90% of infectious diarrheas are caused by ______
•Persistent diarrhea (> 10-14 days) is likely from ______
What is one thing you need to start considering with chronic diarrhea?
HIV status- diarrhea is a BIG problem with AIDs pts.
–Mycobacterium avium intracellulare, CMV
What bugs cause inflammatory diarrhea?
•Enterohemorrhagic E. coli
•Enteroinvasive E. coli
Describe Shigella, E. Coli, and Salmonella (all Enterobactereriaceae)
These are all gram-facultative anaerobic rods that:
are oxidase NEGATIVE (colorless on an oxidase test; i.e. cytochrome c oxidase negative)
-can reduce nitrates to nitrite (positive on a dipstick test)
All are motile except Shigella
What are some antigenic structures of Shigella, E. Coli, and Salmonella?
H (flagellar) antigens
O antigens: O-side chain (polysaccharide) of LPS
K antigen: Capsule
Shigella: O and K only, no H (not motile)
Salmonella: O, H, and Vi (capsular)
E. Coli: O, H, and K
E. coli are part of normal GI flora. Why dont they normally cause infection?
Don’t cause infection because they lack PAI
non-motile (negative on motility test),
glucose fermenting; no lactose fermentation; does not produce H2S (red slant; yellow butt on KIA Slant),
What are some prominent species of Shigella?
–S. dysenteriae: Epidemics in Central/South America
–S. sonnei: 70% of U.S. cases, mostly children
–S. flexneri: 2nd most common in US, most common worldwide
Is Shigella easy to get?
YES!! It is HIGHLY transmittable with a low infectious dose
1 of the most common causes of bloddy diarrhea (resulting in 1 million deaths/yr).
How is Shigella spread?
fecal-oral usually via contaminated water/food
What pts commonly get Shigella?
–Daycare centers, migrant workers, travelers to developing countries, nursing homes
What is this?
Describe the pathogenesis of Shigella
Shigella is taken up by GI epithelial (M) cells in the intestine and proliferate intracellularly, and then escape into the lamina propria where they are phagocytosed by macrophages. Inside macrophages, shigella induced apoptosis, producing an inflammatory response that damages epithelia and allows Shigella to gain access to colonic epithelial cells where they can invade
How does Shigella spread to adjacent cells once in the colonic epithelial cells?
Shigella spreads into adjacent cells via bacterium-induced, membrane- bound protrusions from the surface of the host cell. The formation of these protrusions depends on cellular actin polymerization proteins called formins.
The bacterium lyses the membranes that surround it, freeing itself into the cytoplasm of the new cell
How does Shigellosis present (give the incubation period and duration of illness)?
1 week incubation period following infection followed by:
-onset of watery diarrhea (which progresses to dysentery (bloody) in 50%),
-typically the onset of fever and abdominal pain.
All symptoms are self-limited and last about 1 week, typically
What are some complications of Shigellosis?
–reactive arthritis, urethritis, conjunctivitis (formerly known as Reiter’s syndrome)
What is a unique complication of S. dysenteriae and why?
Hemolytic uremic syndrome, if it produces Shiga (AB) toxin
ABX can be used to shorten the disease course of Shigellosis and reduce the duration of organism shedding in stools (ie. less likely to pass on). What are the preferred ABX options?
Ceftriaxone, Ciprofloxacin, Azithromycin
T or F. E. Coli can cause inflammatory and non-inflammatory diarrhea
What are the 5 major strains of diarrheagenic E. Coli?
–Enterohemorrhagic E. coli (inflammatory)
–Enteropathogenic E. coli (non-inflammatory)
–Enterotoxigenic E. coli (non-inflammatory)
–Enteraggregative E. coli (non-inflammatory)
–Enteroinvasive E. coli (inflammatory)
Describe Enterohemorrhagic E. Coli (aka STEC- Shiga toxin producing E. Coli). What are the common sources?
This is the classic O157:H7 E.Coli caused by ingesting (foodbourne):
inadequately cooked meat (hamburgers), contaminated vegetables and milk (Or human-to-human spread- low infectious dose)
This produces Shiga-like toxins and thus presents clinically very similarly to Shigellosis (S. dysenteriae), requiring hospitalization in 25-50% of pts.
Enterhemorrhagic E. Coli causes ____
Describe the virulence factors of EHEC
–Locus of Enterocyte Effacement (LEE)
•Type III secretion system (Delivers E. coli receptor to host cell)
•Pedestal formation for attachment (Responsible for the diarrhea)
How does EHEC present? Duration of illness?
acute onset of cramps and watery diarrhea initially. Within 24 hrs, the diarrhea becomes bloody (hemorrhagic colitis) and lasts an additional 8 days typically
-O157:H7 strains more likely to cause large outbreaks, bloody diarrhea, hemolytic uremic syndrome, and ischemic colitis
What toxins does EHEC use?
–Shiga toxins (or Shiga-like toxins), which are AB toxins encoded on a lysogenic bacteriophage
How do Shiga AB toxins work?
B subunits bind toxin to its receptor on cells and then:
the A subunit then enters the cytosol and cleaves a specific adenine residue from the 28S rRNA of the 60S ribosomal subunit, halting protein synthesis and causing death
Hemolytic uremic syndrome is a feared, less common complication of ____ and ______
EHEC and Shigellosis (less common)
NOTE: EHEC accounts for over 90% of HUS in children (but only complicates 6-9% of EHEC infections)
HUS caused by EHEC or Shigellosis is one of the main causes of ____ in children under 3 yo