loss of water and ions from the cell. Watery efflux enters the lumen of the gut and massive watery diarrhea ensues
Mechanism of Cholera AB toxin